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Human brain

The human brain is the central organ of the nervous system, a complex structure of nervous tissue weighing approximately 1.4 kilograms (3 pounds) in adults and containing about 86 billion neurons interconnected by trillions of synapses. It serves as the primary control center for the body, processing sensory input from the environment, initiating and regulating voluntary and involuntary movements, managing emotions, and enabling higher cognitive functions such as learning, memory, language, and decision-making. The brain is protected by the bony cranium of the skull, three layers of meninges (dura mater, arachnoid mater, and pia mater), and cerebrospinal fluid (CSF), which cushions it against mechanical shock and maintains a stable internal environment. The brain is divided into three primary regions: the , cerebellum, and brainstem, each with specialized roles in coordinating bodily functions. The cerebrum, comprising about 85% of the brain's mass, is the largest and most evolved part, split into left and right hemispheres connected by the corpus callosum for interhemispheric communication. It features an outer layer of gray matter known as the cerebral cortex, which is highly folded into gyri and sulci to increase surface area for processing complex information. The cerebrum is further subdivided into four lobes: the , responsible for executive functions like planning, problem-solving, and motor control; the , which integrates sensory information such as touch and spatial awareness; the , involved in auditory processing, language comprehension, and memory formation; and the , dedicated to visual processing. The cerebellum, located at the base of the brain, fine-tunes motor movements, maintains balance, and contributes to some cognitive tasks like attention and . The brainstem, connecting the brain to the , regulates vital autonomic functions including heart rate, breathing, sleep-wake cycles, and basic reflexes. Beneath the cerebrum lies the diencephalon, including the (sensory relay station) and (regulator of , hunger, and hormone release). Deep within the brain are subcortical structures like the , which governs emotional responses and memory through components such as the (fear and emotion processing) and (long-term memory consolidation). The brain's functionality relies on a vast network of neurons communicating via electrical impulses and chemical neurotransmitters, supported by glial cells that provide nourishment and insulation. Blood flow, delivered by the cerebral vasculature, supplies oxygen and nutrients, while the blood-brain barrier selectively filters substances to protect neural tissue from toxins. Disruptions to these systems, such as through , , or aging, can profoundly impact cognition and behavior, underscoring the brain's intricate balance.

Structure

Cerebrum

The is the largest region of the human brain, comprising approximately 85% of its total mass and serving as the primary site for higher cognitive and sensory-motor functions. It is divided into two hemispheres, the left and right, separated by the , which allows for some degree of functional lateralization. These hemispheres are interconnected by the , a thick band of containing over 200 million axons that facilitates communication between the two sides. The cerebrum is subdivided into four main lobes, each with distinct anatomical boundaries and specialized roles. The , located anterior to the and superior to the lateral fissure, is the largest lobe and houses the in the , responsible for voluntary movement control, as well as regions for such as , , and problem-solving. The parietal lobe, positioned posterior to the and superior to the , integrates sensory information, with the in the processing touch, pain, temperature, and . The temporal lobe, situated inferior to the lateral fissure, contains the for sound processing, for language comprehension (typically in the left hemisphere), and structures involved in memory formation and emotional processing. The occipital lobe, the most posterior region bounded by the , is dedicated to visual processing, including the that interprets color, shape, motion, and depth from inputs. The cerebral surface is characterized by a convoluted pattern of gyri (elevated ridges) and sulci (shallow grooves), which increase the cortical surface area to about 2,500 square centimeters while fitting within the . Prominent features include the (Rolandic fissure), a deep groove running vertically that separates the frontal and parietal lobes and marks the boundary between motor and sensory cortices, and the lateral fissure (Sylvian fissure), a horizontal groove that delineates the from the frontal and parietal lobes above. These patterns are relatively consistent across individuals but exhibit subtle variations that influence functional organization. Beneath the cortex lies the , consisting of myelinated axon bundles that connect cortical areas and relay signals to subcortical structures. Key tracts include the , a compact V-shaped bundle located between the and , comprising anterior and posterior limbs that carry corticospinal motor fibers, thalamocortical sensory projections, and connections to the and . Another important association tract is the arcuate fasciculus, which arcs around the lateral fissure to link the frontal, parietal, and temporal lobes, particularly Broca's and Wernicke's areas, supporting articulation and repetition. The itself is a thin sheet of gray matter, approximately 2-5 mm thick, organized into six distinct layers that vary slightly by region but follow a laminar pattern in the , which constitutes over 90% of the cortical surface. Layer I (molecular layer) contains mostly dendrites and axons with few bodies; Layer II (external granular) and Layer IV (internal granular) are rich in small cells for local processing; Layers III (external pyramidal) and V (internal pyramidal) feature projection neurons that send outputs to other brain regions; and Layer VI (multiform) includes fusiform cells that feedback to the . Functionally, neurons are arranged in vertical columns, approximately 300-500 micrometers wide, where cells within a column share similar receptive fields and process related information, as exemplified by orientation columns in the or tonotopic organization in auditory areas. The relays sensory inputs to these cortical layers, while the receives its primary blood supply from the internal carotid arteries via the circle of Willis.

Diencephalon

The , situated at the core of the , comprises several interconnected structures that serve as critical relays for sensory information, regulators of endocrine and autonomic functions, and integrators of arousal and circadian rhythms. It lies between the cerebral hemispheres superiorly and the inferiorly, surrounding the third ventricle, and includes the , , , and subthalamus. These components collectively modulate , release, and basic without the extensive cortical layering seen in higher brain regions. The thalamus, the largest diencephalic structure, acts as a primary gateway for sensory and motor signals to the cerebral cortex, consisting of numerous nuclei organized into anterior, medial, lateral, and intralaminar groups. Specific relay nuclei include the lateral geniculate nucleus, which processes visual input from the retina via retinogeniculate projections before relaying to the primary visual cortex, and the ventral posterior nucleus, subdivided into ventral posterolateral (for somatosensory input from the body) and ventral posteromedial (for facial sensations) components that convey tactile and proprioceptive data through thalamocortical fibers to the somatosensory cortex. These thalamocortical projections form reciprocal loops, enabling bidirectional communication that refines sensory perception and attention. The , located ventral to the , integrates autonomic, endocrine, and behavioral responses through its collection of nuclei, exerting control over visceral functions like hunger, , and . Key nuclei include the paraventricular nucleus, which synthesizes and releases (CRH) to initiate the hypothalamic-pituitary-adrenal axis for responses, and oxytocin to modulate social bonding and via projections to the . The , the master circadian pacemaker, receives photic input from the to synchronize physiological rhythms, influencing sleep-wake cycles and hormone secretion through efferents to other hypothalamic regions and the . These nuclei maintain by linking neural signals to autonomic outputs, such as sympathetic activation for cardiovascular regulation. The , forming the dorsal roof of the third ventricle, encompasses the and habenular nuclei, with the serving as the primary site for synthesis to regulate circadian and seasonal rhythms. Composed mainly of pinealocytes, the gland converts serotonin to via enzymes like arylalkylamine N-acetyltransferase, peaking production in darkness to promote sleep and inhibit reproductive hormones, as evidenced by its responsiveness to suprachiasmatic signals. The habenular nuclei, connected to limbic structures, contribute to reward processing and aversion, relaying inputs from the to centers. The subthalamus, positioned inferior to the , primarily includes the subthalamic nucleus, a key node in the circuitry that facilitates through excitatory projections. It receives inputs from the externa and , sending outputs to the interna and pars reticulata to modulate indirect pathway activity, thereby inhibiting unwanted movements and supporting action selection in models where its hyperactivity disrupts balance. These connections integrate with broader loops to refine voluntary motor execution. Enclosing the diencephalon, the choroid plexus in the third ventricle forms the blood-cerebrospinal fluid (CSF) barrier, a selective interface that produces CSF while regulating solute and immune factor exchange between blood and brain extracellular fluid. Unlike the blood-brain barrier, this epithelium features tight junctions and transport proteins, such as sodium-potassium ATPase, to maintain CSF composition for neuronal support and waste clearance, with disruptions linked to hydrocephalus and neuroinflammation.

Cerebellum

The cerebellum, located in the inferior to the occipital lobes of the , constitutes approximately 10% of the total brain volume but contains over half of the brain's neurons. It is separated from the by the tentorium cerebelli, a dural fold that forms part of the and supports the weight of the occipital lobes while providing a barrier between the supratentorial and infratentorial compartments. The is divided into two hemispheres connected by a midline structure known as the vermis, which primarily coordinates axial and proximal movements of the and muscles. Laterally, the hemispheres are further subdivided into an intermediate zone for fine-tuning distal limb movements and a lateral region involved in planning complex motor sequences. Posteriorly, the , separated by the posterolateral fissure, integrates with the to maintain balance and eye movements. Internally, the cerebellar exhibits a highly folded structure called , which maximizes surface area for neural processing, and is organized into three distinct layers. The outermost molecular layer contains the dendrites of s along with inhibitory such as and stellate cells, facilitating local signal modulation. The middle Purkinje layer consists of a single row of large, flask-shaped Purkinje neurons, which serve as the primary output cells of the and project exclusively to the deep nuclei using as a . The innermost granular layer is densely packed with small granule cells, whose axons form parallel fibers that onto Purkinje cell dendrites in the molecular layer, enabling widespread excitatory input. Beneath the lies containing the —dentate, interpositus (including emboliform and globose), and fastigial—which receive convergent inputs from the cortical layers and serve as relay stations for cerebellar efferents. The dentate nucleus predominates in the lateral hemispheres and supports skilled voluntary movements, while the interpositus handles limb coordination and the fastigial manages and . Afferent inputs to the cerebellum arrive primarily via two types of fibers, relaying sensory and motor information for integration. Mossy fibers, originating from the pontine nuclei and other brainstem sites such as the and , provide the main excitatory input using glutamate; they synapse onto granule cells, which in turn excite through parallel fiber pathways, conveying contextual motor commands from the . Climbing fibers, arising exclusively from the contralateral in the medulla, form powerful excitatory synapses directly onto dendrites, with each receiving input from only one climbing fiber, allowing precise signaling of discrepancies in movement execution. Efferent outputs from the cerebellum are channeled through the deep nuclei and exit primarily via the superior cerebellar peduncles, which decussate in the before projecting to the contralateral ventrolateral . From the , these signals reach the motor and premotor cortices, influencing descending motor pathways to refine voluntary actions without direct cortical innervation. The contributes outputs via the inferior cerebellar peduncle to the , supporting axial control. The cerebellum plays a pivotal role in motor coordination, balance, and the fine-tuning of movements by detecting and correcting errors in ongoing actions. It facilitates predictive motor learning by generating internal models that anticipate sensory consequences of intended movements, allowing preemptive adjustments to minimize discrepancies between predicted and actual outcomes. Through climbing fiber signals representing error information and mossy fiber pathways providing contextual data, the cerebellum enables adaptive refinement of motor commands, essential for smooth execution of complex sequences. This circuitry also contributes briefly to cognitive timing processes, such as interval estimation in non-motor tasks.

Brainstem

The brainstem is the posterior part of the brain that connects the and to the , serving as a conduit for ascending and descending neural pathways while regulating essential autonomic functions such as , cardiovascular control, and maintenance. It consists of three main divisions arranged in a rostrocaudal sequence: the superiorly, the in the middle, and the inferiorly. These structures house critical nuclei and tracts that ensure survival reflexes and sensory-motor integration. The , also known as the mesencephalon, is the smallest division and lies between the and . It features a tectum comprising the superior colliculi, which process visual reflexes, and the inferior colliculi, involved in auditory relay. Ventral to the tectum is the , containing the for motor coordination with the and the , a nucleus that projects to the via the to modulate movement. The also includes the , facilitating (CSF) flow. The , bridging the and medulla, contains pontine nuclei that relay cortical inputs to the for refinement and respiratory centers that modulate rhythm. It connects to the via the middle cerebellar peduncles and houses nuclei for several , contributing to sensation and . The medulla oblongata, continuous with the at the , is the most caudal division and controls vital cardiorespiratory functions through specialized centers. It features ventral carrying corticospinal motor fibers, which undergo for contralateral control, and the inferior olivary nuclei that provide climbing fiber inputs to the for . Spanning all three divisions is the reticular formation, a diffuse network of neurons integrating sensory and motor signals. Its ascending components, part of the reticular activating system, project to the and to promote and , while descending components via reticulospinal tracts regulate , , and autonomic reflexes like . This formation integrates with the to sustain . The brainstem contains the nuclei for cranial nerves III through XII, organized in longitudinal columns for motor, sensory, and autonomic functions. In the midbrain, the oculomotor (III) nucleus controls eye muscles and pupillary constriction, and the trochlear (IV) nucleus innervates the for eye rotation. Pontine nuclei include the trigeminal () for facial sensation and mastication, abducens () for lateral eye movement, facial (VII) for facial expression and taste, and vestibulocochlear (VIII) for hearing and balance. In the medulla, the glossopharyngeal (IX) and vagus (X) nuclei manage swallowing, salivation, and parasympathetic visceral control; the accessory (XI) innervates neck muscles; and the hypoglossal (XII) controls tongue movements. Key decussations occur within the to enable contralateral processing. The pyramidal decussation in the caudal medulla crosses approximately 90% of corticospinal motor fibers, forming the for voluntary movement. Sensory pathways, such as the for touch and , decussate in the medulla via the internal arcuate fibers, while the trigeminal lemniscus for facial touch crosses in the or . The lies between the , medulla, and , receiving CSF from the and distributing it through the foramina of Luschka (lateral) and Magendie () into the subarachnoid space and spinal , thus aiding in delivery and waste removal. Its produces a portion of the total CSF volume.

Meninges and ventricles

The are three protective layers that envelop the brain and , providing mechanical support, cushioning against trauma, and facilitating (CSF) circulation. The outermost layer, the , is a thick, fibrous composed of two sublayers: the periosteal layer, which adheres to the inner surface of the , and the meningeal layer, which lies closer to the brain. The dura forms dural reflections, including the , a sickle-shaped fold that separates the cerebral hemispheres along the midline, and the tentorium cerebelli, a tent-like structure that divides the cerebrum from the . These reflections help compartmentalize the brain and house for blood drainage. Beneath the dura lies the arachnoid mater, a delicate, avascular web-like membrane that does not directly contact the brain surface but bridges the cortical sulci. It consists of a superficial mesothelial layer, a central trabecular zone, and a deep collagen-rich layer, with arachnoid villi protruding into the dural sinuses. The arachnoid defines the subarachnoid space, a fluid-filled compartment between it and the innermost pia mater, which contains CSF, major , and delicate trabeculae that span the gap. This space includes enlarged regions known as cisterns, such as the , the largest cistern located between the and , which receives CSF outflow from the and accommodates structures like the vertebral arteries and lower . The , the thinnest and most vascular meningeal layer, closely adheres to the brain's surface, conforming to the gyri and sulci. It features two sublayers—an outer epipial layer with fibers and an inner intima layer with and reticular fibers—and extends along blood vessels as perivascular sheaths, aiding nutrient delivery to neural tissue. Together, the safeguard the brain from mechanical injury while enabling CSF dynamics. The comprises a network of interconnected, CSF-filled cavities within the that produce, store, and circulate this fluid. The , one in each , are C-shaped chambers extending into the frontal, temporal, and occipital lobes, with a body in the parietal region and horns projecting anteriorly, posteriorly, and inferiorly; each holds approximately 7-10 ml of CSF. They connect to the third ventricle via the interventricular foramina of Monro. The third ventricle is a narrow, slit-like cavity situated in the between the thalami and above the , featuring recesses such as the infundibular and optic regions, and it links posteriorly to the through the of Sylvius, a slender 15-18 mm channel traversing the . The , located in the , forms a tent-shaped space bounded anteriorly by the and medulla and posteriorly by the , with a floor and connections to the subarachnoid space via the foramina of Luschka (lateral) and Magendie (median). CSF production occurs primarily in the choroid plexuses, specialized ependymal cell clusters that filter from blood capillaries to generate approximately 500 ml of CSF daily. These plexuses are located in the (along the choroidal fissure between the fornix and ), the roof of the third ventricle (hanging from the ), and the (as T-shaped fringes in the lateral recesses and roof). The filtration mechanism involves selective transport across tight junctions in the choroidal epithelium, creating a that nourishes the and removes waste. CSF reabsorption into the venous system occurs mainly through arachnoid granulations, tuft-like projections of the that extend into the , particularly the . These structures enable bulk flow of CSF into the bloodstream via a pressure-dependent , maintaining a daily turnover where production matches absorption to preserve .

Microanatomy

The microanatomy of the human brain encompasses the cellular and subcellular organization of its neural tissue, primarily composed of neurons and glial cells that form intricate networks for information processing and support. Neurons serve as the fundamental signaling units, while provide structural, metabolic, and protective functions, with outnumbering neurons at approximately a 3:1 ratio in the (16.3 billion neurons and 60.8 billion ), while the overall brain ratio is roughly 1:1 (86 billion each). This organization enables the brain's complex architecture, observable through specialized histological techniques that reveal cellular and connectivity. Neurons in the human brain exhibit diverse morphologies and functions tailored to specific regions. Pyramidal neurons, the predominant excitatory type in the , feature a triangular cell body, a prominent apical extending toward the pial surface, and basal dendrites, with their often projecting to distant targets; they release glutamate as the primary . cells, small and numerous in the , function as inhibitory neurons, receiving inputs from mossy fibers and relaying signals via parallel fibers to Purkinje cells, contributing to . , comprising about 20-30% of cortical neurons, mediate local modulation within circuits, such as cells inhibiting nearby pyramidal neurons or cells targeting initial segments to control firing. Glial cells constitute a heterogeneous population essential for maintaining neural integrity and homeostasis. Astrocytes, star-shaped cells abundant in the cortex and , provide metabolic support to neurons, regulate balance, and form endfeet that interface with blood vessels to influence the blood-brain barrier. Oligodendrocytes, responsible for myelination in the , extend processes to wrap multiple axonal segments in lipid-rich sheaths, facilitating efficient signal propagation. Microglia, the resident immune cells derived from progenitors, constantly survey the for debris or pathogens, pruning synapses during development and responding to injury. Ependymal cells line the ventricles and , featuring cilia that promote circulation and microvilli for nutrient absorption. At the subcellular level, synapses represent the junctions where neurons communicate, consisting of a presynaptic terminal, a narrow synaptic cleft, and a postsynaptic density. The presynaptic terminal, a swollen bouton, contains synaptic vesicles filled with neurotransmitters docked at active zones for release. The synaptic cleft, measuring 20-40 nm in width, serves as the across which neurotransmitters diffuse. The postsynaptic density, a thickened electron-dense on the receiving , anchors receptors and signaling proteins, particularly prominent in excitatory synapses where it organizes and NMDA receptors. Neural circuits in the integrate local and long-range connections to information hierarchically. Local circuits, such as minicolumns—vertical assemblies of about 80-110 neurons (~30-50 μm wide) spanning all layers—and larger cortical columns (hypercolumns, ~300-500 μm wide with thousands of neurons)—enable feature-specific , with minicolumns handling basic sensory elements like orientation in . Long-range circuits include commissural fibers, which traverse the to interconnect homologous regions between , and association fibers, which link disparate cortical areas within the same hemisphere, such as the arcuate fasciculus frontal and temporal lobes for functions. These circuits underpin distributed computation, with pyramidal neurons often serving as principal integrators. Histological staining techniques are crucial for visualizing this microanatomy in fixed tissue sections. The Nissl stain, using basic dyes like , selectively binds to RNA-rich Nissl bodies in neuronal somata and dendrites, highlighting cell bodies and cytoarchitecture while leaving axons pale; it distinguishes cortical layers and identifies neuronal loss in . Other methods, such as silver impregnation (Golgi technique), reveal full neuronal morphology including dendrites and spines in sparse labeling, aiding circuit mapping. with antibodies targets specific proteins, like GFAP for or MBP for , complementing classical stains for detailed identification.

Cerebrospinal fluid

(CSF) is a clear, colorless fluid that surrounds and protects the and , playing a crucial role in maintaining by providing mechanical support, facilitating nutrient exchange, and aiding in waste clearance. Produced primarily within the brain's , CSF circulates through specific pathways to bathe neural tissues, ensuring a stable internal environment despite fluctuations in blood composition. Its dynamic balance between production and is essential for normal brain function. The composition of CSF is tailored to support needs, consisting of approximately 99% water with key solutes including electrolytes such as higher concentrations of sodium (Na⁺, ~145-150 mEq/L), (Cl⁻, ~120-130 mEq/L), and magnesium (Mg²⁺) compared to , alongside lower levels of (K⁺) and calcium (Ca²⁺). It contains low levels of proteins (typically 15-45 mg/dL, much less than plasma's 6000-8000 mg/dL), glucose at about 60-70% of blood levels (40-70 mg/dL), and minimal cellular elements (fewer than 5 cells/mm³, mostly lymphocytes). This ultrafiltrate-like profile, achieved through selective transport, minimizes inflammatory components while enabling metabolic support. CSF is produced at a rate of approximately 400-600 mL per day in adults, primarily by the epithelium through mechanisms involving sodium-potassium pumps and cotransporters that drive fluid secretion from . This process renews the total CSF volume of 125-150 mL about 4-5 times daily. Circulation begins in the brain's ventricles, where CSF flows from the through the third ventricle and into the , then exits via the paired lateral foramina of Luschka and the midline foramen of Magendie into the subarachnoid space surrounding the brain and . Reabsorption occurs mainly at the arachnoid villi, protrusions into the that allow bulk flow back into the bloodstream, with additional drainage via routes and lymphatic pathways. Key functions of CSF include providing to the brain, reducing its effective weight from about 1,500 grams in air to roughly 50 grams—a 97% decrease that prevents mechanical strain on blood vessels and neural tissues—while also interacting with the to offer cushioning against . It delivers essential nutrients and hormones to brain cells, particularly those not transported efficiently across the blood-brain barrier, and facilitates waste removal through the , which clears metabolic byproducts like proteins and amyloid-β peptides during , helping prevent accumulation linked to neurodegenerative diseases. Additionally, its low cellular and protein content contributes to barrier selectivity, limiting entry into the . Intracranial pressure (ICP), largely determined by CSF dynamics, is normally maintained at 7-15 mmHg in the through the equilibrium of CSF production, circulation, and absorption. This is commonly measured via , where a needle is inserted into the subarachnoid space at the lower to assess opening , reflecting overall compliance. Deviations from this range can signal disruptions in , such as or trauma.

Blood supply

The blood supply to the human brain is provided by a network of arteries that deliver approximately 15-20% of the , ensuring a constant supply of oxygen and nutrients essential for neuronal function. The primary arterial sources are the two internal carotid arteries, which originate from the common carotid arteries in the neck, and the two vertebral arteries, which arise from the subclavian arteries and merge to form the . These vessels converge at the base of the brain to form the circle of Willis, a polygonal anastomotic ring that connects the anterior and posterior circulations, allowing for potential redistribution of blood flow. From the circle of Willis, the branch to supply the medial aspects of the frontal and parietal lobes, including the and parts of the . The middle cerebral arteries (MCAs), the largest branches, perfuse the lateral surfaces of the cerebral hemispheres, encompassing the frontal, temporal, and parietal lobes, as well as deep structures like the . The posterior cerebral arteries (PCAs), typically arising from the , provide blood to the , inferior , , and . These arterial territories are largely non-overlapping but interconnected via smaller vessels, minimizing the risk of widespread ischemia from localized occlusions. Venous drainage occurs through a system of superficial and deep veins that ultimately converge into . Superficial cortical veins collect blood from the and drain into the , , or , facilitating the removal of metabolic waste. Deep veins, including the internal cerebral veins and basal veins of Rosenthal, drain the , , and , merging into the great vein of Galen before joining the . Unlike arteries, cerebral veins lack valves and can drain in multiple directions, adapting to pressure gradients. Cerebral blood flow (CBF) is tightly regulated through autoregulation, a process that maintains steady at approximately 50-60 mL per 100 g of tissue per minute despite fluctuations in systemic between 60 and 160 mmHg. This myogenic response involves contraction or relaxation in arteriolar walls, triggered by changes in transmural pressure, ensuring consistent oxygen delivery. Metabolic factors, such as increased CO2 or decreased , can further modulate flow via . The and additional pial anastomoses provide collateral circulation, enabling alternative pathways for blood flow in cases of arterial occlusion, though the completeness of these connections varies among individuals. A complete is present in approximately 20-25% of individuals, offering robust protection against unilateral vessel compromise in those cases. Leptomeningeal collaterals between MCA, ACA, and branches further enhance this reserve, potentially mitigating the effects of focal ischemia.

Blood-brain barrier

The (BBB) is a highly selective semipermeable border that separates the circulating blood from the brain and in the , safeguarding neural tissue from harmful substances while permitting the passage of essential nutrients and signaling molecules. This protective interface is formed primarily by brain endothelial cells, which differ from peripheral by lacking fenestrations and exhibiting continuous tight junctions that restrict paracellular . The BBB's integrity relies on a neurovascular unit involving multiple cell types, ensuring the brain's unique microenvironment is maintained against systemic fluctuations. The structural foundation of the BBB centers on the endothelial cells of brain capillaries, interconnected by complex tight junctions composed of proteins such as , claudins (particularly claudin-5), and junctional adhesion molecules, which seal the intercellular clefts and prevent unregulated leakage of hydrophilic molecules. Surrounding these endothelial cells are end-feet, which envelop approximately 99% of the capillary surface and release factors like agrin that stabilize tight junctions and promote endothelial differentiation. , embedded within the capillary , further reinforce the barrier by regulating endothelial , vascular stability, and immune responses through direct contact and secreted signals. Together, these components form a dynamic interface that actively maintains cerebral . Transport across the BBB occurs via specialized mechanisms that balance protection with nutritional supply. Lipophilic substances such as oxygen (O₂) and (CO₂) cross readily through passive across the lipid-rich endothelial membranes, supporting rapid for neuronal . In contrast, polar hydrophilic nutrients like and require carrier-mediated active or facilitated transport; for instance, the GLUT1 (SLC2A1) facilitates bidirectional of glucose down its concentration gradient, ensuring a steady supply to energy-demanding brain cells. Similarly, dedicated transporters for , such as the large neutral amino acid transporter LAT1, enable their uptake for synthesis and protein production. These systems complement cerebrospinal fluid circulation in delivering nutrients, preventing deficiencies in the avascular brain . To expel potential toxins, the BBB employs efflux pumps, notably (P-gp, encoded by ABCB1), an ATP-binding cassette transporter expressed on the luminal surface of endothelial cells that actively pumps a wide range of lipophilic xenobiotics, drugs, and metabolic byproducts back into the bloodstream, thereby limiting their accumulation in the brain. This multidrug resistance mechanism enhances the barrier's neuroprotective role against environmental and endogenous threats. Regional variations in BBB permeability exist, particularly in circumventricular organs (CVOs) such as the in the medulla, which lack a complete barrier due to fenestrated and sparse tight junctions, allowing direct sensing of blood-borne hormones and peptides to regulate autonomic functions like and cardiovascular control. These specialized sites enable the to systemic signals without compromising the integrity of the broader neural tissue. Pathological conditions can compromise BBB function, leading to increased permeability; during inflammation, pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) disrupt tight junctions by downregulating claudin-5 and , facilitating leukocyte infiltration and edema formation in disorders such as and . This breakdown exacerbates and neuronal damage, highlighting the BBB's vulnerability in disease states.

Development

Embryonic stages

The development of the human brain begins during the third week of with the formation of the , a critical process known as primary . At this stage, the emerges from the ectodermal layer of the , thickening along the midline due to inductive signals from the underlying and surrounding . The folds to form neural folds that elevate and converge, creating a neural groove; by approximately day 22 of , the folds fuse dorsally to enclose the neural groove into a hollow , starting at the cervical level and progressing rostrally and caudally. The anterior neuropore closes around day 25, while the posterior neuropore seals by day 28, marking the completion of primary and establishing the foundational structure for the . This neural tube formation is tightly regulated by molecular signals from the , which secretes Sonic hedgehog (Shh) protein to ventralize the and promote floor plate development, while bone morphogenetic proteins (BMPs) from the overlying and lateral are inhibited to allow dorsal closure and patterning. Shh acts as a to specify ventral cell fates, ensuring proper bending and fusion of the neural folds, whereas BMP antagonists like noggin and chordin, expressed in the and dorsal midline, counteract BMP signaling to induce neural identity in the . Disruptions in these signaling pathways, such as mutations affecting Shh expression, can impair , highlighting their essential role in early brain . By the end of the fourth week of , the rostral portion of the expands and constricts to form three primary brain vesicles: the prosencephalon (), mesencephalon (), and rhombencephalon (). These vesicles represent the initial subdivision of the brain, with the prosencephalon giving rise to the future cerebral hemispheres and , the mesencephalon to the structures, and the rhombencephalon to the , , and . This vesiculation process establishes the basic anteroposterior axis of the brain and sets the stage for further regional specialization. Concurrent with neural tube closure, cells at the crest of the neural folds delaminate to form the , a transient migratory population that differentiates into diverse cell types contributing to the peripheral , including sensory and autonomic ganglia, Schwann cells for myelination of peripheral nerves, and melanocytes. Neural crest cells also contribute to the , particularly the leptomeninges covering the and , by migrating along defined paths influenced by cues and chemotactic signals like those from the slit/robo pathway. This migration begins around the time of neural tube fusion and is crucial for integrating central and peripheral neural components. Throughout these early stages, neural cells in the neuroepithelium exhibit rapid , with divisions occurring every 8-10 hours to expand the through symmetric divisions, followed by asymmetric divisions that generate postmitotic neurons. This proliferative phase is balanced by (), which eliminates overproduced cells; estimates indicate that more than 50% of generated neurons undergo prenatally, regulated by to refine neural circuits and prevent overcrowding. These dynamics ensure controlled growth of the and its derivatives during embryogenesis. Failure of neural tube closure leads to severe congenital defects known as neural tube defects (NTDs). results from incomplete closure of the anterior neuropore, causing absence of the and calvaria, often incompatible with postnatal survival. arises from posterior neuropore closure failure, ranging from occult forms with minimal symptoms to myelomeningocele, where neural tissue and protrude through a vertebral defect, leading to motor and sensory impairments. These defects affect approximately 1 in 1,000 pregnancies worldwide and are linked to , genetic factors, and teratogen exposure during weeks 3-4.

Fetal development

During the fetal period, which begins around the ninth week of following the embryonic stages where the primary brain vesicles differentiate into five secondary vesicles, these structures undergo significant expansion and maturation. The develops into the cerebral hemispheres, including the and , while the forms key components such as the and . Concurrently, the gives rise to the and , and the differentiates into the , establishing the foundational architecture of the and higher brain regions. A hallmark of fetal cortical development is the inside-out layering of neurons in the , occurring primarily between weeks 12 and 28 of . Newly generated neurons in the ventricular and subventricular zones migrate outward along radial glial fibers, with earlier-born neurons settling in deeper layers (such as layer ) and later-born ones positioning in superficial layers (such as layer ), creating the characteristic six-layered . This radial migration, guided by glial scaffolds, ensures precise laminar organization essential for cortical function. The emergence of gyri and sulci, which increase the cortical surface area to accommodate expanding neural tissue, begins in the second trimester and accelerates thereafter. Primary folds, such as the and , appear around the fifth gestational month (approximately 20 weeks), driven by tangential growth and mechanical forces within the cortical plate. Secondary and tertiary folds develop progressively toward birth, with the majority of the adult-like pattern established by term, reflecting the brain's adaptation to rapid neuronal proliferation. Synaptogenesis, the formation of synaptic connections between neurons, intensifies during the third , resulting in the establishment of trillions of synapses across the brain by the end of . This process begins earlier but peaks in rate around 34 weeks, with an estimated 40,000 synapses forming per second in the , supporting the groundwork for sensory and motor circuits. These connections are initially overproduced to allow for later refinement. The plays a crucial role in fetal development by supplying oxygen and nutrients through the , influencing the rate of neural growth and differentiation. Adequate placental ensures sufficient glucose and oxygen delivery to the developing , which consumes a disproportionate share of fetal ; disruptions in this supply can impair cortical expansion and layering. Hormonal factors from the , such as serotonin, further modulate and processes.

Postnatal growth

The human brain undergoes significant postnatal growth and maturation from infancy through , characterized by rapid increases in followed by structural refinement. At birth, the brain constitutes approximately 25-30% of its , doubling in size during the first year and reaching about 80% of by age 3, with further growth bringing it to 90-95% by age 6. This trajectory reflects the expansion of both gray and , driven by , gliogenesis, and vascularization, establishing a foundation for cognitive and sensory functions. Myelination, the process of insulating axons with sheaths to enhance neural transmission speed, progresses in a caudal-to-rostral and posterior-to-anterior sequence during postnatal development. It begins in the and shortly after birth, extends to the and primary sensory-motor areas by the first few years, and continues in association cortices, with the frontal lobes myelinating last into the early 20s. This protracted timeline in higher-order regions supports the gradual maturation of complex cognitive processes. Synaptic pruning refines neural circuits by eliminating excess synapses formed during early development, a use-dependent that peaks during to optimize efficiency and specificity. In regions like the , up to 50% of synaptic connections may be pruned between ages 10 and 20, strengthening frequently used pathways while weakening others. Concurrently, the and undergo targeted maturation essential for and executive control; hippocampal volume and connectivity expand through childhood to support formation, while prefrontal thinning and myelination during enhance and . Environmental factors modulate this postnatal trajectory, influencing brain volume and microstructure. Adequate nutrition, particularly omega-3 fatty acids like (DHA), promotes dendritic growth and synaptic integrity, with deficiencies linked to reduced cortical volume and impaired cognitive outcomes in children. Similarly, enriched stimulation—such as interactive caregiving and sensory experiences—increases hippocampal and prefrontal volumes by up to 10-15% in animal models and correlates with enhanced gray matter density in human infants, underscoring the role of early experiences in shaping neurodevelopmental resilience.

Neuroplasticity

Neuroplasticity refers to the brain's capacity to reorganize its structure, functions, and connections in response to intrinsic or extrinsic stimuli, enabling to experiences, learning, and throughout life. This dynamic process underpins recovery from neurological damage and supports , with evidence from and histological studies demonstrating changes in neural circuits even in adulthood. Building on postnatal that refines neural networks as a baseline for adaptability, neuroplasticity manifests through specific cellular and network-level . Key mechanisms include (LTP), a process where repeated synaptic activation leads to strengthened connections, primarily mediated by N-methyl-D-aspartate (NMDA) receptors that allow calcium influx to trigger signaling cascades for synaptic enhancement. LTP, first described in the , is essential for learning and formation, as it persistently increases synaptic following high-frequency stimulation. Complementing this, dendritic spine growth involves experience-dependent morphological changes, such as increases in spine density and size on pyramidal neurons, which facilitate new synaptic contacts and are observed in response to environmental stimuli or skill acquisition. Neuroplasticity encompasses several types, including , which alters the strength of existing connections through mechanisms like LTP and long-term depression (); structural plasticity, involving physical remodeling such as axonal sprouting and ; and functional plasticity, characterized by where undamaged brain areas assume roles of injured regions to restore function. These types often interact, as seen in activity-dependent shifts in sensory or motor maps following altered input. Critical periods represent windows of heightened , particularly in childhood, when the is exceptionally sensitive to environmental inputs for establishing foundational circuits. For , this period peaks in infancy, with early exposure shaping phonological and grammatical processing via thalamocortical and cortical connections, as disruptions like delayed input impair native-like proficiency. Similarly, sensory map development, such as ocular dominance columns in the , is refined during early postnatal weeks, as demonstrated by Hubel and Wiesel's monocular deprivation experiments in kittens, which showed permanent shifts in cortical representation if deprivation occurs before approximately 3 months in humans, underscoring the role of competitive inputs in forming stable sensory organization. In adults, supports recovery from injury, such as , where perilesional reorganization enhances local excitability and sprouting in surrounding tissue to compensate for lost motor or sensory functions, with functional MRI revealing increased activation in peri-infarct zones during . Learning also drives hippocampal , the birth of new neurons in the , which integrates into existing circuits to aid spatial and ; this process, confirmed in humans using methods such as birth dating and RNA sequencing of postmortem tissue, persists into adulthood but contributes to adaptive plasticity under enriched conditions. Recent studies as of 2025 using genetic and have further affirmed its occurrence into late adulthood. Factors influencing neuroplasticity include physical exercise, which elevates brain-derived neurotrophic factor (BDNF) levels to promote hippocampal volume increases (up to 2% in older adults after aerobic training) and , enhancing cognitive resilience. Environmental enrichment, through cognitive stimulation like novel tasks, boosts dendritic complexity and synaptic density, fostering greater adaptability. However, neuroplasticity declines with age due to reduced BDNF expression and rates, leading to diminished circuit remodeling, though lifestyle interventions can partially mitigate this .

Function

Sensory processing

The human brain processes sensory information from the environment through specialized pathways that decode and inputs from various modalities to cortical areas for and . Most sensory signals, excluding olfaction, pass through thalamic nuclei before reaching the primary sensory cortices, where initial feature extraction occurs. This mechanism filters and organizes incoming data, enabling the brain to construct a coherent of the external world. emphasizes the transformation of raw stimuli into neural codes that support , localization, and basic interpretation. The visual pathway originates in the , where photoreceptors convert light into electrical signals transmitted via the . These signals project to the (LGN) of the , which organizes retinotopic maps preserving spatial relationships, before relaying to the primary () in the . In , neurons detect basic features such as edges and orientations, as demonstrated in classic studies on cortical receptive fields. Further processing in areas like V4 involves color and form detection, while the middle temporal area (MT) specializes in , contributing to object tracking and depth cues. Auditory processing begins in the , where hair cells transduce sound vibrations into neural impulses along the auditory nerve. This information ascends through brainstem nuclei to the (MGN) in the , which then projects tonotopically to the primary auditory cortex (A1) in the . A1 neurons respond to specific frequencies, enabling spectral analysis of sounds. Sound localization relies on cues, including interaural time differences (ITDs) for low frequencies and interaural level differences (ILDs) for high frequencies, processed in superior olivary complexes and cortical areas to determine and . The somatosensory pathway for touch, vibration, and proprioception follows the dorsal column-medial lemniscus route, where peripheral afferents ascend ipsilaterally in the spinal cord's dorsal columns to synapse in the medulla's gracile and cuneate nuclei. Second-order neurons decussate and form the medial lemniscus, projecting to the ventral posterior (VP) nucleus of the thalamus, which relays to the primary somatosensory cortex (S1) in the postcentral gyrus. S1 features a somatotopic organization known as the sensory homunculus, where body parts are represented proportionally to their sensory innervation density, with enlarged areas for the hands and face facilitating fine tactile discrimination. Unlike other senses, the olfactory pathway bypasses the , providing a direct route from the to cortical structures. Olfactory receptor neurons project axons through the to the , where they with mitral and tufted cells that send outputs primarily to the and directly to the (). This thalamic-independent pathway allows rapid emotional and hedonic processing of odors in the , integrating smell with reward and without obligatory relay filtering. Multisensory integration combines inputs from different modalities to enhance , occurring in regions like the for reflexive orienting and parietal association areas for spatial awareness. The merges visual, auditory, and somatosensory signals to guide attention and eye movements, with neurons showing enhanced responses to congruent stimuli. In the of the parietal cortex, convergent inputs from sensory cortices support cross-modal calibration, such as aligning visual and tactile maps for object localization, improving accuracy in dynamic environments.

Motor control

Motor control in the human brain involves a distributed network of cortical and subcortical structures that coordinate the planning, initiation, and execution of voluntary movements, as well as the modulation of involuntary reflexes to ensure smooth and adaptive motor behavior. This system integrates sensory feedback with internal models to generate precise commands for skeletal muscles, enabling everything from fine finger manipulations to whole-body locomotion. Key components include the for high-level planning, subcortical nuclei for selection and inhibition of actions, and spinal circuits for rapid reflexive adjustments. The cortical motor system exhibits a , with the (M1) responsible for the direct execution of movements by sending efferent signals to spinal motor neurons. The (PMC) contributes to planning and preparing goal-directed actions, particularly those guided by external cues, while the (SMA) is involved in sequencing complex movements and internally generated actions, such as those requiring bilateral coordination. This allows for layered processing, where higher areas like the SMA and PMC influence M1 to refine motor output based on context and intention. Subcortical structures, particularly the basal ganglia, form closed loops with the cortex to facilitate or suppress motor programs through direct and indirect pathways. The direct pathway, originating in the striatum and projecting via the globus pallidus internal segment (GPi) to the thalamus, disinhibits thalamocortical circuits to promote selected movements. In contrast, the indirect pathway, involving the striatum, globus pallidus external segment (GPe), and subthalamic nucleus (STN), inhibits competing actions by enhancing thalamic suppression, thus sharpening motor selection. Dopamine from the substantia nigra modulates these pathways, with D1 receptors facilitating the direct route and D2 receptors inhibiting the indirect one. The provides essential control by predicting sensory consequences of movements and correcting errors before they manifest, using internal models updated via fiber inputs from the . This predictive role ensures coordinated timing and smooth trajectories, as seen in its contributions to rapid, adaptive adjustments during reaching or walking. Descending motor commands from the reach the primarily via the , which originates in and provides fine, fractionated control over distal muscles, particularly in the upper limbs, through its lateral component. The , arising from the in the , complements this by influencing proximal limb muscles for gross movements and , though its role is more prominent in non-human than in humans. At the spinal level, involuntary motor control is maintained through reflex arcs, such as the monosynaptic , where muscle spindles detect lengthening and directly excite alpha motor neurons via Ia afferents, rapidly contracting the muscle to resist stretch. This , exemplified by the knee-jerk response, operates independently of higher brain centers but can be modulated by descending inputs to adjust during voluntary actions.31151-9)

Homeostatic regulation

The human brain maintains —the balance of internal physiological conditions essential for survival—primarily through the integration of neural, endocrine, and autonomic mechanisms that monitor and adjust variables such as temperature, fluid balance, energy levels, and circadian timing. Central to this regulation is the , a diencephalic structure that acts as a master integrator, receiving sensory inputs from the body and coordinating responses via hormonal and neural pathways to counteract deviations from set points. This process ensures stability despite external or internal perturbations, with feedback loops preventing overcorrection. For instance, the brain's homeostatic controls influence everything from to , distinguishing them from voluntary motor functions by focusing on involuntary visceral adjustments. A key component is the hypothalamic-pituitary axis (HPA), which orchestrates endocrine through releasing hormones that stimulate the gland. The secretes hormones like (TRH), which prompts the pituitary to release (TSH), thereby regulating function and metabolic rate. loops are integral: elevated inhibit further TRH and TSH release to maintain equilibrium. This axis exemplifies the brain's role in long-term , as disruptions can lead to disorders like . In the brainstem, nuclei such as the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM) handle autonomic aspects of . The NTS integrates visceral afferent signals from and chemoreceptors, relaying information on and to adjust cardiovascular and respiratory functions. Meanwhile, the RVLM generates sympathetic outflow, increasing and in response to , thus stabilizing . These brainstem structures provide rapid neural control, complementing the HPA's slower endocrine actions. The (SCN) in the governs circadian rhythms, synchronizing physiological processes like -wake cycles and release with environmental cues via the . exposure during the day entrains the SCN's , suppressing production at night to promote alertness, while darkness facilitates its release for . This light-dependent synchronization ensures daily homeostatic alignment, with desynchronization linked to disorders. Thermoregulation is mediated by the of the , which detects blood temperature changes and activates effectors like sweating for cooling or for warming. Hypothalamic thermosensitive neurons sense deviations and trigger autonomic responses, such as in heat or piloerection in cold, to restore core body temperature around 37°C. Similarly, involves the , a circumventricular structure lacking a blood-brain barrier, which monitors circulating sodium levels and stimulates release from the to promote water retention in the kidneys when osmolarity rises. These mechanisms highlight the brain's precise, localized controls for fluid and thermal balance.

Language processing

Language processing in the human brain involves specialized neural networks primarily in the left hemisphere, enabling the comprehension, production, and syntactic structuring of communication. , located in the posterior (Brodmann areas 44 and 45), plays a central role in and grammatical processing, facilitating the articulation of words and the assembly of . , situated in the posterior (Brodmann area 22), is essential for language comprehension and semantic interpretation, processing the meaning of spoken words and sentences. These regions integrate with auditory sensory areas to transform acoustic input into meaningful linguistic representations. The arcuate fasciculus, a major tract, connects Broca's and Wernicke's areas, supporting the repetition and integration of linguistic information between production and comprehension systems. This pathway ensures seamless transfer of phonological and semantic details, as evidenced by diffusion tensor imaging studies showing its direct role in word retrieval and fluent repetition. The dual-stream model of language processing further delineates these functions: the dorsal stream, involving the arcuate fasciculus and premotor regions, handles sound-to-articulation mapping for ; the ventral stream, encompassing temporal and inferior frontal pathways, supports semantic access and comprehension. This architecture, proposed by Hickok and Poeppel, accounts for the parallel processing of phonological and conceptual aspects of language. Bilingualism induces structural adaptations in these language hubs, including increased gray matter volume in Broca's and Wernicke's areas, reflecting enhanced neural efficiency and reserve. Structural MRI studies indicate that early bilinguals exhibit greater gray matter density in the left compared to monolinguals, correlating with proficiency in multiple languages. Similarly, sign languages engage homologous left-hemisphere regions, demonstrating comparable perisylvian activation for comprehension and production, with dominance in Broca's and superior temporal areas akin to . Functional imaging in signers confirms left-hemisphere lateralization for syntactic processing, underscoring the modality-independent nature of core language circuitry.

Hemispheric lateralization

The human brain exhibits functional asymmetries between the left and right hemispheres, a phenomenon known as hemispheric lateralization, which contributes to specialized cognitive processing. This lateralization is evident in various domains, with the left hemisphere typically dominating analytical and sequential tasks, while the right hemisphere handles more integrative and spatial functions. The left hemisphere is primarily responsible for analytical and sequential , particularly in language-related activities, where it shows dominance in approximately 95% of right-handed individuals. This specialization supports step-by-step reasoning, logical breakdown of information, and fine for skilled actions like writing or use. In contrast, the right hemisphere excels in holistic , integrating overall patterns and contexts, as seen in spatial and visuospatial tasks. It also plays a key role in prosody and emotional in speech, contributing to the of affective nuances beyond literal meaning. Interhemispheric communication, facilitated by the , enables the integration of these specialized functions across hemispheres. Studies of patients, who have undergone surgical severance of the corpus callosum to treat severe , have been instrumental in elucidating these asymmetries; pioneering work by demonstrated that isolated hemispheres can operate independently, with the left often verbalizing analytical insights and the right excelling in nonverbal, spatial tasks. Handedness correlates strongly with cerebral lateralization, with about 90% of the population being , reflecting a bias toward left-hemisphere control of motor functions. This preference arises from a combination of genetic and environmental influences, including prenatal factors and cultural pressures, though the exact genetic mechanisms remain polygenic and incompletely understood. In cases of early brain injury, neuroplasticity allows for remarkable reorganization, often involving a shift of functions to the contralateral to compensate for damage. For instance, unilateral lesions in infancy can lead to recruitment of homologous areas in the undamaged , preserving abilities like or that might otherwise be severely impaired. This adaptability underscores the brain's capacity for functional redistribution during critical developmental periods.

Emotional processing

The limbic system serves as the core for emotional processing in the human brain, integrating sensory inputs to generate subjective affective states and modulate responses to environmental stimuli. Key structures within this system, including the , , , insula, and reward pathways, interact to appraise emotional valence, form associations, and drive behavioral adaptations. This processing emphasizes the subjective experience of emotions, distinct from cognitive evaluation or physiological , and relies on interconnected circuits that prioritize salience and for survival-oriented actions. The is central to rapid threat detection and , enabling the to associate neutral stimuli with danger through learned responses. Its basolateral nucleus receives sensory information from cortical and thalamic pathways, facilitating the encoding of emotional significance by integrating multimodal inputs such as visual or auditory cues with affective value. In contrast, the central nucleus acts as an output hub, projecting to regions to orchestrate fear-related autonomic and behavioral expressions, such as freezing or . This dual-nuclei organization allows precise threat appraisal and response initiation, as demonstrated in paradigms where lesions impair fear acquisition. The contributes to emotional processing by embedding affective experiences within contextual frameworks, enhancing retrieval in emotionally charged situations. It forms representations of spatial and temporal contexts that modulate emotional intensity, such as linking a specific to fear or reward, thereby influencing adaptive . Through interactions with the , hippocampal activity strengthens emotionally salient memories, ensuring that past contexts inform current emotional states without relying solely on immediate sensory input. The cingulate cortex plays a multifaceted role in refining emotional responses, with its anterior portion focused on detecting and resolving conflicts between competing affective demands. The anterior cingulate monitors discrepancies in emotional salience, such as when approach and avoidance motivations clash, thereby signaling the need for cognitive adjustments to maintain behavioral flexibility. Meanwhile, the posterior cingulate integrates spatial information with emotional processing, supporting the navigation of environments laden with affective cues and facilitating memory-based emotional orientation. The insula provides interoceptive awareness of internal bodily states, translating physiological signals into conscious emotional feelings, particularly for visceral emotions like . It processes signals from the , such as or gut discomfort, to generate subjective aversion and prompt avoidance behaviors. Activation in the anterior insula during disgust elicitation underscores its role in bridging bodily sensations with emotional interpretation, ensuring rapid responses to potential contaminants. Reward circuits, centered on the and , drive positive emotional processing through dopaminergic signaling that reinforces pleasurable experiences. release from neurons projecting to the encodes the motivational value of rewards, enhancing anticipation and pursuit of beneficial outcomes like social bonding or nourishment. This modulates hedonic tone, with activity scaling the intensity of satisfaction to guide goal-directed behavior.

Cognitive processes

Cognitive processes encompass higher-order mental operations that enable humans to acquire, store, manipulate, and apply for . These functions, supported by distributed neural networks, include formation and retrieval, selective , executive control, introspective thought, and value-based decision-making. The human brain integrates these processes across regions like the medial temporal lobe, , and parietal areas to facilitate learning, planning, and problem-solving. Memory systems in the are broadly categorized into declarative and procedural types. Declarative memory, which involves conscious recollection of facts and events, relies on the for encoding and retrieval; it subdivides into for personal experiences tied to context and for general knowledge. In contrast, supports unconscious skill acquisition and habit formation, primarily through the for stimulus-response associations and the for and timing. These systems operate in parallel, with declarative memory enabling flexible, relational learning and fostering automatic, incremental habits. Attention networks modulate the brain's focus on relevant stimuli amid competing inputs. The , involving the and superior , mediates top-down, goal-directed by strategically allocating resources based on expectations or tasks. Conversely, the ventral attention network, encompassing the , ventral frontal , and , handles bottom-up reorientation toward salient or unexpected events, often right-lateralized to detect behavioral relevance. This interplay allows rapid shifts between voluntary control and reflexive responses. Executive functions orchestrate goal-directed behavior through prefrontal mechanisms. The dorsolateral prefrontal cortex supports working memory by maintaining and manipulating information for ongoing tasks, such as sequencing letters and numbers. The orbitofrontal cortex contributes to response inhibition, regulating impulsive actions and emotional control to align behavior with long-term objectives. Lesions in these areas disrupt specific components, with dorsolateral damage impairing cognitive flexibility and orbitofrontal impairment affecting self-regulation. The facilitates and during rest, activating when external demands are low. Centered on the as a connectivity hub, it integrates subsystems involving the and medial temporal lobe to support self-referential thought, retrieval, and future simulation. This network underlies spontaneous , comprising up to 50% of waking thought, and adapts internal mentation for planning and social inference. Decision-making incorporates value assessments, with modeling how gains and losses asymmetrically influence choices, emphasizing . The encodes subjective valuations in this framework, integrating prospective outcomes to guide risk-tolerant or averse selections. Damage or altered activity here shifts relative risk preferences, underscoring its role in computing nonlinear utilities from mixed gambles.

Physiology

Neuronal signaling

Neurons maintain a resting of approximately -70 mV, which arises from the unequal of s across the plasma membrane and the selective permeability of the membrane to those s. This potential is primarily established by the higher permeability to potassium ions (K⁺) through leak channels, allowing K⁺ to diffuse out of the down its concentration , leaving behind negative charges. The sodium-potassium pump actively maintains the gradients by transporting three sodium ions (Na⁺) out of the and two K⁺ ions into the for each ATP hydrolyzed, counteracting the passive leaks and ensuring long-term stability of the resting state. When a receives excitatory input that the beyond a of about -55 mV, an is initiated. This rapid electrical signal is described by the Hodgkin-Huxley model, which mathematically accounts for the dynamics of voltage-gated channels in the . In this model, opens voltage-gated Na⁺ channels, allowing a massive influx of Na⁺ that further the to around +40 mV; subsequently, these Na⁺ channels inactivate, and voltage-gated K⁺ channels open, permitting K⁺ efflux that repolarizes the back toward the . The model integrates these conductances with capacitance to predict the all-or-nothing nature of the , which lasts about 1-2 milliseconds. Action potentials propagate along the without decrement in unmyelinated fibers through continuous local , but in myelinated , propagation occurs via , where the sheath—produced by glial cells—insulates the and forces the action potential to jump between nodes of Ranvier. This mechanism dramatically increases conduction speed, reaching up to 120 m/s in large-diameter mammalian , compared to 0.5-10 m/s in unmyelinated ones. channels in neurons are categorized by their gating mechanisms: channels remain constitutively open to set the ; voltage-gated channels respond to changes in to drive action potentials; and ligand-gated channels open in response to binding, though their role here is primarily in initiating . The passive spread of electrical signals within neuronal processes is governed by , which models the as a cylindrical cable with and , leading to of subthreshold signals over distance due to current leakage across the . Developed by Wilfrid Rall, this theory explains how synaptic inputs attenuate as they travel from dendrites to the , influencing the spatial integration of signals before reaching threshold. Factors like diameter and membrane resistivity modulate this decay, ensuring efficient signal transmission tailored to neuronal morphology.

Synaptic transmission

Synaptic transmission enables chemical communication between at specialized junctions called synapses, where neurotransmitters released from the presynaptic bind to receptors on the postsynaptic or nearby cells. This process underlies most neural signaling in the human brain, allowing for rapid and precise information transfer. Upon arrival of an at the presynaptic terminal, voltage-gated calcium channels open, permitting Ca²⁺ influx that triggers the fusion of synaptic vesicles with the presynaptic membrane through proteins like SNARE complexes. This releases neurotransmitters into the synaptic cleft in discrete packets known as quantal release, ensuring that transmission occurs in measurable units corresponding to individual vesicles. The human brain employs diverse neurotransmitters classified by their effects: excitatory, inhibitory, and modulatory. Glutamate serves as the principal excitatory neurotransmitter, binding to ionotropic receptors such as (which mediate fast depolarization via Na⁺ influx) and NMDA (which allow Ca²⁺ entry and contribute to longer-term signaling). In contrast, (γ-aminobutyric acid) is the primary inhibitory neurotransmitter, activating GABA_A receptors that open Cl⁻ channels, leading to postsynaptic hyperpolarization and reduced neuronal excitability. Modulatory neurotransmitters, which fine-tune synaptic efficacy over broader timescales, include dopamine, which acts via G-protein-coupled receptors to influence reward, motivation, and plasticity in pathways like the mesolimbic system, and , which promotes and through muscarinic and nicotinic receptors in cortical and subcortical regions. Following release, neurotransmitters must be cleared from the synaptic cleft to terminate signaling and prevent overstimulation. This occurs primarily through reuptake via specific plasma membrane transporters, such as the serotonin transporter (SERT) for serotonin, which recycles the neurotransmitter back into the presynaptic neuron for repackaging. Enzymatic degradation provides an alternative clearance mechanism; for instance, monoamine oxidase (MAO) oxidatively deaminates monoamines like dopamine and serotonin in the cytoplasm, while catechol-O-methyltransferase (COMT) methylates catecholamines extracellularly, converting them into inactive metabolites. Astrocytes and other glia assist in this process by uptake and breakdown of excess neurotransmitters, maintaining extracellular homeostasis. Synaptic transmission also supports plasticity, the ability of synapses to strengthen or weaken over time, enabling learning and . A foundational concept is the Hebbian rule, proposed by Donald Hebb, which posits that "cells that fire together wire together"—repeated coincident activity between presynaptic and postsynaptic neurons strengthens the synaptic connection, often through mechanisms like increased receptor insertion or vesicle availability. Neuromodulation extends synaptic transmission by altering its efficacy across networks, distinct from direct point-to-point signaling. In volume transmission, modulatory neurotransmitters like diffuse through the rather than being confined to the synaptic cleft, allowing one-to-many influence on distant receptors and enabling global regulation of excitability, , and . This contrasts with classical synaptic transmission's localized, rapid action, providing the with flexible for complex behaviors.

Metabolic demands

The human brain, representing approximately 2% of total body weight, accounts for about 20% of the body's resting expenditure, highlighting its exceptionally high metabolic demands. This is primarily derived from glucose, with the brain consuming roughly 120 g per day in adults under normal conditions, delivered via blood glucose transport across the blood-brain barrier. The bulk of this supports (ATP) production through , where a substantial portion—estimated at 50-70% based on seminal energy budget analyses—is allocated to sodium-potassium pumps that maintain essential ionic gradients for neuronal excitability and signaling. Glucose is oxidized in neuronal and glial mitochondria to generate ATP via the and , ensuring efficient supply for synaptic transmission and other cellular processes. A key aspect of brain energy metabolism involves intercellular cooperation, exemplified by the astrocyte-neuron lactate shuttle hypothesis. Proposed by Pellerin and Magistretti, this model posits that astrocytes take up glucose and, in response to neuronal activity, perform to produce , which is then released and taken up by neurons for mitochondrial oxidation to produce ATP. This shuttle optimizes energy distribution, as astrocytes preferentially engage in aerobic while neurons rely on for high-energy demands. Supporting evidence includes imaging showing activity-dependent transfer, underscoring the hypothesis's role in matching local metabolic needs during neural activation. Under hypoxic conditions, such as reduced oxygen availability, the brain activates adaptive responses to sustain production. Hypoxia-inducible factor-1α (HIF-1α), a stabilized in low-oxygen environments, upregulates genes involved in and , shifting toward anaerobic pathways like production via pyruvate. However, this is limited in capacity, providing only short-term (yielding 2 ATP per glucose molecule compared to 36 via ), and prolonged leads to deficits and potential cellular damage. HIF-1α's role in the has been demonstrated in ischemic models, where its activation promotes survival genes but can exacerbate if dysregulated. To meet fluctuating energy demands, cerebral blood flow is tightly coupled to neuronal activity through the neurovascular unit, comprising neurons, , endothelial cells, and . play a central role in this coupling by sensing synaptic activity via and releasing vasoactive mediators, such as prostaglandins and epoxyeicosatrienoic acids, to induce and increase local blood flow. This astrocyte-mediated mechanism ensures timely delivery of oxygen and nutrients, preventing metabolic mismatches. Disruptions in neurovascular coupling, as seen in aging or disease, can impair . During fasting or glucose scarcity, the brain adapts by utilizing (primarily β-hydroxybutyrate and acetoacetate) as an alternative fuel, produced by the liver from fatty acids. Ketones cross the blood-brain barrier via monocarboxylate transporters and are oxidized in neuronal mitochondria, providing up to 60% of the brain's energy needs after several days of . This metabolic flexibility spares glucose for glucose-dependent tissues like erythrocytes and supports brain function during prolonged energy restriction, with studies showing preserved ketone uptake even in aging brains.

Consciousness

Consciousness refers to the subjective experience of awareness and , encompassing the "what it is like" quality of mental states in the human brain. It emerges from complex neural interactions that enable integrated , , and response to the , distinguishing conscious from unconscious automatic functions. Key theories and empirical findings highlight specific brain mechanisms underlying this phenomenon, focusing on information integration and global dissemination rather than isolated computations. The global workspace theory posits that consciousness occurs when select neural representations achieve "ignition" and are broadcast across a distributed network, making information globally available for cognitive control and reportability. This process is centered on prefrontal cortical areas and thalamic hubs, which act as ignition sites through recurrent thalamocortical connections, amplifying signals to sustain awareness. In contrast, integrated information theory proposes that consciousness is identical to the brain's capacity for causal integration, quantified by the measure Φ (phi), which assesses the irreducible complexity of informational interactions within a neural system. Higher Φ values indicate greater levels of conscious experience, as they reflect the system's intrinsic ability to generate differentiated yet unified cause-effect structures beyond its parts. Neural correlates of consciousness primarily localize to thalamocortical loops that synchronize activity across sensory and associative regions, enabling the binding of perceptual features into coherent experiences. A "posterior hot zone" in the parieto-temporo-occipital junction serves as a critical , where posterior cortical areas process and integrate sensory content to produce phenomenal , independent of frontal . The reticular activating system in the provides foundational , briefly integrating with these loops to modulate during conscious states. Altered states reveal disruptions in these mechanisms: general impairs by desynchronizing thalamocortical oscillations and reducing global information flow, shifting the toward fragmented, low-integration dynamics. In , both and are absent due to profound loss of neural integration, whereas the preserves cycles but lacks any internal or external , reflecting dissociated thalamocortical function. From an evolutionary perspective, minimal consciousness likely originated in brainstem-mediated basic awareness, enabling adaptive responses to environmental threats through simple associative learning circuits. This foundational sentience, marked by unlimited associative learning of novel stimuli, emerged in early vertebrates around the Cambrian period, predating cortical expansions and providing the substrate for more complex phenomenal experiences.

Disorders and conditions

Traumatic injuries

Traumatic brain injuries (TBIs) result from external mechanical forces applied to the head, leading to immediate and potentially cascading damage to brain tissue. These injuries can range from mild disruptions to severe, life-threatening conditions, often occurring due to falls, vehicular accidents, or assaults. The brain's vulnerability stems from its suspension within the skull, where sudden movements cause tissue deformation and vascular disruption. Common types of TBIs include , contusions, and . A represents a mild TBI characterized by temporary functional disturbance without gross structural , often involving axonal from rotational forces that stretch and disrupt neuronal fibers. Contusions involve focal bruising of brain , typically occurring as coup injuries at the site of impact or contrecoup injuries on the opposite side due to rebound against the . (DAI) is a severe form involving widespread shearing of tracts, particularly at gray- junctions, leading to profound neurological impairment. TBIs progress through primary and secondary injury phases. Primary injury arises directly from the initial mechanical insult, causing immediate cellular disruption, hemorrhage, or tissue laceration through impact or acceleration-deceleration forces. Secondary injury follows, evolving over hours to days via pathophysiological processes such as , ischemia, and , which exacerbate neuronal death and can be mitigated with timely intervention. Severity of TBI is commonly assessed using the (GCS), which evaluates three components: eye-opening response (scored 1-4, from none to spontaneous), verbal response (scored 1-5, from none to oriented conversation), and motor response (scored 1-6, from none to obeys commands). The total GCS score ranges from 3 (deep unconsciousness) to 15 (fully alert), with scores of 13-15 indicating mild TBI, 9-12 moderate, and 3-8 severe. Long-term consequences of TBIs frequently include post-traumatic epilepsy (PTE) and cognitive deficits. PTE develops in approximately 20-30% of severe TBI cases, manifesting as recurrent seizures due to cortical scarring and altered neuronal excitability, often emerging within the first year post-injury. Cognitive impairments, such as deficits in , , executive function, and processing speed, persist in many survivors, contributing to reduced and dependence on support services. Treatment focuses on stabilizing the patient and preventing secondary damage, particularly through () management. Elevated , often exceeding 20 mmHg, is controlled via measures like , osmotherapy with , and to maintain cerebral . In refractory cases, surgically removes a portion of the to allow expansion, reducing ICP and herniation risk, though it carries risks of infection and syndrome of the trephined. The 's can facilitate partial recovery through , enabling rewiring of neural circuits over time.

Neurodegenerative diseases

Neurodegenerative diseases are a group of progressive disorders characterized by the gradual loss of structure or function of neurons, often leading to cognitive, motor, and behavioral impairments in the human brain. These conditions primarily affect older adults and involve protein misfolding, accumulation of toxic aggregates, and neuronal death in specific brain regions. Common examples include , , , and (ALS), each with distinct pathological features but sharing mechanisms of synaptic loss that contribute to dysfunction. Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, marked by the accumulation of amyloid-beta plaques extracellularly and hyperphosphorylated forming neurofibrillary tangles intracellularly, which disrupt neuronal communication and lead to widespread brain atrophy. The , crucial for formation, undergoes significant volume loss early in the disease, correlating with initial cognitive decline. AD progresses through stages beginning with (MCI), where subtle lapses occur without major interference in daily life, advancing to mild with noticeable forgetfulness and disorientation, moderate involving confusion and personality changes, and severe characterized by profound loss and dependency. The rate of progression from MCI to full is approximately 10-15% per year. Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in the , resulting in depletion that impairs circuits in the . Pathologically, aggregates form Lewy bodies within surviving neurons, contributing to cell death. Primary motor symptoms include resting tremor, bradykinesia (slowness of movement), rigidity, and postural instability, often asymmetrically at onset. These deficits arise from disrupted signaling in the . Huntington's disease (HD) is a caused by an expanded trinucleotide repeat in the (HTT), leading to a polyglutamine tract in the huntingtin protein that is toxic to neurons, particularly in the of the . Repeats of 40 or more units are pathogenic, with longer expansions correlating to earlier onset. The disease manifests with —involuntary, jerky movements—due to striatal neuronal loss, alongside progressive cognitive and psychiatric decline. Genetic anticipation occurs as repeats expand across generations, often more so through paternal transmission, resulting in earlier and more severe symptoms in offspring. Amyotrophic lateral sclerosis (ALS) features selective degeneration of upper and lower s in the , , and , leading to , , and eventual while sparing cognitive functions initially. Approximately 20% of familial ALS cases involve mutations in the gene, which encodes 1; these mutations cause protein misfolding and toxic gain-of-function, accelerating death. Sporadic ALS, comprising 90-95% of cases, shares similar but without identified genetic triggers in most instances. Risk factors for these neurodegenerative diseases include advanced age, which increases susceptibility due to cumulative cellular damage and reduced repair mechanisms across all major types. Genetic predispositions, such as the APOE ε4 allele, elevate Alzheimer's risk by up to fourfold in carriers by promoting amyloid-beta accumulation. Environmental exposures, including pesticides like organochlorines and , are linked to higher Parkinson's incidence through and damage.

Psychiatric disorders

Psychiatric disorders encompass a range of conditions characterized by dysregulation in brain circuits governing mood, thought, and behavior, often involving imbalances in neurotransmitter systems and altered neural activity. These disorders, including depression, schizophrenia, anxiety disorders, and bipolar disorder, arise from complex interactions between genetic, environmental, and neurobiological factors, leading to profound impacts on emotional processing and cognitive function. Brain imaging and neurochemical studies have revealed consistent patterns of dysfunction in limbic and prefrontal regions, underscoring the central role of the human brain in these pathologies. Major depressive disorder is linked to the monoamine hypothesis, which posits functional deficiencies in neurotransmitters such as serotonin and norepinephrine within key brain circuits. This hypothesis originated from observations of mood alterations induced by drugs affecting monoamine levels, suggesting that reduced availability of these transmitters in synaptic clefts contributes to depressive symptoms. Additionally, hyperactivity of the axis in leads to elevated levels, impairing feedback mechanisms in the and , which exacerbates mood dysregulation and cognitive deficits. Schizophrenia involves the dopamine hypothesis, which implicates hyperactivity in mesolimbic dopamine pathways and hypofunction in mesocortical pathways, with dopamine D2 receptor blockade by antipsychotics alleviating core symptoms. Structural brain changes, including ventricular enlargement observed via computed tomography and , correlate with disease severity and reflect progressive gray matter loss in frontal and temporal lobes. The disorder manifests through positive symptoms, such as hallucinations and delusions arising from dopaminergic excess, and negative symptoms, including affective flattening and , associated with prefrontal hypoactivity. Anxiety disorders feature amygdala hyperactivity, where exaggerated responses to perceived threats amplify fear processing in limbic circuits. This hyperreactivity is evident in functional imaging studies showing increased activation during emotional stimuli in conditions like and . Concurrently, an imbalance between inhibitory and excitatory disrupts cortical inhibition, leading to heightened arousal and persistent worry, as supported by spectroscopic evidence of altered ratios in affected regions. Bipolar disorder is defined by recurrent manic-depressive cycles, with manic episodes involving elevated energy and linked to dysregulated limbic activation, while depressive phases mirror unipolar but with rapid shifts driven by circadian and stress-related mechanisms. Lithium, a cornerstone treatment, modulates these cycles by depleting levels in the , inhibiting phosphoinositide signaling pathways that regulate mood-stabilizing cascades in the and . Neuroimaging hallmarks across these psychiatric disorders often include reduced prefrontal cortex volume, as meta-analyses of MRI data demonstrate consistent gray matter deficits in dorsolateral and ventromedial regions, correlating with impaired executive function and emotional regulation. These volumetric changes, observed in , , and anxiety, highlight shared vulnerabilities in frontolimbic networks. Emotional circuit involvement, such as altered amygdala-prefrontal connectivity, further contributes to symptom persistence in these conditions.

Brain tumors

Brain tumors are abnormal growths of cells within the brain tissue or surrounding structures, classified broadly into primary tumors that originate in the (CNS) and metastatic tumors that spread from cancers elsewhere in the body. Primary brain tumors account for the majority of CNS neoplasms in adults, with gliomas representing the most common subtype, including astrocytomas graded from I to based on aggressiveness, where grade denotes , the most malignant form. Meningiomas, often benign and arising from meningeal origins, are another prevalent type, typically graded as WHO grade I and comprising about 30-40% of all primary intracranial tumors. In contrast, metastatic brain tumors, which outnumber primary ones by a ratio of approximately 10:1, commonly originate from , , or primaries and involve multiple lesions. The (WHO) classification of CNS tumors, updated in 2021, integrates histological features with for precise categorization, emphasizing integrated diagnoses over purely morphological ones. For gliomas, this includes assessment of IDH mutations, where IDH-wildtype tumors are associated with poorer prognosis and classified as if they exhibit specific genetic hallmarks like TERT promoter mutations or amplification. Astrocytomas with IDH mutations are stratified into grades 2-4, reflecting their proliferative potential and infiltrative nature, while pediatric-type diffuse low-grade gliomas form a distinct category with better outcomes. Meningiomas are graded I-III based on histological , , or , though most remain benign and slow-growing. Symptoms of brain tumors arise primarily from mass effect, where tumor expansion compresses adjacent brain tissue, leading to increased manifested as persistent headaches, , and seizures in up to 40% of patients at . Location-specific deficits further contribute, such as , , or in tumors due to disruption of prefrontal circuits. Tumors may also obstruct (CSF) pathways, causing and additional pressure-related symptoms. Tumor growth dynamics involve robust angiogenesis, driven by vascular endothelial growth factor (VEGF) secreted by hypoxic tumor cells, which stimulates endothelial proliferation to form leaky neovessels supplying nutrients. This process disrupts the blood-brain barrier (BBB), allowing plasma proteins and immune cells to infiltrate, fostering edema and further tumor progression while impairing normal CNS homeostasis. Treatment strategies prioritize maximal safe surgical resection to alleviate and obtain tissue for classification, followed by therapies tailored to tumor type. For , the standard regimen combines with concurrent and , an oral alkylating agent that methylates to inhibit replication, yielding a survival extension from 12 to 15 months compared to alone. targets residual cells post-resection, while temozolomide's efficacy is enhanced in patients with methylated promoter status, though resistance remains a challenge. Benign meningiomas may require only observation or if symptomatic, with reserved for incompletely resected cases.

Epilepsy

Epilepsy is a characterized by recurrent seizures resulting from abnormal, excessive, and synchronous electrical activity in the . These seizures arise due to an imbalance between excitatory and inhibitory neuronal signaling, leading to hyperexcitability in neural networks. In the context of the human , epilepsy affects approximately 50 million people worldwide, with seizures often originating from specific regions or spreading across both hemispheres. Seizures in epilepsy are classified into two main types: focal (also known as partial) and generalized. Focal seizures begin in a specific area of one and may involve an , a subjective sensory or experience such as a peculiar , visual distortion, or , serving as a warning before the seizure intensifies. If the electrical activity spreads, focal seizures can evolve into bilateral tonic-clonic seizures. Generalized seizures, in contrast, involve both hemispheres from the onset and include subtypes like tonic-clonic seizures, which feature initial muscle stiffening (tonic phase) followed by rhythmic jerking (clonic phase), and absence seizures, characterized by brief lapses in awareness with subtle automatisms like eye . The of epilepsy centers on neuronal hyperexcitability, often driven by genetic mutations in ion channels that disrupt the balance of neuronal firing. For instance, mutations in the SCN1A gene, which encodes the voltage-gated NaV1.1 primarily expressed in inhibitory , cause , a severe form of beginning in infancy with prolonged febrile seizures and evolving into multiple seizure types. These loss-of-function mutations reduce inhibitory transmission, leading to network hyperexcitability without altering excitatory pyramidal function. Post-traumatic can also emerge from such imbalances following injury. Electroencephalography (EEG) is essential for diagnosing , revealing characteristic patterns between and during s. Interictal spikes—brief, high-amplitude transients lasting less than 200 milliseconds—indicate epileptogenic foci and are commonly observed in focal epilepsies, while 3 Hz spike-and-wave discharges typify absence seizures in . Ictal EEG patterns include rhythmic activity or low-voltage fast activity at seizure onset, evolving into polyspikes or repetitive spikes during , helping localize the seizure onset zone. Common triggers for seizures include , which lowers the by altering cortical excitability, and flashing lights in , where intermittent photic stimulation at 5-30 Hz induces generalized epileptiform discharges, particularly in adolescents with . Management of epilepsy primarily involves antiepileptic drugs (s) that target ion channels or synaptic transmission to suppress hyperexcitability. , a widely used AED, blocks voltage-gated sodium channels to stabilize neuronal membranes and prevent repetitive firing during seizures. For drug-resistant cases, (VNS) provides an adjunctive therapy by delivering electrical pulses to the , modulating nuclei to reduce seizure frequency by 20-50% in responsive patients.

Vascular disorders

Vascular disorders of the brain primarily encompass conditions arising from disruptions in cerebral blood flow, with being the most common and devastating manifestation. These disorders lead to acute neuronal injury due to either insufficient oxygen delivery or direct vascular rupture, resulting in significant morbidity and mortality worldwide. Ischemic , which account for approximately 87% of all , occur when blood flow to a region of the brain is obstructed, leading to tissue and potential . Ischemic strokes are classified into thrombotic, caused by local plaque buildup and clot formation in , and embolic, resulting from clots originating elsewhere—such as the heart—that travel to the . A critical aspect of ischemic pathology is the distinction between the infarct core, where irreversible has occurred due to prolonged ischemia, and the surrounding penumbra, a viable but at-risk tissue zone that can potentially be salvaged with timely reperfusion. The therapeutic window for interventions like intravenous tissue plasminogen activator (tPA) is typically within 4.5 hours of symptom onset, during which can dissolve the clot and restore blood flow to the penumbra, improving outcomes. Infarct progression begins with cytotoxic , an early cellular swelling triggered by failure of ATP-dependent pumps, leading to sodium and water influx into neurons and within minutes to hours of . Hemorrhagic strokes, comprising the remaining 13% of cases, involve bleeding into or around the and are generally more severe. (ICH) often stems from chronic weakening small vessel walls, causing rupture and blood accumulation within brain , which compresses adjacent tissue and triggers secondary ischemia. (SAH), in contrast, typically results from the rupture of a cerebral , leading to blood spilling into the space between the arachnoid and , often presenting with sudden severe and carrying a high risk of . Major risk factors for vascular disorders include , which narrows arteries and promotes ; (AFib), a common source of cardioembolic strokes due to irregular heart rhythms fostering clot formation; and , which accelerates vascular damage and . Protective mechanisms, such as leptomeningeal collateral circulation—secondary vessels connecting adjacent arterial territories—can mitigate ischemia by providing alternative blood flow pathways, though their efficacy varies with individual vascular and comorbidities. Post-stroke outcomes are assessed using tools like the Stroke Scale (NIHSS), a standardized 11-item evaluation of neurological deficits that scores from 0 to 42, with higher scores indicating greater severity and poorer prognosis; for instance, an NIHSS score of 16 or above predicts a high likelihood of or severe . Rehabilitation plays a pivotal role in recovery, involving multidisciplinary interventions such as physical, occupational, and speech therapy to restore function and independence, particularly in the subacute phase following stabilization.

Developmental malformations

Developmental malformations of the human brain arise from disruptions during early embryonic and fetal stages, leading to congenital anomalies that affect brain structure and function. These defects often stem from failures in formation, prosencephalon division, or proliferation, resulting in a range of neurological impairments from mild cognitive deficits to severe disabilities. Such malformations are typically identified prenatally or at birth through and clinical , with impacts varying based on the extent of structural disruption. Neural tube defects (NTDs) occur when the fails to close properly between the third and fourth weeks of , leading to incomplete formation of the and . , a common NTD, involves the incomplete closure of the spinal , resulting in a gap in the vertebrae that may expose the and cause , dysfunction, and . type 2, frequently associated with myelomeningocele (a severe form of ), arises from the same closure failure and is characterized by the downward displacement of the and tonsils into the , often leading to compression and . These defects are influenced by genetic and environmental factors, including , and can disrupt embryonic processes critical for neural development. Holoprosencephaly (HPE) results from the failure of the prosencephalon () to cleave into distinct cerebral hemispheres during the fourth to fifth weeks of gestation, leading to incomplete brain division and associated midline facial anomalies. In severe cases, such as alobar HPE, the brain remains as a single holosphere without separation into left and right halves, often accompanied by extreme facial defects like , where the eyes fuse into a single midline structure due to disrupted ocular development. This malformation impairs higher cognitive functions and sensory integration, with outcomes ranging from neonatal lethality to profound in less severe forms like semilobar HPE. Etiologies include genetic mutations in signaling pathways (e.g., SHH gene) and chromosomal abnormalities such as trisomy 13. Microcephaly is characterized by an abnormally small and due to impaired and survival of neural progenitor cells during early fetal development, often evident at birth with a head circumference below the third . infection in pregnant individuals disrupts this process by preferentially infecting and depleting human neural progenitor cells, inducing cell-cycle arrest, , and reduced , which culminates in cortical thinning and the microcephalic phenotype. This leads to , seizures, and motor impairments, with postnatal growth further limited by ongoing progenitor deficits. Agenesis of the corpus callosum (ACC) involves the complete or partial absence of the , the primary tract connecting the cerebral hemispheres, arising from disrupted axonal guidance and midline crossing during the 8th to 20th weeks of . This results in reduced interhemispheric connectivity, manifesting as variable symptoms including deficits in complex reasoning, novel problem-solving, , and , though can range from normal to impaired. Isolated ACC often presents with subtle neuropsychological effects, such as slowed information processing and impaired bimanual tasks, without always causing overt disability. Periventricular leukomalacia (PVL) is a injury primarily affecting preterm infants, characterized by and subsequent in the periventricular regions surrounding the , due to vulnerability to hypoxia-ischemia and during the vulnerable period of maturation. This damage to premyelinating disrupts myelination and axonal integrity, leading to , cognitive delays, and visual-motor impairments in survivors. Risk factors include prematurity below 32 weeks and perinatal events like or blood flow changes, with long-term effects on volume and connectivity.

Brain death

Brain death is defined as the irreversible cessation of all functions of the entire , including the , resulting in the complete and permanent loss of brain-mediated activity. This clinical diagnosis signifies the end of equivalent to cardiopulmonary , distinguishing it from other states of profound . The diagnostic criteria for brain death require fulfillment of three essential preconditions: a known irreversible cause of , exclusion of confounding factors such as drugs, (core temperature below 36°C), or metabolic disturbances, and demonstration of complete unresponsiveness. The core clinical examination includes assessment of coma with no motor response to noxious stimuli, absence of all brainstem reflexes—such as (fixed dilated pupils), , oculocephalic and oculovestibular reflexes, and gag or response—and an apnea test confirming no spontaneous respirations after disconnection from the , typically with a PaCO₂ rise to ≥60 mmHg or 20 mmHg above baseline. Ancillary tests, like showing no intracranial blood flow or indicating electrocerebral silence, may be used if clinical testing is incomplete or contraindicated, but are not routinely required. Confirmation of brain death mandates at least two separate clinical examinations by qualified physicians, separated by an observation period of 6 to 24 hours for adults, depending on the , to ensure irreversibility and rule out reversible conditions. These evaluations must adhere to standardized protocols to avoid false positives, emphasizing the need for experienced examiners familiar with anatomy, where reflexes like the originate from nuclei. Pathophysiologically, brain death typically arises from severe global insults such as prolonged or ischemia, often following , severe head trauma, or , leading to widespread , increased exceeding arterial pressure, and cessation of cerebral blood flow. This results in acute energy failure, cytotoxic , disruption of cellular pumps, and eventual neuronal across cortical and subcortical structures, with the succumbing last due to its relative resistance. Legally, brain death is codified in the United States under the 1981 (UDDA), which defines death as either the irreversible cessation of circulatory and respiratory functions or of all functions of the entire brain, including the . Adopted by all 50 states and the District of Columbia, the UDDA standardizes the determination process and facilitates , as brain-dead individuals can maintain cardiopulmonary function via mechanical support, allowing viable organs to be procured for transplantation while respecting the legal equivalence to death. Brain death must be distinguished from the persistent vegetative state (PVS), in which brainstem functions such as spontaneous breathing and sleep-wake cycles are preserved, but there is no of awareness or higher cortical function, correlating with intact subcortical arousal systems but profound damage. Unlike PVS, where of some function may occur, brain death precludes any possibility of restoration due to total brain failure.

Research methods

Historical approaches

Early understandings of the brain emerged in ancient civilizations, where practices like trepanation indicated rudimentary awareness of cranial trauma, though the organ itself was often undervalued. The , dating to around 1700 BC, documents 48 cases of injuries, including 27 involving head trauma and fractures, describing symptoms of such as seizures and linked to head wounds. Ancient performed trepanation to relieve after injuries, using tools to create holes in the , as evidenced by archaeological findings of healed trepanations on mummies and skulls. However, they generally regarded the brain as insignificant, routinely removing it during mummification via the while preserving other organs. In ancient Greece, Aristotle (384–322 BC) rejected the brain as the primary seat of intellect, instead positing the heart as the center of sensation, emotion, and cognition. He argued that "the seat and source of sensation is the region of the heart," viewing it as the origin of pleasure, pain, and voluntary movement in all blooded animals. Aristotle described the brain as a cooling mechanism for the heart's innate heat, noting its cold, fluid nature tempered the heart's "seething," with humans' larger brain enabling superior intelligence through better heat regulation. The Roman physician (129–c. 216 AD) advanced brain-centric views, building on but diverging from by emphasizing the organ's role in higher functions. Through dissections primarily of animal brains, Galen detailed the , proposing the four ventricles as sites for elaborating, storing, and distributing psychic pneuma—a vital spirit responsible for sensation, movement, and intellect. He tentatively associated the anterior ventricle with imagination, the middle with cognition, and the posterior with memory, influencing medieval and neurology despite inaccuracies from his reliance on non-human . During the , (1514–1564) revolutionized anatomical study with his 1543 work De humani corporis fabrica libri septem, based on direct human s that corrected ic errors in brain structure. Vesalius provided precise illustrations of brain anatomy, including the , , and ventricles, revealing the absence of the "rete mirabile"—a vascular network Galen described in oxen but not humans. His emphasis on empirical over textual authority shifted focus toward accurate human , with over 250 images aiding visualization of brain layers and connections. In the late 18th and early 19th centuries, (1758–1828) developed , proposing that mental faculties were localized to specific cortical regions and could be inferred from contours. Gall identified 27 such faculties, arguing that their development caused corresponding cranial "bumps" readable for personality assessment, based on observations of variations correlated with behaviors in humans and animals. Though influential in , faced scientific criticism for its and lack of rigorous evidence, yet it spurred interest in cerebral localization. Pierre Flourens (1794–1867) challenged phrenology's extreme localization through pioneering experiments in the 1820s, removing targeted brain regions in animals like pigeons and rabbits to assess functional deficits. He found that cerebellar impaired coordination, while cerebral lobe removals caused global weakening of , judgment, and will proportional to the damage extent, rather than isolated losses. Flourens concluded the brain operated as an integrated whole under "cerebral equipotentiality," where functions were distributed rather than strictly modular, disproving Gall's modular claims. The introduction of the in the enabled cellular-level brain observations, exemplified by Jan Evangelista Purkinje's (1787–1869) 1837 discovery of large, flask-shaped neurons in the cerebellar . Using an achromatic , Purkinje described these cells' dendritic arborizations in the Purkinje layer, marking a foundational step in neurohistology and recognizing cells as life's functional units. (1824–1880) provided clinico-pathological evidence for localization in 1861, linking to damage in the left through of patient Louis Leborgne, who could only utter "tan." Broca's report, "Perte de la parole; ramollissement chronique et destruction partielle du lobe antérieur gauche du cerveau," established this region—now —as critical for speech production, advancing the debate beyond holistic views.

Neuroimaging techniques

Neuroimaging techniques enable the non-invasive visualization of brain structure and function, revolutionizing the study of the human brain since the late . These methods provide insights into anatomical details, metabolic processes, and neural activity, aiding in the and of various neurological conditions. Key modalities include computed tomography (CT), (MRI) and its variants, (PET), diffusion tensor imaging (DTI), (EEG), and (MEG), each offering unique advantages in spatial and temporal resolution. Computed tomography (CT) scanning, introduced in , uses X-rays to generate cross-sectional images of the , excelling in rapid detection of acute conditions like hemorrhage. It quantifies tissue density via Hounsfield units, ranging from -1000 for air to +1000 for , with typically appearing at 40-80 units in acute phases. This makes CT particularly valuable for emergency assessments of vascular events. Magnetic resonance imaging (MRI), pioneered in 1973, employs magnetic fields and radio waves to produce high-contrast images of anatomy without . T1-weighted images highlight gray-white matter differentiation by emphasizing fat content, while T2-weighted images reveal water-rich areas like and , achieving resolutions down to 0.5 mm. Functional MRI (fMRI), developed in the early , measures activation through blood-oxygen-level-dependent (BOLD) contrast, which detects hemodynamic responses to neural activity—increased oxygenation causes T2* signal changes—offering millimeter for cognitive processes. Positron emission tomography (PET), advanced in 1975 for brain studies, involves injecting radioactive tracers to image metabolic and molecular processes. Fluorodeoxyglucose (FDG) tracks glucose metabolism, revealing hypometabolic regions in disorders like , while ligands for binding assess receptor density in areas like the , aiding Parkinson's research. PET provides quantitative data on cerebral blood flow and systems with 4-6 mm . Diffusion tensor imaging (DTI), introduced in , extends MRI to map microstructure by measuring water diffusion anisotropy. It reconstructs fiber tracts like the , using (FA) values—ranging from 0 (isotropic) to 1 (highly directional)—to quantify tract integrity; reduced FA indicates damage from injury or demyelination. This technique elucidates connectivity in neural networks. Electroencephalography (EEG), first recorded in humans in 1929, captures electrical potentials from scalp electrodes with millisecond , ideal for studying neural synchrony and rapid events. It detects event-related potentials (ERPs), such as the P300 component elicited by stimuli, providing insights into cognitive processing timelines. EEG is portable and cost-effective for real-time monitoring. (MEG), demonstrated in 1972, records magnetic fields from neuronal currents using superconducting sensors, offering comparable to EEG but better spatial localization for superficial sources. It excels in measuring oscillatory synchrony, like alpha rhythms (8-12 Hz), and event-related fields analogous to ERPs, without distortion from conductivity. MEG complements other techniques in presurgical mapping. These techniques, often combined multimodally, enhance understanding of brain disorders such as tumors and by integrating structural, functional, and data.

Electrophysiological methods

Electroencephalographic (EEG) methods noninvasively record electrical activity from the surface, capturing summed postsynaptic potentials of large neuronal populations with high on the order of milliseconds. These techniques are fundamental for studying brain dynamics during , , and cognitive tasks, providing insights into oscillatory patterns that reflect synchronized neural activity. Unlike metabolic , EEG excels in temporal precision but offers limited without advanced processing. The standard EEG electrode placement follows the 10-20 system, which positions electrodes at 10% or 20% intervals along the scalp's perimeter relative to anatomical landmarks like the and inion, ensuring reproducible and comparable recordings across studies. This system, developed in 1958, facilitates the identification of regional activity through up to 21 electrodes in basic setups, expandable for denser coverage. Characteristic EEG rhythms include , which oscillate at 8-12 Hz and predominate over the occipital during relaxed wakefulness with eyes closed, diminishing with visual attention or mental effort. During non-rapid eye movement (NREM) sleep stage 2, sleep spindles emerge as transient bursts of 11-16 Hz activity lasting 0.5-2 seconds, primarily over central and frontal regions, and are implicated in and . For deeper insights, intracranial EEG employs depth electrodes stereotactically implanted into brain tissue, often in patients to map onset zones with millimeter precision. These electrodes, typically hybrid bundles of 8-16 contacts spaced 3-10 mm apart, record from subcortical structures like the , enabling precise localization of epileptogenic foci before surgical resection. , using microelectrodes with tips sharpened to 1-5 μm, isolates action potentials from individual neurons in the human brain, revealing firing patterns during tasks such as memory encoding or . This method, applied intraoperatively or via chronic implants, has elucidated single-neuron selectivity for concepts like faces or places in the medial . At the cellular level, the patch-clamp technique measures ion channel currents in brain slices, allowing direct study of neuronal excitability. Developed by Neher and Sakmann in 1976, it uses a glass micropipette to form a high-resistance seal on the cell membrane, enabling whole-cell recordings. In voltage-clamp mode, the membrane potential is held constant to quantify voltage-gated ion currents, such as sodium or potassium fluxes underlying action potentials; current-clamp mode, conversely, monitors voltage changes in response to injected currents, mimicking synaptic inputs in hippocampal or cortical slices. These configurations have characterized ion channel kinetics essential for synaptic transmission and plasticity. Optogenetics extends electrophysiological control by genetically expressing light-sensitive ion channels in targeted neurons, enabling precise manipulation of firing patterns. Introduced in 2005 using channelrhodopsin-2 (ChR2), a blue-light-gated cation channel from , this method depolarizes neurons within milliseconds upon illumination, achieving spike rates up to 100 Hz without chemical interference. Post-2005 advancements have refined variants for faster kinetics and red-shifted activation, facilitating circuit-level studies in behaving animals and, increasingly, applications via delivery. EEG and related recordings are prone to artifacts from eye blinks, muscle activity, or cardiac signals, which can obscure neural data. Correction involves bandpass filtering (e.g., 0.5-40 Hz to retain physiological rhythms while attenuating noise) and to decompose and subtract non-brain sources. Source localization algorithms, such as dipole modeling or , then estimate underlying generator locations by solving the with head models, improving spatial attribution of electrical signals. These steps ensure reliable interpretation, often integrated briefly with imaging for multimodal validation.

Molecular and genetic studies

Molecular and genetic studies have advanced the understanding of brain function and by elucidating the genetic underpinnings of neurological disorders, the of cellular transcriptomes, and the dynamic molecular networks governing neuronal signaling. These approaches leverage high-throughput technologies to identify causal variants, model diseases , and predict therapeutic responses, providing insights into both healthy brain processes and disease mechanisms. Genome-wide association studies (GWAS) have been instrumental in pinpointing single nucleotide polymorphisms (SNPs) linked to major brain disorders. In , large-scale GWAS by the Psychiatric Genomics Consortium identified 287 risk loci (as of 2022), with the (MHC) locus on emerging as the strongest signal, implicating immune dysregulation in disease etiology through variants affecting and T-cell responses. Similarly, for , GWAS have reinforced the (APOE) ε4 allele as the primary genetic risk factor, with odds ratios up to 12 for homozygous carriers, influencing amyloid-beta clearance and via transport modulation. These findings highlight polygenic contributions to brain disorders, where common variants collectively explain a significant portion of . Single-cell RNA sequencing (scRNA-seq) has unveiled the transcriptomic heterogeneity of neuronal subtypes across brain regions, particularly in the layered . Studies using single-nucleus RNA-seq on postmortem tissue have classified dozens of excitatory pyramidal subtypes in layers 2/3 and 5, distinguished by markers such as FEZF2 for deep-layer projection neurons and SATB2 for upper-layer callosal neurons, revealing layer-specific programs involved in and . This granularity has also exposed disease-associated shifts, such as altered subtype proportions in aging or neurodegeneration, underscoring the role of cellular diversity in brain . CRISPR-Cas9 gene editing enables precise modeling of monogenic brain diseases in human-derived systems like cerebral organoids. For , caused by expanded CAG repeats in the HTT gene, has been used to introduce patient-specific mutations into induced pluripotent stem cell-derived organoids, resulting in disrupted neurodevelopment, including reduced ventricular zone organization and impaired neuronal migration, which mimic early pathogenic events observed . These models facilitate testing of allele-specific silencing strategies, offering a platform to study mutant toxicity without ethical constraints of animal models. Proteomic profiling, particularly phosphoproteomics, has mapped dynamic post-translational modifications in brain signaling cascades. Mass spectrometry-based analyses of human brain tissue have quantified thousands of phosphorylation sites on kinases and synaptic proteins, revealing cascades like MAPK/ERK and PI3K/AKT pathways that regulate neuronal survival and , with dysregulation linked to conditions such as and . For instance, hyperphosphorylation of at specific serine residues disrupts stability, a hallmark of Alzheimer's progression. Pharmacogenomics investigates how genetic variants affect drug responses in the , guiding personalized . Variants in the 2D6 () gene, which metabolizes antidepressants like and , significantly influence efficacy and tolerability; poor metabolizers (e.g., *4/*4 genotypes) exhibit substantially higher drug exposure, increasing the risk of adverse events such as . This has led to dosing guidelines that adjust based on metabolizer status to optimize therapeutic outcomes in mood disorders.

Society and culture

Philosophical concepts of mind

Philosophical inquiries into the human have long centered on the mind-brain relationship, exploring whether mental phenomena are distinct from or reducible to physical processes in the . This debate traces back to ancient thinkers but gained prominence in the with , who posited a substance distinguishing the mind as an immaterial from the extended, material body. In this view, the mind, or res cogitans (thinking thing), is non-spatial and capable of doubt, understanding, and willing, while the body, or res extensa (extended thing), operates mechanistically like a machine. Descartes proposed that the mind interacts with the body via the , a small structure in the he identified as the principal seat of the due to its central, unpaired position, allowing it to receive sensory impressions and initiate motor responses without interference from the brain's divided hemispheres. In contrast, materialist philosophies assert that the mind is entirely composed of or emergent from brain matter, eliminating any non-physical substances. , a 17th-century precursor to this view, argued in that all mental activities, including thought and , arise from the mechanical motions of material particles in the , rejecting immaterial souls as unnecessary for explaining or volition. This tradition evolved into modern identity theory in the mid-20th century, which holds that mental states are identical to specific states or processes. Pioneered by U.T. Place in his 1956 paper "Is Consciousness a Process?" and elaborated by in "Sensations and Processes" (1959), the theory posits that statements about sensations, such as feeling pain, are theoretically equivalent to neurophysiological descriptions, much like is identical to an electrical discharge—though conceptually distinct, they refer to the same event. Functionalism emerged in the 1960s as a response to identity theory's perceived limitations, particularly its assumption of human-brain specificity. Hilary Putnam introduced the idea in "Psychological Predicates" (1967), analogizing the mind to software that can run on different hardware, emphasizing the functional role of mental states defined by their causal relations to sensory inputs, behavioral outputs, and other mental states rather than their intrinsic physical makeup. This leads to the doctrine of multiple realizability, where the same mental state, like pain, could be instantiated by diverse physical systems—human neurons, alien physiologies, or even silicon-based processors—undermining strict psychophysical identities and supporting a broader, non-reductive physicalism. Contemporary philosophy grapples with the "hard problem of consciousness," which questions why physical processes in the brain give rise to subjective experience or qualia—the ineffable, first-person feels of seeing red or tasting salt—beyond mere information processing. David Chalmers articulated this in his 1995 paper "Facing Up to the Problem of Consciousness," distinguishing it from the "easy problems," which involve explaining cognitive functions like attention, reportability, or behavioral control through neural mechanisms amenable to scientific reduction. Chalmers argues that qualia resist functional explanation, suggesting consciousness may require new fundamental principles in physics or even non-physical properties, though he favors naturalistic panpsychism where experience is ubiquitous in the universe. Debates on further intertwine philosophical concepts with function, particularly through empirical challenges to libertarian notions of uncaused . Benjamin Libet's experiments in the measured the readiness potential (), a electrical activity preceding voluntary actions like wrist flexions, finding it begins about 350 milliseconds before conscious of the intent to act, which occurs only 200 milliseconds prior. Libet interpreted this as evidence that unconscious neural processes initiate decisions, potentially undermining by suggesting the "decides" before the mind does, though he proposed a veto power in to interrupt actions, preserving . These findings have fueled compatibilist responses, arguing is compatible with if actions align with one's desires, while critics contend the experiments oversimplify volition by focusing on simple motor tasks rather than deliberative choices.

Brain size and cognition myths

A common misconception posits that larger brain size directly equates to higher intelligence in humans, a notion rooted in outdated pseudoscientific ideas such as , which linked cranial measurements to mental faculties. However, empirical evidence consistently demonstrates that absolute brain volume is a poor predictor of cognitive ability, as intelligence arises from complex neural organization, , and efficiency rather than sheer size. This myth persists despite studies showing only modest correlations between brain volume and IQ, even after accounting for confounding factors like body size. The (), which measures brain mass relative to expected size based on body mass, better illustrates why absolute size misleads. Humans exhibit an of approximately 7.4–7.8, far exceeding that of dolphins at 4–5, despite dolphins having larger absolute brain volumes in some cases; this relative scaling underscores that scales with brain-to-body proportions rather than raw volume. For instance, while brains weigh up to 5 kg compared to the human average of 1.3–1.4 kg, the human highlights evolutionary adaptations for advanced cognition beyond mere enlargement. Examination of exceptional cases, such as Albert Einstein's brain, further debunks direct size-intelligence links. Postmortem analysis revealed that Einstein's was about 15% wider than average, potentially linked to his mathematical and spatial reasoning prowess, yet the absence of the parietal operculum—a feature allowing this expansion—lacks proven causality for his genius, as similar anomalies occur without extraordinary intellect. Later studies have contested the "missing" operculum claim, affirming its presence but noting atypical sulcal patterns; regardless, no establishes brain size variations as the primary driver of Einstein's cognitive exceptionalism. Sex-based differences in brain size also challenge the myth, as males typically possess brains 10–15% larger than females, even after adjusting for body height, yet average IQ scores remain equivalent across sexes when normalized. This parity holds in meta-analyses of over 46,000 children and adults, showing no overall difference in general (g factor). Compensatory factors, such as potentially higher neuronal density in female brains (reflected in greater gray matter-to-white matter ratios), may offset volume disparities without altering cognitive outcomes. Disorders at brain size extremes provide stark evidence against proportional cognition claims. Microcephaly, characterized by a head more than two standard deviations below the mean, often results in due to reduced brain volume and disrupted , as seen in genetic syndromes like those involving MCPH1 mutations. Conversely, —head exceeding two standard deviations above the mean—frequently stems from or and does not confer superior ; affected individuals may exhibit normal or impaired , depending on underlying , as in PTEN-related disorders. These conditions highlight that deviant sizes signal developmental disruptions rather than linear predictors of ability. Large-scale MRI investigations confirm the weak association between brain volume and intelligence. Meta-analyses of neuroimaging data report correlations of r = 0.24–0.33 between total brain volume and IQ after controlling for body size and range restrictions, explaining only 6–10% of variance in cognitive performance. Within-family studies further diminish this link (r ≈ 0.2), suggesting genetic and environmental factors dominate over volumetric measures. These findings emphasize that while modest positive trends exist, brain size alone cannot substantiate myths of deterministic intelligence scaling.

Depictions in popular culture

The human brain has been a recurring motif in science fiction, often portrayed through tropes like mind control and consciousness uploading, which reflect societal anxieties about autonomy and technology. In works such as The Manchurian Candidate (1962 film adaptation), brainwashing techniques are depicted as reprogramming the mind to turn individuals into unwitting assassins, drawing on Cold War fears of psychological manipulation. Similarly, the anthology series Black Mirror explores consciousness uploading in episodes like "San Junipero" (2016), where dying individuals transfer their minds into a simulated afterlife, raising questions about digital immortality and the essence of self. These narratives blend speculative neuroscience with ethical dilemmas, influencing public discourse on brain-computer interfaces. Neuroscience concepts frequently appear in films, dramatizing brain functions for entertainment while sometimes simplifying complex processes. Christopher Nolan's Inception (2010) visualizes dream architecture as layered subconscious realms accessed via shared dreaming technology, inspired by real studies on stages and , though it exaggerates the brain's ability to construct stable virtual worlds. In Limitless (2011), the uses a fictional drug, NZT-48, to unlock hyper-enhanced , including perfect recall and rapid learning, echoing interest in cognitive enhancers but overlooking the drug's neurotoxic side effects in reality. Such portrayals popularize ideas like and synaptic efficiency, yet they often prioritize plot over scientific accuracy. Artistic representations of the brain have evolved from surrealist explorations to contemporary installations incorporating . Salvador Dalí's surrealist works, such as (1931), evoke neural surrealism through melting clocks symbolizing fluid , influenced by his interest in Freudian and imagery. In modern exhibits, brain scans feature prominently; for instance, artist Laura Jacobson's MRI-inspired pieces at Stanford's imaging center (2013) transform functional scans into abstract sculptures, highlighting the brain's aesthetic and diagnostic beauty. Exhibitions like Landscapes of the Mind (Williams College Museum of Art) use brain imagery to contemplate cognition, bridging art and science. Popular media has perpetuated misconceptions about the brain, notably the myth that humans use only 10% of their capacity, reinforced by films like Lucy (2014), where the protagonist evolves superhuman abilities by accessing untapped potential after drug exposure. This trope, debunked by neuroimaging showing whole-brain activity, misrepresents neural efficiency and fuels pseudoscientific beliefs about hidden mental powers. Educational media counters such myths by demystifying the brain for broad audiences. Documentaries like PBS's The Brain with (2015) series dissect , , and through experiments and stories, fostering greater public understanding of brain science. TED Talks on , such as those by on hallucinatory (2017), engage viewers with accessible explanations, promoting accurate views amid cultural . These formats have amplified 's reach, shaping informed perceptions beyond .

Comparative anatomy

Primate comparisons

The human brain is notably larger than that of other primates, with an average adult mass of approximately 1,350 grams compared to about 400 grams in chimpanzees, representing a roughly threefold increase in volume despite similar body sizes. This enlargement is not uniform but disproportionately affects the cerebral cortex, particularly the association areas involved in higher-order processing such as integration of sensory information and executive functions. In humans, the prefrontal cortex, a key association region, exhibits exceptional expansion relative to other primates, comprising a larger proportion of total brain volume and supporting advanced cognitive abilities like planning and decision-making. Comparative studies indicate that this cortical scaling follows a pattern where anthropoid primates, including humans and great apes, show accelerated growth in these regions compared to more basal primates like monkeys. One prominent structural difference is cerebral asymmetry, particularly in the (PT), a region of the implicated in auditory processing and . In humans, the left PT is typically larger than the right, correlating with hemispheric specialization for , a feature absent at the population level in monkeys such as macaques, capuchins, and vervets. This asymmetry emerges early in development and is more pronounced in great apes like chimpanzees, where PT gray matter shows leftward bias similar in magnitude to humans, suggesting an evolutionary gradient tied to enhanced vocal and gestural communication. Functional lateralization in humans thus builds on foundations but is amplified for complex symbolic processing. Von Economo neurons (VENs), also known as spindle neurons, are large, specialized projection cells found primarily in layer Vb of the anterior cingulate and frontoinsular cortices, regions linked to , , and emotional regulation. These neurons are abundant in humans and great apes (chimpanzees, bonobos, , and orangutans) but are sparse or absent in monkeys, indicating a derived in hominoids that may facilitate rapid signaling in social contexts. Their density correlates with group size and across species, underscoring their role in adaptive behaviors like and intuition of others' intentions. Mirror neurons, first identified in the ventral of monkeys, activate both during action execution and observation of similar actions performed by others, providing a neural substrate for understanding intentions and . In humans, this system appears expanded, with broader activation in , parietal, and inferior frontal areas, potentially underlying advanced and critical for cultural transmission and social bonding. While present in monkeys for basic action recognition, the human elaboration supports nuanced emotional mirroring, as evidenced by stronger responses to observed distress. Tool use in correlates with enlargement, particularly in great apes, where this region shows disproportionate growth relative to monkeys, enabling flexible manipulation and planning. Chimpanzees and orangutans, proficient in crafting and using tools like sticks for fishing, exhibit expanded dorsolateral prefrontal areas that integrate sensory-motor information, a precursor to . This neural adaptation highlights how prefrontal scaling across supports increasing behavioral complexity without requiring entirely novel circuitry.

Mammalian variations

The mammalian brain exhibits significant variations across species, reflecting adaptations to diverse ecological niches while sharing core structures with the human . In , the constitutes a substantial portion of the , averaging approximately 3.94% of total brain mass, underscoring its dominant role in scent-based and . In contrast, the human is markedly reduced, comprising only about 0.01% of brain volume, indicative of a diminished reliance on olfaction relative to other sensory modalities. The , essential for spatial , shows structural similarities across mammals but diverges in functional emphasis. In bats and rats, the hippocampus supports precise spatial mapping for echolocation and path integration during movement, with place cells firing in response to specific locations. Humans retain this navigational framework but exhibit an expanded hippocampal capacity for , enabling the recollection of personal events with contextual details beyond mere spatial cues. Interhemispheric connectivity via the varies notably; in cats, this structure is relatively thick, facilitating robust integration of sensory and motor information between hemispheres to support agile predation and environmental responsiveness. However, it is absent in monotremes such as the and , where alternative commissures like the handle limited cross-hemispheric communication. Sleep architecture, including rapid eye movement () phases, differs profoundly; humans allocate about 20% of total sleep to , associated with and emotional processing. , by comparison, exhibit minimal REM sleep, with total daily sleep limited to around 2 hours, reflecting adaptations for prolonged vigilance in open habitats. Electroreception, the ability to detect electric fields, is absent in most mammals, including humans, but present in the monotreme through specialized mucous gland electroreceptors innervated by the , aiding prey detection in murky waters. Despite these variations, basic structures remain conserved across mammals, ensuring fundamental regulatory functions like arousal and autonomic control. brains represent intermediates, blending enhanced olfactory reduction with hippocampal expansions seen in humans.

Evolutionary origins

The evolutionary origins of the human brain trace back to the vertebrate lineage, where foundational structures emerged in early aquatic ancestors. In , the —a rudimentary region—served basic sensory and motor functions with minimal size relative to body mass, laying the groundwork for later cortical expansions. This small pallium evolved into more complex analogs in , where the pallium supports advanced through high neuronal density despite lacking a laminated , demonstrating convergent encephalization independent of mammalian pathways. In mammals, encephalization accelerated with the development of the , driven by endothermy and increased metabolic efficiency, allowing larger brains relative to body size compared to reptiles or . A influential but critiqued framework for mammalian brain evolution is Paul MacLean's model, proposed in the mid-20th century, which posits three layered systems: the reptilian (R-complex) for instinctual behaviors like aggression and territoriality; the paleomammalian for emotional processing and social bonding; and the neomammalian for higher reasoning and . This model suggested a sequential evolutionary addition of these components across reptiles, early mammals, and , respectively. However, it has been widely discredited for oversimplifying brain organization, ignoring interconnections between regions and misrepresenting phylogenetic development as strictly additive rather than integrative and adaptive. Within hominins, brain size expanded markedly, reflecting key adaptive milestones. Early australopiths, such as around 3-4 million years ago, had average endocranial volumes of approximately 400-450 cm³, comparable to great apes and supporting bipedal foraging in varied environments. By the emergence of about 1.8 million years ago, brain volumes averaged around 1000 cm³, enabling enhanced tool use and dispersal from , possibly facilitated by dietary shifts including controlled and cooking that increased caloric intake for neural growth. Modern Homo sapiens, arising around 300,000 years ago, exhibit average brain sizes of about 1350 cm³, with this expansion linked to complex social structures and symbolic behavior, though cooking's role in sustaining such sizes remains a tied to energy availability. Genetic innovations further propelled human brain evolution through duplications and modifications. The gene, critical for neural circuits underlying speech and language, underwent human-specific substitutions—two changes after the human-chimpanzee split—resulting in accelerated protein evolution that likely enhanced vocal learning and for articulation. Similarly, ARHGAP11B arose via partial duplication of ARHGAP11A around 3-5 million years ago exclusively in the human lineage, promoting proliferation of basal progenitor cells in the and contributing to its folded, expanded architecture. These gene-level changes underscore how subtle genomic tweaks drove disproportionate cortical growth in hominins. Sexual selection also influenced brain evolution in , manifesting as dimorphism in size. In early species like H. erectus, males had larger brains than females, reflecting reduced but persistent compared to australopiths and potentially arising from mate competition that favored cognitive traits for social dominance and coalition-building. This pattern persisted in H. sapiens, where male brains average 100-150 cm³ larger than female brains, though overall dimorphism decreased compared to australopiths, suggesting a shift toward mutual pressures on over physical prowess.

References

  1. [1]
    Brain Basics: Know Your Brain
    Feb 25, 2025 · This three-pound organ is the seat of intelligence, interpreter of the senses, initiator of body movement, and controller of behavior.
  2. [2]
    Physiology, Brain - StatPearls - NCBI Bookshelf
    [1] The brain is an organ of nervous tissue that commands task-evoked responses, movement, senses, emotions, language, communication, thinking, and memory. The ...
  3. [3]
    Scientists build largest maps to date of cells in human brain - NIH
    Oct 31, 2023 · The human brain is made up of about 86 billion nerve cells, along with many other types of cells. They interact and link together in unique ...<|control11|><|separator|>
  4. [4]
    Definition of brain - NCI Dictionary of Cancer Terms
    The organ inside the head that controls all body functions of a human being. Made up of billions of nerve cells, the brain is protected by the cranium.
  5. [5]
    Neuroanatomy, Cranial Meninges - StatPearls - NCBI Bookshelf - NIH
    The chief function of the meninges is to protect the contents of the brain and spinal cord. ... The primary functions of the CSF are to cushion the brain ...
  6. [6]
    Brain components - Health Video: MedlinePlus Medical Encyclopedia
    Apr 1, 2025 · There are three major components of the brain. The cerebrum is the largest component, extending across the top of the head down to ear level.
  7. [7]
    Chapter 1: Overview of the Nervous System
    The largest and most obvious parts of the human brain are the cerebral hemispheres. The cerebrum has an outer layer - the cortex, which is composed of neurons ...
  8. [8]
    The Human Brain: Major Structures and Functions - NIDA
    Jul 28, 2016 · THE FRONTAL LOBE is for personality and emotions, higher thinking skills, like problem solving; and controlling movement. · THE TEMPORAL LOBE ...
  9. [9]
    Physiology, Cerebral Spinal Fluid - StatPearls - NCBI Bookshelf
    Aug 9, 2025 · CSF supports the brain by providing protection ... Meningitis refers to inflammation of the meninges, the protective coverings of the brain.
  10. [10]
    Neuroanatomy, Cerebral Hemisphere - StatPearls - NCBI Bookshelf
    The cerebrum controls somatosensory, motor, language, cognitive thought, memory, emotions, hearing, and vision. The cerebrum is divided into the left and right ...
  11. [11]
    Neuroanatomy, Cerebral Cortex - StatPearls - NCBI Bookshelf - NIH
    It is the gray matter of the brain. Lying right under the meninges, the cerebral cortex divides into four lobes: frontal, temporal, parietal and occipital lobes ...
  12. [12]
    A taxonomy of the brain's white matter: twenty-one major tracts for ...
    The internal capsule (Fig. 2) is positioned between the caudate and thalamus medially and the putamen and globus pallidus laterally. It can be divided into the ...
  13. [13]
    The Anatomy of the Cerebral Cortex - NCBI - NIH
    Molecular (Plexiform) layer I: consists of apical dendritic tufts of the pyramidal neurons, horizontally organized axons, Cajal-Retzius cells and glial cells.Abstract · HISTOLOGICAL STRUCTURE... · FUNCTIONAL AREAS OF THE...
  14. [14]
    An Overview of Cortical Structure - Neuroscience - NCBI Bookshelf
    The neocortex has six cellular layers, with regional differences. Each layer has primary inputs/outputs, vertical and horizontal connections, and radial groups ...Missing: anatomy | Show results with:anatomy
  15. [15]
    Neuroanatomy, Thalamus - StatPearls - NCBI Bookshelf - NIH
    The thalamus is a gray matter structure in the diencephalon, located near the brain's center, that relays sensory and motor signals and regulates consciousness.
  16. [16]
    Neuroanatomy, Thalamic Nuclei - StatPearls - NCBI Bookshelf - NIH
    Thalamic nuclei are about 60 regions in the thalamus, divided into lateral, medial, and anterior groups, and categorized as relay, reticular, and intralaminar.
  17. [17]
    The Human Thalamus Is an Integrative Hub for Functional Brain ...
    Jun 7, 2017 · The thalamus can be divided into the following two types of nuclei: first-order and higher-order thalamic nuclei (Sherman, 2007). First-order ...Thalamic And Cortical Nodal... · Parcellation Of The Thalamus · Thalamic Lesions Have Global...
  18. [18]
    Physiology, Hypothalamus - StatPearls - NCBI Bookshelf
    Paraventricular nucleus: Decrease in the secretion of oxytocin. Suprachiasmatic nucleus: Circadian rhythm dysfunction. These impairments can be caused by ...
  19. [19]
    Hypothalamus Control of Blood Pressure & Variability
    The paraventricular nucleus (PVN) is a highly organized structure of the hypothalamus that has a key role in regulating cardiovascular and osmotic homeostasis.
  20. [20]
    Physiology of the Pineal Gland and Melatonin - Endotext - NCBI - NIH
    Oct 30, 2022 · Both AA-NAT and serotonin availability play a role limiting melatonin production. AA-NAT mRNA is expressed mainly in the pineal gland, retina, ...
  21. [21]
    The morphological and functional characteristics of the pineal gland
    The pineal gland is a photo-neuro-endocrine organ situated inside the brain, that secretes serotonin, melatonin and N,N-dymethyltriptamine.Physiology · Melatonin · Histology
  22. [22]
    Neuroanatomy, Basal Ganglia - StatPearls - NCBI Bookshelf
    The subthalamic nucleus (STN), located ventral to the thalamus, receives many different projections from the cortex, GPe, SN, and the pontine reticular ...
  23. [23]
    Architecture of the subthalamic nucleus | Communications Biology
    Jan 10, 2024 · The STN is part of the hyperdirect and indirect pathway of the basal ganglia motor circuitry. The indirect pathway works antagonistically to the ...
  24. [24]
    Basal Ganglia (Section 3, Chapter 4) Neuroscience Online
    The subthalamic nucleus makes glutamatergic, excitatory connections onto both segments of the globus pallidus and the SNr. This pathway is the only purely ...
  25. [25]
    Blood—Cerebrospinal Fluid Barrier - Basic Neurochemistry - NCBI
    CSF (gray) is secreted by the choroid plexus present in the cerebral ventricles and by extrachoroidal sources. It subsequently circulates through the ...Missing: primary | Show results with:primary
  26. [26]
    Choroid plexus and the blood–cerebrospinal fluid barrier in disease
    May 6, 2020 · The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite ...
  27. [27]
    Neuroanatomy, Cerebellum - StatPearls - NCBI Bookshelf - NIH
    Jul 24, 2023 · Tentorium cerebelli, an extension of the dura matter, separates the cerebellum from the cerebrum. It is composed of two hemispheres joined ...
  28. [28]
    Recent advances in understanding the mechanisms of cerebellar ...
    Jul 26, 2018 · Located above the granular layer are two additional layers: the Purkinje cell layer and the molecular layer. These three layers contain the ...
  29. [29]
    Cerebellum Lecture: the Cerebellar Nuclei—Core ... - PubMed Central
    In the cerebellar cortex the afferent information undergoes extensive computational processing and then is projected via the Purkinje cells (PC) to the CN, ...
  30. [30]
    Circuits within the Cerebellum - Neuroscience - NCBI Bookshelf - NIH
    The axons from the pontine nuclei and other sources are called mossy fibers because of the appearance of their synaptic terminals. Mossy fibers synapse on ...
  31. [31]
    Cerebellum (Section 3, Chapter 5) Neuroscience Online
    Climbing fibers originate exclusively in the inferior olive and make excitatory projections onto the cerebellar nuclei and onto the Purkinje cells of the ...
  32. [32]
    Projections from the Cerebellum - Neuroscience - NCBI Bookshelf
    Consequently, the dentate axons exit the cerebellum via the superior cerebellar peduncle, cross at the decussation of the superior cerebellar peduncle in the ...
  33. [33]
    The Errors of Our Ways: Understanding Error Representations in ...
    The cerebellum is essential for error-driven motor learning and is strongly implicated in detecting and correcting for motor errors.
  34. [34]
    Cerebellum, Predictions and Errors - PMC - PubMed Central
    Jan 15, 2019 · The cerebellum has been viewed as a key component of the motor system providing predictions about upcoming movements and receiving feedback about motor errors.
  35. [35]
    Prediction signals in the cerebellum: Beyond supervised motor ... - NIH
    Mar 30, 2020 · This review will highlight both current evidence for predictive cerebellar circuit function that extends beyond the classical view of error-driven supervised ...<|control11|><|separator|>
  36. [36]
    Neuroanatomy, Brainstem - StatPearls - NCBI Bookshelf
    Jul 4, 2023 · It is composed of three sections in descending order: the midbrain, pons, and medulla oblongata.Introduction · Structure and Function · Blood Supply and Lymphatics · Nerves
  37. [37]
    Neuroanatomy, Reticular Formation - StatPearls - NCBI Bookshelf
    The reticular formation is a complex network of brainstem nuclei and neurons that serve as a major integration and relay center for many vital brain systems.
  38. [38]
    Neuroanatomy, Fourth Ventricle - StatPearls - NCBI Bookshelf - NIH
    The fourth ventricle is the most inferiorly located ventricle, draining directly into the central canal of the spinal cord.Missing: circulation | Show results with:circulation
  39. [39]
    Anatomy, Head and Neck, Subarachnoid Space - StatPearls - NCBI
    The cisterns are enlarged pockets of CSF created due to the separation of the arachnoid mater from the pia mater based on the anatomy of the brain and spinal ...Missing: human | Show results with:human
  40. [40]
    Neuroanatomy, Ventricular System - StatPearls - NCBI Bookshelf - NIH
    ... fourth ventricle through the cerebral aqueduct of Sylvius. The space of the third ventricle is lined by ependyma and is traversed by a mass of grey matter ...
  41. [41]
    Neuroanatomy, Choroid Plexus - StatPearls - NCBI Bookshelf - NIH
    CSF then flows from the third to the fourth ventricle via the cerebral aqueduct of Sylvius. Lastly, CSF flows from the fourth ventricle to the subarachnoid ...
  42. [42]
    Stratification of astrocytes in healthy and diseased brain - PMC
    Based on morphological criteria, in the human neocortex astrocytes accounted for ∼ 20%–40%, oligodendrocytes for 50%–75% and microglia for 5%–10% of the total ...Evolution Of Glia... · Human Astrocytes And... · Table 2
  43. [43]
    Neurons and Glia | The Human Brain - Yale University
    Pyramidal neurons are excitatory, meaning that the synapses formed from the terminal axon branches release glutamate, the primary excitatory neurotransmitter ...
  44. [44]
    Variation in Pyramidal Cell Morphology Across the Human Anterior ...
    Pyramidal neurons are the most abundant and characteristic neuronal type in the cerebral cortex and their dendritic spines are the main postsynaptic ...
  45. [45]
    Organization of Cell Types (Section 1, Chapter 8) Neuroscience ...
    These have been further sub-categorized into Golgi type II cells that are small neurons, usually interneurons, and Golgi type I cells that are large multipolar ...
  46. [46]
    Organization and function of neural circuits | Luo Lab
    *We have discovered that cerebellar granule cells, comprising by far the most numerous neurons in the mammalian brain, encode expectation of reward and share ...
  47. [47]
    Central Nervous System - Duke Histology
    Pyramidal cells in layers III and V tend to be larger because their axons contribute to efferent projections that extend to other regions of the CNS –pyramidal ...
  48. [48]
    Histology, Glial Cells - StatPearls - NCBI Bookshelf - NIH
    The most notable glial cells include oligodendrocytes, Schwann cells, astrocytes, microglia, and ependymal cells. Most glial cells are capable of mitotic ...Missing: human | Show results with:human
  49. [49]
    Mapping human brain cell type origin and diseases through single ...
    Oct 6, 2025 · ... astrocytes, oligodendrocytes, microglia, and ependymal cells [97]. Astrocytes regulate blood flow, ion homeostasis, neurotransmitter cycling ...
  50. [50]
    Glial Contributions to Neural Function and Disease - PMC
    The main types of CNS glia include astrocytes, oligodendrocytes, ependymal cells, radial glia, and microglia. In the PNS, the main glial cells are Schwann cells ...
  51. [51]
    Nervous Tissue - Histology Guide
    However, non-neural cells (i.e., glial cells) provide support and protection in the CNS (oligodendrocytes, astrocytes, ependymal cells, and microglia) and ...MHS 283 Brain · MHS 284 Brain · MHS 240 Spinal Cord · UCSF 163 Spinal Cord<|control11|><|separator|>
  52. [52]
    Physiology, Synapse - StatPearls - NCBI Bookshelf
    Mar 27, 2023 · Synapse is the transmission site from the pre-synaptic to the post-synaptic neuron. The structures found on either side of the synapse vary ...Missing: density | Show results with:density
  53. [53]
    Synaptic changes in psychiatric and neurological disorders - Nature
    Aug 12, 2024 · Overview of the synapse. The synapse comprises a presynaptic terminal, the synaptic cleft and the postsynaptic density (Fig. 1a). In the ...
  54. [54]
    The Postsynaptic Organization of Synapses - PMC - PubMed Central
    Excitatory synapses are characterized by a morphological and functional specialization of the postsynaptic membrane called the postsynaptic density (PSD), which ...
  55. [55]
    The neocortical circuit: themes and variations - PMC - NIH
    Neurons can be classified according to different criteria: their morphology; their patterns of local and long-range connectivity; their developmental history ...
  56. [56]
    [PDF] White Matter Anatomy
    The major long tracts include cingulum, supe- rior and inferior occipitofrontal fasciculus; unci- nate fasciculus; superior longitudinal fasciculus (SLF), ...
  57. [57]
    The cortical column: a structure without a function - PMC
    Language cortex in humans contains columnar, horizontal, long-range connections that are spaced 20% more widely in the left hemisphere (Galuske et al. 2000) ...
  58. [58]
    [PDF] NEURONAL CIRCUITS OF THE NEOCORTEX
    We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local ...
  59. [59]
    Improved method for combination of immunocytochemistry and Nissl ...
    Nissl-staining is a widely used method to study morphology and pathology of neural tissue. After standard immunocytochemistry, the Nissl-staining labels ...
  60. [60]
    Franz Nissl (1860-1919), noted neuropsychiatrist and ... - NIH
    Consequently, Nissl staining was extremely useful for distinguishing neurons and glia from one to another and for studying the arrangement, cytoarchitecture, of ...
  61. [61]
    Brain (cresyl violet) | Nervous Tissue - Histology Guide
    Cresyl violet is a basic dye that binds nucleic acids and preferentially stains RNA. Nissl (i.e., chromophil) substance in the form of granules is found in some ...
  62. [62]
    [PDF] Histological Analysis of Neurodegeneration in the Mouse Brain
    Nissl staining is a standard immuno- histochemistry method that shows basic brain morphological features and allows comparison of brain architecture between sam ...
  63. [63]
    Neuroanatomy, Cerebrospinal Fluid - StatPearls - NCBI Bookshelf
    Jul 7, 2025 · From the 3rd ventricle, the fluid continues through the cerebral aqueduct of Sylvius into the 4th ventricle. From the 4th ventricle, the ...Missing: third fourth
  64. [64]
    Cerebrospinal fluid dynamics and intracranial pressure elevation in ...
    Apr 10, 2019 · CSF serves as a protective fluid to the brain and spinal cord, cushioning them from mechanical injury, and acts to reduce the brain's effective ...Csf Secretion · Csf Drainage · Csf Dynamics And Icp...
  65. [65]
    Intracranial Pressure Monitoring - StatPearls - NCBI Bookshelf - NIH
    Jan 23, 2024 · The normal intracranial pressure (ICP) ranges from 7 to 15 mm Hg, while it does not exceed 15 mm Hg in the vertical position.
  66. [66]
    Anatomy, Head and Neck: Cerebral Blood Flow - StatPearls - NCBI
    Blood Supply: The blood supply to the brain is primarily by the two internal carotid arteries (ICA) and two vertebral arteries which anastomose together to form ...
  67. [67]
    Neuroanatomy, Cerebral Blood Supply - StatPearls - NCBI Bookshelf
    Jul 24, 2023 · Four principal arteries supply the brain, namely one internal carotid artery (ICA) and one vertebral artery on each side.
  68. [68]
    Neuroanatomy, Circle of Willis - StatPearls - NCBI Bookshelf
    The circle of Willis acts to provide collateral blood flow between the anterior and posterior circulations of the brain, protecting against ischemia in the ...Introduction · Structure and Function · Embryology · Physiologic Variants
  69. [69]
    The Blood Supply of the Brain and Spinal Cord - Neuroscience - NCBI
    The brain receives blood from two sources: the internal carotid arteries, which arise at the point in the neck where the common carotid arteries bifurcate, and ...
  70. [70]
    Anatomy and Ultrastructure - The Cerebral Circulation - NCBI - NIH
    The arterial blood supply to the human brain consists of two pairs of large arteries, the right and left internal carotid and the right and left vertebral ...
  71. [71]
    Neuroanatomy, Brain Veins - StatPearls - NCBI Bookshelf
    Jun 25, 2025 · An intricate network of venous sinuses enables this drainage, collecting blood from the brain parenchyma, meninges, eyes, and cerebrospinal fluid (CSF).
  72. [72]
    Anatomy, Head and Neck: Cerebral Venous System - NCBI - NIH
    These two venous systems function to drain deoxygenated blood with carbon dioxide and metabolic waste away from the brain, allowing oxygenated blood to take ...
  73. [73]
    Physiology, Cerebral Autoregulation - StatPearls - NCBI Bookshelf
    Cerebral autoregulation is the ability of the cerebral vasculature to maintain stable blood flow despite changes in blood pressure.Introduction · Mechanism · Related Testing · Clinical Significance
  74. [74]
    Regulation of Cerebral Blood Flow - PMC - PubMed Central - NIH
    Jul 25, 2011 · This paper will discuss the three main regulatory paradigms involved in the regulation of cerebral blood flow: cerebral autoregulation, flow-metabolism ...
  75. [75]
    Collateral Circulation in Ischemic Stroke: An Updated Review - PMC
    The circle of Willis (CoW) is a ring of interconnected mediumsized arteries located at the base of the brain (Figure 1C). It connects the anterior and posterior ...
  76. [76]
    Blood-Brain Barrier Overview: Structural and Functional Correlation
    Dec 6, 2021 · First, tight junctions (TJs), which are a major component of the barrier, tie the endothelial cells that line the walls of these capillaries ...
  77. [77]
    The blood–brain barrier: Structure, regulation and drug delivery
    May 25, 2023 · Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood.
  78. [78]
    Basic physiology of the blood-brain barrier in health and disease
    A continuous basement membrane, pericytes and astrocyte endfeet surrounding the endothelium provide anatomical support to the BBB. Physical barrier (Tight ...Missing: paper | Show results with:paper
  79. [79]
    The Blood–Brain Barrier - PMC - PubMed Central
    Astrocytes extend processes that ensheath the blood vessels, such that the outline of the blood vessels can be visualized by the endfeet of these processes ( ...
  80. [80]
    A blood–brain barrier overview on structure, function, impairment ...
    Nov 18, 2020 · In this review, we will focus more on BBB as it is the main barrier contributing to CNS protection and maintaining the brain homeostasis. Unlike ...Missing: paper | Show results with:paper
  81. [81]
    Blood-brain barrier transporters: An overview of function, dysfunction ...
    Examples of SLC transporters that function in a passive facilitative manner include the glucose transporters (GLUTs), such as GLUT1 which facilitates the ...
  82. [82]
    Blood-Brain Barrier Active Efflux Transporters - PubMed Central - NIH
    The ABC efflux transporter P-glycoprotein (Pgp) has been demonstrated as a key element of the BBB that can actively transport a huge variety of lipophilic drugs ...
  83. [83]
    key roles for the efflux pump P-glycoprotein in the blood-brain barrier
    The efflux transporter P-glycoprotein (P-gp) is a key element of the molecular machinery that confers special permeability properties to the BBB.
  84. [84]
    A definitive guide to the blood-brain barrier - PMC - PubMed Central
    First, the brain contains circumventricular organs that lack a conventional blood-brain barrier. Namely, the organum vasculosum lamina terminalis (OVLT) ...
  85. [85]
    Glial functions in the blood-brain communication at the ...
    Oct 6, 2022 · The circumventricular organs (CVOs) are located around the brain ventricles, lack a blood-brain barrier (BBB) and sense blood-derived molecules.
  86. [86]
    The blood–brain barrier in systemic infection and inflammation
    Sep 30, 2021 · A number of studies have shown that solute permeability at the BBB is increased during systemic inflammation or infection. A systematic review ...
  87. [87]
    The effect of systemic inflammation on human brain barrier function
    Evidence from in vitro and preclinical in vivo studies indicate that systemic inflammation impairs blood-brain barrier function.
  88. [88]
    Embryology, Neural Tube - StatPearls - NCBI Bookshelf - NIH
    The neural tube formation during gestational development is a complicated morphogenic process that requires various cell signaling and regulation by a variety ...Introduction · Development · Cellular · Molecular Level
  89. [89]
    Formation of the Neural Tube - Developmental Biology - NCBI - NIH
    The neural tube arises from a solid cord of cells that sinks into the embryo and subsequently hollows out (cavitates) to form a hollow tube.
  90. [90]
    Neuroanatomy, Neural Tube Development and Stages - NCBI - NIH
    The neural folds converge and convert the neural groove into the neural tube. The fusion of the neural folds to form a neural tube requires a cadherin molecule ...Introduction · Structure and Function · Embryology · Blood Supply and Lymphatics
  91. [91]
    https://www.ncbi.nlm.nih.gov/books/NBK557414/
  92. [92]
    The Basics of Brain Development - PMC - PubMed Central
    This chapter is intended to provide an overview of some very basic principles of brain development, drawn from contemporary developmental neurobiology.
  93. [93]
    https://pmc.ncbi.nlm.nih.gov/articles/PMC2989000/
  94. [94]
    Embryology, Central Nervous System - StatPearls - NCBI Bookshelf
    Brain. During brain formation, there are 3 primary brain vesicles that differentiate into 5 secondary brain vesicles (see Image. Brain Vesicles).
  95. [95]
    Inside-out radial migration facilitates lineage-dependent neocortical ...
    Neocortical excitatory neurons migrate radially along the glial fibers of mother radial glial progenitors (RGPs) in a birth date-dependent inside-out manner ...
  96. [96]
    Integrative Mechanisms of Oriented Neuronal Migration in the ...
    Successive waves of migrating neurons arrive to occupy progressively more superficial cortical layers in an inside-out fashion; in other words, neurons ...
  97. [97]
    Development of fetal gyri, sulci and fissures - PubMed
    The gestational ages at which the structures were first imaged were: the callosal sulcus, from 14 weeks; the lateral sulcus, from 18 weeks; the parieto- ...Missing: human | Show results with:human
  98. [98]
    The Development of Gyrification in Childhood and Adolescence - PMC
    The development of gyrification begins prior to birth (see Figure 1), with the early stages of gyral and sulcal formation taking place between 10 to 15 weeks ...
  99. [99]
    Quantification of sulcal emergence timing and its variability in early ...
    May 7, 2023 · The timeline of sulcal emergence in the developing fetal brain may provide early indicators of normality of fetal brain development associated ...
  100. [100]
    Prenatal Programming of Human Neurological Function - PMC
    The rate of synaptogenesis reaches an astonishing peak so that at gestational week 34 through 24 months postpartum, there is an increase of 40,000 synapses per ...
  101. [101]
    Regulation of the brain-placental axis, and its relevance to ... - PubMed
    Oct 6, 2025 · It supplies nutrients and oxygen to the fetus, collects fetal waste, and safeguards the fetus from infections and adverse pregnancy conditions.
  102. [102]
    Association between placental oxygen transport and fetal brain ...
    Oct 26, 2023 · We observed that the fetuses with slower placental oxygen delivery had reduced volumetric and surface growth of the cerebral cortex. Moreover, ...
  103. [103]
    Placental protection of the fetal brain during short-term food ... - NIH
    This study has shown a direct role for placental metabolic pathways in modulating fetal brain development by the production of serotonin and indicates that ...<|control11|><|separator|>
  104. [104]
    Regulation of Placental Development and Its Impact on Fetal Growth ...
    The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for ...
  105. [105]
    Imaging structural and functional brain development in early childhood
    Note doubling of overall brain size between birth and 1 year with more gradual growth after age 1. In the neonate T1 scan, note that most white matter is not ...Missing: triples | Show results with:triples
  106. [106]
    The Development of Brain White Matter Microstructure - PMC
    By age 6 years, total brain volume has reached approximately 90% of adult values, with incremental increases continuing through the remainder of childhood and ...2. Introduction · 3. Healthy Brain Development · 3.3 Developmental Timing
  107. [107]
    Developmental Biology of Myelin - Basic Neurochemistry - NCBI - NIH
    Myelination follows the order of phylogenetic development. As the nervous system matures, portions of the PNS myelinate first, then the spinal cord and the ...
  108. [108]
    Myelination - an overview | ScienceDirect Topics
    Myelination follows a fixed pattern progressing from caudal (spinal cord) to rostral parts (brain) and spreads from central (diencephalon, pre- and postcentral ...Missing: 20s | Show results with:20s
  109. [109]
    Maturation of the adolescent brain - PMC - PubMed Central - NIH
    The brain also experiences a surge of myelin synthesis in the frontal lobe, which is implicated in cognitive processes during adolescence. Brain maturation ...
  110. [110]
    Adolescent Neurodevelopment - PMC - PubMed Central - NIH
    Pruning during adolescence is highly specific and can be pronounced, resulting in a loss of close to 50% of the synaptic connections in some regions, but with ...
  111. [111]
    A role for synaptic plasticity in the adolescent development ... - Nature
    Mar 5, 2013 · Synaptic pruning of excitatory contacts is the signature morphologic event of late brain maturation during adolescence. Mounting evidence ...
  112. [112]
    Structural Development of the Hippocampus and Episodic Memory
    Jun 25, 2013 · Until recently, it was thought that the hippocampus completed its development early in postnatal life, due to evidence of important ...
  113. [113]
    Development of prefrontal cortex | Neuropsychopharmacology
    Oct 13, 2021 · The prefrontal cortex (PFC) is considered to be the substrate of highest cognitive functions. Although neurons of the PFC are generated before birth.
  114. [114]
    The Importance of Marine Omega-3s for Brain Development and the ...
    Aug 4, 2020 · Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity ...Missing: volume | Show results with:volume
  115. [115]
    Environmental enrichment ameliorates perinatal brain injury and ...
    Feb 19, 2020 · Further, environmental stimulation promotes structural changes in myelin, resulting in the modulation of neural circuits and neurological ...
  116. [116]
    How the environment helps to shape the brain - Innovation District
    Aug 23, 2017 · In experimental models, enriched environments supported brain health by increasing the volume and length of myelinated fibers, the volume of ...Missing: postnatal | Show results with:postnatal
  117. [117]
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7031237/
  118. [118]
    https://innovationdistrict.childrensnational.org/environment-helps-shape-brain/
  119. [119]
    https://doi.org/10.1038/361031a0
  120. [120]
    https://doi.org/10.1016/j.neuron.2012.06.009
  121. [121]
    https://doi.org/10.3389/fncel.2017.00076
  122. [122]
    https://doi.org/10.1113/jphysiol.1970.sp009022
  123. [123]
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7614361/
  124. [124]
    The Dorsal Column-Medial Lemniscus System - Neuroscience - NCBI
    The dorsal column-medial lemniscus pathway carries the majority of information from the mechanoreceptors that mediate tactile discrimination and proprioception.
  125. [125]
    Mapping the primate lateral geniculate nucleus: A review of ...
    The figure on the left shows the pathway of visual information imaged on the retina as it passes through the LGN and arrives at the primary visual cortex (V1).
  126. [126]
    Mechanisms Underlying Development of Visual Maps and ...
    In the retina, SC, LGN, and visual cortex, functionally distinct visual pathways arise through layer-specific axonal and dendritic connections. A few ...Spontaneous Retinal Waves · Retinotopic Mapping · Ocular Dominance Column...
  127. [127]
    The Auditory Cortex - Neuroscience - NCBI Bookshelf
    The primary auditory cortex (A1) is located on the superior temporal gyrus in the temporal lobe and receives point-to-point input from the ventral division of ...
  128. [128]
    Psychophysics and Neuronal Bases of Sound Localization in Humans
    The two main binaural cues are differences in the time of arrival (the interaural time difference, ITD, or interaural phase difference, IPD) and differences in ...
  129. [129]
    The 'creatures' of the human cortical somatosensory system - PMC
    The homunculus, a 'grotesque creature' depicting the proportional representation of the human body on the primary somatosensory cortex, is a most influential ...
  130. [130]
    Memory and Plasticity in the Olfactory System: From Infancy ... - NCBI
    Similarly, there is no obligatory thalamic relay for olfactory information to reach the orbitofrontal cortex. Indeed, although the piriform cortex sends ...
  131. [131]
    The Olfactory System: Basic Anatomy and Physiology for General ...
    Olfactory nerve fibers project to the primary olfactory cortex without thalamic relay, which elicits immediate emotional and memory recall. The orbitofrontal ...
  132. [132]
    Parietal connectivity mediates multisensory facilitation - PMC - NIH
    Multisensory integration reliably occurs in brain areas that receive inputs from multiple primary sensory modalities, including the cortex, midbrain, and ...
  133. [133]
    Multisensory maps in parietal cortex - PMC - PubMed Central
    Oct 2, 2013 · A new parietal multisensory area integrates lower body and lower visual field. Rearrangement of parietal areas in human and non-human primates is rationalized.
  134. [134]
    Motor Cortex (Section 3, Chapter 3) Neuroscience Online
    Pyramidal and non-pyramidal neurons in motor cortex. The cerebral cortex is organized into six layers. These layers contain different proportions of the two ...<|control11|><|separator|>
  135. [135]
    The Primary Motor and Premotor Areas of the Human Cerebral Cortex
    In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ...<|separator|>
  136. [136]
    The Roles of the Cortical Motor Areas in Sequential Movements
    In this review, I will focus on the roles of the SMA, PMd, and M1 in skilled sequential movements, i.e., those acquired through repetitive practice and ...
  137. [137]
    Basal ganglia for beginners: the basic concepts you need to know ...
    Aug 3, 2023 · The basal ganglia are a subcortical collection of interacting clusters of cell bodies, and are involved in reward, emotional, and motor circuits.
  138. [138]
    Cerebellar contribution to feedforward control of locomotion - Frontiers
    If prediction fails (G), then an error signal is activated by the cerebellar output system (H), and feedforward control is interrupted or corrected.Cerebellum and Feedforward... · Sequencing and Prediction · Cerebellar Gait
  139. [139]
    Spinal Reflexes and Descending Motor Pathways (Section 3 ...
    Descending motor pathways arise from multiple regions of the brain and send axons down the spinal cord that innervate alpha motor neurons, gamma motor neurons, ...
  140. [140]
    Corticospinal vs Rubrospinal Revisited: An Evolutionary Perspective ...
    Jun 11, 2021 · Both are descending motor pathways and have remarkably similar functional properties. It has been proposed that each system is primarily active ...
  141. [141]
    Neuroanatomy, Broca Area - StatPearls - NCBI Bookshelf
    Structure and Function. The primary functions of the Broca area are both language production and comprehension. While the exact role in the production is ...Bookshelf · Neuroanatomy, Broca Area · Clinical SignificanceMissing: seminal | Show results with:seminal
  142. [142]
    From Sound to Meaning: Navigating Wernicke's Area in Language ...
    Sep 21, 2024 · Wernicke's area, a critical brain region associated with language comprehension, was first identified by Carl Wernicke in the late 19th century.
  143. [143]
    The cortical organization of speech processing: Feedback control ...
    The dual stream model (Hickok & Poeppel, 2000, 2004, 2007) holds that early stages of speech processing occurs bilaterally in auditory regions on the dorsal STG ...
  144. [144]
    Functional Contributions of the Arcuate Fasciculus to Language ...
    Jun 25, 2021 · Current evidence strongly suggests that the arcuate fasciculus (AF) is critical for language, from spontaneous speech and word retrieval to repetition and ...
  145. [145]
    Word learning is mediated by the left arcuate fasciculus - PNAS
    Jul 24, 2013 · ... connections between Broca's and Wernicke's territories in the left hemisphere. This study suggests that our ability to learn new words ...
  146. [146]
    The cortical organization of speech processing - Nature
    Apr 13, 2007 · Hickok and Poeppel describe a dual-stream model of speech processing and discuss how this model can account for some of the field's ...
  147. [147]
    The influence of bilingualism on gray matter volume in the ... - NIH
    Jul 20, 2023 · Bilingualism is associated with higher gray matter volume (GMV) as a form of brain reserve in brain regions such as the inferior frontal gyrus (IFG) and the ...
  148. [148]
    Brain gray matter morphometry relates to onset age of bilingualism ...
    Feb 8, 2024 · These findings suggest that bilingualism, as a life-course factor, can offer brain structural reserve in healthy aging, making the neural system ...
  149. [149]
    New Perspectives on the Neurobiology of Sign Languages - Frontiers
    The first 40 years of research on the neurobiology of sign languages (1960–2000) established that the same key left hemisphere brain regions support both ...
  150. [150]
    Sign and speech: amodal commonality in left hemisphere ...
    These results demonstrate amodal commonality in the functional dominance of the left cortical regions for comprehension of sentences.
  151. [151]
    Neuroanatomy, Limbic System - StatPearls - NCBI Bookshelf
    The limbic system is an aggregation of brain structures that are generally located lateral to the thalamus, underneath the cerebral cortex, and above the ...Introduction · Structure and Function · Clinical Significance
  152. [152]
    Fear conditioning and the basolateral amygdala - PubMed Central
    Jan 28, 2020 · In this review, we describe the circuits in the basolateral amygdala that mediate fear learning and its expression as the conditioned response.
  153. [153]
    The Central Nucleus of the Amygdala and Corticotropin-Releasing ...
    The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned ...
  154. [154]
    The role of the hippocampus in the consolidation of emotional ...
    Various models of contextual emotional learning involve the hippocampus in combination with other valence-related structures. CFC is the canonical model for ...
  155. [155]
    Adaptive emotional memory: the key hippocampal–amygdalar ...
    The hippocampal and amygdalar systems not only regulate each other and their functional outcomes, but also qualify specific emotional memory representations ...<|separator|>
  156. [156]
    Conflict monitoring and anterior cingulate cortex: an update
    The first claim of the conflict-monitoring theory is that specific brain structures, and in particular the ACC, respond to the occurrence of conflict.
  157. [157]
    The cingulate cortex and limbic systems for emotion, action, and ...
    The anterior/midcingulate cortex is activated in humans when there is conflict between possible responses, or when there is a change in response set, but ...
  158. [158]
    Attenuated sensitivity to the emotions of others by insular lesion - PMC
    Some studies show that insular lesions yield an inability for understanding and representing disgust ... insula for interoception and emotional awareness.
  159. [159]
    Activation of nucleus accumbens projections to the ventral tegmental ...
    Mar 11, 2024 · The key component of the reward system is the ventral tegmental area (VTA), which primary contains dopaminergic cells that release dopamine in ...
  160. [160]
    The Neuroanatomical, Neurophysiological and Psychological Basis ...
    Jun 30, 2017 · There are four types of implicit memory, including procedural, associative, non-associative, and priming. Declarative/Explicit Memory. Explicit ...
  161. [161]
    The role of the basal ganglia in learning and memory
    These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of ...
  162. [162]
    The Attention System of the Human Brain: 20 Years After - PMC
    The dorsal attention network (light green) consists of frontal eye fields (FEF) and the intraparietal sulcus/superior parietal lobe (IPS/SPL). The ventral ...The Attention System Of The... · Elaborations Of The... · Executive Control<|separator|>
  163. [163]
    Executive functions after orbital or lateral prefrontal lesions
    Jun 25, 2012 · The dorsolateral PFC (DLPFC) is primarily associated with cognitive executive functions ... inhibition, working memory and mental switching. It ...
  164. [164]
    The Brain's Default Network and its Adaptive Role in Internal ... - NIH
    The human brain increases its activity across a set of midline and lateral cortical brain regions known as the “default network.”
  165. [165]
    Neural loss aversion differences between depression patients and ...
    Prospect theory, a prominent model of decision-making, features a value function with parameters for risk and loss aversion. Recent work with normal ...
  166. [166]
    Physiology, Resting Potential - StatPearls - NCBI Bookshelf - NIH
    Since the plasma membrane at rest has a much greater permeability for K+, the resting membrane potential (-70 to -80 mV) is much closer to the equilibrium ...Missing: source | Show results with:source
  167. [167]
    [PDF] Jens C. Skou - Nobel Lecture
    The Na*, K*-. ATPase has thus a key function in the exchange of substances across the cell membrane. A problem was where to place the Na,K-ATPase in the ...Missing: discovery | Show results with:discovery
  168. [168]
    A quantitative description of membrane current and its application to ...
    HODGKIN A. L., HUXLEY A. F. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. J Physiol. 1952 Apr;116(4):449–472.
  169. [169]
    Saltatory Conduction - an overview | ScienceDirect Topics
    Myelinated axons can conduct at velocities up to 120 m/sec, whereas unmyelinated axon conduction velocities range from about 0.5 to 3 m/sec. Human ...
  170. [170]
    Ion Channels and the Electrical Properties of Membranes - NCBI - NIH
    The main types of stimuli that are known to cause ion channels to open are a change in the voltage across the membrane (voltage-gated channels), a mechanical ...
  171. [171]
    Calcium Control of Neurotransmitter Release - PMC - PubMed Central
    Ca2+ triggers synaptic vesicle exocytosis, thereby releasing the neurotransmitters contained in the vesicles and initiating synaptic transmission. This ...
  172. [172]
    Vesicular release probability sets the strength of individual Schaffer ...
    Oct 17, 2022 · Information processing in the brain is controlled by quantal release of neurotransmitters, a tightly regulated process.
  173. [173]
    Overview of the Glutamatergic System - Glutamate-Related ... - NCBI
    Glutamate is the major excitatory neurotransmitter in the nervous system. Glutamate pathways are linked to many other neurotransmitter pathways.
  174. [174]
    Neurotransmitters and Receptors Expressed by rNST Neurons - NCBI
    GABA, the main inhibitory neurotransmitter in the mammalian brain, activates two distinct classes of receptors that mediate synaptic inhibition. GABAA receptors ...
  175. [175]
    Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity ...
    Dopamine (DA) is a key neurotransmitter involved in multiple physiological functions including motor control, modulation of affective and emotional states, ...
  176. [176]
    Biochemical Anatomy of the Basal Ganglia and Associated Neural ...
    Glutamate and aspartate are excitatory amino acid neurotransmitters present in many neurons throughout the brain (Chap. 15). They are involved in basal ...Excitatory Amino Acids... · Acetylcholine Is The... · Dopamine Is The...<|separator|>
  177. [177]
    Neurotransmitter transporters and their impact on the development ...
    Jan 9, 2006 · The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets ...Missing: MAO | Show results with:MAO
  178. [178]
    Monoamine Neurotransmitter - an overview | ScienceDirect Topics
    Many therapeutic and recreational drugs alter monoamine transmission, often by affecting monoamine receptors, transporters, enzymatic degradation, or uptake.
  179. [179]
    Modulation of excitatory neurotransmission by neuronal/glial ...
    Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, ...
  180. [180]
    The Synaptic Theory of Memory: A Historical Survey and ...
    Oct 26, 2018 · Our argument is that memory, as conceived by Hebb, consists of both synaptic plasticity and “intrinsic plasticity” of the neurons (Sehgal et al.
  181. [181]
    Mechanisms of neuromodulatory volume transmission - Nature
    May 24, 2024 · Volume transmission doesn't rely on synaptic contact sites and is the main mode of monoamines and neuropeptides, important neuromodulators in the brain.
  182. [182]
    A neuronal model of a global workspace in effortful cognitive tasks
    The global workspace is the seat of a particular kind of “brain-scale” activity states characterized by the spontaneous activation, in a sudden, coherent and ...
  183. [183]
    From the Phenomenology to the Mechanisms of Consciousness: Integrated Information Theory 3.0
    Summary of each segment:
  184. [184]
    Integrated information theory: from consciousness to its physical substrate - Nature Reviews Neuroscience
    ### Summary of Neural Correlates of Consciousness, Thalamocortical Loops, and Posterior Hot Zone from https://www.nature.com/articles/nrn.2016.44
  185. [185]
    Rapid fragmentation of neuronal networks at the onset of propofol ...
    We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which ...
  186. [186]
    The nature of consciousness in anaesthesia - PMC - PubMed Central
    The brain of anaesthetised patients goes through a series of different states with variable mental content and perception of the environment. As a consequence, ...
  187. [187]
    The Transition to Minimal Consciousness through the Evolution of ...
    We propose unlimited associative learning (UAL) as the marker of the evolutionary transition to minimal consciousness (or sentience).
  188. [188]
    Traumatic Brain Injury (TBI)
    Jul 21, 2025 · Diffuse axonal injury (DAI). DAI is one of the most common types of TBIs. It refers to widespread damage to the brain's white matter. DAI ...
  189. [189]
    Traumatic Brain Injury - StatPearls - NCBI Bookshelf
    Feb 17, 2025 · The different types of CHI can be broken down to include concussion, contusion ... diffuse axonal injury (DAI), and can be very debilitating.
  190. [190]
    Traumatic Brain Injury: Current Treatment Strategies and Future ...
    Contusions generally take place as a result of coup and contrecoup forces. Coup injuries occur at the site of impact, while contrecoup injuries typically take ...<|control11|><|separator|>
  191. [191]
    The neuropathology of traumatic brain injury - PMC - NIH
    Diffuse axonal injury. Traumatic axonal injury (TAI) is damage to axons caused by trauma and may be focal, multifocal or diffuse (Graham et al., 2002). The ...
  192. [192]
    Glasgow Coma Scale - StatPearls - NCBI Bookshelf
    Jun 23, 2025 · This course reviews the fundamental components of the scale—eye, verbal, and motor responses—highlighting scoring methodology, clinical ...Continuing Education Activity · Introduction · Function · Clinical Significance
  193. [193]
    Glasgow Coma Scale (GCS) - CDC
    *GCS comprises three tests: eye, verbal, and motor responses. The lowest possible GCS score (sum) is 3 (deep coma or death), while the highest score is 15 ...
  194. [194]
    Post-traumatic epilepsy: an overview - PMC - NIH
    As summarized in a review article by Bushnik et al., these issues include anxiety, depression, poor self-esteem, cognitive impairment, social isolation, ...Missing: deficits | Show results with:deficits
  195. [195]
    Chronic impact of traumatic brain injury on outcome and quality of life
    Cognitive impairment. TBI causes deficits of attention, memory, information processing speed, and executive functioning. High-level cognitive functions depend ...Background · Biology Of Traumatic Brain... · White Matter Degradation
  196. [196]
    Decompressive craniectomy for the treatment of high intracranial ...
    The benefits of DC in TBI are to facilitate the control of ICP, improve cerebral perfusion pressure, and avoid brain herniation and brainstem compression ( ...
  197. [197]
    Decompressive craniectomy for traumatic brain injury: a review ... - NIH
    Apr 14, 2025 · DC is a surgical procedure employed to alleviate elevated intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).
  198. [198]
    Long-Term Consequences of Traumatic Brain Injury - PubMed Central
    ... injury cascades leading to prolonged motor and cognitive deficits. ... Cognitive impairment following traumatic brain injury: the effect of pre ...
  199. [199]
    Alzheimer Disease - StatPearls - NCBI Bookshelf - NIH
    [22] This means that the amount of tau deposits in the brains of patients with AD correlates better with dementia severity than the amount of amyloid deposits.
  200. [200]
    The neuropathological diagnosis of Alzheimer's disease - PMC
    Aug 2, 2019 · Evidence suggests that amyloid deposition and tau pathology in AD can precede structural changes in the brain, including hippocampal volume loss ...
  201. [201]
    Alzheimer's Stages - Early, Middle, Late Dementia Symptoms | alz.org
    Alzheimer's disease typically progresses slowly in three stages: early, middle and late (sometimes referred to as mild, moderate and severe in a medical ...Mild Cognitive Impairment (MCI) · Late-Stage Caregiving · I Have Alzheimer's
  202. [202]
    Parkinson's Disease | National Institute of Neurological Disorders ...
    Mar 5, 2025 · Studies have shown that most people with PD have lost 60 to 80% or more of the dopamine-producing cells in the substantia nigra by the time ...
  203. [203]
    Parkinson Disease - StatPearls - NCBI Bookshelf - NIH
    The disorder is associated with the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. Most cases are idiopathic.
  204. [204]
    Dopamine and Parkinson's Disease - NCBI - NIH
    The biochemical imbalance manifests with typical clinical symptoms that include resting tremor, rigidity, bradykinesia, i.e., a gradual slowness of spontaneous ...
  205. [205]
    Huntington Disease - StatPearls - NCBI Bookshelf - NIH
    Apr 6, 2025 · Huntington disease is a hereditary neurodegenerative disorder, inherited in an autosomal dominant manner, caused by an expansion of CAG trinucleotide repeats ...
  206. [206]
    Huntington Disease - GeneReviews® - NCBI Bookshelf
    Oct 23, 1998 · The phenomenon of anticipation arises from instability of the CAG repeat during spermatogenesis [Semaka et al 2013a]. Large expansions (i.e., an ...
  207. [207]
    Amyotrophic Lateral Sclerosis (ALS)
    Mar 26, 2025 · Amyotrophic lateral sclerosis (ALS), formerly known as Lou Gehrig's disease, is a neurological disorder that affects motor neurons.How is amyotrophic lateral... · What are the latest updates on...
  208. [208]
    SOD1 mutations associated with amyotrophic lateral sclerosis ...
    Jan 7, 2022 · Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper ...
  209. [209]
    Genetic and environmental factors in Alzheimer's and Parkinson's ...
    Aug 11, 2021 · Genetic and environmental risk factors for neurodegenerative diseases ... The APOE genotype is the strongest prevalent genetic risk factor for AD.
  210. [210]
    Environmental pollutants as risk factors for neurodegenerative ...
    Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD.
  211. [211]
    Adult Central Nervous System Tumors Treatment - NCI
    Jan 5, 2024 · Tumors that start in the brain are called primary brain tumors. Primary brain tumors may spread to other parts of the brain or to the spine.
  212. [212]
    The 2021 WHO Classification of Tumors of the Central Nervous ...
    Jun 29, 2021 · The 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification.
  213. [213]
    Brain tumor - Symptoms and causes - Mayo Clinic
    Frontal lobe brain tumors might cause balance problems and trouble walking. There might be personality changes, such as forgetfulness and lack of interest ...Missing: specific | Show results with:specific
  214. [214]
    Tumor Development and Angiogenesis in Adult Brain Tumor
    Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma ...
  215. [215]
    Radiotherapy plus concomitant and adjuvant temozolomide for ...
    Mar 10, 2005 · The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy.
  216. [216]
    Epilepsy and Seizures | National Institute of Neurological Disorders ...
    Apr 7, 2025 · Tonic seizures cause a stiffening of muscles of the body, generally in the back, legs, and arms. Clonic seizures cause repeated jerking ...Missing: partial | Show results with:partial
  217. [217]
    Epilepsy - Symptoms and causes - Mayo Clinic
    Seizures are classified as either focal or generalized, based on how and where the brain activity causing the seizure begins. When seizures appear to result ...
  218. [218]
    Seizures and Epilepsy: An Overview for Neuroscientists - PMC
    Seizures are divided into three categories: generalized, focal (formerly called partial), and epileptic spasms. Focal seizures originate in neuronal networks ...
  219. [219]
    Types of Seizures | Epilepsy - CDC
    May 15, 2024 · There are two main types of seizures: generalized and focal seizures. ... "Tonic-clonic" seizures are a kind of generalized motor seizure ...Missing: aura | Show results with:aura
  220. [220]
    Seizure - StatPearls - NCBI Bookshelf - NIH
    For generalized seizures with associated motor movements, the convulsion typically has a stiffening or tonic phase followed by clonic movements - rhythmic ...
  221. [221]
    DRAVET SYNDROME Insights into pathophysiology and therapy ...
    More than 300 mutations in the exons of the SCN1A gene, which codes for the α subunit of the Nav1.1 sodium channel, have been identified in patients with SMEI, ...
  222. [222]
    Dravet syndrome: novel insights into SCN1A-mediated epileptic ...
    Jul 23, 2025 · De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 1327–1332. doi ...
  223. [223]
    Dravet Syndrome: A Sodium Channel Interneuronopathy - PMC
    Dec 23, 2017 · ... mutations in a NaV channel cause epilepsy. Two mouse genetic models ... mutation in forebrain GABAergic interneurons quantitatively recapitulates ...
  224. [224]
    EEG Abnormal Waveforms - StatPearls - NCBI Bookshelf
    Apr 6, 2025 · Most interictal EEG patterns are observed in both scalp and intracranial recordings, while rhythmic epileptiform discharge types 1 and 2 are ...
  225. [225]
    How Can We Identify Ictal and Interictal Abnormal Activity? - PMC
    Epileptiform EEG activity has been categorized as ictal, meaning during a seizure, postictal, meaning after a seizure and interictal, meaning between seizures.
  226. [226]
    EEG in the Epilepsies - Electroencephalography (EEG) - NCBI - NIH
    Ictal EEG shows initial generalized polyspikes building up to a frequency of approximately 10 Hz (the so-called “epileptic recruiting rhythm”) during the tonic ...
  227. [227]
    Juvenile Myoclonic Epilepsy - StatPearls - NCBI Bookshelf - NIH
    A large proportion (30%-40%) of JME patients exhibit photosensitivity and flashing lights, sunlight, TV, and computer can trigger seizures. Photosensitive ...<|separator|>
  228. [228]
    Frequently asked questions and answers on Visually-Provoked ...
    Feb 10, 2025 · A: In individuals with photosensitive (visually-provoked) seizures, seizures can be brought on by rapidly changing or flashing lights with high ...
  229. [229]
    Overview of Drugs Used For Epilepsy and Seizures - PubMed Central
    Common older drugs include valproic acid, phenytoin, carbamazepine, primidone, ethosuximide, clonazepam, and phenobarbital.Epilepsy Syndromes · Alternative Agents · Appendix A
  230. [230]
    Antiepileptic drug therapy in patients with autoimmune epilepsy - NIH
    May 10, 2017 · Indeed, sodium-channel blocking agents such as carbamazepine and phenytoin have been successfully used to treat autoimmune VGK channelopathies ...
  231. [231]
    Synergistic effects of vagus nerve stimulation and antiseizure ... - NIH
    Jun 27, 2023 · Since VNS is approved only as an adjunctive therapy for epilepsy treatment, all patients with VNS also receive antiseizure medication (ASM). As ...Missing: block | Show results with:block
  232. [232]
    Stroke Facts - CDC
    Oct 24, 2024 · About 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked. ... Statistics Committee; Stroke Statistics ...
  233. [233]
    Ischemic Stroke - StatPearls - NCBI Bookshelf - NIH
    Feb 21, 2025 · [40] IV tPA should be administered at a dose of 0.9 mg/kg, with a maximum dose of 90 mg. The first 10% of the dose is given as an initial bolus ...
  234. [234]
    Tissue Plasminogen Activator for Acute Ischemic Stroke (Alteplase ...
    Dec 3, 2024 · When administered quickly after stroke onset (within three hours, as approved by the FDA), tPA helps to restore blood flow to brain regions ...
  235. [235]
    Molecular Mechanisms of Ischemic Stroke: A Review Integrating ...
    Apr 7, 2024 · This condition, known as cytotoxic edema, can be observed within minutes to hours of the stroke and has a sensitivity and specificity of 88–100 ...
  236. [236]
    Hemorrhagic Stroke - StatPearls - NCBI Bookshelf
    The usual causes of spontaneous subarachnoid hemorrhage (SAH) are ruptured aneurysm, arteriovenous malformation, vasculitis, cerebral artery dissection, dural ...
  237. [237]
    Hemorrhagic Stroke
    They occur when a weakened vessel ruptures and bleeds into the surrounding brain. The blood accumulates and compresses the surrounding brain tissue. The two ...
  238. [238]
    Stroke - Causes and Risk Factors | NHLBI, NIH
    May 26, 2023 · Strokes are caused by blocked blood flow to the brain (ischemic stroke) or sudden bleeding in the brain (hemorrhagic stroke).Causes · Ischemic Stroke · Hemorrhagic Stroke
  239. [239]
    The Pathophysiology of Collateral Circulation in Acute Ischemic Stroke
    Smoking, chronic kidney disease, and metabolic syndrome have also been associated with poor collaterals [18]. 2.4. The Role of Cerebral Hypoperfusion. The ...
  240. [240]
    Baseline NIH Stroke Scale score strongly predicts outcome after stroke
    The NIHSS score strongly predicts the likelihood of a patient's recovery after stroke. A score of > or =16 forecasts a high probability of death or severe ...
  241. [241]
    NIH Stroke Scale
    Jul 10, 2025 · Developed through research supported by NINDS, the widely used NIH Stroke Scale helps health care providers assess the severity of a stroke.Missing: rehabilitation | Show results with:rehabilitation
  242. [242]
    Neural Tube Defects (NTDs)
    NTDs occur when the spinal cord, brain, and related structures do not form properly. NTDs are congenital anomalies that are present at birth. They usually occur ...
  243. [243]
    Spina bifida - Symptoms and causes - Mayo Clinic
    Dec 19, 2023 · Spina bifida is a condition that occurs when the spine and spinal cord don't form properly. It's a type of neural tube defect.
  244. [244]
    Chiari Malformation Type 2 - StatPearls - NCBI Bookshelf - NIH
    Feb 25, 2024 · Chiari 2 malformation is almost always associated with myelomeningocele and is characterized by caudal displacement of the cerebellar vermis, ...Introduction · History and Physical · Evaluation · Treatment / Management
  245. [245]
    Holoprosencephaly - StatPearls - NCBI Bookshelf
    Jun 7, 2024 · The etiology of HPE is genetic or sporadic. Genetic causes can be further classified into syndromic and nonsyndromic causes.
  246. [246]
    Holoprosencephaly: Review of Embryology, Clinical Phenotypes ...
    Mar 30, 2023 · Disruption of midline patterning, as seen in HPE, results in the failure of prosencephalon cleavage into distinct right and left hemispheres.
  247. [247]
    Zika Virus Disrupts Neural Progenitor Development and Leads to ...
    Jul 7, 2016 · ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly.Missing: proliferation | Show results with:proliferation
  248. [248]
    Zika Virus Depletes Neural Progenitors in Human Cerebral ... - NIH
    Dang et al. show that Zika virus (ZIKV) attenuates growth in cerebral organoids from human embryonic stem cells by targeting neural progenitors.
  249. [249]
    Corpus Callosum Agenesis - StatPearls - NCBI - NIH
    The core syndrome of primary agenesis of corpus callosum consists of the following symptoms[11]: ... Deficits in complex reasoning and novel problem-solving.Missing: connectivity | Show results with:connectivity
  250. [250]
    The Neuropsychological Syndrome of Agenesis of the Corpus ... - NIH
    The cores syndrome includes: (1) Reduced interhemispheric transfer of sensory-motor information; (2) Reduced cognitive processing speed; (3) Deficits in complex ...Missing: loss | Show results with:loss
  251. [251]
    Periventricular Leukomalacia
    Jul 19, 2024 · The disorder is caused by a lack of oxygen or blood flow to the periventricular area of the brain. The periventricular area is the area around ...
  252. [252]
    White Matter Injury of Prematurity: Its Mechanisms and Clinical ...
    In preterm infants, antepartum bleeding of placenta previa is a risk factor for PVL [55]. When Wharton et al. [56] performed a case-control study to examine the ...
  253. [253]
    Brain Death - StatPearls - NCBI Bookshelf - NIH
    [10] This leads to prolonged cessation of cerebral blood flow, resulting in anoxia, cellular membrane pump failure, disturbed osmoregulation, and severe brain ...
  254. [254]
    Pediatric and Adult Brain Death/Death by Neurologic Criteria ...
    This guideline provides recommendations on the evaluation of brain death/death by neurologic criteria for both children and adults.
  255. [255]
    The 2023 AAN/AAP/CNS/SCCM Pediatric and Adult Brain Death ...
    An updated, evidence-informed consensus-based guideline for pediatric and adult brain death/death by neurologic criteria (BD/DNC) determination.
  256. [256]
    New Guidance Issued on the Determination of Brain Death
    Oct 11, 2023 · Brain death is declared if a person has a catastrophic brain injury, has no possibility of recovering any brain function, is completely ...
  257. [257]
    Hypoxic Brain Injury - StatPearls - NCBI Bookshelf - NIH
    Jan 27, 2023 · Ischemic cell death occurs via 2 different pathways: necrosis and apoptosis. During hypoxia-ischemia of the brain, acute energy failure leads to ...
  258. [258]
    Revise the Uniform Determination of Death Act to Align the Law With ...
    The members recommended that neurologic criteria for death be defined as “the complete and permanent loss of brain function as defined by an unresponsive coma ...
  259. [259]
    What is the Uniform Determination of Death Act (UDDA)? - FindLaw
    Jun 7, 2023 · Under the legal standard for death (or the "brain death standard"), all brain functions, including the brain stem, stop. This is the ...
  260. [260]
    Brain Death vs. Persistent Vegetative State: What's the Legal ...
    Jun 1, 2023 · In brain death, there is an irreversible cessation of all functions of the entire brain. A person in a persistent vegetative state is ...
  261. [261]
    Brain death and the persistent vegetative state: similarities ... - PubMed
    Brain death is equivalent to death, while PVS is not; management of the latter is more complex because of medical, social, ethical and legal factors.
  262. [262]
    Ancient Legacy of Cranial Surgery - PMC - NIH
    Officially speaking, trepanation discovery dates back to Paul Broca, Victor Horsley, and the era of Hippocrates, but some archeological findings have revealed ...
  263. [263]
    [PDF] Aristotle on the Brain - PolyU
    correct view [is] that the seat and source of sensation is the region of the heart. (PA656a, see Box). ... the motions of pleasure and pain, and generally ...
  264. [264]
    Galen and the ventricular system - PubMed
    According to him, the purpose of the ventricles was to elaborate, store and distribute psychic pneuma, the motive force of Galenic neurology, throughout the ...
  265. [265]
    Andreas Vesalius: Celebrating 500 years of dissecting nature - PMC
    Vesalius, considered as the founder of modern anatomy, had profoundly changed not only human anatomy, but also the intellectual structure of medicine.
  266. [266]
    Full article: Gall and phrenology: New perspectives
    Dec 13, 2019 · Some of the roots of Gall's later thinking about brain, mind, and behavior can be discerned in this medical treatise.
  267. [267]
    Marie-Jean-Pierre Flourens (1794–1867) and Cortical Localization
    Mar 17, 2009 · To test Gall's assertions, Flourens developed ablation as a procedure to explore the workings of the brain. By removing anatomically defined ...
  268. [268]
    Jan Evangelista Purkinje: A Passion for Discovery - PubMed Central
    Feb 1, 2018 · In 1837, he discovered and described the large brain cells found in the middle layer of the cerebellum (Purkinje cells). Two years later, he ...
  269. [269]
    The Long View of Language Localization - PMC - NIH
    May 24, 2019 · Paul Broca's (1824–1880) interpretation of the autopsy findings of Louis Victor Lebornge (Broca, 1861) established the clinico-pathological ...
  270. [270]
    Multimodal neuroimaging computing: a review of the applications in ...
    In this paper, we review the recent advances in multimodal neuroimaging (MRI, PET) and electrophysiological (EEG, MEG) technologies, and their applications to ...Missing: seminal | Show results with:seminal
  271. [271]
    Computerized transverse axial scanning (tomography): Part 1 ...
    Description of system. G. N. Hounsfield. G. N. Hounsfield. Central Research ... British Journal of Radiology, Volume 46, Issue 552, 1 December 1973, Pages ...Missing: CT | Show results with:CT
  272. [272]
    https://pubmed.ncbi.nlm.nih.gov/11619860/
  273. [273]
    Examples Employing Nuclear Magnetic Resonance | Nature
    a new way of seeing. In 1973, Paul Lauterbur described an imaging technique that removed the usual resolution limits due to the ...
  274. [274]
    Brain magnetic resonance imaging with contrast dependent ... - PNAS
    Dec 15, 1990 · The results suggest that BOLD contrast can be used to provide in vivo real-time maps of blood oxygenation in the brain under normal physiological conditions.
  275. [275]
    Application of Annihilation Coincidence Detection to Transaxial ...
    Mar 1, 1975 · Application of annihilation coincidence detection to transaxial reconstruction tomography. M E Phelps, J Nucl Med, 1975. Design and performance ...
  276. [276]
    MR diffusion tensor spectroscopy and imaging - Cell Press
    ABSTRACT This paper describes a new NMR imaging modality-MR diffusion tensor imaging. It consists of estimating an effective diffusion tensor, Deff, ...
  277. [277]
    Über das Elektrenkephalogramm des Menschen
    Berger, H. Über das Elektrenkephalogramm des Menschen. Archiv f. Psychiatrie 87, 527–570 (1929). https://doi.org/10.1007/BF01797193
  278. [278]
    Magnetoencephalography: Detection of the Brain's Electrical Activity ...
    Measurements of the brain's magnetic field, called magnetoencephalograms (MEG's), have been taken with a superconducting magnetometer in a heavily shielded ...
  279. [279]
    Removal of Artifacts from EEG Signals: A Review - PMC - NIH
    Feb 26, 2019 · This paper tends to review the current artifact removal of various contaminations. We first discuss the characteristics of EEG data and the types of different ...
  280. [280]
    EEG Source Imaging: A Practical Review of the Analysis Steps - PMC
    Filtering the data can have important effects on the time-courses and the phases of the data (39, 40), as well as on the localization of the waveforms' local ...
  281. [281]
    The ten-twenty electrode system of the International ... - PubMed
    The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology.Missing: placement seminal paper
  282. [282]
    Forgotten rhythms? Revisiting the first evidence ... - PubMed Central
    The 'large amplitude, first‐order waves' (Berger, 1929) with a frequency of between 8 and 11 Hz were termed alpha (from Berger, onwards), whereas ...
  283. [283]
    Characterizing sleep spindles in 11630 individuals from the National ...
    Jun 26, 2017 · Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep ...
  284. [284]
    Depth versus surface: A critical review of subdural and depth ...
    May 9, 2024 · The goal of IEEG is to identify the EZ and assess its proximity to the eloquent cortex.
  285. [285]
    A critical review of subdural and depth electrodes in intracranial ...
    This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization.
  286. [286]
    The Architecture of Human Memory: Insights from Human Single ...
    Feb 3, 2021 · Here, we review some contributions that recordings from neurons in humans implanted with electrodes for clinical purposes have made toward this goal.
  287. [287]
    How Human Single-Neuron Recordings Can Help Us Understand ...
    Mar 30, 2021 · Each electrode contains a set of eight microwires capable of recording single neurons. The placement of deep brain stimulation (DBS) electrodes ...
  288. [288]
    Whole-cell Patch-clamp Recordings in Brain Slices - PMC
    Jun 15, 2016 · Sakmann B, Neher E. Patch clamp techniques for studying ionic channels in excitable membranes. Annu Rev Physiol. 1984;46:455–472. doi ...
  289. [289]
    Millisecond-timescale, genetically targeted optical control of neural ...
    Aug 14, 2005 · We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission.
  290. [290]
    High-efficiency channelrhodopsins for fast neuronal stimulation at ...
    Apr 19, 2011 · Optogenetic stimulation of neurons using Channelrhodopsin-2 (ChR2) has become a widely used tool in neuroscience. ChR2, a directly light-gated ...
  291. [291]
    Artifact Reduction in Simultaneous EEG-fMRI: A Systematic Review ...
    Mar 11, 2021 · This paper presents a systematic review of methods for artifact reduction in simultaneous EEG-fMRI from literature published since 1998.
  292. [292]
    Mutant huntingtin impairs neurodevelopment in human brain ...
    Aug 22, 2024 · The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization.
  293. [293]
    Global quantitative analysis of the human brain proteome ... - Nature
    Sep 28, 2020 · This comprehensive human brain proteome and phosphoproteome dataset will serve as a valuable resource for the identification of biochemical, cellular and ...Missing: cascades seminal
  294. [294]
    Clinical Pharmacogenetics Implementation Consortium (CPIC ...
    Apr 9, 2023 · Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing ...
  295. [295]
    [PDF] Sensations and brain processes - andrew.cmu.ed
    The problem to which the Mind-Brain Identity Theory is offered as a solution was set by Descartes. For it was Descartes who per- suaded modern philosophy to ...
  296. [296]
    [PDF] 1 Realization and Multiple Realization, Chicken and Egg Thomas W ...
    Putnam (1967) hypothesized that the relation between brain and mind is also realization. He contrasted his hypothesis—which he dubbed 'functionalism'—with the.
  297. [297]
    [PDF] Facing Up to the Problem of Consciousness
    The hard problems are those that seem to resist those methods. The easy problems of consciousness include those of explaining the following phenomena:
  298. [298]
    Brain size does not predict general cognitive ability within families
    Seven recent studies using magnetic resonance imaging (MRI) to estimate brain volume have shown a substantial correlation (mean r = ≈0.4) between brain size and ...
  299. [299]
    Dolphin cognition - ScienceDirect.com
    But many dolphins possess EQs in the 4–5 range, tantalizingly close to the modern human level, and significantly higher than all other animals. Like humans, ...
  300. [300]
    Comparative analysis of encephalization in mammals reveals ...
    Mar 21, 2012 · Results demonstrated that anthropoid primates and cetaceans exhibit the greatest variance in EQ values among mammals.<|separator|>
  301. [301]
    The Impasse on Gender Differences in Intelligence: a Meta-Analysis ...
    Sep 22, 2022 · This meta-analysis reviews 79 studies (N = 46,605) that examined the existence of gender difference on intelligence in school-aged children.
  302. [302]
    Sex differences in brain size and general intelligence (g)
    The effect of sex/gender was greater on WM than GM; that is, the higher GM:WM ratios in women were a result of reduced WM in women compared to men.
  303. [303]
    From microcephaly to megalencephaly: determinants of brain size
    Apr 1, 2022 · Thorough review of the genetic literature reveals that human microcephaly and megalencephaly are caused by mutations of a rapidly growing number ...
  304. [304]
    Intellectual Disability - Medscape Reference
    Nov 16, 2021 · Head circumference: Microcephaly correlates highly with cognitive deficits; macrocephaly may indicate hydrocephalus, is associated with some ...
  305. [305]
    Meta-analysis of associations between human brain volume and ...
    Our results showed significant positive associations of brain volume and IQ (r = .24, R 2 = .06) that generalize over age (children vs. adults), IQ domain.
  306. [306]
    [PDF] The Sci-Fi Brain: Narratives in Neuroscience and Popular Culture
    The article explores how these narratives are presented and used in popular culture and how neuroscientists relate to the narratives when describing their work.
  307. [307]
    Brain technology in Black Mirror - IU Blogs - Indiana University
    Dec 28, 2019 · San Junipero is a virtual afterlife into which people can upload their consciousness after they pass away. They can also visit this virtual ...
  308. [308]
    The Sci-Fi Brain: Narratives in Neuroscience and Popular Culture
    Aug 6, 2025 · This article explores cultural narratives of what the brain is and how it functions in two different contexts-among neuroscientists and within ...
  309. [309]
    The Neuroscience of Inception - WIRED
    Jul 26, 2010 · The scientists found that when adults were watching the film their brains showed a peculiar pattern of activity, which was virtually universal.
  310. [310]
    Enhancing the brain and drinking blood: The science behind 'Limitless'
    Mar 17, 2021 · NZT-48 is a designer drug that maximizes his cognitive abilities. It gives him perfect memory and allows him to analyze details previously missed.
  311. [311]
    Inception and the Neuroscience of Sleep | Discover Magazine
    Aug 10, 2010 · The film raises the issue of how much we understand about the neuroscience of dreams. Due to its need for invasive experiments, neuroscience ...
  312. [312]
    Salvador Dalí. The Persistence of Memory. 1931 - MoMA
    Hard objects become inexplicably limp in this bleak and infinite dreamscape, while metal attracts ants like rotting flesh.
  313. [313]
    Artwork inspired by MRI brain scans installed at Stanford imaging ...
    Jun 18, 2013 · The pieces by artist Laura Jacobson, a Stanford alumna, are inspired by MRIs of the human brain and reflect the work of the center to ...
  314. [314]
    Landscapes of the Mind: Contemporary Artists Contemplate the Brain
    Featuring artwork drawn from or inspired by the brain, this exhibition brings together the artwork of four contemporary artists—Susan Aldworth (British, b.
  315. [315]
    Lucy and the 10 Percent Brain Myth - BrainFacts
    Jul 16, 2014 · The idea that we only use 10 percent of our brains is a myth. “The crazy thing about this belief is that despite being totally false, it is so well-known,” ...
  316. [316]
    Sorry, Lucy: The Myth Of The Misused Brain Is 100 Percent False
    Jul 27, 2014 · The new Scarlett Johannson movie, Lucy, is based on the idea that most people only use only 10 percent of their brains. As it turns out, that idea is ...
  317. [317]
    The Brain with David Eagleman | PBS
    Neuroscientist David Eagleman explores the human brain in an epic series that reveals the ultimate story of us, why we feel and think the things we do.
  318. [318]
    Ideas about Neuroscience - TED Talks
    A collection of TED Talks (and more) on the topic of Neuroscience. Video playlists about Neuroscience. The most popular TED Talks of 2022.Missing: culture | Show results with:culture
  319. [319]
    The Brain with David Eagleman
    Six one-hour episodes tell the story of the inner workings of the brain and take viewers on a journey into their thoughts, actions, and beliefs.
  320. [320]
    The human brain: rewired and running hot - PMC - NIH
    Studies comparing humans to chimpanzees and other great apes reveal that human brain ... Human brains are about three times the volume of those of chimpanzees ...
  321. [321]
    The prefrontal cortex: from monkey to man - PMC - PubMed Central
    The most striking difference between human and non-human primates regarding the prefrontal cortex is its size. Indeed, of all mammal species, it is in humans ...
  322. [322]
    Brain size expansion in primates and humans is explained by a ...
    May 22, 2019 · Results hereby suggest that the expansion of the CCS is the primary driver of brain expansion in anthropoid primates.
  323. [323]
    Planum temporale grey matter asymmetries in chimpanzees (Pan ...
    We show that the three monkey species do not show population-level asymmetries in this region whereas the chimpanzees do, suggesting that the evolutionary brain ...
  324. [324]
    Planum Temporale Surface Area and Grey Matter Asymmetries in ...
    When compared to previously published data in humans, the direction and magnitude of PT grey matter asymmetries were similar between humans and apes; however, ...
  325. [325]
    Planum Temporale Grey Matter Asymmetries in Chimpanzees ... - NIH
    In short, humans have a naturally greater “split-brain” compared to other primates, which some suggest led to greater functional and anatomical asymmetries ...
  326. [326]
    The von Economo neurons in apes and humans - PubMed - NIH
    The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex (ACC) in great apes and humans but not ...Missing: monkeys | Show results with:monkeys
  327. [327]
    The von Economo neurons in fronto-insular and anterior cingulate ...
    The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in ...Missing: monkeys | Show results with:monkeys
  328. [328]
    Mirror neurons: Enigma of the metaphysical modular brain - PMC - NIH
    In 1990s, a group of neurophysiologists placed electrodes in the ventral premotor cortex of the macaque monkey to study neurons specialized for the control of ...
  329. [329]
    The human mirror neuron system: A link between action observation ...
    ... monkey to a system critical for social skills in humans. It is ... neurons of primary motor cortex: an electrophysiological study in the macaque monkey.<|separator|>
  330. [330]
    Mirroring others' emotions relates to empathy and interpersonal ...
    That is, mirror neurons have often been shown to fire at a higher rate when the monkey executes an action itself than when it observes that same action being ...
  331. [331]
    Cortical areas associated to higher cognition drove primate brain ...
    Jan 18, 2025 · Exceptional evolutionary expansion of prefrontal cortex in great apes and humans. ... tool use. In: Evolution of nervous systems: second ...
  332. [332]
    The Representation of Tool Use in Humans and Monkeys
    ... apes diverged from monkeys. Apes use tools readily (Whiten et al., 1999) and modify herb stems to make them a more efficient tool, which implies that they ...
  333. [333]
    Greater addition of neurons to the olfactory bulb than to the cerebral ...
    Apr 11, 2014 · Within orders, olfactory bulb size varies 25-fold in primates (from 0.008 g in the marmoset to 0.200 g in the galago), 93-fold in glires (from ...
  334. [334]
    The evolution of episodic memory - PMC - PubMed Central
    The function of the hippocampus is also well conserved across mammalian species. In fact, the hippocampus is critical for spatial memory in rats (reviewed in ...
  335. [335]
    The functional characterization of callosal connections - PMC
    Callosal connections play a modulatory function, in addition to a driving role. •. The corpus callosum participates in learning and interhemispheric transfer of ...
  336. [336]
    The functional and anatomical organization of marsupial neocortex
    Finally, in terms of gross brain organization, perhaps the most notable feature of the neocortex in all marsupials (and monotremes) is the lack of a corpus ...
  337. [337]
    Neurobiology of REM sleep - ScienceDirect.com
    The percentage of REM sleep declines rapidly in early childhood so that by approximately age 10 the adult percentage of REM sleep is reached, 20% of total sleep ...Missing: proportions | Show results with:proportions
  338. [338]
    Sleep function: an evolutionary perspective - PMC - PubMed Central
    African bush elephants (Loxodonta africana) in the wild average only 2·1 h of sleep per day, which is the shortest amount of sleep reported in any mammal, and ...
  339. [339]
    Electroreception in monotremes - Company of Biologists journals
    May 15, 1999 · All three extant monotreme species have electroreception, judged by the presence of mucous gland electroreceptors in the bill skin. The platypus ...
  340. [340]
    Comparisons of static brain–body allometries across vertebrates ...
    Sep 23, 2019 · Release from these energetic constraints in birds and mammals laid the foundation for their encephalization: only these lineages could afford to ...
  341. [341]
    Different ways of evolving tool-using brains in teleosts and amniotes
    Jan 12, 2024 · Mammals and birds have taken two different trajectories of encephalization that have converged onto a process of “telencephalization”, whereby ...
  342. [342]
    The embodied brain: towards a radical embodied cognitive ...
    Apr 13, 2015 · This division is perhaps best exemplified in Paul MacLean's discredited triune model of the mammalian brain (MacLean, 1952, 1990; for criticisms ...
  343. [343]
    The Brain Is Adaptive Not Triune: How the Brain Responds to Threat ...
    Apr 1, 2022 · The triune brain theory is an evolutionary theory of brain development that emphasizes three key brain regions consisting of the brainstem, the limbic system, ...
  344. [344]
    The Evolution of the Brain, the Human Nature of Cortical Circuits ...
    May 16, 2011 · Homo heidelbergensis, existed 650,000 years ago and had a larger brain (cranial capacity of 1,350 cm3) than H. erectus (brain volume between 800 ...
  345. [345]
    Island Rule, quantitative genetics and brain–body size evolution in ...
    Jun 21, 2017 · erectus, including Dmanisi forms classified by some as H. georgicus) up to 1000 cm3 (the mean brain volume of late H. erectus in China [33,34]).
  346. [346]
    Accelerated protein evolution and origins of human-specific features
    FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated ...
  347. [347]
    Human-specific ARHGAP11B induces hallmarks of neocortical ... - NIH
    Abstract. The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans.
  348. [348]
    Body size, brain size, and sexual dimorphism in Homo naledi from ...
    Homo erectus and later humans have enlarged body sizes, reduced sexual dimorphism, elongated lower limbs, and increased encephalization compared to ...
  349. [349]
    Sexual Selection and the Evolution of Brain Size in Primates - NIH
    Dec 20, 2006 · The present research examines the evolutionary relationship between brain size and two components of primate sexual selection, sperm competition and male ...