Fact-checked by Grok 2 weeks ago

Forebrain

The forebrain, or prosencephalon, is the anterior-most and largest division of the vertebrate brain, encompassing structures essential for higher cognitive processes, sensory integration, and autonomic regulation.^[1] It originates embryologically from the primary brain vesicle at the rostral end of the neural tube during the third week of gestation, differentiating into two secondary vesicles: the telencephalon and the diencephalon.^[1] The telencephalon primarily develops into the cerebrum, including the cerebral cortex divided into frontal, parietal, occipital, and temporal lobes, as well as subcortical components such as the basal ganglia, amygdala, and hippocampus.^[2] These structures facilitate voluntary motor control, language, memory formation, emotional processing, and spatial navigation.^[2] In contrast, the diencephalon forms the thalamus, hypothalamus, epithalamus, and subthalamus, serving as a relay for sensory and motor signals while regulating homeostasis, hormone release, sleep-wake cycles, and stress responses.^[1] The forebrain's intricate architecture, featuring gray matter for neuronal cell bodies and white matter for myelinated axons, along with cortical convolutions (gyri and sulci) that expand surface area, underscores its role in complex neural computation.^[1] Overall, the forebrain integrates sensory inputs with executive functions, enabling adaptive behavior and consciousness in humans and other vertebrates.^[2]

Anatomy

Major Divisions

The forebrain, also known as the prosencephalon, is the anterior-most region of the vertebrate brain, developing from the rostral end of the neural tube and comprising the telencephalon and diencephalon.^[3] It serves as the primary site for higher cognitive processing and sensory integration in humans.^[4] Spatially, the forebrain occupies a rostral position relative to the midbrain and hindbrain, enveloping much of the central brain structures and extending forward to form the bulk of the cranial vault. In adult humans, it accounts for approximately 80-90% of the total brain volume, with the telencephalon dominating this proportion due to the expansion of the cerebral hemispheres.^[3] The diencephalon lies centrally, nestled beneath the telencephalon and surrounding the third ventricle.^[3] The key components of the forebrain include the telencephalon, which encompasses the cerebral hemispheres and major components of the basal ganglia (such as the striatum and globus pallidus), and the diencephalon, consisting of the thalamus, hypothalamus, epithalamus, and subthalamus.^[3] The cerebral hemispheres form the outer mantle, while the basal ganglia provide subcortical nuclei for motor control; in the diencephalon, the thalamus acts as a relay hub, the hypothalamus regulates homeostasis, the epithalamus includes the pineal gland, and the subthalamus contributes to basal ganglia circuits.^[3] Interconnections within the forebrain are facilitated by extensive white matter tracts, such as the corpus callosum, which links the two cerebral hemispheres of the telencephalon to enable interhemispheric communication.^[4] Additional tracts, including projection fibers from the diencephalon to the telencephalon, integrate signals across these divisions.^[3] Histologically, forebrain regions feature diverse neuron types, including pyramidal neurons predominant in the cerebral cortex with their characteristic triangular somata, apical dendrites, and long axons forming corticofugal pathways, and granular neurons found in structures like the dentate gyrus with small, round somata and short dendrites.^[4] Glial cells, particularly astrocytes and oligodendrocytes, provide essential support, with astrocytes maintaining the blood-brain barrier and regulating synaptic environments uniquely adapted to the forebrain's high metabolic demands.^[4]

Telencephalon

The telencephalon, the anterior portion of the forebrain, encompasses the cerebral hemispheres and serves as the primary site for higher cognitive functions, including perception, voluntary movement, and complex decision-making. It is structurally divided into the outer cerebral cortex and deeper subcortical nuclei, with the cortex featuring a convoluted surface that maximizes neural packing. The cerebral cortex comprises two main types: the neocortex, characterized by six distinct layers of neurons and glia that facilitate advanced processing, and the allocortex, which has fewer layers (typically three to five) and is involved in more primitive functions like olfaction and memory.^[5]^[6]^[7] Subcortical components of the telencephalon include the striatum and globus pallidus, which are key parts of the basal ganglia and the limbic system, which modulate motor control and emotional responses, respectively. The basal ganglia consist of the striatum (comprising the caudate nucleus and putamen), the globus pallidus, and the subthalamic nucleus, forming interconnected circuits that refine voluntary movements and habit formation.^[8] The limbic system incorporates the amygdala for emotional processing, the hippocampus for memory consolidation, and the cingulate gyrus for integrating cognitive and affective information, linking these structures to broader telencephalic networks.^[9] Cortical organization is further delineated by gyri (raised folds) and sulci (grooves), which partition the surface into functional lobes, while cytoarchitectonic maps like Brodmann areas provide finer parcellation based on cellular structure; for instance, areas 1–3 process primary somatosensory input, area 4 handles primary motor output, and area 17 receives visual signals from the retina.^[5]^[10] Hemispheric lateralization enhances efficiency, with the left hemisphere typically specializing in language production and analytical tasks, and the right in spatial navigation and holistic perception.^[11]^[12] The telencephalon's white matter underlies the cortex, consisting of myelinated axons that facilitate communication. Projection fibers, such as those in the internal capsule, connect cortical regions to subcortical and spinal structures, transmitting motor and sensory signals. Association fibers link different cortical areas within the same hemisphere, supporting intra-hemispheric integration, while commissural fibers, including the anterior commissure, enable inter-hemispheric coordination by crossing the midline.^[13]^[14] In humans, the telencephalon accounts for about 80–85% of total brain mass, averaging 1,200–1,400 grams, with notable asymmetry and sex differences: male telencephala are typically 8–15% larger in volume than female counterparts, even after adjusting for body size, though females often exhibit proportionally greater cortical folding.^[15]^[16]^[17] Blood supply to the telencephalon arises mainly from the anterior cerebral artery, which perfuses medial frontal and parietal regions, and the middle cerebral artery, which vascularizes lateral temporal and frontal areas, both originating from the internal carotid arteries to ensure oxygenated delivery for high metabolic demands. Venous drainage bypasses traditional veins, instead channeling through superficial and deep cerebral veins into the dural sinuses, which converge to form the internal jugular veins for systemic return.^[18]^[19]

Diencephalon

The diencephalon, a midline structure of the forebrain, serves as a critical relay and integration center, comprising four primary subdivisions: the thalamus, hypothalamus, epithalamus, and subthalamus. Positioned between the telencephalon and midbrain, it surrounds the third ventricle and facilitates the processing of sensory, motor, and regulatory signals. The thalamus occupies the dorsal portion as the principal relay nucleus, while the hypothalamus forms the ventral regulatory center, with the epithalamus and subthalamus providing specialized supportive functions.^[20] The thalamus, constituting approximately 80% of the diencephalon, consists of paired ovoid masses of gray matter that act as a gateway for sensory and motor information to the cerebral cortex. It contains numerous nuclei, including specific relay nuclei such as the lateral geniculate nucleus, which relays visual inputs from the retina to the primary visual cortex, and the medial geniculate nucleus, which conveys auditory signals from the inferior colliculus to the auditory cortex. Additionally, intralaminar nuclei contribute to arousal and attention by projecting diffusely to the cortex and basal ganglia.^[20]^[20] The hypothalamus, located ventrally, regulates homeostasis through its diverse nuclei and is divided into regions including the paraventricular and supraoptic nuclei. The paraventricular nucleus primarily synthesizes oxytocin, which promotes uterine contractions and milk ejection, while the supraoptic nucleus mainly produces vasopressin (antidiuretic hormone), which enhances water reabsorption in the kidneys; both hormones are transported via axons to the posterior pituitary for release. These magnocellular neurosecretory cells enable direct hormonal output in response to osmotic and stress signals.^[21]^[21] The epithalamus, situated dorsally near the third ventricle, includes the pineal gland and habenular nuclei. The pineal gland secretes melatonin to modulate circadian rhythms and reproductive functions, receiving sympathetic input via the superior cervical ganglion. The habenula, divided into medial and lateral components, integrates limbic signals; the lateral habenula influences reward processing by projecting to midbrain dopaminergic areas, while the medial habenula is involved in aversion via connections to the interpeduncular nucleus.^[22]^[22] The subthalamus, positioned ventral to the thalamus, primarily encompasses the subthalamic nucleus, which integrates with the basal ganglia circuitry. It receives glutamatergic inputs from the cerebral cortex (hyperdirect pathway) and globus pallidus externus, and sends excitatory projections to the globus pallidus internus and substantia nigra pars reticulata, modulating motor control and inhibiting unwanted movements.^[23]^[23] Key connectivities underscore the diencephalon's integrative role, with thalamocortical projections forming the primary pathway for relaying information to the cortex via radiations through the internal capsule, including anterior fibers to the frontal lobe and posterior fibers to parietal-occipital areas. The hypothalamus links to the pituitary via the hypothalamic-pituitary axis, where the median eminence serves as a neurohemal interface for releasing factors to the anterior pituitary and axonal tracts from paraventricular/suprachiasmatic nuclei to the posterior pituitary.^[24]^[25] Protective barriers in the diencephalon exhibit regional variations, particularly in the hypothalamus, where circumventricular organs such as the median eminence and subfornical organ lack a complete blood-brain barrier to allow direct sensing of circulating hormones and nutrients, facilitating rapid endocrine responses while maintaining barrier integrity elsewhere in the thalamus and subthalamus.^[25]

Development

Embryonic Formation

The embryonic formation of the forebrain begins during the third week of gestation, when the neural tube emerges from the neural plate induced by signals from the underlying notochord and prechordal mesoderm. By the end of week 3, the rostral portion of the neural tube differentiates into the primary brain vesicles, with the prosencephalon representing the initial forebrain vesicle. This process is critically regulated by Sonic Hedgehog (SHH) signaling, secreted from the prechordal plate, which patterns the ventral forebrain and promotes midline development.^[26]^[27]^[28] By week 5, the prosencephalon subdivides into the telencephalon and diencephalon, establishing the major divisions of the forebrain. This vesicle division is followed by the evagination of the cerebral hemispheres from the telencephalon around weeks 7-8, where the hemispheres expand rostrally and dorsally to initiate the formation of the longitudinal fissure. Key transcription factors guide this patterning: FOXG1 is essential for telencephalon specification and ventral identity, enabling cells to respond to morphogens like SHH and FGF8 to adopt subpallial fates. Similarly, OTX2 defines diencephalon boundaries, particularly at interfaces such as between the thalamus and prethalamus, preventing caudal expansion and ensuring regional identity.^[29]^[30]^[31]^[32]^[33] Cellular processes during this period include neurogenesis, which peaks from weeks 6 to 20 as cortical neurons generated in the ventricular zone undergo radial migration along glial scaffolds to form the cortical plate. Gliogenesis subsequently follows, with progenitors differentiating into astrocytes and oligodendrocytes primarily after the main wave of neuronal production, supporting the emerging neural architecture. A critical milestone is the risk of holoprosencephaly if the SHH pathway is disrupted, resulting in failed separation of the cerebral hemispheres and a spectrum of midline defects from mild facial anomalies to severe brain malformation.^[34]^[35]^[27]

Postnatal Maturation

Postnatal maturation of the forebrain involves extensive structural refinements that shape its functional architecture, extending from birth through adolescence and into early adulthood. During the first two years of life, rapid dendritic arborization occurs in cortical neurons, expanding the surface area for synaptic connections and supporting early learning processes. This phase coincides with a surge in synaptogenesis, where synaptic density in the cerebral cortex reaches peak levels around age 2-3 years. Subsequently, synaptic pruning predominates, eliminating excess connections to optimize neural efficiency; in the cortex, this process intensifies between ages 3 and 10, reducing synaptic density by approximately 40-50% to refine circuits for specialized functions.^[36] Myelination of forebrain white matter progresses gradually, beginning posteriorly in sensorimotor regions and advancing anteriorly into association areas. This process enhances signal conduction speed and efficiency, with significant increases in the first decade of life followed by continued development through adolescence. In humans, neocortical myelination remains protracted compared to other primates, with white matter maturation in prefrontal and temporal regions extending into the mid-20s, achieving peak myelin content around age 25-30.^[37]^[38] Environmental factors profoundly influence forebrain plasticity during sensitive developmental windows, particularly through modulation of molecular mechanisms like brain-derived neurotrophic factor (BDNF) expression, which promotes synaptic strengthening and circuit refinement. For instance, the critical period for native language acquisition, encompassing phonological and grammatical learning, spans from birth to approximately age 7, after which plasticity declines but remains viable for certain aspects until puberty. BDNF signaling facilitates this neuroplasticity by regulating dendritic growth and synaptic stability in language-related areas such as Broca's and Wernicke's regions.^[39]^[40]^[41] Sexual dimorphisms emerge prominently during postnatal forebrain maturation, influenced by gonadal hormones. Females typically exhibit earlier onset and peak of white matter myelination, reaching adult-like patterns by late adolescence, whereas males show a steeper trajectory in white matter volume increase during this period. By puberty, the male amygdala enlarges more substantially relative to females, correlating with testosterone levels and contributing to differences in emotional processing circuits.^[42]^[43] As forebrain maturation stabilizes in early adulthood, subtle signs of aging begin to appear, with cortical gray matter volume in prefrontal regions starting to decline around the mid-30s at a rate of about 0.2-0.5% per year. This early loss reflects initial synaptic and dendritic retraction, setting the stage for more pronounced changes later in life.^[44]^[45]

Functions

Cognitive and Executive Processes

The forebrain, particularly the telencephalon, orchestrates higher cognitive functions through intricate networks centered in the prefrontal cortex (PFC) and associative areas. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive functions, including planning and decision-making, by integrating goal-directed behavior and suppressing habitual responses to facilitate flexible adaptation to complex tasks.^[46] Lesion studies have demonstrated that damage to the DLPFC impairs value-based decision-making, as evidenced by altered risk assessment and reward evaluation in patients.^[47] These processes rely on the DLPFC's ability to maintain cognitive control, coordinating attention and inhibitory mechanisms to prioritize relevant information over distractions.^[48] Working memory, essential for temporarily holding and manipulating information, is supported by persistent neural firing in the PFC during delay periods of tasks, such as delayed-response paradigms where subjects must remember spatial locations or stimuli.^[49] This sustained activity, first identified in seminal electrophysiological recordings from nonhuman primates, encodes item-specific representations that bridge sensory input and motor output, enabling tasks like problem-solving.^[50] Associative cortices further refine these functions: the parietal cortex directs spatial attention, modulating visuospatial orienting and feature integration to enhance perceptual salience in dynamic environments.^[51] Meanwhile, the temporal cortex, especially its anterior regions, integrates semantic memory by linking conceptual knowledge across modalities, as shown in functional imaging studies where it activates during tasks requiring word meaning retrieval and categorical associations.^[52] Large-scale network models highlight the forebrain's distributed architecture for cognition. The default mode network (DMN), encompassing medial PFC and posterior cingulate regions, activates during introspection and self-referential thinking, supporting mind-wandering and autobiographical memory retrieval when external demands are low.^[53] In contrast, the salience network, anchored in the anterior insula and anterior cingulate cortex, prioritizes emotionally or behaviorally relevant stimuli, dynamically switching between internal reflection (DMN) and goal-directed action (central executive network).^[54] Neurotransmitter systems modulate these processes; dopamine projections from the ventral tegmental area to the nucleus accumbens facilitate reward-based learning by signaling prediction errors, reinforcing adaptive behaviors through midbrain-forebrain loops.^[55] Synaptic plasticity underpins memory consolidation within forebrain circuits. Long-term potentiation (LTP) in hippocampal-entorhinal pathways strengthens connections following high-frequency stimulation, stabilizing episodic memories over extended periods, as demonstrated in rodent models where LTP persists for months post-induction. This mechanism, involving NMDA receptor activation and AMPA receptor trafficking, enables the entorhinal cortex to relay contextual information to the hippocampus, consolidating declarative knowledge essential for executive processes.^[56]

Sensory and Motor Integration

The forebrain's sensory-motor integration begins with thalamic relay nuclei, which serve as critical gateways for ascending sensory information to the cerebral cortex. The ventral posterolateral (VPL) nucleus of the thalamus receives input from the spinothalamic tract, conveying sensations of pain, temperature, and crude touch from the body, while the ventral posteromedial (VPM) nucleus handles similar inputs from the face. Similarly, the lateral geniculate nucleus (LGN) acts as the primary relay for visual information, receiving retinotopic projections from the optic tract and relaying them to the visual cortex while preserving spatial organization. These first-order thalamic nuclei filter and modulate sensory signals before transmission, ensuring efficient processing in higher cortical areas.^[57]^[58]^[59]^[60] In the cerebral cortex, primary sensory areas initiate detailed processing of these relayed inputs. The primary somatosensory cortex (S1), located in the postcentral gyrus, maps somatosensory information topographically via the homunculus, enabling precise localization of touch and proprioception. The primary visual cortex (V1), in the occipital lobe, processes basic features like edges and orientation from LGN inputs. Higher integration occurs in association areas, such as the middle temporal (MT) area, which specializes in motion perception by combining inputs from V1 and analyzing direction and speed of visual stimuli. These cortical stages transform raw sensory data into perceptually meaningful representations that inform motor planning.^[61]^[62]^[63] Motor output is organized hierarchically within forebrain structures, linking sensory integration to action. The premotor cortex plans and sequences movements based on sensory cues, generating motor commands for complex behaviors like reaching. These commands descend to the primary motor cortex (M1) in the precentral gyrus, which executes fine motor control by activating specific muscle groups through the corticospinal tract. Basal ganglia loops, involving the striatum, globus pallidus, and subthalamic nucleus, refine these outputs by inhibiting unwanted movements and facilitating smooth, goal-directed actions via parallel circuits that modulate thalamic projections back to the cortex.^[64]^[65]^[66] Cross-modal integration in the forebrain unifies inputs from different senses to enhance perceptual accuracy. The superior temporal sulcus (STS), particularly its posterior region, fuses audiovisual information, such as matching speech sounds with lip movements, through convergent projections from auditory and visual association areas. This multisensory convergence improves detection thresholds and response times in dynamic environments.^[67]^[68] Feedback loops via corticothalamic projections from cortical layer 6 neurons modulate thalamic activity, refining sensory-motor integration. These projections enhance attentional focus by amplifying relevant sensory signals in the thalamus, such as boosting visual contrast in the LGN during selective attention, while suppressing irrelevant inputs through inhibitory interneurons. This bidirectional communication creates dynamic gain control, adapting sensory relay to behavioral demands.^[69]^[70]^[71]

Homeostatic and Endocrine Regulation

The forebrain, particularly the hypothalamus within the diencephalon, plays a central role in homeostatic and endocrine regulation by integrating neural and hormonal signals to maintain physiological balance, including energy homeostasis, circadian timing, and stress responses. Key hypothalamic nuclei detect circulating factors and environmental cues, coordinating autonomic outputs and pituitary hormone release to adjust bodily functions such as appetite, body temperature, and fluid balance. This regulation ensures adaptation to internal and external demands, preventing disruptions in metabolism and survival mechanisms.^[72] The arcuate nucleus of the hypothalamus is pivotal for appetite regulation, sensing adiposity signals like leptin from peripheral fat stores to modulate feeding behavior and energy expenditure. Leptin binds to receptors on arcuate neurons, inhibiting orexigenic agouti-related peptide (AgRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons, which project to other hypothalamic regions to suppress hunger during sufficient energy states. Disruptions in this leptin signaling pathway, as seen in obesity models, lead to hyperphagia and impaired satiety. Similarly, the suprachiasmatic nucleus serves as the master circadian pacemaker, receiving photic input via the retinohypothalamic tract to synchronize peripheral clocks and orchestrate daily rhythms in sleep-wake cycles, hormone secretion, and metabolism. Lesions here abolish rhythmic behaviors, underscoring its essential role in temporal homeostasis.^[73]^[74] The hypothalamus interfaces directly with the pituitary gland to regulate endocrine functions, exerting control over both anterior and posterior lobes. For the anterior pituitary, hypothalamic releasing hormones such as corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH) are transported via the hypophyseal portal system to stimulate adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone (TSH) secretion, respectively, influencing stress and metabolic responses. The posterior pituitary, by contrast, stores and releases antidiuretic hormone (ADH, or vasopressin) synthesized in hypothalamic magnocellular neurons, aiding osmoregulation and fluid balance. In stress responses, CRH neurons in the paraventricular nucleus activate the hypothalamic-pituitary-adrenal (HPA) axis, triggering glucocorticoid release from the adrenal cortex to mobilize energy during threats; chronic activation can dysregulate this axis, contributing to disorders like anxiety.^[75]^[76] Autonomic control is mediated by the lateral hypothalamus, which promotes sympathetic activation to enhance arousal, cardiovascular output, and thermogenesis during wakefulness or energy demands, integrating with orexin neurons to link feeding and activity. Connections from the hypothalamus to the periaqueductal gray facilitate pain modulation, where descending pathways inhibit nociceptive transmission during stress or defensive behaviors, involving opioid release to prioritize survival. Temperature regulation centers on the preoptic area, which contains thermosensitive neurons acting as effectors to elicit shivering or vasodilation via autonomic efferents; adjacent osmoreceptors in the median preoptic nucleus detect plasma osmolarity changes, coordinating with ADH release to maintain hydration and thermal stability.^[77]^[78]^[79]^[80]

Evolution and Comparative Anatomy

In Non-Mammalian Vertebrates

In basal vertebrates such as fish and amphibians, the forebrain exhibits a relatively simple organization without the laminated structures seen in mammals. The pallium functions as a non-laminated sensory integration center, processing inputs from olfactory, visual, and somatosensory pathways, while the subpallium contains homologs of the basal ganglia, including striatal regions that modulate motor and reward-related behaviors through GABAergic projection neurons.^[81]^[82] This nuclear organization reflects an evolutionary precursor to more complex pallial expansions, with the pallium in ray-finned fish showing everted morphology that differs from the evaginated form in tetrapods.^[83] In reptiles, the forebrain maintains a predominantly nuclear architecture, with the dorsal ventricular ridge (DVR) serving as a functional equivalent to the mammalian cortex by receiving thalamic inputs for sensory processing. The reptilian forebrain shows olfactory dominance, as evidenced by the large size of the olfactory bulbs and their extensive projections to the pallium, which prioritize chemosensory integration over visual or somatosensory modalities in many species.^[84]^[85] The telencephalon constitutes a smaller proportion of the total brain volume in reptiles than in mammals, underscoring the constrained expansion of higher cognitive regions.^[86] Avian forebrains demonstrate specialized adaptations within this nuclear framework, particularly in pallial regions. The hyperpallium, including the Wulst, is a prominent dorsal structure dedicated to visual processing and spatial navigation, receiving direct retinal and thalamic inputs for binocular vision and motion detection.^[87] In songbirds, the nidopallium houses circuits essential for vocal learning and production, with nuclei like the high vocal center integrating auditory feedback and motor control through dopaminergic modulation.^[88] Across non-mammalian vertebrates, evolutionary constraints limit forebrain complexity, lacking the neocortical lamination that enables layered processing in mammals and instead relying on clustered nuclear organization for parallel sensory-motor integration. This arrangement supports essential survival functions but restricts advanced associative cognition observed in mammalian expansions.^[89]^[90]

Mammalian Adaptations

The mammalian forebrain underwent significant evolutionary modifications, most notably the emergence of the neocortex, a six-layered structure that distinguishes it from the simpler nuclear organization seen in reptilian dorsal ventricular ridge (DVR). This reorganization is thought to have arisen through the transformation of the reptilian DVR into a laminated cortex. These changes likely occurred in the common ancestor of mammals, enabling greater processing capacity for sensory integration and behavior.^[91]^[92] A key metric of mammalian forebrain advancement is the encephalization quotient (EQ), which measures brain size relative to body mass and correlates with cognitive capabilities. Primates exhibit notably higher EQ values, with humans reaching approximately 7.5, compared to about 1 in cats, reflecting the disproportionate expansion of the forebrain in lineages adapted for advanced problem-solving and social interaction.^[93]^[94] In primates, the forebrain's prefrontal cortex expanded significantly, comprising up to 29% of the cerebral cortex in humans versus about 11% in other mammals, driving advancements in social cognition such as theory of mind and empathy. This region hosts mirror neuron systems, first identified in macaque monkeys, which activate during both action performance and observation, facilitating imitation and social learning critical for group dynamics.^[95]^[96] Across mammals, gyrification—the folding of the cortical surface—increases with brain and body size to accommodate more neurons within a compact skull, with the gyrification index rising allometrically. Dolphins, for instance, display indices rivaling those of humans (around 3.0-3.5 in odontocetes versus 2.6 in humans), allowing their large forebrains to support sophisticated echolocation and social behaviors despite aquatic constraints.^[97]^[98] Fossil evidence from endocasts reveals rapid forebrain growth in hominins, with Homo erectus achieving an average volume of about 1,000 cc by 1.8 million years ago, nearly double that of earlier australopiths and indicative of selective pressures for enhanced cognition in early human ancestors.^[99]^[100]

Clinical Significance

Developmental Disorders

Developmental disorders of the forebrain encompass a range of congenital malformations arising from disruptions during embryonic and early fetal brain development, primarily affecting the prosencephalon and leading to incomplete division or abnormal neuronal organization. These conditions often result from genetic mutations, chromosomal anomalies, or environmental teratogens, manifesting as structural defects that impair cognitive, motor, and sensory functions. Holoprosencephaly (HPE) represents the most severe and common forebrain malformation, characterized by failed cleavage of the prosencephalon into distinct hemispheres.^[101] HPE is classified into types based on severity, with alobar HPE featuring a single holosphere, fused thalami, and a monoventricle, while semilobar HPE shows partial separation of the hemispheres posteriorly but fused frontal lobes.^[102] Mutations in the sonic hedgehog (SHH) gene, which plays a critical role in midline patterning, account for approximately 37% of familial autosomal dominant HPE cases, though overall genetic contributions from SHH and related genes like ZIC2, SIX3, and TGIF1 explain about 25% of nonsyndromic instances.^[103]^[104] The incidence of HPE is estimated at 1 in 10,000 live births, though higher (up to 1 in 250) in early conceptuses due to significant prenatal lethality.^[105] A strong correlation exists between the degree of brain malformation and facial anomalies, such as cyclopia or midline clefts in alobar forms, reflecting the shared developmental fields of the forebrain and face; milder brain involvement often pairs with subtler facial dysmorphisms like hypotelorism.^[102] Agenesis of the corpus callosum (ACC), another key forebrain disorder, involves the partial or complete absence of the midline commissure connecting the cerebral hemispheres, disrupting interhemispheric communication. ACC can occur in isolated forms, where it presents without other anomalies, or as part of syndromic conditions, such as Aicardi syndrome, which combines ACC with chorioretinal lacunae and infantile spasms, almost exclusively in females and leading to profound intellectual disability.^[106] Diagnosis relies on magnetic resonance imaging (MRI), which reveals the absent callosum, associated Probst bundles (misdirected white matter), and potential ventriculomegaly.^[107] In isolated ACC, cognitive outcomes vary, with many individuals achieving normal intelligence quotients but exhibiting deficits in processing speed, executive function, social cognition, and novel problem-solving due to impaired hemispheric integration.^[108] Lissencephaly, or "smooth brain," arises from defective neuronal migration during the 12th to 24th gestational weeks, resulting in a lack of cortical gyri and sulci, thick cortex, and disorganized lamination. Mutations in the LIS1 gene (PAFAH1B1), encoding a microtubule-associated protein essential for cytoskeletal dynamics, cause classical lissencephaly subtype I, often in Miller-Dieker syndrome due to contiguous gene deletions.^[109] This leads to a pachygyric brain surface with agyria or polymicrogyria, severe developmental delays, and hypotonia evolving to spasticity. Epilepsy affects more than 90% of individuals with lissencephaly, typically presenting as infantile spasms or refractory seizures in early infancy.^[109] Both genetic and environmental factors contribute to these forebrain disorders, with prenatal disruptions increasing risks of midline fusion failures like HPE. Maternal pregestational diabetes significantly elevates HPE risk (up to 200-fold in some studies), potentially through hyperglycemia-induced oxidative stress impairing SHH signaling.^[110] Periconceptional alcohol exposure also heightens odds (adjusted OR ≈ 2.0), likely via interference with retinoic acid pathways critical for ventral forebrain patterning.^[111] Prognosis varies by malformation severity; alobar HPE carries near-universal early mortality, with most infants not surviving beyond the first months due to hypothalamic-pituitary dysfunction and apnea. Semilobar HPE offers a more favorable outlook, with about 50% surviving past infancy, though survivors often face profound intellectual disability, seizures, and endocrine issues requiring lifelong management.^[101] Isolated ACC generally permits longer survival and better function than syndromic forms, while lissencephaly prognosis remains guarded, with median survival into adolescence but high rates of epilepsy-related complications.^[112]

Acquired Pathologies

Acquired pathologies of the forebrain arise from external injuries, progressive degeneration, vascular insults, or infectious processes, primarily affecting the cerebral cortex, limbic structures, thalamus, hypothalamus, and basal ganglia, resulting in disrupted neural connectivity and function. These conditions lead to symptoms such as cognitive decline, sensory alterations, motor impairments, and behavioral changes, with pathophysiological mechanisms involving neuronal loss, protein aggregation, inflammation, and ischemia. Understanding these pathologies is crucial for delineating the forebrain's vulnerability to post-developmental insults. Traumatic brain injury (TBI) frequently targets the forebrain, particularly through frontal lobe contusions that cause direct cortical damage and secondary effects like edema and hemorrhage. Frontal contusions often result from acceleration-deceleration forces in high-impact trauma, leading to personality changes such as increased impulsivity, apathy, and emotional dysregulation due to disruption of prefrontal executive networks. These alterations persist chronically in moderate to severe cases, impairing social functioning and self-awareness. Complementing cortical damage, diffuse axonal injury (DAI) in TBI shears white matter tracts throughout the forebrain, including the corpus callosum and subcortical projections, due to rotational forces that exploit the viscoelastic properties of axons. This microstructural disruption propagates Wallerian degeneration and demyelination, contributing to widespread cognitive and motor deficits by interrupting inter-regional communication. In neurodegenerative disorders, Alzheimer's disease (AD) prominently affects forebrain structures like the hippocampus and temporal lobes through accumulation of amyloid-beta plaques and neurofibrillary tangles. Amyloid plaques form extracellular deposits that trigger neuroinflammation and synaptic loss in the hippocampus, a key forebrain region for memory, leading to anterograde amnesia and spatial disorientation as early symptoms. Hippocampal atrophy, detectable via volumetric MRI, correlates with plaque burden and tau pathology spreading from the entorhinal cortex. Frontotemporal dementia (FTD), another tau-mediated pathology, targets the prefrontal cortex, causing neuronal loss and gliosis that manifest as behavioral disinhibition, apathy, and executive dysfunction. Tau inclusions in prefrontal neurons disrupt microtubule stability, accelerating degeneration in frontal lobes and anterior temporal regions, with atrophy patterns confirmed by neuroimaging. Parkinson's disease (PD) involves forebrain basal ganglia pathology, characterized by progressive dopamine loss in the substantia nigra projections to the striatum, compounded by alpha-synuclein Lewy body formation. This dopaminergic depletion impairs motor circuits, resulting in bradykinesia and rigidity, while Lewy bodies in basal ganglia neurons contribute to non-motor symptoms like cognitive fluctuations through widespread protein misfolding. Vascular pathologies in the forebrain include ischemic strokes in the middle cerebral artery (MCA) territory, which supplies the lateral cerebral cortex, including sensory-motor areas. MCA occlusions lead to infarction of the frontal, parietal, and temporal lobes, causing contralateral hemiparesis, sensory deficits, and aphasia due to ischemia-induced excitotoxicity and penumbral cell death. In the forebrain's subcortical components, thalamic lacunar infarcts from small vessel disease produce pure sensory loss by damaging the ventral posterior nucleus, which relays somatosensory information to the cortex. These lacunes, often hypertensive in origin, result in hemisensory syndromes affecting touch and pain modalities without motor involvement, stemming from focal ischemia in thalamocortical pathways. Infectious processes can selectively invade forebrain regions, as seen in herpes simplex virus type 1 (HSV-1) encephalitis, which preferentially targets the limbic system including temporal lobes and cingulate gyrus. HSV-1 reactivation causes necrotizing inflammation with edema and hemorrhage, leading to acute symptoms like seizures, memory impairment, and psychiatric disturbances due to viral tropism for limbic neurons. Sepsis-related hypothalamic involvement exacerbates forebrain dysfunction through systemic inflammation penetrating the blood-brain barrier, inducing cytokine-mediated neuronal apoptosis and microglial activation in the hypothalamus. This hypothalamic pathology disrupts autonomic regulation and contributes to sepsis-associated encephalopathy, manifesting as delirium and long-term cognitive deficits via amplified inflammatory signaling.

Diagnostic and Therapeutic Approaches

Diagnostic approaches to forebrain disorders rely on advanced neuroimaging techniques to assess structural and functional integrity. Functional magnetic resonance imaging (fMRI), particularly resting-state fMRI, maps forebrain functional connectivity by identifying networks such as the default mode network, which spans cortical and subcortical regions, aiding in the diagnosis of conditions like Alzheimer's disease where network disruptions are evident. Diffusion tensor imaging (DTI) evaluates white matter integrity in the forebrain by quantifying fractional anisotropy in tracts like the corpus callosum, revealing demyelination or axonal damage in traumatic brain injury. Positron emission tomography (PET) using fluorodeoxyglucose (FDG) measures glucose metabolism in forebrain structures, with hypometabolism in the temporal and parietal lobes serving as a biomarker for early dementia detection. Electrophysiological methods provide complementary insights into forebrain electrical activity. Electroencephalography (EEG) detects abnormal rhythms and epileptiform discharges in the cerebral cortex, essential for diagnosing focal seizures originating in forebrain regions like the frontal or temporal lobes. Magnetoencephalography (MEG) offers superior spatial resolution for localizing sources in deeper forebrain structures, such as the thalamus, by measuring magnetic fields from neuronal currents, which is particularly useful in presurgical planning for epilepsy. Therapeutic interventions target specific forebrain circuits to alleviate symptoms in various pathologies. Deep brain stimulation (DBS) of the subthalamic nucleus, a key forebrain-adjacent structure, modulates basal ganglia-forebrain loops, significantly reducing motor symptoms in Parkinson's disease with long-term efficacy demonstrated in randomized trials. Stem cell therapies, including mesenchymal stem cell infusions, aim to promote neuroregeneration in forebrain areas affected by ischemic stroke; phase II and III trials as of 2025 have shown modest improvements in motor function and safety profiles in ischemic penumbra regions.^[113] Pharmacologically, cholinesterase inhibitors like donepezil enhance cholinergic signaling in the forebrain, slowing cognitive decline in Alzheimer's by increasing acetylcholine levels in the cortex and hippocampus. For schizophrenia, involving forebrain glutamate imbalances, low-dose anti-NMDA receptor modulators address hypofunction of NMDA receptors in cortical circuits, though primarily explored in adjunctive therapy settings. Emerging techniques hold promise for precise forebrain interventions. Optogenetics in animal models precisely activates or inhibits hypothalamic circuits within the forebrain, offering insights into disorders like obesity and informing potential human translation via light-sensitive proteins.^[114] AI-assisted lesion mapping, leveraging machine learning on multimodal imaging data, has advanced post-2023 to predict functional outcomes from forebrain lesions with over 85% accuracy in stroke cohorts, enhancing personalized rehabilitation planning. As of 2025, phase 3 trials like TREASURE continue to evaluate allogeneic stem cells for acute ischemic stroke, with promising safety and efficacy data. AI models have achieved up to 87% accuracy in predicting outcomes from stroke lesions.^[115]^[116]

References

[1]
Anatomy, Central Nervous System - StatPearls - NCBI Bookshelf - NIH
Oct 10, 2022 · The forebrain separates to form the telencephalon and diencephalon, and the hindbrain splits to form the metencephalon and the ...
[2]
Internal Brain Anatomy – Foundations of Neuroscience
The diencephalon coordinates sensory and homeostatic functions, while the basal ganglia regulate movement and the limbic structures process emotion and memory.
[3]
Major Structures and Functions of the Brain - NCBI - NIH
The preponderance of the cerebral cortex (which, with its supporting structures, makes up approximately 80 percent of the brain's total volume) is actually a ...
[4]
Physiology, Brain - StatPearls - NCBI Bookshelf
Function · Frontal lobe: Responsible for motor function, language, and cognitive processes, such as executive function, attention, memory, affect, mood, ...Physiology, Brain · Cellular Level · Clinical Significance
[5]
The Anatomy of the Cerebral Cortex - NCBI - NIH
The superolateral surface shows the central sulcus that separates the pre-central and post-central gyri. The parietal lobe is divided by the interparietal ...Missing: lateralization | Show results with:lateralization
[6]
Cerebral cortex | Radiology Reference Article - Radiopaedia.org
Jul 8, 2024 · Approximately 90% of the human cortex consists of six layers forming the neocortex, while 10% of the cortex has only three layers, forming the ...
[7]
Development and Arealization of the Cerebral Cortex - ScienceDirect
Sep 25, 2019 · Neocortex is defined by the presence, at some point during development, of six distinct anatomical layers parallel to the cortical surface with ...
[8]
Neuroanatomy, Basal Ganglia - StatPearls - NCBI Bookshelf
The basal ganglia is a cluster of nuclei found deep to the neocortex of the brain. It has a multitude of functions associated with reward and cognition.
[9]
Neuroanatomy, Limbic System - StatPearls - NCBI Bookshelf
The limbic system forms from different components that rise from the mesencephalon, diencephalon, and telencephalon as described above. Go to: Surgical ...Missing: ganglia | Show results with:ganglia
[10]
Neuroanatomy, Cerebral Cortex - StatPearls - NCBI Bookshelf - NIH
The occipital lobe is the center for the processing of visual input in humans. The primary visual cortex is located in Brodmann Area 17, on the medial side of ...
[11]
Choosing words: left hemisphere, right hemisphere, or both ...
Language is considered to be one of the most lateralized human brain functions. Left hemisphere dominance for language has been consistently confirmed in ...
[12]
Hemispheric lateralization of verbal and spatial working memory ...
Mar 16, 2013 · We found significant left hemispheric lateralization for verbal WM, most notably in the frontal and parietal lobes, as well as right hemisphere lateralization ...
[13]
White matter tracts | Radiology Reference Article - Radiopaedia.org
Jul 9, 2024 · White matter tracts in the brain, also known as white matter fibers, are classified into three categories: projection fibers · association ...
[14]
Commissural fibers of telencephalon - e-Anatomy - IMAIOS
The corpus callosum is the largest set of commissural fibers in the brain and is a pathway of crucial importance to speech-language functions. The anterior ...
[15]
Brain Facts and Figures
Percentage of total cerebral cortex volume (human): frontal lobe = 41%; temporal lobe = 22%; parietal lobe = 19%; occipital lobe = 18%. (Kennedy et al ...
[16]
Fraction of mass of different parts of brain - Human Homo sapiens
Fraction of mass of different parts of brain out of total brain mass ; 81.8% cerebral cortex 10.3% cerebellum 7.8% rest of brain Figure link - link % · Human Homo ...<|separator|>
[17]
Brain size, sex, and the aging brain - PMC - NIH
A well‐established finding of these studies is that men demonstrate an on average larger total brain volume than women with an approximate 8–15% larger brain in ...Missing: telencephalon | Show results with:telencephalon
[18]
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 ...Missing: dural sinuses
[19]
Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in ...
Jan 12, 2021 · All venous drainage occurs through dural venous sinuses that drain toward the neck veins. ... middle cerebral arteries and anterior cerebral ...
[20]
Neuroanatomy, Thalamus - StatPearls - NCBI Bookshelf - NIH
The thalamus is a paired gray matter structure of the diencephalon located near the center of the brain. It is above the midbrain or mesencephalon, allowing for ...Missing: subdivisions epithalamus
[21]
Physiology, Hypothalamus - StatPearls - NCBI Bookshelf
Vasopressin and oxytocin are 2 hormones made in the hypothalamus itself which travel in hypothalamic neurons directly to the posterior pituitary. Vasopressin ...
[22]
The Neuroanatomy of the Habenular Complex and Its Role in the ...
Jan 3, 2024 · The habenular complex is a diencephalic structure divided into the medial and lateral divisions that lie within the epithalamus of most vertebrates.
[23]
Anatomy and Connectivity of the Subthalamic Nucleus in Humans ...
Apr 21, 2020 · The Subthalamic Nucleus (STh) is an oval-shaped diencephalic structure located ventrally to the thalamus, playing a fundamental role in the circuitry of the ...
[24]
Neuroanatomy, Thalamocortical Radiations - StatPearls - NCBI - NIH
Jul 24, 2023 · Thalamocortical radiations are the nerve fibers between the thalamus and the cerebral cortex. Functionally, thalamocortical radiations ...
[25]
Functional Anatomy of the Hypothalamus and Pituitary - NCBI - NIH
Nov 28, 2016 · Although the hypothalamus comprises only 2% of the total brain volume, it is a key regulator of pituitary function and homeostatic balance.
[26]
Neuroanatomy, Neural Tube Development and Stages - NCBI - NIH
The neural tube gives rise to three primary vesicles: Forebrain(Prosencephalon), Midbrain(Mesencephalon), and Hindbrain(Rhombencephalon).
[27]
Mutations in the human Sonic Hedgehog gene cause ... - Nature
Nov 1, 1996 · Holoprosencephaly (HPE) is a common developmental defect of the forebrain and frequently the midface in humans, with both genetic and ...
[28]
Molecular Bases of Human Malformation Syndromes Involving the ...
Dec 2, 2021 · In this review, we summarize the molecular mechanisms and role in embryonic morphogenesis of the SHH pathway, then classify the phenotype of each malformation ...
[29]
Neural - Prosencephalon Development - Embryology
### Timeline for Prosencephalon, Telencephalon, and Diencephalon Formation in Human Embryo
[30]
Embryology, Weeks 6-8 - StatPearls - NCBI Bookshelf
Oct 10, 2022 · The prosencephalon later develops into the diencephalon and telencephalon. The diencephalon gives rise to the thalami, hypothalamus, optic ...
[31]
The human brain at stage 16, including the initial evagination of the ...
The cerebral hemispheres grow rostrally and dorsally, thereby forming the beginning of the longitudinal fissure. Apart from the commissure of the superior ...
[32]
The transcription factor Foxg1 regulates the competence of ...
Foxg1 is required for development of the ventral telencephalon in the embryonic mammalian forebrain. Although one existing hypothesis suggests that failed ...
[33]
Molecular Regionalization of the Diencephalon - Frontiers
Otx2, orthodenticle homeobox 2 is expressed in the boundary between the embryonic thalamus and prethalamus, in the boundary between the pretectum and thalamus, ...
[34]
Human Cortical Neurons Originate from Radial Glia and Neuron ...
Previous studies from our laboratory showed that at the beginning of cortical neurogenesis [5 gestational weeks (gw)], human RGs are just one of several cell ...
[35]
Developmental Dynamics of Neurogenesis and Gliogenesis in the ...
May 9, 2021 · We now know that new neurons and glia are continuously added to the brain at postnatal stages, even in mature adults of various mammalian species, including ...
[36]
The Basics of Brain Development | Neuropsychology Review
Nov 3, 2010 · This paper will review some of the major events that contribute to the development of the human brain from its early embryonic state through adolescence.The Basics Of Brain... · Abstract · Imaging Studies Of Brain...<|control11|><|separator|>
[37]
Prolonged myelination in human neocortical evolution - PNAS
Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees.Abstract · Results · Discussion
[38]
An atlas for human brain myelin content throughout the adult life span
Jan 11, 2021 · In most brain regions, myelin content followed a quadratic pattern of increase during the third decade of life, plateau at a maximum around the ...Missing: timeline forebrain mid- 20s
[39]
Brain Mechanisms in Early Language Acquisition - PubMed Central
Studies indicate, for example, that the critical period for phonetic learning occurs prior to the end of the first year, whereas syntactic learning flourishes ...
[40]
The critical period: neurochemical and synaptic mechanisms shared ...
Sep 8, 2021 · The critical period is a time of (i) heightened inhibition; (ii) reduced expression of brain-derived neurotrophic factor (BDNF); and (iii) synaptic imbalance.<|separator|>
[41]
Brain-Derived Neurotrophic Factor Regulates the Maturation of ... - NIH
Because BDNF is suggested to regulate the initiation of plasticity, our results strongly indicate that BDNF is involved in the regulation of the critical period ...
[42]
Sex differences in the adolescent brain - PMC - PubMed Central - NIH
Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males.
[43]
Sex Steroids and the Organization of the Human Brain
May 16, 2012 · In humans, white matter sexual dimorphisms also become more prominent during puberty and adolescence: in boys, white matter microstructure ...
[44]
How the Brain Changes With Age - BrainFacts
Aug 30, 2019 · As we enter midlife, our brains change in subtle but measurable ways. The overall volume of the brain begins to shrink when we're in our 30s or ...Missing: forebrain | Show results with:forebrain
[45]
Brain aging mechanisms with mechanical manifestations - PMC
Morphologically, brain aging is primarily characterized by brain volume loss ... Ventricular CSF volume starts to increase around age 30 as a result of early ...
[46]
The role of prefrontal cortex in cognitive control and executive function
Concepts of cognitive control (CC) and executive function (EF) are defined in terms of their relationships with goal-directed behavior versus habits.
[47]
Lesion mapping of cognitive control and value-based decision ...
Aug 20, 2012 · Abstract. A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various ...
[48]
Dorsolateral Prefrontal Cortex - an overview | ScienceDirect Topics
The dorsolateral prefrontal cortex (DLPFC) is defined as a brain region central to executive functions, involved in organizing behavioral responses, ...
[49]
Persistent neural activity in the prefrontal cortex - PubMed Central
Neurons of the prefrontal cortex exhibit persistent firing during the delay period of working memory tasks. Despite extensive studies, the mechanisms ...Missing: original | Show results with:original
[50]
Role of Prefrontal Persistent Activity in Working Memory - Frontiers
Persistent neuronal firing in prefrontal cortex has been observed even in the absence of performance of a task, or even learning of a task, while subjects view ...
[51]
Role of right posterior parietal cortex in maintaining attention to ...
Recent models of human posterior parietal cortex (PPC) have variously emphasized its role in spatial perception, visuomotor control or directing attention.
[52]
The anterior temporal cortex is a primary semantic source of top ...
This suggests a need to revisit current theories of object recognition, incorporating the ATL that interfaces high-level vision with semantic knowledge.Missing: papers | Show results with:papers
[53]
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.”
[54]
The Salience Network: A Neural System for Perceiving and ...
Dec 11, 2019 · The term “salience network” refers to a suite of brain regions whose cortical hubs are the anterior cingulate and ventral anterior insular (ie, frontoinsular) ...
[55]
Dopamine reward circuitry: two projection systems from the ventral ...
A model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function.
[56]
Induction and Experience-Dependent Consolidation of Stable Long ...
Nov 1, 2002 · We report that high-frequency stimulation (HFS) paradigms applied to the rat dentate gyrus can elicit stable LTP lasting months and up to at least 1 year.
[57]
Neuroanatomy, Spinothalamic Tract - StatPearls - NCBI Bookshelf
The spinothalamic tract (STT) is a sensory tract carrying nociceptive, temperature, crude touch, and pressure from skin to the thalamus.
[58]
Ventral Posterolateral Nucleus - an overview | ScienceDirect Topics
The VPL serves as a primary relay for somatosensory information, receiving afferents from the spinal cord and dorsal column nuclei and projecting to the primary ...
[59]
Neuroanatomy, Nucleus Lateral Geniculate - StatPearls - NCBI - NIH
The lateral geniculate nucleus (LGN) belongs to the category of sensory projection nuclei of the thalamus and plays an essential role in normal visual ...Missing: forebrain | Show results with:forebrain
[60]
The lateral geniculate nucleus: Current Biology - Cell Press
The lateral geniculate nucleus (LGN) relays visual information from the retina to the visual cortex, regulating how visual information gains access to the ...<|separator|>
[61]
Neuroanatomy, Somatosensory Cortex - StatPearls - NCBI Bookshelf
Nov 7, 2022 · A larger association cortex is needed to assess more complex input. The S2 region helps to process the sensory information delivered to S1.Missing: V1 MT
[62]
Chapter 15: Visual Processing: Cortical Pathways
Visual processing starts in the retina, then goes to the lateral geniculate nucleus (LGN) of the thalamus, and finally to the striate cortex (V1) in the ...Missing: relay | Show results with:relay
[63]
Cortico–Cortical Connections of Primary Sensory Areas ... - eNeuro
Dec 21, 2016 · Here we examine the cortico–cortical circuitry in the migraine brain relating to the principle primary sensory areas (vision, audition, and somatosensation).
[64]
Motor Cortex (Section 3, Chapter 3) Neuroscience Online
The primary motor cortex, or M1, is located on the precentral gyrus and on the anterior paracentral lobule on the medial surface of the brain. Of the three ...
[65]
Basal Ganglia (Section 3, Chapter 4) Neuroscience Online
The basal ganglia and motor cortex form a processing loop whereby the basal ganglia enables the proper motor program stored in motor cortex circuits via the ...
[66]
Hierarchically Organized Medial Frontal Cortex-Basal Ganglia ...
Aug 16, 2017 · We found strong evidence that this behavioral phenomenon reflects a hierarchical organization of premotor regions in posterior medial frontal ...Fmri Experiment · Fmri-Guided Rtms Experiment · Fmri Data
[67]
The Role of the Posterior Superior Temporal Sulcus in Audiovisual ...
In this study we investigate previous claims that a region in the left posterior superior temporal sulcus (pSTS) is more activated by audiovisual than unimodal ...
[68]
Crossmodal Adaptation in Right Posterior Superior Temporal Sulcus ...
May 14, 2014 · We used dynamic audiovisual stimuli in which affective information was independently and parametrically manipulated in each modality and used ...
[69]
Corticothalamic feedback locally modulates network state - Nature
Jul 1, 2025 · The most likely role is the top-down fine tuning of sensory and other inputs at the thalamic level, for example during selective attention.
[70]
Robust effects of corticothalamic feedback and behavioral state on ...
Mar 22, 2022 · We conclude that CT feedback modulates visual information on its way to cortex in a stimulus-dependent manner, but largely independently of behavioral state.
[71]
Corticothalamic Synaptic Noise as a Mechanism for Selective ...
Corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different ...
[72]
Hypothalamic circuits regulating appetite and energy homeostasis
The hypothalamus, especially the arcuate nucleus, regulates feeding and metabolism by sensing nutrient status and integrating signals. The hypothalamus is a ...
[73]
Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways ...
The arcuate nucleus of the hypothalamus (ARC) is of pivotal importance for primary sensing of adiposity signals, such as leptin and insulin, and circulating ...
[74]
Generation of circadian rhythms in the suprachiasmatic nucleus
Jun 22, 2018 · ... suprachiasmatic nucleus (SCN) of the hypothalamus acts as the principal pacemaker for circadian rhythms, which are powerful regulators of ...Missing: hypothalamus | Show results with:hypothalamus
[75]
The hypothalamus-pituitary-thyroid (HPT)-axis and its role in ...
Apr 5, 2021 · The production and secretion of hormones by the anterior lobe of the pituitary are under the regulation of the hypothalamus. The anterior lobe ...1. Introduction · 2. The Functional Anatomy... · 5. Interactions Of...
[76]
Regulation of the hypothalamic-pituitary-adrenocortical stress ...
HPA axis stress responses are initiated by corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). Stressors ...Dynamics Of The Hpa Axis... · Stressor Specificity... · Chronic Stress<|separator|>
[77]
The Hypothalamus and Autonomic Regulation: An Overview
The hypothalamus regulates autonomic function, connecting with sympathetic and parasympathetic neurons, and receiving inputs from visceral, blood, and external ...Inputs to hypothalamic... · Relationship Between... · Hypothalamic Control of the...
[78]
The contribution of periaqueductal gray in the regulation ... - Frontiers
PAG receives afferents from various structures known to be activated by threats, including amygdala, hypothalamus, and premammillary nucleus (Hadjipavlou et al.
[79]
A hypothalamic circuit that controls body temperature - PNAS
Jan 4, 2017 · Previous studies have shown that the preoptic area (POA) of the hypothalamus plays an important role in maintaining a stable Tcore via afferent ...Missing: osmoreceptors | Show results with:osmoreceptors
[80]
Integration of thermal and osmotic regulation of water homeostasis
The hypothalamus plays a central role in monitoring core body temperature and in activating responses aimed at either increasing or decreasing body temperature.Regulation Of Water Balance · Cellular/molecular... · Trpv1
[81]
Spatially resolved cell atlas of the teleost telencephalon and deep ...
May 21, 2024 · Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium ...
[82]
Basal ganglia organization in amphibians: evidence for a common ...
Tetrapod vertebrates share a common pattern of basal ganglia organization. This pattern includes the existence of dorsal and ventral striatopallidal systems.
[83]
comparisons of forebrain organization in basal ray-finned fishes and ...
Sep 2, 2009 · Compared to land vertebrates and the other fishes, the basal ray-finned fishes and teleosts have morphologically unusual forebrains.Missing: amphibians | Show results with:amphibians
[84]
Olfaction, navigation, and the origin of isocortex - Frontiers
While in reptiles and birds the most expanding component (the dorsal ventricular ridge) displays an overall nuclear shape and derives from the lateral and ...
[85]
Neural progenitors, patterning and ecology in neocortical origins
Nov 12, 2013 · ... reptilian cortex is quite small as compared to the expansive mammalian neocortex. Nonetheless, reptiles possess the dorsal ventricular ridge ...Missing: dominance | Show results with:dominance
[86]
The evolution of brain neuron numbers in amniotes - PNAS
Mar 7, 2022 · Compared to reptiles, mammals and birds have dramatically increased neuron numbers in the telencephalon and cerebellum, which are brain parts ...
[87]
Organization and evolution of the avian forebrain - Reiner - 2005
Oct 3, 2005 · The large avian cerebrum reflects expansion of both the basal ganglia as well as the regions above the basal ganglia, referred to as the pallium ...
[88]
Songbirds and the Revised Avian Brain Nomenclature - PMC
The magnocellular nucleus of the anterior neostriatum (MAN) is a vocal nucleus of the anterior telencephalon that is necessary for song learning,– and is active ...
[89]
Vertebrate brains and evolutionary connectomics: on the origins of ...
The volume of the BVR relative to the DVR is about the same ratio as represented by the basal ganglia to remainder of the telencephalon in mammals—i.e. thus ...
[90]
Neuronal Circuits Arise Independently of Lamination - ScienceDirect
Jan 7, 2013 · The hypothesis that cortical cells and circuits evolved in nonmammalian vertebrates prior to the overt lamination typical of the mammalian brain.
[91]
Genetic Mechanisms Underlying Cortical Evolution in Mammals - PMC
In this review I propose a journey through the evolutionary history of the cortex in mammals. From the appearance of the six-layered neocortex in an ancestor ...Missing: Protocadherins | Show results with:Protocadherins
[92]
Comparative Analysis of Protocadherin-11 X-Linked Expression ...
Our results suggest that the enriched expression of protocadherin-11 X-linked is involved in primate brain evolution and that some similarity exists between ...
[93]
Encephalization Quotient - an overview | ScienceDirect Topics
Within primates, humans have the highest EQ of 7.4–7.8 meaning that the human brain is seven to eight times larger than an average mammal of the same body size ...
[94]
10 Facts About Your Cat's Brain - FirstVet
Apr 18, 2022 · For domestic cats, the EQ value is between 1-1.71 while the human EQ is 7.44-7.8.
[95]
Molecular and cellular evolution of the primate dorsolateral ...
Aug 25, 2022 · The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition.
[96]
From Neurons to Social Beings: Short Review of the Mirror Neuron ...
Research on MNS across human, primates and other non-primate animals emphasize the idea of an ancient phylogenetic origin of the mirror mechanism and propose ...
[97]
Cetacean brains: How aquatic are they? - Marino - 2007
May 21, 2007 · Therefore, the gyrification index for modern humans is approximately 1.75. In the bottlenose dolphin (Tursiops truncatus) and common dolphin ...Large Brains And High... · Neuroanatomical Evidence · Eq, Telencephalic Surface...
[98]
Anatomical and volumetric description of the guiana dolphin (Sotalia ...
Apr 25, 2024 · The GI calculated for the Guiana dolphin was 3.08, which is relatively high compared to other mammals, including primates, afrotherians, ...
[99]
(PDF) The primitive brain of early Homo - ResearchGate
erectus dispersed from Africa into Eurasia before 1.8 million years ago ... Thus, among Asian Homo erectus, brain size was on average 1000 cc (Anton et ...
[100]
The primitive brain of early Homo - Science
Apr 10, 2021 · The African fossil record extends back to the origins of Homo at around 2.8 million years ago (Ma) (24), but critical endocranial evidence is ...
[101]
Holoprosencephaly - StatPearls - NCBI Bookshelf
Jun 7, 2024 · Holoprosencephaly is a rare and complex congenital disorder that significantly impacts the development of the human brain.Missing: correlation | Show results with:correlation
[102]
Holoprosencephaly Overview - GeneReviews® - NCBI Bookshelf
Dec 27, 2000 · Holoprosencephaly (HPE), the most common malformation of the forebrain in humans, is a structural anomaly of the brain resulting from failed or incomplete ...Missing: incidence | Show results with:incidence
[103]
The mutational spectrum of the sonic hedgehog gene in ... - PubMed
Mutations in SHH were detected in 10 of 27 (37%) families showing autosomal dominant transmission of the HPE spectrum, based on structural anomalies.Missing: percentage | Show results with:percentage
[104]
Nonsyndromic holoprosencephaly - Genetics - MedlinePlus
Sep 1, 2010 · Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face.Missing: incidence | Show results with:incidence
[105]
Holoprosencephaly - MN Dept. of Health
Sep 6, 2024 · By birth, the prevalence is 1 in 8,000 to 1 in 10,000 live births and stillbirths. Sometimes HPE can be caused by environmental causes. The most ...
[106]
Aicardi Syndrome - GeneReviews® - NCBI Bookshelf
Jun 30, 2006 · Aicardi syndrome is a neurodevelopmental disorder that affects primarily females. Initially it was characterized by a typical triad of agenesis of the corpus ...Missing: syndromic impacts
[107]
Corpus Callosum Agenesis: An Insight into the Etiology and ...
Patients with this disorder usually present with microcephaly, a wide range of callosal anomalies from thinning to complete agenesis, intellectual disability, ...
[108]
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 ...
[109]
Lissencephaly - StatPearls - NCBI Bookshelf
A study of lissencephaly in the Netherlands estimated the prevalence of around 1.2/100,000 births. [20][21] The diagnosis and the prevalence of lissencephaly ...
[110]
Nongenetic risk factors for holoprosencephaly: An updated review of ...
Holoprosencephaly (HPE) is a major structural birth defect of the brain that occurs in approximately 1 in 10,000 live births. Although some genetic causes of ...
[111]
Risk factors for cytogenetically normal holoprosencephaly in California
Maternal periconceptional exposures associated with increased risks for nonsyndromic holoprosencephaly included alcohol consumption (OR=2.0, 95% C.I. 0.9 ...
[112]
In-depth investigations of adolescents and adults with ...
Previous studies support low survival rates in newborns with isolated nonsyndromic alobar HPE, but there have not been accurate data on survival of individuals ...