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Uncus

The uncus is a hook-shaped, limbic structure forming the anteromedial portion of the parahippocampal gyrus within the medial temporal lobe of the brain.^[1] It is situated lateral to the mammillary bodies, posterior perforated substance, and cerebral crus, and anterior to the lateral geniculate body, separated from the apex of the temporal lobe by the rhinal sulcus.^[1]^[2] Structurally, the uncus consists of an anterior segment, which includes the ambient gyrus and semilunar gyrus overlying the amygdala and featuring the entorhinal cortex at its forefront, and a posterior segment containing the head of the hippocampus, demarcated by the uncal sulcus and connected via the band of Giacomini.^[1]^[2] Its blood supply arises primarily from uncal branches of the anterior choroidal artery, with additional contributions from the internal carotid, middle cerebral, and posterior cerebral arteries.^[1]^[2] Functionally, the uncus belongs to both the limbic and olfactory systems, housing the primary olfactory cortex and receiving fibers from the olfactory tract via the lateral olfactory stria, thereby contributing to olfaction, emotional processing, and memory formation.^[1]^[2] Clinically, it is notable for its involvement in temporal lobe epilepsy, where seizures originating here—known as uncinate fits—can produce olfactory or gustatory hallucinations, and in uncal herniation, a life-threatening condition during increased intracranial pressure where the uncus compresses the brainstem.^[2]

Anatomy

Location and Gross Structure

The uncus is a hook-shaped medial extension of the parahippocampal gyrus located on the anteromedial aspect of the temporal lobe.^[3] It lies anterior to the hippocampus and forms part of the inferomedial surface of the temporal lobe, positioned within the middle cranial fossa.^[4] This structure contributes to the limbic system and is visible as a prominent bulge on the medial temporal lobe when viewed from an inferior perspective.^[5] Grossly, the uncus exhibits a curved, hook-like morphology with a medial convexity that forms the medial wall of the temporal horn of the lateral ventricle.^[3] It measures approximately 1 cm in rostrocaudal length and 10–12 mm in overall extent, varying slightly between individuals.^[6] The uncus is subdivided into an anterior segment, an apex, and a posterior segment, with the posterior segment featuring distinct inferior and posteromedial surfaces.^[3] Laterally, it is bounded by the rhinal sulcus, which separates it from the apex of the temporal lobe.^[4] The surface anatomy of the uncus includes superior, inferior, medial, and lateral aspects, each relating to adjacent intracranial structures.^[3] The anteromedial surface bears the semilunar gyrus superiorly and the ambient gyrus inferiorly/medially, while the posteromedial surface is divided by the uncal sulcus into the uncinate gyrus, band of Giacomini, and intralimbic gyrus superiorly, with the entorhinal area below.^[6]^[5] These gyri contribute to the convoluted appearance of the uncus, emphasizing its role in the medial temporal region's complex topography.^[3]

Borders and Relations

The uncus, forming the medialmost anterior extension of the parahippocampal gyrus, is defined by specific anatomical borders that position it within the medial temporal lobe. It lies inferior to the optic tract anteriorly and the cerebral peduncle posteriorly as they course around the midbrain. The inferior border abuts the tentorium cerebelli, the dural fold separating the supratentorial compartment from the infratentorial space, thereby anchoring the uncus in the supratentorial region.^[8] Medially, the uncus relates to the ambient cistern and the brainstem, including the midbrain tegmentum and cerebral peduncle, which lie adjacent within the perimesencephalic subarachnoid spaces.^[9] Laterally, it borders the temporal horn of the lateral ventricle, separated by the hippocampal formation and surrounding white matter.^[10] Key spatial relations of the uncus are critical for understanding its role in neurosurgical approaches and neuroimaging. It maintains close proximity to the oculomotor nerve (cranial nerve III), with the uncus apex positioned immediately lateral to the nerve as it traverses the interpeduncular and crural cisterns.^[9] The posterior cerebral artery courses nearby in the ambient cistern, running parallel to the medial aspect of the uncus and contributing to its vascular supply.^[9] Additionally, the entorhinal cortex occupies much of the uncus's inferior surface, integrating it with broader limbic circuitry.^[11] The uncus also forms a component of the floor of the middle cranial fossa, resting on the petrous temporal bone and greater wing of the sphenoid.^[9] In clinical imaging, the uncus is readily identifiable on both MRI and CT scans as a characteristic medial bulge of the temporal lobe, best appreciated in coronal sections where it protrudes into the suprasellar and ambient cisterns.^[11] This visibility aids in assessing normal anatomy and detecting subtle displacements relevant to surgical planning.^[9]

Connections

Afferent Inputs

The uncus, as part of the primary olfactory cortex including the rostral piriform cortex and semilunar gyrus, receives direct primary afferent projections from the olfactory bulb through the lateral olfactory tract and anterior olfactory nucleus. These fibers terminate primarily in the rostral portion of the uncus, conveying unprocessed olfactory sensory information without thalamic relay, enabling rapid processing of odor stimuli. This pathway originates from mitral and tufted cells in the olfactory bulb, which synapse onto pyramidal neurons in the uncus's superficial layers, facilitating initial odor discrimination and association.^[12]^[13] The entorhinal cortex component of the uncus receives extensive afferent projections from neocortical association areas, including the prefrontal, parietal, temporal, insular, and cingulate cortices. These inputs convey multimodal sensory information (e.g., visual, auditory, somatosensory) as well as cognitive and spatial signals, which are integrated in layers II and III of the entorhinal cortex to support memory formation and contextual processing.^[14]

Efferent Outputs

The uncus, particularly through its entorhinal cortex component, sends major efferent projections to the dentate gyrus and other hippocampal subfields via the perforant pathway, a critical conduit for relaying processed sensory and mnemonic information that supports memory consolidation. These projections originate primarily from layers II and III of the entorhinal cortex and exhibit topographic organization, with lateral entorhinal areas targeting the distal portions of the dentate gyrus and medial areas projecting more proximally. Efferent connections from the uncus extend to the amygdala, with the lateral entorhinal cortex providing dense projections to the basolateral, lateral, and central amygdaloid nuclei, facilitating the integration of olfactory and contextual signals into emotional processing.^[15] These pathways contribute to the ventral amygdalofugal route, which conveys signals from the uncus-amygdala complex to the hypothalamus, influencing neuroendocrine and autonomic responses tied to limbic functions.^[16] Additional outputs from the uncus target the orbitofrontal cortex, primarily via efferents from the anterior perirhinal cortex to orbital and medial prefrontal regions, enabling higher-order integration of olfactory and reward-related information.^[17] Connections to brainstem nuclei, such as those in the periaqueductal gray and pontine tegmentum, occur indirectly through hypothalamic relays, supporting autonomic regulation in response to olfactory and emotional cues.^[16]

Function

Olfactory Processing

The uncus serves as a key component of the primary olfactory cortex, receiving direct monosynaptic projections from the mitral and tufted cells of the olfactory bulb via the lateral olfactory stria.^[12] This pathway is unique among sensory systems, as it bypasses the thalamus entirely, enabling rapid transmission of olfactory information to the cortex for immediate processing and detection of odors.^[18] These projections terminate primarily in the anterior portion of the uncus, where the piriform cortex is prominently located, facilitating the initial cortical relay of raw olfactory signals without thalamic modulation.^[19] Within the uncus, olfactory processing advances through integration in the piriform cortex, which supports the discrimination of odor qualities by synthesizing distributed inputs from the olfactory bulb.^[13] This structure encodes odor identity through sparse, overlapping representations of molecular features, allowing differentiation between similar scents such as floral versus citrus profiles, as demonstrated in functional imaging studies of odor categorization tasks.^[20] The piriform cortex's layered architecture, with its superficial layer II receiving bulb afferents and deeper layers providing associative feedback, enables this qualitative parsing, contributing to perceptual acuity in everyday olfaction.^[21] The uncus also plays a role in olfactory memory formation by linking odor percepts to emotional contexts via reciprocal connections with the amygdala, which is partially embedded within or adjacent to the uncus.^[22] These bidirectional pathways allow olfactory inputs to modulate amygdala activity, strengthening memory traces for emotionally salient smells, such as those associated with fear or reward, as evidenced by neuropsychological cases showing impaired odor recognition following amygdala lesions.^[23] This integration supports the encoding of episodic olfactory memories, where scents evoke contextual recall, without relying on higher-order semantic processing.^[24]

Role in Emotion and Memory

The uncus, as a key component of the limbic system within the medial temporal lobe, facilitates the integration of olfactory, emotional, and memory signals through its dense connections to the hippocampus and amygdala. These projections, including the perforant path from the entorhinal cortex (a major constituent of the uncus), provide critical input to the hippocampus, enabling the encoding of episodic memories that incorporate sensory and affective elements. The close anatomical adjacency of the uncus to the amygdala allows for bidirectional communication, whereby olfactory cues processed in the uncus can be modulated by amygdalar emotional signals, enhancing the salience of experiences during memory formation.^[5]^[16]^[25] The uncus contributes to fear conditioning and the emotional tagging of experiences through its connections with the amygdala, allowing neutral odors to acquire emotional valence, such as in associative learning where scents become triggers for fear or aversion, supported by uncinate fasciculus pathways that connect the uncus to orbitofrontal regions involved in emotional evaluation. Such integration ensures that memories are not only stored but also imbued with affective context, aiding adaptive behavioral responses. Recent studies as of 2024 suggest that residual uncus tissue may support working memory and recall functions in patients with developmental amnesia.^[26]^[27]^[28] Lesion studies, often derived from temporal lobectomy procedures for epilepsy that include uncus resection, reveal deficits in odor-evoked memories and emotional processing. Patients exhibit impaired recall of emotionally charged autobiographical events triggered by smells, alongside reduced enhancement of memory for affective stimuli, indicating the uncus's role in linking olfaction to limbic emotional networks. These findings underscore how uncus damage disrupts the consolidation of emotionally relevant episodic memories, leading to broader impairments in affective cognition.^[29]^[30]^[5]

Clinical Significance

Uncal Herniation

Uncal herniation represents a life-threatening subtype of transtentorial herniation, characterized by the medial displacement of the uncus of the temporal lobe through the tentorial notch due to supratentorial mass effect. This condition arises from elevated intracranial pressure (ICP), often exceeding compensatory mechanisms as described by the Monro-Kellie doctrine, leading to failure of intracranial volume accommodation.^[31] The primary mechanism involves a space-occupying lesion, such as a hematoma, tumor, or cerebral edema from trauma, causing asymmetric hemispheric expansion that forces the uncus inferiorly and medially. This herniation compresses the ipsilateral cerebral peduncle against the tentorial edge and the ipsilateral midbrain (including the red nucleus), while also impinging on the midbrain and cranial nerves, particularly the oculomotor nerve (CN III). Progression can distort the brainstem, impairing vital centers and potentially leading to irreversible damage or death within hours if untreated.^[31]^[32] Clinically, uncal herniation manifests with early signs of ipsilateral oculomotor nerve palsy, including ptosis, mydriasis (fixed dilated pupil, often termed "Hutchinson's pupil"), and impaired pupillary light reflex, alongside headache, nausea, and vomiting from rising ICP. As herniation advances, patients develop contralateral hemiparesis due to compression of the corticospinal tract, altered consciousness ranging from confusion to stupor, and Cushing's triad (hypertension, bradycardia, irregular respirations). Untreated, it rapidly progresses to coma, decerebrate posturing, and cardiorespiratory arrest.^[31]^[33] Diagnosis relies on prompt clinical recognition followed by neuroimaging; non-contrast computed tomography (CT) is the initial modality of choice, revealing medial displacement of the uncus, effacement of the suprasellar cistern, and midline shift greater than 5 mm as indicators of herniation. Magnetic resonance imaging (MRI) provides superior detail for underlying etiology but is less feasible in emergencies due to time constraints. Historical cases, dating to the 19th century, were often linked to intracranial tumors or trauma; for instance, Jonathan Hutchinson in 1867 described unilateral pupillary dilation in tumor patients, while experimental work by Hill in 1896 demonstrated transtentorial pressure gradients in animal models of mass lesions. James Collier's 1904 analysis of 161 tumor cases formalized the syndrome, noting false localizing signs in 12.4% of instances.^[31]^[34]

Associated Pathologies

The uncus plays a significant role in the pathogenesis of temporal lobe epilepsy (TLE), particularly through its involvement in auras featuring olfactory hallucinations, commonly referred to as uncinate fits. These episodes, first linked to uncus lesions by John Hughlings Jackson in the late 19th century, typically involve perceptions of unpleasant odors, such as rotten or burned smells, arising from epileptic discharges in the uncus and adjacent piriform cortex.^[35] Olfactory auras occur in approximately 0.6–16% of TLE cases and are relatively specific to mesial temporal structures, aiding in localizing seizure onset without providing lateralizing information.^[36] Intracranial electroencephalography studies confirm that such hallucinations correlate with ictal activity in the uncus region, underscoring its epileptogenic potential due to dense olfactory connections.^[36] Tumors originating in or invading the uncus, including gliomas and meningiomas, frequently manifest with seizures and memory disturbances by disrupting local neural circuits. Glioneuronal tumors, a subtype of low-grade glioma, commonly affect the uncus and amygdala, leading to drug-resistant TLE in affected individuals despite preserved hippocampal function.^[37] Surgical resection of these lesions via transcortical approaches achieves complete tumor removal and seizure freedom (Engel class I) in over 90% of cases, with minimal impact on verbal or visual memory as assessed by standardized neuropsychological tests.^[37] Similarly, mass lesions in the uncus, such as those initially suspected to be gliomas, can produce symptoms including vertigo, sensory deficits, and postoperative memory impairments that improve with targeted treatment.^[38] Meningiomas invading the uncus from adjacent dural sites may exacerbate these effects through mass effect, though specific cases highlight cognitive and seizure-related presentations.^[39] In neurodegenerative conditions, uncus atrophy contributes to disruptions in uncus-hippocampal circuits, prominently in Alzheimer's disease (AD) and mesial temporal sclerosis (MTS). Medial temporal lobe atrophy in predementia AD involves volume reductions in the hippocampus and bordering uncus, detectable via high-resolution MRI and correlating with early memory decline across subjective cognitive decline and mild cognitive impairment stages.^[40] Longitudinal analyses show accelerated atrophy in these regions among amyloid-positive individuals, with the uncus serving as an anatomical boundary in segmentation protocols that reveal posterior hippocampal changes preceding broader deficits.^[40] MTS, often underlying chronic TLE, features uncus-adjacent hippocampal volume loss with neuronal dropout in CA1–CA4 sectors and gliosis, identified in about 36% of epilepsy surgeries and linked to initial precipitating injuries like febrile seizures.^[41] This sclerosis extends laterally in some cases, amplifying memory impairments through impaired limbic connectivity.^[42]

References

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Uncus: definition, structure and function | Kenhub
The uncus is a limbic structure on the anteromedial part of the parahippocampal gyrus of the medial temporal lobe. Learn its anatomy on Kenhub!
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