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Midbrain
Figure shows the midbrain (A) and surrounding regions; sagittal view of one cerebellar hemisphere. B: Pons. C: Medulla. D: Spinal cord. E: Fourth ventricle. F: Arbor vitae. G: Nodule. H: Tonsil. I: Posterior lobe. J: Anterior lobe. K: Inferior colliculus. L: Superior colliculus.
Inferior view in which the midbrain is encircled blue.
Details
PronunciationUK: /ˌmɛsɛnˈsɛfəlɒn, -kɛf-/, US: /ˌmɛzənˈsɛfələn/;[1]
Part ofBrainstem
Identifiers
Latinmesencephalon
MeSHD008636
NeuroNames462
NeuroLex IDbirnlex_1667
TA98A14.1.03.005
TA25874
FMA61993
Anatomical terms of neuroanatomy

The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons.[2] It consists of the cerebral peduncles, tegmentum, and tectum.

It is functionally associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation.[3]

The name mesencephalon comes from the Greek mesos, "middle", and enkephalos, "brain".[4]

Structure

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Brainstem (dorsal view)
A:Thalamus B:Midbrain C:Pons
D:Medulla oblongata
7 and 8 are the four colliculi.

The midbrain is the shortest segment of the brainstem, measuring less than 2cm in length. It is situated mostly in the posterior cranial fossa, with its superior part extending above the tentorial notch.[2]

The principal regions of the midbrain are the tectum, the cerebral aqueduct, tegmentum, and the cerebral peduncles. Rostrally the midbrain adjoins the diencephalon (thalamus, hypothalamus, etc.), while caudally it adjoins the hindbrain (pons, medulla and cerebellum).[5] In the rostral direction, the midbrain noticeably splays laterally.

Sectioning of the midbrain is usually performed axially, at one of two levels – that of the superior colliculi, or that of the inferior colliculi. One common technique for remembering the structures of the midbrain involves visualizing these cross-sections (especially at the level of the superior colliculi) as the upside-down face of a bear, with the cerebral peduncles forming the ears, the cerebral aqueduct the mouth, and the tectum the chin; prominent features of the tegmentum form the eyes and certain sculptural shadows of the face.

Tectum

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Further information: Superior colliculus and Inferior colliculus
Principal connections of the tectum

The tectum (Latin for roof) is the part of the midbrain dorsal to the cerebral aqueduct.[2]The position of the tectum is contrasted with the tegmentum, which refers to the region in front of the ventricular system, or floor of the midbrain.

It is involved in certain reflexes in response to visual or auditory stimuli. The reticulospinal tract, which exerts some control over alertness, takes input from the tectum,[6] and travels both rostrally and caudally from it.

The corpora quadrigemina are four mounds, called colliculi, in two pairs – a superior and an inferior pair, on the surface of the tectum. The superior colliculi process some visual information, aid the decussation of several fibres of the optic nerve (some fibres remain ipsilateral), and are involved with saccadic eye movements. The tectospinal tract connects the superior colliculi to the cervical nerves of the neck, and co-ordinates head and eye movements. Each superior colliculus also sends information to the corresponding lateral geniculate nucleus, with which it is directly connected. The homologous structure to the superior colliculus in non mammalian vertebrates including fish and amphibians, is called the optic tectum; in those animals, the optic tectum integrates sensory information from the eyes and certain auditory reflexes.[7][page needed][8]

The inferior colliculi – located just above the trochlear nerve – process certain auditory information. Each inferior colliculus sends information to the corresponding medial geniculate nucleus, with which it is directly connected.

Cerebral aqueduct

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Ventricular system anatomy showing the cerebral aqueduct, labelled centre right.

The cerebral aqueduct is the part of the ventricular system which links the third ventricle (rostrally) with the fourth ventricle (caudally); as such it is responsible for continuing the circulation of cerebrospinal fluid. The cerebral aqueduct is a narrow channel located between the tectum and the tegmentum, and is surrounded by the periaqueductal grey,[9] which has a role in analgesia, quiescence, and bonding. The dorsal raphe nucleus (which releases serotonin in response to certain neural activity) is located at the ventral side of the periaqueductal grey, at the level of the inferior colliculus.

The nuclei of two pairs of cranial nerves are similarly located at the ventral side of the periaqueductal grey – the pair of oculomotor nuclei (which control the eyelid, and most eye movements) is located at the level of the superior colliculus,[10] while the pair of trochlear nuclei (which helps focus vision on more proximal objects) is located caudally to that, at the level of the inferior colliculus, immediately lateral to the dorsal raphe nucleus.[9] The oculomotor nerve emerges from the nucleus by traversing the ventral width of the tegmentum, while the trochlear nerve emerges via the tectum, just below the inferior colliculus itself; the trochlear is the only cranial nerve to exit the brainstem dorsally. The Edinger-Westphal nucleus (which controls the shape of the lens and size of the pupil) is located between the oculomotor nucleus and the cerebral aqueduct.[9]

Tegmentum

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Cross-section of the midbrain at the level of the superior colliculus
Cross-section of the midbrain at the level of the inferior colliculus.

The midbrain tegmentum is the portion of the midbrain ventral to the cerebral aqueduct, and is much larger in size than the tectum. It communicates with the cerebellum by the superior cerebellar peduncles, which enter at the caudal end, medially, on the ventral side; the cerebellar peduncles are distinctive at the level of the inferior colliculus, where they decussate, but they dissipate more rostrally.[9] Between these peduncles, on the ventral side, is the median raphe nucleus, which is involved in memory consolidation.

The main bulk of the tegmentum contains a complex synaptic network of neurons, primarily involved in homeostasis and reflex actions. It includes portions of the reticular formation. A number of distinct nerve tracts between other parts of the brain pass through it. The medial lemniscus – a narrow ribbon of fibres – passes through in a relatively constant axial position; at the level of the inferior colliculus it is near the lateral edge, on the ventral side, and retains a similar position rostrally (due to widening of the tegmentum towards the rostral end, the position can appears more medial). The spinothalamic tract – another ribbon-like region of fibres – are located at the lateral edge of the tegmentum; at the level of the inferior colliculus it is immediately dorsal to the medial lemiscus, but due to the rostral widening of the tegmentum, is lateral of the medial lemiscus at the level of the superior colliculus.

A prominent pair of round, reddish, regions – the red nuclei (which have a role in motor co-ordination) – are located in the rostral portion of the midbrain, somewhat medially, at the level of the superior colliculus.[9] The rubrospinal tract emerges from the red nucleus and descends caudally, primarily heading to the cervical portion of the spine, to implement the red nuclei's decisions. The area between the red nuclei, on the ventral side – known as the ventral tegmental area – is the largest dopamine-producing area in the brain, and is heavily involved in the neural reward system. The ventral tegmental area is in contact with parts of the forebrain – the mammillary bodies (from the Diencephalon) and hypothalamus (of the diencephalon).

Cerebral peduncles

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Brain anatomy – forebrain, midbrain, hindbrain.

The cerebral peduncles each form a lobe ventrally of the tegmentum, on either side of the midline. Beyond the midbrain, between the lobes, is the interpeduncular fossa, which is a cistern filled with cerebrospinal fluid [citation needed].

The majority of each lobe constitutes the cerebral crus. The cerebral crus are the main tracts descending from the thalamus to caudal parts of the central nervous system; the central and medial ventral portions contain the corticobulbar and corticospinal tracts, while the remainder of each crus primarily contains tracts connecting the cortex to the pons. Older texts refer to the crus cerebri as the cerebral peduncle; however, the latter term actually covers all fibres communicating with the cerebrum (usually via the diencephalon), and therefore would include much of the tegmentum as well. The remainder of the crus pedunculi – small regions around the main cortical tracts – contain tracts from the internal capsule.

The portion of the lobes in connection with the tegmentum, except the most lateral portion, is dominated by a blackened band – the substantia nigra (literally black substance)[9] – which is the only part of the basal ganglia system outside the forebrain. It is ventrally wider at the rostral end. By means of the basal ganglia, the substantia nigra is involved in motor-planning, learning, addiction, and other functions. There are two regions within the substantia nigra – one where neurons are densely packed (the pars compacta) and one where they are not (the pars reticulata), which serve a different role from one another within the basal ganglia system. The substantia nigra has extremely high production of melanin (hence the colour), dopamine, and noradrenalin; the loss of dopamine-producing neurons in this region contributes to the progression of Parkinson's disease.[11]

Blood supply

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The midbrain is supplied by the following arteries:

Venous blood from the midbrain is mostly drained into the basal vein as it passes around the peduncle. Some venous blood from the colliculi drains to the great cerebral vein.[12]

Development

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Further information: Isthmic organizer
Mesencephalon of human embryo

During embryonic development, the midbrain (also known as the mesencephalon) arises from the second vesicle of the neural tube, while the interior of this portion of the tube becomes the cerebral aqueduct. Unlike the other two vesicles – the forebrain and hindbrain – the midbrain does not develop further subdivision for the remainder of neural development. It does not split into other brain areas. While the forebrain, for example, divides into the telencephalon and the diencephalon.[13]

Throughout embryonic development, the cells within the midbrain continually multiply; this happens to a much greater extent ventrally than it does dorsally. The outward expansion compresses the still-forming cerebral aqueduct, which can result in partial or total obstruction, leading to congenital hydrocephalus.[14] The tectum is derived in embryonic development from the alar plate of the neural tube.

Function

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The midbrain is the uppermost part of the brainstem. Its substantia nigra is closely associated with motor system pathways of the basal ganglia. The human midbrain is archipallian in origin, meaning that its general architecture is shared with the most ancient of vertebrates. Dopamine produced in the substantia nigra and ventral tegmental area plays a role in movement, movement planning, excitation, motivation and habituation of species from humans to the most elementary animals such as insects. Laboratory mice from lines that have been selectively bred for high voluntary wheel running have enlarged midbrains.[15] The midbrain helps to relay information for vision and hearing.

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The term "tectal plate" or "quadrigeminal plate" is used to describe the junction of the gray and white matter in the embryo. (ancil-453 at NeuroNames)

See also

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Wikimedia Commons has media related to Mesencephalon.
Look up midbrain in Wiktionary, the free dictionary.

References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Midbrain

View on Grokipedia
from Grokipedia
The midbrain, also known as the mesencephalon, is the uppermost and smallest portion of the , measuring approximately 1.5 cm in length, and is situated between the superiorly and the inferiorly. It functions primarily as a relay center for ascending and descending neural pathways, integrating sensory and motor information while mediating critical reflexes such as pupil and dilation. Key structures within the midbrain include the tectum, , and cerebral peduncles, which collectively support roles in visual and auditory processing, movement regulation, and arousal. Structurally, the midbrain is divided into dorsal, ventral, and central components. The tectum, forming the roof, consists of the corpora quadrigemina—comprising the superior colliculi for visual reflexes and the inferior colliculi for auditory reflexes. The tegmentum, the floor, encompasses the for and arousal, the matter for pain modulation, the for motor coordination, the for dopamine-mediated movement control, and the involved in reward pathways. Anteriorly, the cerebral peduncles house descending corticospinal tracts for voluntary motor function and connections to pontine nuclei. At its core lies the , which facilitates flow between the third and fourth ventricles. Functionally, the midbrain plays a pivotal role in both sensory and motor systems. It processes auditory and visual reflexes via the colliculi, relays pain and temperature sensations through the , and regulates eye movements via the oculomotor (cranial III) and trochlear (cranial IV) nuclei. Motor functions are supported by extrapyramidal pathways, including rubrospinal tracts from the and dopaminergic projections from the , which are crucial for fine-tuning movements and are implicated in disorders like due to neuronal degeneration. Additionally, the midbrain contributes to sleep-wake cycles, emotional responses, and autonomic regulation through its reticular and periaqueductal components. The midbrain receives its blood supply from branches of the anteriorly, the laterally, and the posteriorly, making it vulnerable to ischemia in vascular events. Clinically, midbrain lesions can result in syndromes such as Parinaud's (dorsal involvement affecting upward gaze) or Weber's (ventromedial damage causing ipsilateral oculomotor and contralateral ), highlighting its integration in broader neural networks.

Anatomy

Location and boundaries

The midbrain, also known as the mesencephalon, constitutes the uppermost segment of the , serving as a critical conduit between the and the . It is positioned rostrally to the and caudally to the , forming part of the brainstem's continuity within the . The midbrain's anatomical boundaries are precisely defined: superiorly, it is delimited by the at the level of the , where it passes through the incisura of the tentorium cerebelli; inferiorly, it borders the along the superior pontine sulcus (also termed the pontomesencephalic sulcus); anteriorly, its ventral surface features the , a midline depression between the cerebral peduncles; and posteriorly, it is outlined by the quadrigeminal plate cistern, which overlies the tectum. Measuring approximately 2 cm in length, the midbrain's rostral-caudal extent spans from the superior colliculi superiorly to the inferior aspect of the cerebral peduncles inferiorly, making it the shortest division of the . Laterally, it relates to the superior cerebellar peduncles, which connect it to the ; superiorly, it adjoins the third ventricle via the ; and inferiorly, it approaches the through its continuity with the . In terms of gross external features, the midbrain comprises three primary regions: the ventral basis, formed by the cerebral peduncles; the central ; and the dorsal tectum, visible on the posterior surface as the quadrigeminal plate.

Tectum

The tectum forms the dorsal roof of the midbrain, consisting of a thin, folded plate of gray matter that gives rise to the quadrigeminal bodies, also known as the corpora quadrigemina. These bodies comprise two pairs of elevations: the superior colliculi rostrally and the inferior colliculi caudally, positioned immediately inferior to the . The tectum's layered architecture supports its role as a substrate for reflex processing, with superficial layers primarily receiving visual inputs and deeper layers facilitating multimodal integration. The superior colliculi are paired, oval-shaped elevations on the rostral aspect of the tectum, each exhibiting a highly organized, seven-layered structure divided into superficial, intermediate, and deep zones. The superficial layers include the stratum zonale, stratum griseum superficiale, and stratum opticum, which process visual information from inputs. The intermediate layers, comprising the stratum griseum intermedium and stratum album intermedium, integrate visual, auditory, and somatosensory modalities to contribute to orienting reflexes. Deep layers, such as the stratum griseum profundum and stratum album profundum, handle associative functions, providing a structural basis for coordinated responses. At the junction with the superior colliculi lies the , which interfaces with visual reflex pathways. The inferior colliculi appear as paired, rounded swellings on the caudal tectum, serving as key auditory relay structures. Each contains a central nucleus that acts as the primary hub for ascending auditory pathways, receiving inputs from lower brainstem nuclei and organizing tonotopic representations. The commissure of the inferior colliculi connects the paired structures, enabling bilateral integration of auditory signals via crossing fibers. The tectum connects ventrally to the , allowing coordination between sensory relay and integrative nuclei.

Cerebral aqueduct

The cerebral aqueduct, also known as the aqueduct of Sylvius, is a narrow channel within the midbrain that measures approximately 15-20 mm in length and 1-2 mm in diameter. It is lined by ciliated cuboidal to columnar ependymal cells and is surrounded by the periaqueductal gray matter. This conduit courses through the of the midbrain, connecting the third ventricle in the to the fourth ventricle in the and . The aqueduct's roof is formed by the tectum, while its floor consists of the ; laterally, it features recesses adjacent to the superior and inferior colliculi. The (PAG) matter encircling the aqueduct comprises a ring of neuronal clusters in the midbrain gray matter, extending from the to the and organized into four longitudinal columns: dorsal, dorsolateral, lateral, and ventrolateral. Stenosis of the can obstruct ventricular communication, posing a risk for .

Tegmentum

The forms the central core of the midbrain, positioned ventral to the cerebral aqueduct and dorsal to the cerebral peduncles, serving as an integrative region for various neural pathways. This area encompasses key nuclei and fiber tracts, including the , , midbrain , cranial nerve nuclei, and the decussation of the superior cerebellar peduncles. The , a prominent ovoid structure within the , is divided into two main parts: the magnocellular portion, located more caudally and involved in motor functions through its large neurons, and the parvocellular portion, situated rostrally with smaller neurons connected to cerebellar pathways. The magnocellular part gives rise to the , which descends contralaterally to influence spinal motor neurons in laminae V, VI, and VII. In contrast, the parvocellular division projects via the to the , facilitating cerebello-olivary connections. Adjacent to the lies the , a pigmented nucleus divided into the dorsally, which contains densely packed neurons, and the pars reticulata ventrally, characterized by scattered neurons. The serves as the origin of the , projecting fibers to the to modulate circuits. Meanwhile, the pars reticulata provides inhibitory output to structures such as the and . The midbrain reticular formation occupies much of the tegmentum as a diffuse network of interconnected neurons and nuclei, extending without clear boundaries and integrating ascending and descending pathways. This net-like structure includes the pedunculopontine nucleus in its posterior region, which features cholinergic neurons projecting to various brainstem and forebrain targets. Within the tegmentum, the oculomotor nucleus (cranial nerve III) is located in the medial gray matter ventral to the periaqueductal gray, comprising somatic motor neurons for extraocular muscles and parasympathetic preganglionic neurons in the Edinger-Westphal subnucleus. Its fascicles course ventrally through the red nucleus and medial longitudinal fasciculus before exiting the midbrain. The trochlear nucleus (cranial nerve IV), positioned more dorsally and caudally near the midline, innervates the contralateral superior oblique muscle, with its fascicles looping around the aqueduct before decussating and emerging from the posterior midbrain surface. The decussation of the superior cerebellar peduncles occurs prominently in the central tegmentum at the level of the inferior colliculi, where these fiber bundles cross the midline to connect cerebellar outputs to contralateral red nucleus and thalamic targets. This crossing forms a dense midline structure that partially obliterates the central gray matter.

Cerebral peduncles

The cerebral peduncles are paired, pillar-like white matter projections forming the ventral aspect of the midbrain, extending inferiorly from the cerebral hemispheres to the pons and serving as major conduits for descending fibers. They appear as prominent longitudinal bundles on the anterior surface of the midbrain, separated by a midline cleft. Each peduncle is structurally divided into an anterior portion, the crus cerebri, comprising approximately the anterior three-fifths and consisting primarily of densely packed white matter tracts, and a posterior portion, the substantia nigra, occupying about the posterior two-fifths and characterized by gray matter nuclei. The crus cerebri contains key descending fiber bundles, including frontopontine fibers medially, followed by corticospinal and corticobulbar tracts in an intermediate position, and temporopontine fibers laterally, organized in a somatotopic manner where corticospinal fibers for the upper body are positioned more medially within their group relative to lower body representations. This arrangement facilitates orderly transmission of cortical outputs to subcortical and spinal targets. The forms the dorsal limit of the crus cerebri, transitioning to the . Between the two cerebral peduncles lies the , a shallow midline depression on the ventral midbrain surface that houses the basal vein of Rosenthal, which drains deep cerebral structures. The posterior boundary of the cerebral peduncles with the overlying is delineated by transverse fibers within the midbrain, including decussating elements. Laterally, each peduncle gives attachment to the , which emerges from the upper lateral aspect to connect the with higher regions. The interfaces dorsally with the and is covered in detail in the tegmentum section.

Blood supply

The midbrain is primarily supplied by the vertebrobasilar arterial system, with contributions from branches of the and its terminal bifurcation into the posterior cerebral arteries (PCAs). These vessels deliver blood to the midbrain's core structures, including the , tectum, and cerebral peduncles, through a network of penetrating and circumferential arteries. Arterial follows a segmental pattern: paramedian branches arise directly from the and proximal PCAs to vascularize the midline and interpeduncular region; short circumferential branches from the supply lateral aspects of the ; and long circumferential branches, including those from the (SCA), extend to the cerebral peduncles. Specific perforating vessels include the posterior choroidal arteries, which arise from the PCAs and supply the tectum and surrounding ; the collicular artery (often a branch of the SCA or PCA), which perfuses the quadrigeminal bodies; and peduncular perforators from the P1 segment of the PCA, targeting the crus cerebri. These end-arteries ensure targeted oxygenation but limit redundancy in flow distribution. Venous drainage from the midbrain converges anteriorly into the basal vein of Rosenthal, which courses laterally around the midbrain to join the (vein of Galen), while posterior drainage flows via the internal cerebral veins into the same confluence. This system efficiently clears deoxygenated blood from midbrain tissues toward the dural sinuses. Watershed zones in the midbrain occur at the territorial borders between the PCA and SCA, particularly in the lateral , where reduced perfusion pressure can lead to ischemic vulnerability. Anastomoses among these penetrating branches are sparse, heightening the risk of localized infarcts from even minor occlusions.

Development

Embryonic origins

The midbrain originates during early embryonic development from the , specifically deriving from the mesencephalic vesicle, which forms as the second of the three primary brain vesicles around the fourth week of gestation. This vesicle emerges following the closure of the neural folds, which begins in the third week and completes by days 21 to 28, marking the initial formation of the . By the fifth week, evagination of the leads to the subdivision of the primary vesicles into secondary structures, with the mesencephalic vesicle persisting as the precursor to the midbrain. In the prosomere model of brain development, the midbrain is conceptualized as mesomere 1 (M1), a transverse neuromeric unit positioned between the prosomeres of the anteriorly and the rhombomeres of the rhombencephalon posteriorly. This model emphasizes the segmental organization of the along the rostrocaudal axis, where the midbrain's identity is established through early patterning events that delineate its boundaries. The specification of the midbrain involves key patterns and signaling pathways, including the transcription factors Otx2, En1, and En2, which define midbrain fate in the anterior . Additionally, Fgf8 signaling from the organizer at the mid-hindbrain junction plays a critical role in maintaining midbrain boundaries and promoting its regionalization. These processes are induced by inductive signals from the and floor plate, which provide vertical cues to pattern the ventral midline of the .

Key developmental processes

Following the initial formation of the midbrain vesicle, key developmental processes involve the patterned differentiation and migration of neuronal populations, establishing the structural and functional architecture of midbrain components. Neuronal migration is particularly critical in the ventral midbrain, where neurons originate from the plate and migrate to form clusters such as the . These neurons undergo radial migration along glial scaffolds followed by tangential displacement to their final positions in the mantle zone, a process essential for organizing the . Guidance cues like netrin-1 and slit-2 proteins play pivotal roles in directing this migration and neurite outgrowth, attracting or repelling growth cones to ensure precise positioning of neurons in the . Patterning along the anterior-posterior (A-P) axis of the midbrain is orchestrated by signaling from the organizer at the midbrain-hindbrain boundary, where Wnt1 and sonic hedgehog (Shh) provide inductive cues to define midbrain identity and regionalize structures like the tectum and . Wnt1 expression in the promotes midbrain expansion and dorsal identity, while Shh from the and plate reinforces ventral fates along the A-P gradient. Complementing this, dorsoventral (D-V) patterning is achieved through opposing gradients: Shh ventralizes the neural to specify tegmental and progenitors, inducing expression of ventral markers like Foxa2, whereas bone morphogenetic proteins (BMPs) from the roof plate dorsalize the tectum, promoting superior and inferior colliculi formation. This Shh-BMP antagonism ensures segregated domains, with the peduncles housing descending motor tracts and the tectum integrating sensory inputs. Myelination of midbrain white matter tracts occurs progressively, supporting efficient signal transmission in motor and sensory pathways. In the cerebral peduncles, fibers begin myelinating in late gestation, around 36-40 weeks, with initial differentiation in the posterior limb of the extending into the peduncles. This process continues postnatally, reaching substantial completion by 2-3 years of age, coinciding with refinement and reflecting the caudal-rostral progression of sheath formation. The tectum undergoes layered differentiation starting in the seventh gestational week, when progenitor proliferation in the alar plate gives rise to the stratified organization of the superior and inferior colliculi. By week 8, nascent layers emerge, with superficial strata receiving early retinofugal inputs that establish retinotopic mapping—a topographic representation of visual space aligned with projections. This mapping refines through activity-dependent mechanisms, ensuring precise visuomotor integration in the colliculi. Concomitantly, the forms as a narrow conduit lined by ependymal cells derived from the neuroepithelium, with a functional ependymal lining established by the eighth gestational week to facilitate flow between the third and fourth ventricles. Disruptions in this lining, such as reactive from or injury, can lead to , narrowing the lumen and impeding fluid circulation. Postnatally, the midbrain continues to mature, with and circuit refinement extending into to optimize and networks. This prolonged development integrates ascending projections from lower nuclei, enhancing the reticular activating system's role in modulating and through strengthened and noradrenergic inputs. Recent advances as of 2025 include the use of human midbrain organoids derived from stem cells to model development and maturation, providing insights into genetic regulation and disease mechanisms such as . Additionally, single-cell sequencing has enabled detailed cellular atlases of the developing human midbrain, revealing spatiotemporal patterns and neuronal diversity.

Function

Sensory integration

The midbrain serves as a critical hub for the initial and integration of sensory from visual, auditory, and somatosensory modalities, facilitating rapid reflexive responses to environmental stimuli. Structures within the tectum, particularly the colliculi, process these inputs to construct multimodal representations of , enabling the to orient toward salient events without higher cortical involvement. This sensory convergence supports reflexive behaviors such as orienting movements and autonomic adjustments, with projections from lower and spinal pathways converging on midbrain nuclei to form topographic maps of the external world. The receives direct retinotectal projections from the , which convey visual information essential for initiating saccadic eye movements toward targets in the . These projections form a retinotopic in the superficial layers, where neurons encode the location of visual stimuli relative to the current direction, integrating with head and eye orientation signals to compute motor vectors for rapid shifts in . Multimodal integration occurs as auditory and somatosensory inputs from deeper layers modulate these visual maps, enhancing localization accuracy for behaviorally relevant objects. The functions as an obligatory relay in the ascending auditory pathway, receiving inputs from both cochlear nuclei and to process and intensity. It exhibits a tonotopic , with neurons arranged in bands representing different sound frequencies, allowing for precise spectral analysis. Efferent projections from the central nucleus of the target the of the , conveying processed auditory signals for further thalamic and cortical relay. Somatosensory inputs reach the tectum via the spinotectal tract, which originates from neurons and terminates in the intermediate and deep layers of the , contributing to the localization of painful or aversive stimuli. This pathway provides crude somatotopic representation of the body surface, aiding in reflexive orienting toward tactile threats without fine discriminatory detail. The pretectal nuclei, located anterior to the , form a key component of the arc, receiving direct retinal afferents via the brachium of the to detect changes in ambient illumination. Bilateral projections from the olivary pretectal nucleus to the Edinger-Westphal nucleus activate parasympathetic outflow through the , constricting the pupils in response to light onset. Tectal layers enable cross-modal processing by superimposing sensory maps in the , where superficial visual layers align with deeper auditory and somatosensory strata to facilitate audio-visual integration for enhanced stimulus detection. For instance, coincident auditory and visual cues in aligned spatial registers amplify neuronal responses, supporting reflexive head turns toward multimodal events like approaching predators.

Motor coordination

The midbrain plays a crucial role in through its descending tracts and modulatory nuclei, facilitating voluntary movements, posture, and eye control via interactions with the , , and . Key structures within the midbrain, including the and , contribute to the initiation and refinement of motor actions by integrating cortical inputs and providing feedback loops. The , located in the ventral , releases that modulates circuits to facilitate movement initiation. This projection influences the direct pathway, which promotes movement by disinhibiting thalamocortical circuits, and the indirect pathway, which suppresses unwanted movements through inhibitory outputs to the external . binding to D1 receptors in the direct pathway enhances excitatory signals, while D2 receptor activation in the indirect pathway reduces inhibition, thereby balancing motor output for smooth execution. The , situated in the rostral , gives rise to the , which primarily facilitates flexion of the upper limbs and coordinates distal muscle movements. This tract originates from magnocellular neurons in the , receiving inputs from the and , and decussates immediately to descend contralaterally, synergizing with the to refine voluntary . In primates, the rubrospinal system supports precise hand and arm movements, compensating for corticospinal deficits when needed. Within the cerebral peduncles, the carries descending motor fibers from the , enabling fine voluntary movements of the limbs and trunk. These fibers traverse the ventral peduncles before most decussate at the medullary pyramids, forming the for skilled distal control. Adjacent corticopontine fibers in the peduncles relay cortical commands to the pontine nuclei, which cross to the contralateral , supporting coordinated motor planning and execution. The oculomotor and trochlear nuclei in the innervate essential for eye movements and conjugate gaze. The (cranial nerve III) controls the medial rectus, inferior rectus, superior rectus, and inferior oblique muscles ipsilaterally, enabling medial, vertical, and torsional gaze, while the trochlear nucleus (cranial nerve IV) innervates the contralateral superior oblique for downward and inward eye deviation. These nuclei coordinate via and the to produce synchronized binocular movements during voluntary saccades and pursuit. The nigrostriatal loop provides feedback for action selection by linking the to the dorsal , where dynamically biases competing motor programs. This pathway reinforces selected actions through phasic release, updating output to prioritize contextually relevant movements over alternatives. Such modulation ensures adaptive motor behavior by integrating reward signals with ongoing circuit activity.

Regulation of arousal

The midbrain's reticular formation plays a central role in the regulation of arousal through its integration into the ascending reticular activating system (ARAS), a network that originates in the brainstem and projects to the thalamus and cerebral cortex to promote wakefulness and maintain consciousness. The ARAS, encompassing neurons in the midbrain reticular formation, facilitates cortical activation by modulating attention and alertness via diffuse projections that enhance neuronal excitability across higher brain regions. This system ensures sustained vigilance during wakeful states, with midbrain components serving as key relay hubs for ascending signals from lower brainstem areas. Within the , the pedunculopontine tegmental nucleus (PPTg) and connections to the laterodorsal tegmental nucleus provide inputs essential for regulating rapid eye movement (REM) and attentional processes. neurons in the PPTg discharge tonically during and phasically during REM , contributing to the desynchronization of cortical electroencephalographic activity that characterizes these states. These nuclei modulate by influencing thalamic relay neurons, thereby supporting focused and the transition between stages without directly governing motor output. The (PAG) matter surrounding the in the midbrain exerts descending control over inhibition and autonomic functions, indirectly supporting arousal . Through opioid-mediated pathways, the PAG inhibits nociceptive transmission at the spinal level, which helps preserve overall by mitigating distracting signals during wakeful periods. Additionally, the PAG coordinates autonomic responses, such as respiratory and cardiac adjustments, to sustain physiological balance essential for maintained . Noradrenergic arousal is further amplified via connections from the , a pontine nucleus that projects densely to midbrain structures including the and PAG, releasing norepinephrine to heighten global brain excitability. These projections enhance by activating α1- and β-adrenergic receptors in midbrain hubs, promoting rapid shifts in vigilance and stress responses. The midbrain serves as a critical nexus for integrating these noradrenergic signals with local circuits to regulate overall wake-sleep transitions. Integrity of the midbrain is vital for ; lesions here disrupt ARAS function, often resulting in or persistent vegetative states characterized by preserved sleep-wake cycles but absent awareness. Damage to these midbrain pathways impairs the ascending projections necessary for cortical , leading to profound reductions in responsiveness and behavioral output. In such states, the loss of midbrain-mediated activation underscores its foundational role in sustaining the neural substrate for conscious experience.

Clinical significance

Associated disorders

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily involving degeneration of neurons in the of the midbrain, leading to depletion in the . This midbrain-centric pathology manifests as cardinal motor symptoms, including bradykinesia, resting , rigidity, and later postural instability, with the serving as the epicenter of neuronal loss estimated at 60-80% by symptom onset. The accumulation of aggregates in Lewy bodies within these midbrain neurons drives the degeneration, exacerbated by genetic (e.g., SNCA mutations) and environmental factors. Recent post-2020 research highlights the prion-like propagation of from peripheral sites to the midbrain, influencing where midbrain involvement (stage 3) correlates with motor symptom emergence and disease progression. Progressive supranuclear palsy (PSP), a rare , features abnormal accumulation of 4-repeat in neurons and , prominently affecting the and structures like the and . This leads to midbrain atrophy, visible as the "hummingbird sign" on , and disrupts vertical control via involvement of the rostral interstitial nucleus of the . Key symptoms unique to midbrain include early vertical supranuclear palsy—initially slowed saccades progressing to complete loss, often starting with downgaze—and severe postural with backward falls within the first year of onset, distinguishing PSP from typical . Congenital aqueductal stenosis represents an embryonic malformation obstructing (CSF) flow through the midbrain's , resulting in noncommunicating with dilation of the lateral and third ventricles. Etiologically linked to genetic factors such as X-linked L1CAM mutations or associated malformations like rhombencephalosynapsis, it arises during early development around weeks 4-8 of . In infants, midbrain involvement presents as due to progressive ventricular enlargement and increased , affecting up to 40% of cases and often requiring ventriculoperitoneal shunting to mitigate neurodevelopmental risks. Midbrain infarcts, particularly those affecting the cerebral peduncles, can produce through ischemia of paramedian branches of the , leading to in the ventral midbrain. This etiology, often tied to cardioembolic or thrombotic events in the context of vascular risk factors like , results in ipsilateral —manifesting as ptosis, , and eye deviation—combined with contralateral from involvement in the peduncle. Such focal midbrain vascular pathology accounts for approximately 0.7% of posterior circulation strokes and underscores the region's vulnerability to perforator occlusion. Narcolepsy type 1 involves selective loss of orexin (hypocretin)-producing neurons in the lateral hypothalamus, with cerebrospinal fluid orexin levels reduced to one-third of normal, triggering excessive daytime sleepiness and cataplexy via disrupted arousal regulation. Although the primary degeneration is hypothalamic, midbrain relay involvement occurs through orexin projections to the midbrain reticular formation, which modulates wakefulness and REM sleep suppression; this pathway's impairment contributes to the intrusion of REM-like states during wakefulness. The condition's autoimmune etiology, associated with HLA DQB1*0602 in 90% of cases, indirectly affects midbrain arousal circuits, amplifying sleep fragmentation.

Lesions and syndromes

Lesions of the midbrain can result in distinct neurological syndromes due to the region's compact organization of critical pathways, including oculomotor nuclei, , cerebral peduncles, and vertical gaze centers. These focal injuries, often from ischemic infarcts, hemorrhages, tumors, or trauma, produce characteristic combinations of ipsilateral cranial nerve deficits and contralateral motor or sensory impairments, reflecting the patterns within the . Common etiologies include occlusion of paramedian branches of the , which supply ventral and tegmental structures, as detailed in vascular anatomy discussions. Weber syndrome arises from lesions in the ventral midbrain, specifically involving the and fascicles. It presents with ipsilateral (CN III) palsy, manifesting as ptosis, , and impaired eye adduction, elevation, and depression, alongside contralateral hemiparesis due to involvement. This syndrome typically results from of paramedian mesencephalic perforators of the , though hemorrhages, tumors, or demyelination can also cause it. Benedikt syndrome involves tegmental midbrain damage, affecting the , fascicles of the , and portions of the . Clinically, it features ipsilateral CN III palsy similar to Weber syndrome, combined with contralateral hemiataxia, tremor (often ), or choreoathetosis from and disruption. Vascular causes predominate, such as or posterior cerebral artery branch occlusion, but trauma, tumors, or iatrogenic injury may contribute. Parinaud syndrome, also known as dorsal midbrain syndrome, stems from lesions compressing or infarcting the tectum and , particularly around the and rostral interstitial nucleus of the . Key features include of upward , convergence-retraction on attempted upgaze, and light-near pupillary dissociation, with possible lid retraction (Collier sign). Pineal region tumors or midbrain compression are frequent causes, alongside infarcts or hemorrhages. Claude syndrome results from paramedian midbrain infarcts affecting the fibers and rubrospinal tracts near the and . It is characterized by ipsilateral partial CN III palsy (often sparing the pupil) and contralateral hemiataxia or , without significant . The syndrome is predominantly vascular, involving branches of the supplying the ventromedial midbrain. A partial form of can occur with bilateral ventral midbrain lesions, such as peduncular infarcts sparing the . This leads to quadriplegia from corticospinal tract damage in the cerebral peduncles, with preserved and vertical eye movements via intact midbrain and oculomotor pathways. Reported cases involve bilateral vertebral or thrombosis causing peduncular ischemia. Traumatic midbrain lesions, particularly in the cerebral peduncles from acceleration-deceleration forces, disrupt descending motor fibers and can mimic or contribute to midbrain syndromes. These injuries often present with altered consciousness, , or oculomotor deficits, commonly seen in severe head trauma without focal hemorrhage.

and

Magnetic resonance imaging (MRI) serves as the cornerstone for visualizing midbrain and due to its superior soft-tissue contrast. T1-weighted sequences delineate the midbrain's structural boundaries, including the and tectum, while T2-weighted images highlight gray-white matter differentiation and detect hyperintensities indicative of or demyelination. (FLAIR) sequences are particularly sensitive for identifying periventricular edema or inflammatory changes in the midbrain cisterns, suppressing signal to enhance conspicuity. (DWI) excels in detecting acute ischemic events, showing restricted as hyperintense signals in midbrain infarcts, often corroborated by apparent diffusion coefficient maps to distinguish from T2 shine-through effects. In (PSP), mid-sagittal MRI reveals characteristic midbrain atrophy, manifesting as the "hummingbird sign," where the atrophied resembles a hummingbird's against a preserved ; this sign demonstrates high specificity (approximately 100%) but variable sensitivity (46-92%) for PSP diagnosis compared to . Computed tomography (CT) angiography is employed to assess vascular occlusion contributing to midbrain infarcts, visualizing the and paramedian branches with high to identify stenoses or thrombi. CT complements this by mapping the ischemic penumbra, quantifying cerebral blood flow and volume deficits in the midbrain territory to guide eligibility, with mismatch between core infarct and hypoperfused tissue predicting salvageable tissue. Functional imaging techniques provide insights into midbrain physiology. (PET) using (DAT) ligands, such as [123I]FP-CIT, detects reduced uptake in the midbrain in , aiding early differentiation from with sensitivity exceeding 90%. (fMRI) captures tectal activation during visuomotor tasks, revealing involvement in saccadic eye movements via blood-oxygen-level-dependent signals. Transcranial Doppler ultrasound noninvasively evaluates flow to the midbrain, measuring mean flow velocities (typically 40-60 cm/s) to detect stenoses or , with depths of 90-120 mm in the suboccipital window. Recent advances in the include 7T MRI, which offers enhanced resolution for microstructural details in the , such as dopaminergic nuclei delineation, surpassing 3T capabilities in visualizing the and . Artificial intelligence-assisted lesion segmentation improves accuracy in delineating midbrain pathologies on MRI, reducing interobserver variability and processing time for infarcts or tumors through models trained on annotated datasets. Differential diagnosis of midbrain versus pontine lesions relies on MRI assessment of cistern spaces; midbrain involvement spares the pontine cistern while compressing ambient cisterns, whereas pontine lesions expand the prepontine cistern, aiding distinction in T2-hyperintense brainstem pathologies like infarcts or gliomas.

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