Mesencephalon (Midbrain)

Anatomy

• Between the pons and the diencephalon; the cerebral aqueduct (of Sylvius) runs through its center.
• Tectum: superior colliculus (visual orienting, saccades), inferior colliculus (auditory).
• Tegmentum: substantia nigra pars compacta (nigrostriatal dopamine), ventral tegmental area (VTA — mesolimbic/mesocortical dopamine), red nucleus, periaqueductal gray (PAG), nuclei of cranial nerves III and IV.
• Cerebral peduncles (crus cerebri): corticospinal and corticopontine fibers. Blood supply: PCA, superior cerebellar artery.

Functions

• Dopaminergic systems: movement (SNc) and reward–motivation–learning (VTA → NAcc, PFC).
• Reflexive gaze and head orienting (superior colliculus), auditory orienting.
• PAG: defensive behaviors (freezing/flight), endogenous opioid pain control, vocalization.
• Eye movements (III, IV), pupillary reflex (Edinger-Westphal), wakefulness (reticular formation).

Connections and chemistry

• Nigrostriatal pathway (SNc → dorsal striatum)
• Mesolimbic pathway (VTA → NAcc, amygdala, hippocampus)
• Mesocortical pathway (VTA → PFC)
• PAG ↔ amygdala, hypothalamus
• Superior colliculus ↔ FEF, pulvinar

Development

Developmental course through childhood and adolescence.

• Mesocortical dopamine projections are reorganized in adolescence; striatal dopamine receptors peak in adolescence (animal studies) — reward sensitivity.
• The newborn’s orienting to faces is partly explained by a subcortical (superior colliculus–pulvinar) route (Johnson).

Clinical

• ADHD: the dopamine hypothesis; methylphenidate and amphetamines act on the dopamine transporter (DAT).
• Schizophrenia: mesolimbic hyperdopaminergia (positive symptoms), mesocortical hypodopaminergia (negative/cognitive symptoms).
• Substance use: plasticity in VTA dopamine neurons.
• Tourette syndrome: dopamine hypersensitivity; D2 antagonist and partial agonist treatments.
• Pineal region tumors (adolescents): compression of the dorsal midbrain — Parinaud syndrome, aqueductal stenosis and hydrocephalus.

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• Treatments targeting the dopamine system (stimulants, antipsychotics, the new non-D2 antipsychotic xanomeline-trospium) are on the VTA and SN cards. A
• Hydrocephalus from aqueductal stenosis in pineal region tumors: endoscopic third ventriculostomy or a shunt; tumor-specific surgery, chemotherapy, radiotherapy. A
• Diffuse midline glioma (H3 K27M) can also arise in the midbrain and thalamus; treatment is on the pons card.

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Pupillary light and near reflexes, eye movement examination
• PET dopamine imaging (research)
• Reward prediction error paradigms

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Parinaud syndrome: upgaze palsy, light–near dissociation.
• Weber syndrome: ipsilateral third nerve palsy + contralateral hemiparesis.
• Peduncular hallucinosis; aqueductal stenosis → obstructive hydrocephalus.

In the model

How this structure is defined in the 3D model, and the data source.

Upper part of the CerebrA brainstem label (z ≥ −21 mm).

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Howes OD et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012;69(8):776–786. DOI: 10.1001/archgenpsychiatry.2012.169
2. Johnson MH. Subcortical face processing. Nat Rev Neurosci 2005;6(10):766–774. DOI: 10.1038/nrn1766
3. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science 1997;275(5306):1593–1599. DOI: 10.1126/science.275.5306.1593
4. Teicher MH, Andersen SL, Hostetter JC. Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens. Brain Res Dev Brain Res 1995;89(2):167–172. DOI: 10.1016/0165-3806(95)00109-q
5. Volkow ND et al. Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA 2009;302(10):1084–1091. DOI: 10.1001/jama.2009.1308