The Anatomy of the Midbrain

The midbrain functions as a relay system, transmitting information necessary for vision and hearing. It also plays an important role in motor movement, pain, and the sleep/wake cycle. 

The midbrain, also called the mesencephalon, is a part of the central nervous system. It is located below your cerebral cortex and at the top of your brainstem.

Anatomy

The midbrain is the most superior region of the brainstem.

Structure

Your brainstem connects your brain to your cervical spinal cord (neck) and consists of three main parts:

• Midbrain
• Pons
• Medulla oblongata

(Sometimes, the diencephalon is also considered part of the brainstem.)

Together, these three parts work to regulate various involuntary functions, such as breathing, heart rate, and blood pressure. Your brainstem also plays a critical role in sleep and consciousness.

Your midbrain can then be broken down into two main parts:

• Tegmentum: This anterior surface of the midbrain contains numerous structures including the reticular formation, the periaqueductal gray (PAG) matter, certain cranial nerve nuclei, sensory and motor nerve pathways (the corticospinal and spinothalamic tract), the red nucleus, the substantia nigra, and the ventral tegmental area (VTA).
• Tectum: The posterior surface of the midbrain contains the corpora quadrigemina, which contains clusters of nerve cells called the superior and inferior colliculus.

Location

The midbrain measures around 1.5 centimeters in length and is sandwiched between the diencephalon (which includes the thalamus and hypothalamus) and the pons.

The midbrain receives blood supply from the basilar artery and its branches, including the posterior cerebral artery and the superior cerebellar artery.

There are also two cranial nerves present in the midbrain:

• The oculomotor nerve (cranial nerve III)
• The trochlear nerve (cranial nerve IV).

Function

The midbrain is a complex region of your brainstem that serves many functions.

Tegmentum

The structures within the tegmentum serve these specific functions:

• Reticular formation: This highly diverse and integrative area contains a network of nuclei responsible for many vital functions including arousal, consciousness, sleep-wake cycles, coordination of certain movements, and cardiovascular control.
• Periaqueductal gray (PAG) matter: This area plays a primary role in processing pain signals, autonomic function, and behavioral responses to fear and anxiety. Recently, this structure has been linked to controlling the defensive reactions associated with post-traumatic stress disorder (PTSD).
• Cranial nerve nuclei: Oculomotor nerve nuclei are responsible for controlling the pupil and most eye movements. The trochlear nerve nuclei innervate the superior oblique muscle of the eye, which abducts, depresses, and internally rotates the eye. 
• Spinothalamic tract: This major nerve pathway carries information about pain and temperature sensation from the body to the thalamus of the brain.
• Corticospinal tract: This major nerve pathway carries movement-related information from the brain to the spinal cord.
• Red nucleus: This region is involved in motor coordination. It is called the "red" nucleus because of its pinkish color, resulting from the presence of iron.
• Substantia nigra: This area contains nerve cells that make the neurotransmitter (brain chemical) dopamine. It serves as a relay station for nerve signals responsible for controlling movement.
• Ventral tegmental area (VTA): This structure contains dopamine-producing cell bodies and plays a key role in the reward system.

Tectum

Nerve cells within the superior colliculi process vision signals from the retina of the eye before channeling them on to the occipital lobe located at the back of the head. The superior colliculi of the midbrain is also responsible for generating eye movements and neck muscle activity.

The inferior colliculi is responsible for processing auditory (hearing) signals before they are channeled through the thalamus and eventually to the primary auditory cortex in the temporal lobe. In addition to sound localization, the inferior colliculus is responsible for the following:

• Creating the startle response
• Orienting the body towards certain stimuli
• Discriminating pitch and rhythm

Associated Conditions

The midbrain may be affected by a number of different pathological processes including stroke, tumor, a demyelinating process, infection, or a neurodegenerative disease.

Examples of specific conditions include the following:

Oculomotor (Third) Nerve Palsy

Any lesion within the midbrain (stroke, tumor, inflammation, infection) may damage the oculomotor nerve, resulting in an eye that is positioned in a downward and outward direction.

Other symptoms of an oculomotor nerve palsy include:

• A dilated pupil
• Droopy eyelid
• Diplopia (double vision)
• Inability to accommodate

Trochlear (Fourth) Nerve Palsy

As with an oculomotor nerve palsy, a lesion within the midbrain may cause a trochlear nerve palsy. Symptoms of a trochlear nerve palsy include:

• Upward deviation of the eye
• Blurry vision
• Diplopia
• Tilting of the head towards the unaffected side to compensate for visual changes

Midbrain Syndromes

There are five classic midbrain syndromes:

• Parinaud’s syndrome: Also known as the dorsal midbrain syndrome, this condition usually results from the mass effect of an adjacent pineal gland tumor. Symptoms may include a downward gaze at rest, pupils that are poorly reactive to light, eyelid retraction, and convergence-retraction nystagmus (when you have uncontrollable, jerky eye movements)
• Weber's syndrome: Also known as midbrain stroke syndrome and superior alternating hemiplegia, this condition is caused by a stroke in a branch of either the basilar artery or the posterior cerebral artery. It results in ipsilateral (same-sided) third nerve palsy and contralateral (opposite side) weakness.
• Claude's syndrome: This condition results from a stroke within the dorsal (upper side) tegmentum of the midbrain. It results in ipsilateral oculomotor nerve palsy with contralateral cerebellar ataxia (incoordinated movements).
• Benedikt's syndrome: Like Claude's syndrome, this condition results from a stroke within the tegmentum of the midbrain. In addition to oculomotor nerve palsy and ataxia, there is damage to the corticospinal tract, resulting in contralateral weakness.
• Nothnagel's syndrome: This condition usually results from a tumor of the midbrain, such as a glioma. Symptoms include unilateral or bilateral oculomotor nerve paralysis and ipsilateral cerebellar ataxia.

Multiple Sclerosis

Multiple sclerosis (MS) occurs when a person's own immune system attacks the insulating covering (myelin) of nerve fibers in their brain, spinal cord, and/or eyes.

If the brainstem is affected, a patient may experience symptoms like:

• Vision changes, including diplopia
• Problems swallowing (dysphagia)
• Problems speaking (dysarthria)
• Altered sensation or weakness of the face
• Hearing difficulties
• Ataxia
• Headache that resembles a migraine
• Rarely, problems that affect vital functions (e.g., breathing or heart rate)

Parkinson's Disease

Parkinson’s disease is a progressive neurological disease (meaning symptoms are subtle at first and slowly get worse). It is caused by the death of dopamine-producing nerve cells in the substantia nigra.

As a result of this dopamine depletion, various symptoms may develop, including:

• Resting tremor
• Slowness of movement
• Stiffness and shuffling gait
• Small handwriting
• Sleep troubles

Congenital Malformations

Rarely, a person's midbrain may not form correctly during fetal development. Midbrain dysplasia is one such genetic malformation that results in microcephaly, spasticity, intellectual disability, and seizures.

Treatment

Treatment depends on the specific pathology that is affecting the midbrain.

For example, patients with a brain tumor that affects the midbrain may require surgery, radiation, and/or chemotherapy.

Likewise, an ischemic stroke (caused by a blood clot) within the midbrain may warrant treatment with a "clot-busting" medication called tissue-type plasminogen activator. In addition, a patient will need an extensive workup to sort out the cause behind the stroke (e.g., heart disease, atrial fibrillation, etc.).

From there, various therapies may be advised including medications, like an anticoagulant, and rehabilitation therapy (e.g. physical and occupational therapy).

MS-related inflammation of the midbrain often requires short-term treatment with corticosteroids and long-term treatment with a disease-modifying therapy. Rehabilitation therapies to manage symptoms is also often warranted.

The treatment of Parkinson's disease requires engaging in physical and occupational therapy and taking medications aimed at replacing dopamine or optimizing dopamine's action in the brain (e.g., levodopa).