Neuroscience Clerkship at UH/VA
 


NEUROANATOMY CLINICAL REVIEW

Adapted from Robert S. Fisher, M.D., Ph.D.

The neuroanatomy required for clinical diagnosis is quite simple. Below is a "no-frills" summary of clinical anatomy for neurology and neurosurgery students. The neurology student should be familiar with the origin, termination, and function of each of the major tracts discussed below and of the cranial nerves. This is necessary for interpretation of clinical findings, and for localization of neurological lesions.

I.  SPINAL CORD

A.  Corticospinal Tract

This is the most important of the descending (motor) tracts.  It originates with pyramidal cells in contralateral cerebral cortex, which send their axons successively through hemispheric white matter (corona radiata), internal capsule (which is just white matter compressed between thalamus and basal ganglia), cerebral peduncles, pontine corticospinal tracts (basis pontis), medullary pyramids, and (after decussating at the junction of medulla and cervical cord) the corticospinal tracts.  The most important component of the system in the cord is the crossed lateral corticospinal tract.  Lateral corticospinal tract fibers synapse in the grey matter upon interneurons or motor neurons.  About a third end in dorsal horn, presumably to regulate sensory input.  A chronic lesion of the lateral corticospinal tract causes an ipsilateral (because fibers have already crossed) upper motor neuron syndrome: weakness, disuse atrophy, spastic tone, increased reflexes, clonus, and a Babinski response.  Acutely (in the period hours to weeks after an upper motor neuron lesion at any level), a "spinal shock" picture may dominate with flaccidity and areflexia, gradually giving way to the upper motor neuron syndrome in the ensuing days to weeks.

Schematic of the spinal cord.  From Duus P.  Topical diagnosis in neurology, 1983. (click on image for a larger view)

B.  Lateral Spinothalamic Tract

This is one of the two important ascending (sensory) tracts.  The tract carries pain and temperature information from spinal cord to brainstem and thalamus.  These sensations originate in peripheral nerve fibers whose cell bodies reside in dorsal root ganglia.  Central processes of the dorsal root ganglia cell enter cord via dorsal root and horn and synapse there.  The lateral spinothalamic tract carries axons of the second-order neurons (it is always the second-order neurons in sensory tracts which decussate [although in this instance some investigators maintain that there is an intercalated neuron in dorsal horn]).  Crossing lateral spinothalamic tract fibers traverse the anterior white commissure while ascending one to three spinal segments.  In the lumbosacral cord, only leg and genital fibers exist.  At higher levels, fibers in the anterior white commissure emerge to push the sacral fibers laterally.  Therefore, the lateral spinothalamic tract is laminated with leg lateral and arm medial.  In the brainstem, collaterals are given off to the reticular formation; other fibers ascend to ventral posterolateral thalamus.

Lesions of the lateral spinothalamic tract cause loss of pain and temperature sense on the opposite side of the body beginning at a level one to three segments below the site of the lesion.  Some tests distinguish a separate anterior spinothalamic tract, said to carry crude touch sensation, but this tract is contiguous with the lateral spinothalamic tract; furthermore, touch sensation is carried in several other tracts unrelated to the spinothalamic tract system.

Partial lesions of the lateral spinothalamic tract may affect only leg or arm because of the lamination with leg lateral and arm medial.  Lesions which begin centrally in the cord (e.g., tumor, syrinx) may exhibit "sacral sparing" of pain and temperature loss, although sacral sparing is far from pathognomonic for intrinsic cord lesions.

A lesion of the anterior white commissure will destroy pain and temperature sensation bilaterally just below the level of crossing; for example, with a C6 lesion may cause sensory loss in both hands with normal sensation above and below this level.  This is one example of a so-called "suspended sensory level."

C.  Dorsal Columns

The fibers in the dorsal columns are axons of first-order neurons (cell bodies in dorsal root ganglia) which receive information from specialized skin and joint receptors.  Fibers ascend to synapse in the medullary dorsal column nuclei (gracilis-medial-leg; cuneatus-lateral-arm).  Second-order fibers cross to the contralateral medial lemniscus and ascend to ventral posterolateral thalamus.

Dorsal column loss leads to decreased appreciation of joint position, discriminative touch sensations, and perhaps to vibration sense, though the latter is a conglomerate perception carried in several tracts (and most affected clinically by large-fiber peripheral neuropathy).  The columns may be damaged by midline posterior compressive lesions, e.g., a foramen magnum meningioma, or by nonstructural problems such as B12 deficiency, demyelination, tabes dorsalis, and hereditary ataxias.

D.  Spinocerebellar Tracts

There are dorsal and ventral spinocerebellar tracts traveling on the lateral rim of the cord. The tracts convey information on joints, tendons, muscles, and muscle spindles. As is usual, the first-order neuron lies in the dorsal root ganglia. The spinocerebellar tracts themselves originate from cells in and around the dorsal horns. The ventral spinocerebellar tract partially crosses in the spinal cord and enters the superior cerebellar peduncle. The dorsal spinocerebellar tract is uncrossed and enters the inferior cerebellar peduncle.
Isolated spinocerebellar lesions are not seen clinically, but tract degeneration is important in Freidreich's ataxia.

E.  Ventral Horn

The ventral horn contains motor neurons and associated interneurons.  The horn is large in the cervical and lumbar cord where innervation to the extremity originates.  Lesions give a lower motor neuron syndrome with weakness, severe atrophy, decreased tone, decreased reflexes, and fasciculations.

F.  Lateral (or intermediate) Horn

The lateral horn exists at levels T1 through L2.  Herein reside the cells of preganglionic sympathetics whose axons are bound for the sympathetic chains and ganglions.  Afferents to the lateral horn come from as rostrally as hypothalamus via reticulospinal fibers.  Lesions of the lateral horn cells, of their reticulospinal afferents, or of the sympathetic chain in its paravertebral location will cause an ipsilateral loss of sweating and vasodilation.  If the lesion involves T1, an ipsilateral Horner's syndrome will be produced with ptosis, miosis, and anhidrosis.

G.  Other Tracts

Other tracts in the spinal cord that are less important clinically include:

1.  Vestibulospinal: from the lateral vestibular nucleus ipsilaterally.  Large, fast fibers travel anteriorly in cord.  Maintains extensor (postural) tone and balance reflexes. 

2.  Rubrospinal: from the contralateral red nucleus in midbrain.  Travels near the corticospinal tract.  Maintains flexor tone, especially in the proximal arms.

3.  Reticulospinal: separates tracts from pons and medulla.  Tracts have mixed laterality.  Lie in anterior cord.  They carry the drives to automatic respiration and some primitive motor information and sympathetics.

H.  Some Points of Note Generally About the Spinal Cord

1.  There are 31 pairs of spinal nerves: eight cervical (C1 does very little); 12 thoracic; five lumbar; five sacral; and one coccygeal.

2.  The cord in the adult ends opposite L1; below that are roots of the cauda equina, each of which exits at its appropriate intervertebral foramen.

3.  The C1 roots exit over the top of C1, C2 over the top of C2, i.e., in the C1- C2 interspace, and so on to C7 which exits at the C7-T1 interspace.  This resets the pattern, so T1 root exits between T1-T2, L4 between L4-L5, etc.  To repeat, the formula for cervical roots is: Cn exits at the C(n-1)-Cn interspace.  For T, L, S roots, root n exits at the - (n+1) interspace.

4.  Lumbar disks usually compress the root exiting from the interspace below the disk, because most disks here are lateral and protrude below the root exiting at the affected interspace.  For example, an L4-L5 herniated disc will usually spare exiting L4 and pinch L5.  L5 and S1 are most vulnerable.

5.  In the cervical region, C5, C6, and C7 are most commonly affected by radiculopathy due to spondylosis.

6.  The blood supply to the spinal cord is fairly simple.  There is a midline anterior spinal artery formed from the vertebrals and radicular feeding vessels; the most important of these is the artery of Adamkewicz, usually coming from T10, T11, or T12 on the left.  Damage to the anterior spinal artery or artery of Adamkewicz may infarct ventral horns and spinothalamic tracts bilaterally.  The picture is usually catastrophic.  The rest of the cord is supplied by posterior spinal arteries which are paired and rarely occlude.
 

II.  MEDULLA

A.  Pyramids

The descending corticospinal tracts, not yet crossed, travel in the pyramids.  At any level, including the medulla, an upper motor neuron lesion will cause a so-called pyramidal pattern of weakness.  The pyramidal tract may be thought of as a system designed to allow limbs to break away from gravity for purposes of making fine finger movements.  To recall which muscles are weak in pyramidal lesions, picture which muscles are used to break away from an antigravity posture (think of us on all fours: that's how we were when this system was developed).  The pyramidal weakness would then involve finger extensors, wrist extensors, deltoids (extensors in the arm plus the triceps, which does not fit into the mnemonic scheme) and tibialis anterior, hamstrings, and iliopsoas (flexors in the leg).

B.  Inferior Olive

A structural landmark.  The inferior olive is part of the cerebellar afferent system.  Isolated clinical lesions are rare except for degenerative conditions, such as olivopontocerebellar atrophy.

C.  Medial Lemniscus

The medial lemniscus is a continuation of the dorsal column system, already crossed, carrying discriminative touch sensation and joint position.  It is en route to ventral posterolateral thalamus.  In the medulla, the medial lemniscus "stands upright" with leg fibers positioned most ventrally.

Schematic of the medulla. From Afifi AK, Bergman RA.  Basic neuroscience 1986.  (click on image for a larger view)

D.  Spinal Nucleus and Tract of V

The nucleus and adjacent descending spinal tract of V is to the face what the spinothalamic tract is to the body.  Cell bodies are in the trigeminal (Gasserian) ganglion, which sits in middle fossa adjacent to brainstem.  Fibers enter at a mid-pons level, descend as far down as the upper cervical cord segments and synapse in the adjacent spinal nucleus of V.  It used to be thought that the ophthalmic division descended farthest caudally and the mandibular descended least before synapsing, but this is now disputed.  After synapsing, a second-order neuron sends an axon across the midline to travel close to the medial lemniscus in an indistinct trigeminothalamic tract (not pictured), ultimately to end in ventral posteromedial thalamus.  A lesion of spinal V in the medulla will cause partial numbness, loss of pain, and temperature sensation over the ipsilateral half of the face.  The blink reflex is partially mediated by spinal V and partially by main sensory (see below).

E.  Nucleus Ambiguus

This nucleus is invisible in adult brain sections but is clinically well defined and important.  In is the analogue of the anterior horn for the muscles of the pharynx, larynx, derived from branchiomeric arches of old.  It contributes motor fibers to cranial nerves IX (for the stylopharyngeous muscle -- the only important motor component of IX), X (the main motor nerve to pharynx and larynx), and XI (for the cranial portion of XI -- fibers destined for the recurrent laryngeal nerve which will soon join up with the vagus.  Recall that the SCM and trapezius are innervated by the spinal portion of XI or originating in C1-4 special lateral roots joining to ascend through the foramen magnum, then back out the jugular foramen).  A unilateral lesion of the nucleus ambiguus causes dysphagia, hoarseness, sagging of the ipsilateral palate, and paresis of the ipsilateral vocal cord.  A bilateral lesion may cause failure of automatic respiration.

F.  Nucleus and Tractus Solitarius

The nucleus solitarius is the receiving center for visceral information, carried predominantly by the vagus nerve.  Rostrally, the nucleus solitarius is called the "gustatory nucleus" as it receives taste inputs from cranial nerves VII (anterior two-thirds of tongue via chorda tympani), IX (posterior one-third of tongue), and X (taste buds near epiglottis).  It also seems important in the generation of automatic respiration and control of blood pressure.  Isolated clinical lesions occur very rarely.

G.  Hypoglossal (XII) Nucleus

This is the "ventral horn" for the tongue.  Lesions of the nucleus or of the exiting nerve fascicles on the left will cause the tongue to deviate to the left.

H.  Dorsal Motor Vagus (X)

This is one of the main parasympathetic output nuclei of the body, with the vagus carrying ipsilateral parasympathetic input to glands, heart, bronchioles, stomach, and proximal bowel.  The other parasympathetic centers are in sacral cord (junction of dorsal and ventral horn around S1-S3), the Edinger-Westphal nucleus to the pupil via cranial nerve III, and salivatory gland inputs via central nerves VII and IX.

I.  Vestibular Nuclei

The vestibular complex of four nuclei mediates the senses of static and rotational acceleration.  Because the system is close to the cerebellar peduncles, it is sometimes clinically difficult to distinguish vestibular from cerebellar deficits.  In general, a patient with a left vestibular system lesion will tend to veer to the left and past-point to the left.  A slow drift of the eyes to the left will be observed with corrective fast-phase nystagmus to the right (nystagmus usually is named for the direction of the compensatory fast-phase, but this is not always the case.  It is better to specify direction, e.g., "right beating nystagmus." Involvement of otolith connections might cause strange perceptions of the world tilting: in response to damaged otolith connections, a skew of the eyes might develop, with the eye ipsilateral to the lesion usually lower.

J.  Reticular Formation

Volumes have been written about the reticular formation, but requirements for clinical understanding are few.  The region of brainstem influences respiratory rhythms, heart rate, blood pressure, and descending sympathetic fibers.  Collaterals are received from most of the sensory afferent systems.  Influences on the motor system are attempted by reticulospinal control over the gamma-bias on muscle spindles.  Lesions of the descending reticulospinal tracts in the vicinity of brainstem reticular formation will cause an ipsilateral Horner's syndrome.  If a lesion is bilateral (e.g., cerebellar tonsillar herniation crushing brainstem), vital functions may suffer.


III.  PONS

A.  Pontine Nuclei

Cells in the pontine nuclei are the major relay stations between cerebral cortex and cerebellum.  Corticopontine fibers descend in the medial and lateral thirds of the cerebral peduncles to synapse in the pontine nuclei.  Recipient neurons send axons across the midline to the contralateral middle cerebellar peduncle and thereby to cerebellar cortex of the lateral hemispheres.  The clinical effects of lesions to this system are uncertain, but new information suggests that ipsilateral or contralateral cerebellar signs may be produced, depending upon whether the lesion affects neurons predominantly before or after their decussation.

B.  Pontine Corticospinal Tract

These descending fibers have just emerged from the cerebral peduncles above and are to be gathered into the medullary pyramids below.  Their dispersion is consequent to the prominent pontine nuclei.  Lesions at this level cause contralateral upper motor neuron signs.

C.  Medial Lemniscus

This is a continuation of the ascending dorsal column system.  The leg fibers have begun to swing laterally.  All sensory afferent systems traversing the brainstem are in process of migrating laterally and dorsally as they move toward thalamus.

D.  Facial (VII) Nucleus

The facial nucleus is comprised of motor neurons to the muscles of facial expression.  This excludes muscles of mastication, swallowing, and extraocular movements.  Because of the embryonic migration of the nucleus, fibers of VII have become looped over the VIth nucleus and doubled back on themselves.  Lesions of the facial nucleus or nerve cause ipsilateral paralysis of the muscles of facial expression.  The upper motor neuron innervation to the lower-face portion of the nucleus is important and contralateral but to the forehead portion, rudimentary.  Because of this quirk, upper motor neuron lesions weaken the lower face more than the upper face.  After the motor fibers of VII exit the brainstem, they are joined by autonomics to the nasopharynx and salivary glands, by the nerve to stapedius (to dampen the tympanic membrane in response to loud noises), and by the chorda tympani carrying taste from the anterior two-thirds of the tongue.  Analysis of these associated functions is helpful in distinguishing pontine disease from a Bell's palsy.

E.  Cochlear Nuclei

The dorsal and ventral cochlear nuclei (not shown because they are slightly caudal to the plane of section) hang suspended over the dorsolateral pons where it joins the medulla.  Afferents are received from the spiral ganglia in the cochlea.  Auditory information passes bilaterally to trapezoid body and superior olive (it bears no relation functionally to the inferior olive), then via the lateral lemniscus (not shown) to the medial geniculate body of thalamus.  Relays are then made to the primary auditory cortex deep in the folds of the sylvian fissure posteriorly.  Lesions of the cochlea or VIIIth nerve will cause ipsilateral deafness.  Lesions more centrally will have little clinical effect because of the bilateral representation of auditory information. Computer-averaged brainstem auditory- evoked responses to repeated clicks can chart the auditory signal through its course, thereby serving as a test of "nerve conduction" within the brainstem.

The vestibular component of the VIIIth nerve enters the pontine and medullary vestibular nuclei discussed above.

F.  Main Sensory and Motor Nucleus of V (Trigeminal)

The descending or spinal tract of V, carrying pain and temperature sensation from the face, was detailed above.  Neurons in main sensory V situated slightly rostral to the plane of section, like those in the spinal nucleus of V, receive afferents from cells whose bodies lie in the trigeminal ganglion.  The main sensory nucleus of V is equivalent to the dorsal column nuclei as it mediates discriminative sensation from the ipsilateral face.  Efferents cross in the substance of the pons and ascend in another ill-defined tract to ventroposteromedial thalamus.

Motor V lies just medial to sensory V; it contains lower motor neurons for the muscles of mastication: masseter pterygoids and temporalis.  The masseters close the jaw, and pterygoids open and protrude the jaw.  Since the pterygoids deviate the jaw to the opposite side as they lower the mandible, a left Vth palsy will result in jaw deviation to the left upon mouth opening.

Fibers analogous to the spinocerebellar system and important in mediation of the jaw-jerk reflex originate in the mesencephalic nucleus of V, located in the lateral boundaries of the fourth ventricle.

The trigeminal complex thus comprises four separate, but related, nuclei: spinal V for pain and temperature; main sensory V for discriminative touch; and motor V for jaw power and mesencephalic V for unconscious joint and muscle jaw sensation.

G.  Abducens (VI) Nucleus

Within the abducens nucleus lie two populations of neurons.  Abducens motor neurons project in the VIth cranial nerve to innervate the ipsilateral-lateral rectus muscle.  Abducens internuclear neurons cross the midline and ascend in the contralateral medial longitudinal fasciculus to the medial rectus division of the oculomotor nucleus.  Thus, the abducens nucleus is responsible for the yoking of eye movements during conjugate gaze.  Lesions of the VIth nerve nucleus cause a total ipsilateral conjugate gaze palsy.  A VIIth nerve palsy is a constant accompaniment, because the genu of the facial nerve sweeps around the abducens nucleus.  The abducens nucleus receives inputs from the vestibular nuclei and the adjacent paramedian pontine reticular formation.  The paramedian pontine reticular formation contains cells responsible for saccadic and, probably, pursuit eye movements.  Lesions of the paramedian pontine reticular formation cause a gaze palsy that may spare vestibular eye movements.

H.  Medial Longitudinal Fasciculus

Lesions of the medial longitudinal fasciculus cause internuclear ophthalmoplegia in which the ipsilateral eye adducts incompletely or slowly for conjugate eye movements.  Vergence eye movements may be normal.  Nystagmus of the other abducting eye is often present; the cause for this is uncertain.  Bilateral internuclear ophthalmoplegia also interferes with vertical vestibular and pursuit movements, which depend on the medial longitudinal fasciculus; the usual cause is multiple sclerosis.  Unilateral internuclear ophthalmoplegia is usually due to brainstem infarction.
 

IV.  MIDBRAIN

A.  Basis Pedunculi

The basis pedunculi or cerebral peduncles contain descending corticospinal tract fibers from the ipsilateral hemisphere and descending corticopontine and corticomedullary fibers.  Corticospinal fibers occupy about the middle one-third, with leg fibers represented most laterally.  Corticobulbar (the bulb is the pons plus the medulla) are just medial to the corticospinal fibers.  Frontopontine fibers occupy the medial one-third and temporoparieto- occipitopontine fibers, the lateral one-third.  In these latter fibers are the connections with the pontocerebellar nuclei with centers for gaze, with reticuar formation, and other uncertain systems.

B.  Substantia Nigra

The substantia nigra is a gray matter component of the extrapyramidal motor system.  Nigrostriatal fibers containing dopamine are deficient in Parkinson's disease.

C.  Red Nucleus

The red nucleus is another gray matter component of the extrapyramidal motor system.  It gives rise to the rubrospinal tract which crosses near its origin in midbrain and descends just ventral to the corticospinal tract in the lateral spinal cord.  The rubrospinal tract influences flexor tone, particularly of proximal arm muscles.  Lesions of the nucleus are never clinically pure, as signs are dominated by effects of damage to the superior cerebellar peduncle.  The so-called "rubral tremor" is probably due to the cerebellar outflow lesion.

D.  Superior Cerebellar Peduncle

The superior cerebellar peduncle or brachium conjunctivum contain the bulk of cerebellar outflow.  Fibers cross in the prominent decussation, fan around and through (with some fibers synapsing) the red nucleus, and then head up to ventrolateral nucleus of thalamus.  Lesions cause profound intention and postural tremor, the laterality of which depends upon the site of the lesion relative to the decussation.

Schematic of the medulla.  From Afifi AK, Bergman RA.  Basic neuroscience 1986.(click on image for a larger view)

E.  Lemnisci

The medial lemnisci, spinothalamic tracts, trigeminothalamic tracts, and lateral lemnisci all converge in the dorsolateral midbrain en route to thalamus.

F.  Oculomotor (III) Nucleus

The oculomotor nucleus provides innervation to ipsilateral inferior rectus, inferior oblique, medial rectus, contralateral superior rectus, and bilateral levator palpebrae muscles.  The Edinger-Westphal nucleus caps the IIIrd nucleus and supplies parasympathetic pupilloconstrictor fibers and accommodation fibers to the lens.  The latter fibers cause the lens to become more round and better able to focus on near objects.  Despite the presence of crossed and uncrossed efferents from the nucleus, the exiting IIIrd nerve innervates strictly ipsilateral muscles.  A complete oculomotor lesion causes ophthalmoplegia with retained ability only for lateral gaze (VI) and slight downgaze (IV -- but note that IV is in a position of disadvantage with the eye abducted), large fixed pupils, and ptosis.  (What other lesion can give ptosis?) As a mnemonic, remember, a third nerve palsy is like an intern: "down, out and blown!"

The pupilloconstrictor fibers run on the outside of the superior portion of IIIrd nerve.  This detail becomes important in external compressions of N.  III, usually from aneurysm or herniating temporal lobe, since the pupil will be affected before a substantial ophthalmoplegia develops.  The reverse holds true for infarcts of the IIIrd nerve, e.g., diabetic or vasculitic in which there is relative sparing of the pupil.

In analyzing oculomotor palsies, first try to place the deficit within the action of one oculomotor nerve.  If this proves impossible, think of more central (e.g., hemispheral gaze palsies, internuclear ophthalmoplegias) or more peripheral (e.g., cavernous sinus lesions affecting III, IV, V1, or VI or muscle problems from diseases such as myasthenia, thyroid disease, orbital masses or pseudotumor, and ophthalmic myopathies).

G.  Pretectum

The pretectal region (not shown) lies just rostral to the region of the IIIrd nucleus, dorsal to the cerebral aqueduct, and just below the pineal.  In this region lies the posterior commissure and several poorly understood nuclei.  The region is clinically important for two reasons: it appears to be concerned with upward gaze; and it is the region for mediation of the pupillary light reflex.  Certain clinical conditions (for example, neurosyphilis or a pineal tumor) may block reaction to light but preserve accommodation-induced pupillary constriction.  This is called "light-near dissociation." The syndrome of light-near dissociation, limited upgaze (Parinaud's syndrome), and retractory nystagmus on attempted upgaze is strong evidence for a dorsal midbrain lesion.

H.  Periaqueductal Gray

The periaqueductal gray is part of the reticular formation activating system, although its relation to the reticular formation in pons and midbrain is tenous.  Profound coma may be caused by lesions in the periaqueductal gray, otherwise obtainable only by widespread bilateral lesions in both cerebral hemispheres.

I.  Aqueduct of Sylvius (Cerebral Aqueduct)

Along with the foramina of Monroe, Magendie, and Luschka, this is a "bottle-neck" of the ventricular system (review the normal flow of cerebrospinal fluid).  Lesions here will cause a non-communicating hydrocephalus with dilation of the lateral and third ventricles.

J.  Colliculi

Superior colliculi are primitive processing centers for visual information and the inferior for auditory.  They are largely supplanted in higher mammals by cortex but still play a role in orienting to light or sound and in light reflexes.
 

V.  CEREBELLUM

The functions of the cerebellum are not well understood, particularly when one considers that there are more neurons in the granular cell layer alone of the cerebellum than in the rest of the entire central nervous system (CNS).  Clinically, lesions of the cerebellum affect balance and movement.

A.  Vestibulocerebellum

The vestibulocerebellum consists of the flocculonodular lobe with connections to the vestibular nuclei and eye movement centers.  Lesions in this system (the oldest part phylogenetically) cause tilting to the side of the lesion, gaze-evoked nystagmus (worse when looking to the side of the lesion), impaired smooth pursuit, and downbeat nystagmus.  Saccades are normal.

B.  Vermis and Anterior Lobe

This portion of the cerebellum, located midline and anteriorly, is referred to as the paleocerebellum.  It governs truncal balance, leg coordination, and saccadic eye movements.  Connections are received from the spinocerebellar tracts among other systems.  Lesions lead to truncal instability when sitting or standing, ataxia on heel-shin testing, and inability to tandem-walk.  There may be saccadic dysmetria.  Alcohol toxicity predominantly affects this portion of the cerebellum.

C.  Lateral Hemispheres

Lateral hemispheres comprise the main bulk of the cerebellum, lateral to the vermis and posterior to the primary fissure (in front of which is the anterior lobe, grouped functionally with the midline cerebellum).  This portion is called the neocerebellum, because it matured phylogenetically with growth in importance of upper-limb and head coordination.  Lesions of this system affect speech, face, and throat coordination and fine movements of the hands.  Certain eye movements may also depend upon the lateral hemispheres.  Lesions of the hemispheres cause ipsilateral intention tremor on finger-to-nose testing, inability to perform rapid alternating movements ("dysdiadochokinesis"), difficulty with rhythmic motor activities, and an abnormal modulation of the voice.  Motor tone may be decreased or unchanged.  Reflexes are unaffected unless the decrease of tone allows a limb to swing back and forth in an imitation of a pendulum -- so-called "pendular" reflexes.

The outflow from the cerebellum is through deep nuclei which receive afferents from the cerebellar Purkinje cells in cerebellar cortex.  The outflow nucleus for the neocerebellum is the dentate nucleus.  Fibers leave the dentate via the brachium conjunctivum, pass to and around the red nucleus after decussation, and on up to ventrolateral nucleus of thalamus.  This nucleus projects to motor cortex.  Motor cortex, in turn, projects down to the pontocerebellar system, thereby forming a functional loop from cortex to pons to neocerebellum to dentate to ventrolateral thalamus to motor cortex. 


VI.  THALAMUS

The thalamus is the relay station for all sensory and motor system inputs to neocortex with the exception of smell.  Clinical opinion holds that certain forms of perception, e.g., pain, are mediated primarily at a thalamic level.  Thalamic nuclei are defined as primary, association, or reticular, depending upon whether they interconnect with primary sensory or motor cortex, association cortex, or diffuse regions of brain, respectively.  The most important thalamic nuclei are listed below.

A.  Ventroposterolateral and Ventroposteromedial Thalamus (Primary)

Ventroposterolateral thalamus receives somatosensory afferents from the body (spinothalamic tract, dorsal columns via medial lemniscus) and relays to postcentral gyrus.  Ventroposteromedial thalamus is the adjacent and corresponding relay station for somatosensory input from the face.

B.  Medial and Lateral Geniculates (Primary)

These are the relay stations for audition and vision, respectively, to cortex in the Sylvian fissure posteriorly for audition and to medial occipital cortex for vision.  Please review the course of visual fibers from retina to cortex with attention to field cuts produced by lesions at specific sites.

C.  Ventralis Lateralis (Primary)

Ventralis lateralis is the most important motor nucleus of thalamus, serving as a target of fibers from cerebellum, basal ganglia, and motor cortex.  It projects to the motor cortex.  Despite its importance, lesions restricted to ventralis lateralis do not cause paralysis (this only happens if lesions extend laterally to internal capsule), and surgeons occasionally lesion ventralis lateralis to reduce tremor associated with cerebellar or basal ganglia disease.  The nucleus ventralis anterior is partly related to ventralis lateralis and partly to the reticular thalamic nuclei.

D.  Anterior Group (Association)

The anterior group of nuclei are important relays in the circuit of Papez, which links the limbic system (postulated to be concerned with emotions, visceral function, and memory) to cortex.  The anterior nuclei receive connections from the fornix, which is the outflow tract of the hippocampus, and also from the hypothalamus via the mammillothalamic tract.  Anterior nuclei send afferents to cingulate cortex.  The white matter of the cingulate gathers as the cingulum bundle and wraps around near the lateral ventricle to synapse in the cortex overlying the hippocampus.  Thus, Papez's circuit is hippocampus-fornix-anterior thalamus-cingulate gyrus-cingulum bundle-perihippocampal cortex-hippocampus.

This is a convenient place to list the structures sometimes classed as part of the limbic system (there is not general agreement): hippocampus, perihippocampal cortex, olfactory association cortex, amygdala, anterior thalamus, and cingulate cortex.  Hypothalamus should probably be included, but it usually is not.  The amygdala is a deep collection of nuclei in the anterior temporal lobe, situated just inside the bulge of the uncus.  It has been said to mediate the "four Fs: feeding, fighting, fleeing, and sex." Both amygdala and hippocampus play prominent roles in temporal lobe seizures.  A structural lesion in the region of the uncus or adjacent orbitofrontal cortex will cause an "uncinate fit" with a smell aura and subsequent psychomotor seizure.

E.  Reticular Group of Nuclei

The reticular group of thalamic nuclei will not be named separately, but many of them are located within lamina separating other thalamic nuclear groups, so they may be referred to as "intralaminar" thalamus.  These nuclei are the rostral extent of the reticular formation.  Stimulation with regular pulses of electricity will cause widespread and synchronous EEG potentials in cortex.

Comment: Clinical lesions generally do not affect an isolated nucleus of thalamus.  Consideration of a thalamic problem comes up in a few particular circumstances.

1.  In a setting of a small stroke where pain and temperature sensation are diminished, perhaps in conjunction with certain localized motor deficits attributable to the adjacent internal capsule but where cortical function is preserved.  In this instance, an occlusion of a deep perforating branch of the posterior cerebral may be suspected, causing a thalamic infarct.

2.  Thalamic pain syndrome of Dejerine-Roussy: partial lesions of thalamus may lead to an unpleasant and difficult-to-treat type of burning pain in the contralateral face and body year later.

3.  Massive hemorrhages may occur in the region of thalamus.  Mass effect on the pretectal region leads to paresis of upgaze and "irritative" accommodation, so that the patient looks down at his nose.  This, plus a dense sensory deficit, will be a clue to thalamic hemorrhage.

4.  As noted above, lesions may be placed in ventrolateral intentionally to treat tremor.  This was a much more common procedure before the advent of L-dopa in treatment of parkinsonism.
 

VII.  HYPOTHALAMUS

It is not necessary for the student to distinguish individual hypothalamic nuclei, as the functional groups are regional in hypothalamus and not linked to specific nuclei.  As a whole, hypothalamus borders the lower part of the third ventricle and sits just above the optic chiasm and pituitary.  It is the probably origin of autonomic and hormonal influences, and it is closely related to the limbic system.  A few regions are worth specific mention.

A.  Supraoptic and Paraventricular Nuclei

These sit anteriorly in the thalamus in the region above the optic chiasm and send neurosecretory fibers into the posterior pituitary.  Evidence suggests that the supraoptic nucleus secretes antidiuretic hormone and the paraventricular nucleus, oxytocin.  Many CNS and extra-CNS lesions can lead to a syndrome of "inappropriate secretion of antidiuretic hormone," whereby the kidney holds on to too much water.  If the supraoptic nucleus is rendered inactive, then the opposite condition, diabetes insipidus, occurs.

B.  Anterior Hypothalamus

In addition to the nuclei listed above, the anterior hypothalamus comprises "cooling centers" which sense elevated temperature and direct a response of sweating and cutaneous vasodilation.  Anterior hypothalamic lesions may result in hyperthermia.  A posterior center concerned with heat retention is less certain.

C.  Medial Hypothalamus

The ventromedial portion of hypothalamus is thought to contain a "satiety" center for feeding.  Lesions in this area lead to overeating and also a condition known as "sham rage."

D.  Lateral Hypothalamus

The lateral hypothalamic region appears to contain "feeding centers." Bilateral lesions here abolish the desire to eat.  Through the lateral hypothalamus courses the medial forebrain bundle, arising from olfactory and limbic structures and continuing down to the brainstem.  Animals and humans will work very hard to deliver stimuli to the region of the medial forebrain bundle, whereby colloquial usage has designated this region as one of the "pleasure centers" of the brain.  In actuality, many regions are positively reinforcing, and many others are negatively reinforcing.

E.  Mammillary Bodies

These protruberances are located in the posterior hypothalamus.  Because of their deterioration in cases of Wernicke's encephalopathy (thiamine deficiency), they have been presumed to be involved in memory.  Nonetheless, many periventricular lesions are found in Wernicke's (from medial thalamus to periaqueductal gray and bulbar cranial nerve nuclei) besides the mammillary bodies.  The hippocampus, which is also thought to be involved in memory, projects a major component of the fornix to the mammillary bodies.  As noted above, mammillary bodies, in turn, project the mammillothalamic tract to the anterior nuclear group for a sideloop on the limbic circuit of Papez.

F.  Hypophysial Portal System

Branches of the internal carotid artery surround the pituitary stalk.  Evidence is strong that factors with hormonal activity are secreted by cells in hypothalamus to be transported via the portal vessels to anterior pituitary.  Hormones affected are: growth hormone; prolactin; the gonadotrophins, luteinizing hormone and follicle-stimulating hormone; thyroid-stimulating hormone; and adrenocorticotrophic hormone.  Studies of these relations comprises the rapidly expanding field of neuroendocrinology.
 

VIII.  HEMISPHERES

The cerebral hemispheres comprise the cortex, subcortical white matter, basal ganglia, thalamus, subthalamus, hypothalamus and cerebral ventricles.  The cerebral cortex reflects the highest evolutionary development of the animal kingdom, and a correspondingly great diversity of function.  Only the briefest outline can be presented here.

Cortex can be divided into primary sensory-motor areas and association areas.  The motor cortex lies in the frontal lobe anterior to the Rolandic (central) sulcus.  Pre-motor cortex lies anterior and supplementary motor cortex anterior and superior to pre-motor cortex.  Electrical stimulation of motor cortex produces elementary movements.  The superior regions relate to leg movements, lateral cortical areas to trunk and hand, inferior cortex to face.  More anterior stimulation produces more complex motor behaviors.  Motor cortex interacts with association cortex, ventrolateral and anterior thalamus, basal ganglia and cerebellum.  It gives rise to the corticospinal tract and extra-pyramidal movement systems.  A lesion of motor cortex lesion produces a contralateral upper motor neuron syndrome, with disuse paralysis or slowness of fine movements, spasticity and hyperreflexia.

Primary sensory cortices include somatosensory cortex in parietal lobe, posterior to the Rolandic sulcus.  There is a sensory representation parallel to the motor homunculus, with leg superior and face inferior.  Lesions here produce loss of discriminative sensation: textures, 2-point discrimination, joint position, graphesthesia (Vibration and crude touch sensation may be mediated thalamically).

Visual cortex includes the occipital tip and medial occiput along the banks of the lingual gyrus.  The input to this system arises in the retina, half crosses in the optic chiasm, then fibers travel to the lateral geniculate nucleus of thalamus, and to the occipital cortex. 

Fiber collaterals are given off to the superior colliculus in midbrain to mediate the pupillary reflexes.  Several different patterns of visual system lesions are important for lesion localization.  Two rules are important to understand the system.  First, visual field lesions (scotoma) are always localized with respect to the patient's perspective.  A left superior scotoma means the patient cannot see clearly up and to his or her left.  Second, the lens inverts up to down and left to right.  A right inferior retinal lesion thus produces a left superior field cut.  A retinal lesion (e.g., retinal hemorrhage or infarction) produces an irregular scotoma in the visual field of one eye.  Lesions of fibers after crossing in the chiasm produce homonymous field deficits (similar shape in both visual fields).  Total destruction of the right occipital pole would produce a left homonymous hemianopsia.  Due to embryological growth of the temporal lobe laterally, the fibers (called Meyer's loop) from inferior retina sweep laterally into the posterior temporal lobe.  Superior retinal fibers take a straighter course through parietal white matter.  Lesions of the right posterior temporal lobe may therefore involve only those fibers from the left inferior retina, which see the right visual field.  This will produce a right superior quadrantinopsia, mnemonically recalled as "pie-in-the-sky." Discovery of pie-in-the-sky visual field cuts should mandate a search for a contralateral posterior temporal lobe lesion.  Pituitary adenomas or craniopharyngiomas are midline tumors that may impinge directly on the optic chiasm.  This destroys the decussating fibers from medial retinas (temporal fields).  Bi-temporal heteronomous hemianopsias result, i.e., patient can not see past either midline laterally.

Auditory deficits are rarely produced from cortical lesions, since the auditory inputs are highly crossed and bilateral.  Fibers travel from the cochlea via the VIIIth nerve to the dorsal and ventral cochlear nuclei in the pons, then to the superior olive and trapezoid body.  Fibers here ascend crossed and uncrossed to the medial geniculate body (with collaterals to the inferior colliculus) and then to auditory cortex (Heschel's gyrus) in the posterior bank of the Sylvian fissure.

Olfactory bulb connects to ipsilateral olfactory tract to olfactory stria on the undersurface of the frontal lobe.  These have clinical significance in at least 3 areas.  Olfactory lesions (anosmia) will diminish the sense of taste, and sometimes give clues to the presence of a sphenoid ridge lesion, such as a meningioma.  Secondly, olfactory cortex in frontal lobe has strong connections to medial inferior temporal structures, including the amygdala.  This is a key structure (along with hippocampus) for temporal lobe seizures.  A stereotyped bad smell may be a warning of an impending temporal lobe seizure.  Third, structures in the region of olfactory cortex include the nucleus of the diagonal band and the nucleus basalis of Meynert.  These regions provide much of the cholinergic input to forebrain, and appear deficient in people with Alzheimer's Disease.

Functions of frontal and parietal association areas are poorly understood.  The frontal association area is involved in sequencing behavior in time: one over-simplification would be to think of this area as a "delayed gratification" center.  People with frontal lobe lesions have difficulty planning for the future and inhibiting expression of immediate needs.  Parietal association regions integrate numerous sensory and motor functions.  Parietal lesions produce deficits of attention, spatial construction, appreciation of part-whole relationships.  A variety of agnosias ("not knowing") and apraxias ("not performing") result from parietal lesions.

In clinical practice a major fraction of cortical lesions result from stroke.  Three main vessels supply cortex: anterior, middle and posterior cerebral arteries.  Infarction in the territory of the anterior cerebral produces frontal lobe signs and weakness greater in leg than arm or face.  Middle cerebral artery infarcts produce contralateral hemiparesis, greatest in hand and face.  If the stroke is on the speech dominant side there will also be aphasia.  Posterior cerebral infarcts produce visual deficits and mesial temporal infarcts, which may impair memory.