Neuroanatomy

Note: Significant diseases are indicated in bold and syndromes in italics.

I. Cerebral Cortex

Figure 1–1 Important gyri, lobes, and Brodmann areas. (A) lateral surface; (B) medial surface. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:276, Fig. 8.23. Reprinted by permission.)

ii.     mesocortex: exhibits five or six poorly defined layers, located at transition between isocortex and allocortex (e.g., parahippocampal gyrus)

iii.  allocortex: exhibits only three layers; includes the inferior and mesial temporal lobes (hippocampal formation)

b. general functional subtypes

i.    primary motor and sensory areas

ii.   monomodal association areas

(1) monomodal motor association areas: receive input from the primary and monomodal association sensory areas, and project to the primary motor area

(2) monomodal sensory association areas: receive input from the primary sensory area, and project to the heteromodal association areas and primary motor area

iii.  heteromodal association areas: receive input from monomodal association areas; project to other heteromodal association and paralimbic areas, and the basal ganglia

iv.   limbic and paralimbic areas

Figure 1–2 Types of cortical neurons. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:262, Fig. 8.11. Reprinted by permission.)

A. Motor Systems

1. Primary motor cortex (Brodmann area 4)

Figure 1–3 Sensory (A) and motor (B) homunculi. Note the proximity of the thumb to the forehead. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:273, Fig. 8.20. Reprinted by permission.)

(1) global akinesia with speech arrest that develops into hypokinesia (contralateral > ipsilateral), reduced speech, and reduced facial expression; chronically, patients will exhibit only poor hand coordination

(2) ideomotor apraxia, which may be associated with a contralateral alien hand phenomenon characterized by unconscious reflexive movements

ii.   stimulation causes bilateral posturing movements, contralateral head and body rotation, and vocalizations {salutary seizures}

3. Subcortical projections

a. corticobulbar tract: the ventral division travels with the corticospinal tract and synapses in the facial nucleus; the dorsal division travels closer to the medial lemniscus and synapses in other cranial nerve nuclei and the reticular formation

b. corticospinal tract: composed of fibers not only from the primary motor cortex (25%) and monomodal motor association cortex (30%) but also the primary somatosensory cortex (30%) and superior parietal lobule (Brodmann areas 5 and 7; 15%)

i.    terminates in the cervical spinal cord (55%), thoracic spinal cord (20%), and lumbosacral spinal cord (25%)

ii.   the majority (80%) of the corticospinal tract decussates at cervicomedullary junction (upper extremity fibers decussate rostral to the lower extremity fibers)

(1) the rest of the corticospinal tract does not decussate until it arrives at its terminal cervical and upper thoracic spinal cord levels (ventral corticospinal tract)

B. Somatosensory Systems

1. Primary sensory cortex (Brodmann areas 3-1-2)

a. subdivided according to sensory modality

i.    Brodmann area 3a receives deep sensation from muscle spindles and Golgi tendon organs

ii.   Brodmann area 3b receives superficial sensation from exteroceptors and cutaneous receptors

b. somatotopic organization: similar to the motor homunculus, but less well defined and may extend caudally into Brodmann areas 5 and 7

i.    face and body are bilaterally represented; limbs are unilaterally represented

c. lesions cause loss of proprioception (but not vibration sensation), poor localization of stimuli {topagnosia}, difficulty with two-point discrimination, reduced object recognition through touch {astereognosis}, tactile hallucinations, rapid fatigability of prolonged sensory stimulation, and paresthesias

i.    primary modality sensory loss is pronounced with postcentral gyrus lesions that involve the posterior insula and underlying white matter

d. stimulation produces numbness and paresthesias, and often a sensation of movement

2. Secondary sensory cortex (supramarginal gyrus; Brodmann area 40): Posterior to the inferior part of the primary somatosensory cortex

a. exhibits bilateral inputs with contralateral predominance, and is somato-topically organized into a separate homunculus that may be related to pain sensation

3. Unimodal somatosensory association area (Brodmann area 5): Involved in recognition of object shape by tactile sensation {stereognosis}

4. Subcortical afferents: anterolateral system/spinothalamic tract, dorsal columns, and trigeminal pathways terminate in the ventroposteromedial and ventroposterolateral thalamic nuclei that then project to the primary sensory cortex

C. Special Sensory Systems

D. Heteromodal Association Areas

1. Frontal heteromodal association area/prefrontal cortex: involves all the cortex located anterior to the monomodal motor association areas

a. unlike other heteromodal association areas, the prefrontal cortex

i.    projects to the amygdala and caudate

ii.   receives indirect projections from the hippocampus through the dorsomedial thalamus and direct projections from the cingulate gyrus and hypothalamus

i.    alexia

ii.   Gerstmann’s syndrome—classically involves agraphia, finger agnosia, acalculia, and left-right confusion; lesions are located on the angular gyrus (Brodmann area 39)

iii.  contralateral tactile neglect and spatial inattention

iv.   somatotopic ideomotor apraxia

b. nondominant-sided lesions produce

i.    contralateral tactile neglect and spatial inattention, which may be so severe that the patient does not recognize the deficit {anosognosia}

ii.   constructional and dressing apraxias

iii.  spatial disorientation

iv.   impersistence; inattention; static confusional state/encephalopathy

E. Language Areas

1. Dominant hemisphere language areas

i.    lesions produce

(1) Broca’s aphasia—classically involves Broca’s area, the mouth representations of the primary motor and somatosensory cortices, and the underlying white matter

(a) symptoms include nonfluent speech that is slow and agrammatic as well as dysarthric, and impaired repetition; writing is minimal and agrammatic

b. Wernicke’s area

i.    includes posterior superior and middle temporal gyri, planum temporale (Brodmann area 42; a monomodal auditory association area), and heteromodal association areas of the parietal lobe (angular and supra-marginal gyri; Brodmann areas 39 and 40)

ii.   lesions cause Wernicke’s aphasia

(1) characterized by excessive speech of normal cadence and prosody associated with impaired naming, comprehension, and repetition, and the presence of paraphasias and neologisms; writing is similarly excessive with paraphasias and neologisms

(2) impairment of comprehension can be particularly pronounced with specific subjects, thereby giving the false appearance of a fluctuant deficit

c. secondary language areas (i.e., the cortex surrounding Broca’s and Wernicke’s areas): lesions produce the transcortical aphasias because they isolate the primary language areas without directly injuring them; all have preservation of repetition

i.    subtypes of transcortical aphasias

(1) transcortical motor aphasia—generally caused by lesions anterior or superior to Broca’s area, or by lesions in the supplementary motor area

(2) transcortical sensory aphasia—can be caused by lesions surrounding Wernicke’s area, but otherwise is usually poorly localized

(3) mixed transcortical aphasia—caused by large areas of dominant hemisphere injury that spare the perisylvian regions (e.g., as in watershed infarction or dementias)

d. subcortical connections of Broca’s and Wernicke’s areas: lesions produce

i.    conduction aphasia—caused by disconnection of Broca’s and Wernicke’s areas, most commonly the result of a subcortical white matter lesion that interrupts the arcuate fasciculus (in the superior longitudinal fasciculus; and/or the extreme capsule

(1) symptoms: isolated loss of repetition with occasional paraphasic errors

ii.   anomia—generally has no localizing value when mild, but significant anomia may reflect lesions in the basal temporal lobe that interrupt hippocampal projections to Wernicke’s area

2. Nondominant hemisphere language areas

a. areas related to the variation of pitch, intonation, melody, rhythm, and loudness of speech {prosody}

i.    affective prosody—involves the expression of mood and emotion in speech; caused by lesions in the nondominant hemisphere in areas that are anatomical and functional parallels to Broca’s and Wernicke’s areas of the dominant hemisphere

(1) affective prosody is most commonly observed in psychiatric diseases (e.g., motor and sensory aprosodies in schizophrenia, motor hyperprosody in mania)

ii.   propositional prosody—defines a phrase as a question or a statement; can occur after lesions of either hemisphere

b. areas related to gesturing that accompanies speech {kinesia}: poorly localized

c. areas related to singing: an acquired inability to sing {amelodia} is caused by lesions of the posterior inferior frontal lobe or anterior parietal lobe

F. Paralimbic Cortex

1. Paralimbic cortex: collects inputs from heteromodal association areas, monomodal association areas, and limbic areas (hippocampal formation and amygdala); projects primarily to the hippocampal formation

2. Paralimbic cortex includes

a. anterior and posterior cingulate gyrus

b. parahippocampal gyrus (entorhinal cortex and piriform/periamygdaloid cortex)

c. insular and orbitofrontal cortex

d. temporal poles: lesions cause

i.    Kluver-Bucy syndrome—occurs only after bilateral anterior temporal cortex destruction, usually from temporal lobectomy; does not have to involve the amygdala or hippocampus to produce all of its symptoms

(a) placidity

(b) hypersexuality

(c) hyperorality and increased manual exploration, which likely reflects an inability to recognize objects by vision alone {visual agnosia}

(d) memory impairment, dementia

(e) hyperphagia

ii.   rage—caused by bilateral anterior and inferior temporal lesions, usually due to trauma or herpes encephalitis

G. Limbic Areas

1. Hippocampal formation: includes the hippocampus, dentate gyrus, and subiculum

Figure 1–4 The circuit of Papez. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:206, Fig. 5.20. Reprinted by permission.)

Figure 1–5 Intrinsic hippocampal connections. (From Kahle W, Color Atlas/Text of Human Anatomy, Vol. 3: Nervous System and Sensory Organs. 4th ed. Stuttgart, Germany: Georg Thieme; 1993:221, Fig. A. Reprinted by permission.)

(1) electroencephalogram (EEG): can rule out nonconvulsive temporal lobe seizures

(2) magnetic resonance imaging (MRI) may exhibit increased diffusion-weighted imaging signal in the mesial temporal lobes

v.    treatment: none specific

vi.   prognosis: gradual return of memory over 12–24 hours; recurs in 20% of patients

2. Amygdala

a. subdivisions

i.    corticomedial amygdala: interconnected with the olfactory bulb via the lateral olfactory tract, the hypothalamus, and the septum via the stria terminalis

i.    olfactory sensory processing and integration of olfactory-visceral reflexes

ii.   coordination of emotional behavior and autonomic nervous system responses

iii.  association of memories with their emotional content

c. lesions generally produce a loss of aggressive behavior; stimulation produces fear or defense reactions

II. Subcortical White Matter

1. Corona radiata/Centrum semiovale

a. pathophysiology

i.    leukoaraiosis: can be part of, but is not identical to, vascular dementia or Binswanger’s disease

(2) hemi-sensory loss (60%)

(3) aphasia or neglect (60%)

c. association fibers

i.    short association fibers/“U” fibers: short-range cortical–cortical projections

Figure 1–7 Internal capsule. (From Greenberg MS, Handbook of Neurosurgery. 3rd ed. Greenberg Press; 1994:114, Fig. 23.12. Reprinted by permission.)

Figure 1–8 Long association fibers. (A) Lateral view; (B) transected hemisphere at the level of the insula. (Left, from Mumenthaler M, Neurological Differential Diagnosis. 2nd ed. Stuttgart, Germany: Georg Thieme; 1992:49, Fig. 18 and right, from Kahle W, Color Atlas/Text of Human Anatomy, Vol. 3: Nervous System and Sensory Organs. 4th ed. Stuttgart, Germany: Georg Thieme; 1993:247, Fig. D. Reprinted by permission.)

(3) superior longitudinal fasciculus: connects the parietal and temporal lobes with the frontal lobe; includes the arcuate fasciculus, lesions of which cause conduction aphasia

(4) inferior longitudinal fasciculus: connects the occipital cortex with the inferior temporal and fusiform gyri; important for the ventral occipitotemporal neural network, which is involved in face and object recognition (the “what” pathway)

(5) superior occipitofrontal fasciculus: interconnects all the lobes; important for the dorsal parietofrontal neural network, which is involved in spatial orientation (the “where” pathway)

(6) inferior occipitofrontal fasciculus: connects the inferior temporal, fusiform, and lingual gyri with the frontal lobe

d. commissures

i.    corpus callosum: regions of the cortex project through the corpus callosum to symmetric regions in the contralateral hemisphere, and occasionally to other regions; fibers originate from cortex layer 3

(1) pathophysiology

(a) transection of the corpus callosum: symptoms are generally detectable only by specific testing, and include

(i)    inability to name objects or read words presented in the visual hemifield of the nondominant hemisphere

(ii)   inability to name objects felt by the nondominant hand

(iii)  inability to write with the nondominant hand

(iv)   impaired spatial construction skills with the dominant hand

(v)    callosal alien hand syndrome—discoordination of simultaneous voluntary hand movements

ii.   anterior commissure: connects the caudal orbitofrontal, anterior temporal, and parahippocampal cortices as well as the contralateral olfactory nerve to the piriform cortex for bilateral olfactory representation

iii.  posterior commissure: carries fibers of the medial longitudinal fasciculus, posterior thalamus, pretectal nuclei, mesencephalic accessory ocular motor nuclei, and superior colliculi

iv.   hippocampal commissure: minimal size and function in humans

Figure 1–9 The basal forebrain posterior to the nucleus accumbens demonstrating the olfactory cortex, septal nuclei, and ventral basal ganglia (inferior to the anterior commissure). (From Kahle W, Color Atlas/Text of Human Anatomy, Vol. 3: Nervous System and Sensory Organs. 4th ed. Stuttgart, Germany: Georg Thieme; 1993:201, Fig. B; 211. Reprinted by permission.)

(a) type I spiny neurons: contain GABA and enkephalin, and express D2 receptors; act in the indirect pathway from the putamen

(b) type II spiny neurons: contain GABA, substance P, and dynorphin, and express D1 receptors; act in the direct pathway from the putamen

ii.   aspiny neurons: the interneurons of the striatum

(1) subtypes

(a) type I aspiny neurons: contain GABA

(b) type II (large) aspiny neurons: contain acetylcholine

(c) type III aspiny neurons: contain somatostatin and neuropeptide Y

Figure 1–10 Superficial view of the diencephalic roof. (From Kahle W, Color Atlas/Text of Human Anatomy, Vol. 3: Nervous System and Sensory Organs. 4th ed. Stuttgart, Germany: Georg Thieme; 1993:207, Fig. B. Reprinted by permission.)

b. effects of lesions

i.    caudate lesions cause contralateral choreoathetosis, abulia, and behavioral disinhibition

ii.   putamen lesions cause

(1) contralateral hemidystonia (70%) > hemichorea or hemiparkinsonism

(2) hypophonic dysarthria with a transcortical motor aphasia-like language impairment due to bradykinesia

(3) impairment of short-term memory

(4) contralateral tilting and falling (in lesions that involve the globus pallidus)

2. Globus pallidus: contains large motor-type neurons and interneurons

a. unilateral lesions cause contralateral hemidystonia and/or hemiparkinsonism, abulia, and short-term memory loss; bilateral lesions may also cause akinetic mutism

3. Substantia nigra: lesions produce contralateral parkinsonism; subdivisions include

a. pars compacta (dopaminergic): has a predominantly afferent function in the basal ganglia loops; projects to the striatum via the nigrostriatal dopaminergic pathway

b. pars reticulata (GABAergic): has a predominantly efferent function in the basal ganglia loops; projects to the ventral anterior and ventral lateral nuclei of the thalamus

4. Ventral tegmental area: projects to the nucleus accumbens via the mesolimbic dopaminergic pathway; analogous to the substantia nigra for the limbic striatum

5. Subthalamic nucleus

a. lesions cause hypotonia and continuous flailing movements of the extremities sparing the face due to uncontrollable contractions of the proximal musculature {ballismus}

i.    ballismus typically involves the contralateral half of the body {hemiballismus}, and may involve only a single extremity {monoballismus}

ii.   ballismus is a violent type of chorea, and it may resolve over time into chorea

iii.  ballismus may occur with lesions elsewhere in the basal ganglia, thalamus, or motor cortex, although these forms are generally milder than that caused by subthalamic nucleus lesions

Figure 1–11 Coronal section of the thalamus at the level of the mammillary bodies. (From Kahle W, Color Atlas/Text of Human Anatomy, Vol. 3: Nervous System and Sensory Organs. 4th ed. Stuttgart, Germany: Georg Thieme; 1993:163, Fig. B. Reprinted by permission.)

(1) transient dysfunction of the basal ganglia may underlie a rapidly reversible form of hemiballismus that occurs during hyperglycemia

iv.   treatment: antipsychotic medications that have antagonist properties on D2 receptors (i.e., not clozapine); stereotactic lesioning or deep brain stimulation of the internal globus pallidus or ventral anterior–ventral lateral thalamus

i.    thalamus via ansa lenticularis and the lenticular and thalamic fascicles

ii.   subthalamic nucleus

(1) ventral anterior nuclei

(2) ventral lateral nuclei: afferents involve not only globus pallidus and substantia nigra reticulata, but cerebellum as well

(a) lesions cause contralateral

Figure 1–12 Functional divisions of the thalamus. (From Duus P, Topical Diagnosis in Neurology. Stuttgart, Germany: Georg Thieme; 1998:275, Fig. 8.22. Reprinted by permission.)

(i)    hemiataxia, usually with hemiparesis and/or sensory loss from involvement of nearby structures; develops acutely after injury

(ii)   intention tremor: develops several weeks after injury

(iii)  dystonia: develops several months or years after injury

(4) medial geniculate

(5) ventral posterior nuclei

(a) ventral posterolateral nucleus has distinct areas for proprioception (i.e., the shell of the nucleus) and cutaneous (i.e., the core) inputs from body

(b) ventral posteromedial nucleus receives trigeminal inputs for facial sensation and inputs from the solitary tract nucleus via the solitary tract conveying taste

(c) lesions cause

(i)    chiro-oral syndrome—symptoms include the contralateral loss of all sensory modalities and paresthesias of the mouth, tongue, and hand

1. face, trunk, and proximal extremities are bilaterally represented (with a contralateral preference) in the ventral posterior thalamus, and so their sensation is preserved in unilateral lesions

1. generally develops weeks or months after the initial lesion; occasionally develops acutely after injury

2. symptoms: burning pain that may be continuous or triggered by innocuous stimuli, and that is aggravated by emotional stress; sensory loss (proprioception > other modalities; deep sensation > cutaneous sensation)

a. threshold for pain is paradoxically increased in the affected regions

3. treatment: thalamotomy of the intralaminar thalamic nuclei

b. association nuclei

(1) specific afferents are from limbic structures (ventral basal ganglia, amygdala, hippocampal formation) and hypothalamus

(2) bilateral lesions cause

(a) hypersomnolence with reduced non-REM sleep

(b) akinetic mutism, coma

(c) anterograde amnesia, when they occur in conjunction with bilateral anterior thalamic lesions

(d) Klein-Levin syndrome—symptoms include recurrent episodes lasting several days or weeks of compulsive eating, sexual disinhibition, hypersomnia with normal sleep structure, and impaired memory

(i)    likely involves some simultaneous dysfunction of the posterior hypothalamus

(ii)   more common in adolescent boys, and spontaneously remits in adulthood

(iii)  treatment: lithium, valproate

ii.   pulvinar has poorly defined visual and language functions

c. intralaminar thalamic nuclei (ITN): connections involve

i.    rostral nuclei: reticular formation → ITNr → entire telencephalon and diencephalon

ii.   caudal nuclei: reticular formation → ITNc → motor telencephalon and diencephalon

d. reticular thalamic nucleus (RTN): forms a thin shell on the lateral surface of the thalamus

i.    connections: reticular formation, collaterals of thalamocortical projections (particularly from intralaminar thalamus group), and cortex → RTN → all thalamic nuclei and reticular formation

2. Chemoanatomy: glutamate and aspartate are released from all thalamic nuclei except the reticular thalamic nucleus, which is GABAergic

b. maintains visceral activity, metabolic activity, and body temperature

c. participates in goal-directed behavior and motivation, affective behavior (particularly aggressive behaviors), and sleep–wake cycling

(3) lateral preoptic nucleus: promotes sleep onset, and inhibits brain regions that are necessary for maintaining arousal by GABAergic and galanin projections

ii.   supraoptic region

(1) neurohormonal/magnocellular nuclei (paraventricular and supraoptic nuclei): project to the posterior pituitary where they directly release hormones

(2) suprachiasmatic nucleus: the pacemaker of circadian rhythms (e.g., sleep–wake cycle, body temperature, cortisol and growth hormone release)

(a) receives direct input from the retina; projects predominantly to the preoptic region and neurohormonal nuclei

(b) lesions cause irregular timing of sleep–wake behaviors; otherwise a normal amount of time is spent in each sleep phase

iii.  tuberal region