GENERAL FEATURES
The basal ganglia initiate and provide gross control over skeletal muscle move ments. The major components of the basal ganglia include:
•Striatum, which consists of the caudate nucleus and the putamen (telen- cephalon)
•External and internal segments of the globus pallidus (telencephalon)
•Substantia nigra (in midbrain)
•Subthalamic nucleus (in diencephalon)
Together with the cerebral cortex and the ventrolateral (VL) nucleus of the thal amus, these structures are interconnected to form 2 parallel but antagonistic circuits known as the direct and indirect basal ganglia pathways (Figures IV-7- 1 and IV-7-2). Both pathways are driven by extensive inputs from large areas of cerebral cortex, and both project back to the motor cortex after a relay in the VL nucleus of the thalamus. Both pathways use a process known as "disinhibition'' to mediate their effects, whereby one population of inhibitory neurons inhibits a second population ofinhibitory neurons.
Direct Basal Ganglia Pathway
In the direct pathway, excitatory input from the cerebral cortex projects to striatal neurons in the caudate nucleus and putamen. Through disinhibition, activated inhibitory neurons in the striatum, which use y-aminobutyric acid (GABA) as their neurotransmitter, project to and inhibit additional GABA neurons in the internal segment ofthe globus pallidus.
The GABA axons ofthe internal segment ofthe globus pallidus project to the thala mus (VL). Because their input to the thalamus is disinhibited, the thalamic input excites the motor cortex. The net effect of the disinhibition in the direct pathway results in an increasedlevel ofcortical excitation and the promotion ofmovement.
Indirect Basal Ganglia Pathway
In the indirect pathway, excitatory input from the cerebral cortex also projects to striatal neurons in the caudate nucleus and putamen. These inhibitory neurons in the striatum, which also use GABA as their neurotransmitter, project to and inhibit additional GABA neurons in the external segment ofthe globus pallidus.
The GABA axons ofthe external segment ofthe globus pallidus project to the sub thalamic nucleus. Through disinhibition, the subthalamic nucleus excites inhibi tory GABA neurons in the internal segment ofthe globus pallidus, which inhibits the thalamus. This decreases the level of cortical excitation, inhibiting movement. The net effect of the disinhibition in the indirect pathway results in a decreased level ofcortical excitation, and a suppression ofunwanted movement.
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Section IV • Neuroscience
Figure IV-7-4. Coronal Section through Basal Ganglia and Other Subcortical Structures
(A)caudate nucleus (B) putamen (C) globus pallidus external segment
(D)globus pallidus internal segment (E) septal nuclei (F) fornix (G) lateral ventricle (H) anterior commissure (I) optic chiasm (J) basal nucleus of Meynert (K) preoptic hypothalamus (L} internal capsule, anterior limb
Section IV • Neuroscience
Clinical Correlate
Lesions or Diseases ofthe Basal Ganglia
Lesions or diseases ofthe basal ganglia generally present with movement disorders, known as dyskinesias, and an involuntary tremor, ortremor at rest.
Most basal ganglia disorders seem to preferentially affect either the direct or the indirect pathways, altering the balance between the two.
Lesions ofthe direct pathway
Lesions of the direct pathway result in an underactive cortex and hypokinetic disturbances in which there is a slowing or absence of spontaneous movements. The best-known disorder of the direct pathway is caused by the degeneration of dopaminergic neurons of the substantia nigra in Parkinson disease. Because the cortex is underactive, Parkinson patients have problems initiating movements, combined with a reduction in the velocity and amplitude of the movements. The tremor at rest is the classic pill-rolling tremor seen in the fingers. Skeletal muscles in the upper limbs exhibit a cogwheel rigidity because of increased muscle tone. Patients also present with a stooped posture, an expressionless face, and a festinating or accelerating gait during which individuals seem to chase their center of gravity. One strategy for Parkinson patients is to give them L-dopa, a dopamine precursor that crosses the blood-brain barrier. Another strategy is to give anticholinergic drugs to inhibit the effects of acetylcholine on the indirect pathway.
Lesions ofthe indirect pathway
Other common disorders of the basal ganglia (chorea, athetosis, dystonia, tics) result from lesions to parts of the indirect pathway, which result in an overactive motor cortex. An overactive cortex produces hyperkinetic disturbances, expressed in numerous spontaneous movements. The involuntary tremors seen in these diseases range from being dancelike in chorea to ballistic with lesions to the subthalamic nucleus.
Chorea produces involuntary movements that are purposeless, quick jerks that may be superimposed on voluntary movements. Huntington chorea exhibits autosomal dominant inheritance (chromosome 4) and is characterized by severe degeneration of GABA neurons in the striatum. In addition to chorea, these patients frequently sufferfrom athetoid movements, progressive dementia, and behavioral disorders. Sydenham chorea is a transient complication in some children with rheumatic fever.
Athetosis refers to slow, worm like, involuntary movements that are most noticeable in the fingers and hands but may involve any muscle group. It is present in Huntington disease and may be observed in many diseases that involve the basal ganglia.
Dystonia refers to a slow, prolonged movement involving predominantly the truncal musculature. Dystonia often occurs with athetosis. Blepharospasm (contraction ofthe orbicularis oculi causing the eyelids to close), spasmodic torticollis (in which the head is pulled toward the shoulder), and writer's cramp (contraction ofarm and hand muscles on attempting to write) are all examples
of dystonic movements.
(Continued)
Chapter 7 • Basal Ganglia
Clinical Correlate (Continued)
Hemiballismus results from a lesion of the subthalamic nucleus usually seen in hypertensive patients. Hemiballismus refers to a violent projectile movement of a limb and is typically observed in the upper limb contralateral to the involved subthalamic nucleus.
Tourette syndrome involves facial and vocaltics that progress to jerking movements ofthe limbs. It is frequently associated with explosive, vulgarspeech.
Wilson disease results from an abnormality of copper metabolism, causing the accumulation of copper in the liver and basal ganglia. Personality changes, tremor, dystonia, and athetoid movements develop. Untreated patients usually succumb because of hepatic cirrhosis. A thin brown ring around the outer cornea, the Kayser-Fleischer ring, may be present and aid in the diagnosis.
ChapterSummary
•The basal ganglia play important motor functions in starting and stopping
voluntary motor functions and inhibiting unwanted movements. The basal ganglia consists of 3 nuclei masses deep in the cerebrum (caudate nucleus, putamen, and globus pallidus), one nucleus in the midbrain (substantia nigra), and the subthalamic nucleus ofthe diencephalon. The striatum combines the caudate nucleus and the putamen while the corpus striatum
consists ofthese 2 nuclei plus the globus pallidus.
•There are 2 parallel circuits (direct and indirect) through the basal ganglia. These circuits receive extensive input from the cerebral cortex that project back to the motor cortex after a relay in the ventrolateral (VL) nucleus ofthe thalamus. Both ofthese pathways demonstrate disinhibition. The direct pathway increases the level of cortical excitation and promotes movement. The indirect pathway decreases the level of cortical excitation and suppresses unwanted movement.
•The striatum is the major input center and the globus pallidus is the major output centerforthe pathways through the basal ganglia. Critical to proper function ofthe striatum is dopamine production by the substantia nigra.
Dopamine excites the direct pathway and inhibits the indirect pathway.
•Lesions of the direct pathway result in an underactive cortex, which produces hypokinetic motor disturbances. The classic disorder caused by degeneration of dopaminergic neurons of the substantia nigra is Parkinson disease. These patients are characterized by tremor at rest (pill-rolling), increased muscle tone, mask face, and hypokinetic movement.
•Hyperkinetic disorders result from lesions ofthe indirect pathway and cause an overactive motor cortex. These movements occur spontaneously at rest and cannot be controlled by the patient. Examples ofthese disorders include chorea (multiple quick movements), athetosis (slow serpentine movements), and hemiballismus (violent flinging movements). Hemiballismus results from hemorrhagic destruction ofthe contralateral subthalamic nucleus.
Section IV • Neuroscience
Open-Angle Glaucoma
A chronic condition (often with increased intraocular pressure [IOP]) due to de creased reabsorption of aqueous humor, leading to progressive (painless) visual loss and, ifleft untreated, blindness. IOP is a balance between fluid formation and its drainage from the globe.
Narrow-Angle Glaucoma
An acute (painful) or chronic (genetic) conditionwith increased IOP due to block ade ofthe canal ofSchlemm. Emergencytreatmentprior to surgeryoften involves cholinomimetics, carbonic anhydrase inhibitors, and/or mannitol.
VISUAL REFLEXES
Pupillary Light Reflex
When light is directed into an eye, it stimulates retinal photoreceptors and results in impulses carried in the optic nerve to the pretectal area. Cells in the pretectal area send axons to the Edinger-Westphal nuclei on both sides.
The Edinger-Westphal nucleus is the parasympathetic nucleus ofthe oculomotor nerve and gives rise to preganglionic parasympathetic fibers thatpass in the third cranial nerve to the ciliary ganglion. Because cells in the pretectal area supply both Edinger-Westphal nuclei, shining light into one eye results in constriction of both the ipsilateral pupil (direct light reflex) and contralateral pupil (consensual light reflex).
Accommodation-Convergence Reaction
This reaction occurs when an individual attempts to focus on a nearbyobject after looking at a distant object. The oculomotor nerve carries the efferent fibers from the accommodation-convergence reaction, which consists of3 components: ac commodation, convergence, and pupillary constriction.
Accommodation refers to the reflex that increasesthe curvature ofthe lens needed for nearvision. Preganglionic parasympathetic fibers arise in the Edinger-Westphal nucleus and pass via the oculomotor nerve to the ciliary ganglion. Postganglionic parasympathetic fibers from the ciliaryganglionsupplythe ciliarymuscle. Contrac tion ofthis muscle relaxes the suspensory ligaments and allows the lens to increase its convexity (become more round). This increases the refractive index ofthe lens, permittingtheimage ofa nearbyobject to focus on the retina.
Convergence results from contraction ofboth medial rectus muscles, which pull the eyes to look toward the nose. This allows the image ofthe near object to focus on the same part ofthe retina in each eye.
Pupillaryconstriction (miosis) results from contraction ofthe constrictor mus cle ofthe iris. A smalleraperturegives the optic apparatus agreater depth offield. With Argyll Robertson pupils, both direct and consensual light reflexes are lost, but the accommodation-convergence reaction remains intact. This type ofpupil is often seen in cases ofneurosyphilis; however, it is sometimes seen in patients with multiple sclerosis, pineal tumors, or tabes dorsalis. The lesion site is believed to occur near the pretectal nuclei just rostral to the superior colliculi.
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