Basal Ganglia: Anatomy and Function

Basal Ganglia Overview

• The basal ganglia and cerebellum influence movement by interacting with the cerebral cortex, not by directly projecting to lower motor neurons.
• Damage to the basal ganglia or cerebellum results in movement disorders without prominent weakness.
• The basal ganglia also interact with broader cortical areas, influencing cognition and emotions.

Components of the Basal Ganglia

• The basal ganglia comprise interconnected nuclei in the cerebral hemisphere, diencephalon, and brainstem.
• The striatum and globus pallidus are the main components in the cerebral hemisphere.
• The striatum includes the caudate nucleus, putamen, and nucleus accumbens.
• The putamen is centrally located, underlying the insula.
• The caudate nucleus forms the lateral wall of the anterior horn, borders the body of the ventricle, and curves into a tail in the inferior horn.
• The nucleus accumbens provides continuity between the putamen and caudate nucleus.
• Strands of gray matter cross the internal capsule from the caudate nucleus to the putamen, creating a striped appearance in the striatum.
• The globus pallidus has two segments: an external segment adjacent to the putamen and an internal segment adjoining the internal capsule.
• The putamen and globus pallidus are often referred to as the lenticular nucleus.
• The diencephalic subthalamic nucleus and substantia nigra are also basal ganglia components.

Basal Ganglia Disorders

• Basal ganglia disorders involve combinations of positive (involuntary muscle contractions) and negative (paucity of muscle contraction) signs.
• Parkinson's disease is a classic example, involving resting tremor, rigidity, and slow movements (bradykinesia).
• Other disorders can include chorea (rapid movements), athetosis (slow, writhing movements), and ballism (flailing movements).
• Dystonia is a condition where body parts are twisted into fixed positions.

Connections of the Basal Ganglia

• The basal ganglia affect movement by modifying output from the cerebral cortex, not by direct projections to the brainstem and spinal cord.
• The striatum (caudate nucleus + putamen + nucleus accumbens) is the input portion, and the internal segment of the globus pallidus (GPi) is the output portion.
• Axons leaving the striatum and globus pallidus use GABA for inhibitory synapses.
• GPi neurons inhibit thalamic neurons, and the balance of excitatory and inhibitory inputs to GPi determines the effect on cortical output.
• Diminished output from GPi disinhibits thalamic neurons, enhancing thalamocortical outputs (positive signs).
• Increased output suppresses thalamocortical outputs (negative signs).
• The primary direct circuit involves a loop from the cerebral cortex to the striatum, then to GPi, to the thalamus, and back to the cerebral cortex; it is primarily uncrossed.
• Corticostriatal projections are excitatory, leading to GPi inhibition and facilitating excitatory thalamocortical transmission.

Subthalamic Nucleus

• A subset of striatal neurons provides the primary inhibitory input to GPi, while the subthalamic nucleus provides the principal excitatory input.
• Another subset of striatal neurons projects to the external segment of the globus pallidus (GPe), which projects to the subthalamic nucleus.
• The subthalamic nucleus sends excitatory projections to GPi, serving as a key link in an indirect circuit.
• Increased cortical input to the indirect circuit disinhibits the subthalamic nucleus, exciting GPi and suppressing thalamocortical transmission.
• Damage to the subthalamic nucleus can cause hemiballismus, with flailing movements of contralateral limbs.

Substantia Nigra

• The substantia nigra has two laminated parts: the reticular part and the compact part.
• The reticular part contains GABAergic neurons connected like a displaced piece of GPi, with inputs from the striatum and subthalamic nucleus, and outputs to the thalamus.
• The compact part contains pigmented neurons that project to the striatum, releasing dopamine to modulate excitability in direct and indirect circuits.
• Dopamine binds to D₁ receptors in the direct circuit, depolarizing neurons, and to D₂ receptors in the indirect circuit, hyperpolarizing neurons.
• Degeneration of substantia nigra neurons causes Parkinson's disease, decreasing activity in the direct pathway and increasing activity in the indirect pathway, increasing thalamus inhibition by GPi.

Parallel Pathways in the Basal Ganglia

• Several parallel subcircuits exist within the basal ganglia, each starting and ending with cortical areas and using portions of the striatum, globus pallidus, subthalamic nucleus, and thalamus.
• One circuit is primarily involved in motor functions and uses the putamen as its input.
• Somatosensory and motor cortex areas project to the putamen, which projects to the globus pallidus and thalamus (ventral anterior and ventral lateral nuclei).
• The thalamic output projects mainly to the supplementary motor area, projecting to the motor cortex.
• A second loop is involved in cognition and uses the caudate nucleus as its input.
• Association areas of the cerebral cortex project to the caudate nucleus, then to the globus pallidus and thalamus (mostly dorsomedial nucleus).
• From the thalamus, projections go to prefrontal association areas.
• Damage restricted to the head of the caudate nucleus can cause changes in judgment.
• A limbic loop uses nucleus accumbens and ventral parts of the caudate and putamen (ventral striatum).
• The ventral striatum projects to the ventral pallidum, which projects to parts of the thalamus connected to limbic cortex.
• Nucleus accumbens plays a role in initiating rewarding behaviors.

Pharmacology and Clinical Medicine

• Parkinson's disease is associated with a loss of dopaminergic neurons; attempts have been made to replace the lost dopamine to ameliorate the disease.
• Dopamine cannot cross the blood-brain barrier directly but its precursor L-dopa (levodopa) can cross the barrier and treat Parkinson's disease.
• Surgical treatments for Parkinson's disease attempt to suppress excess basal ganglia activity.
• Treatments include electrolytic lesions in GPi and the subthalamic nucleus.
• High-frequency stimulation through implanted electrodes has replaced lesions.
• Deep brain stimulation is targeted at the subthalamic nucleus.

Genetics

• Huntington's disease is inherited in an autosomal dominant fashion.
• Huntington’s results from an expanded cytosine-adenosine-guanine (CAG) repeat on chromosome 4.
• The longer the repeat, the earlier the onset of the disease and the worse its severity.
• Basal ganglia disorders can produce nonmotor deficits.
• Many Parkinson's patients become demented or depressed.
• Huntington's disease causes chorea and dementia.
• Changes in mood and personality can be present with Huntington's disease.