L62. Neuroscience - Basal Ganglia

• Basal ganglia, also known as basal nuclei, are essential for motor control, influencing movement via pathways to upper motor neurons (UMN).
• Motor deficits caused by basal ganglia disease are termed "extrapyramidal".

Anatomical Organization

• Basal ganglia (BG) comprise of four interconnected nuclei, influencing motor behavior by regulating UMN activity.
• The main UMN system regulated by the basal ganglia is the pyramidal tract.
• Striatum (STR) is the main nucleus, derived from the telencephalon, consisting of the caudate nucleus (medial) and putamen (lateral).
• The anterior limb of the internal capsule separates the caudate nucleus and putamen, which are functionally similar.
• The caudate nucleus is a C-shaped structure adjacent to the lateral ventricle, which has a rostral head related to the anterior horn, a body that tapers caudally, and a tail associated with the inferior horn in the temporal lobe.
• Globus pallidus (GP) and Striatum (STR) are derived from the telencephalon, located deep to the cerebral cortex
• Subthalamic nucleus (STN) and Substantia nigra (SN) are located in the diencephalon and mesencephalon.
• The putamen and globus pallidus together form a lens-shaped structure called the lentiform or lenticular nucleus, which is often used in neuroradiology
• Substantia nigra (SN) is located posterior (dorsal) to the cerebral peduncles in the ventral midbrain, divided into pars compacta (SNc) and pars reticulata (SNr).
• Pars compacta (SNc) contains dopamine neurons that produce melanin, which is a product of catecholamine synthesis.
• The SNc appears as a dark stripe in the gross brain
• Pars reticulata (SNr) lies ventral to the SNc and between the SNc and the cerebral peduncle.
• Two output pathways connect BG nuclei, namely the globus pallidus, to their targets, forming the Ansa Lenticularis (AL) and Lenticular Fasciculus (LF).

Blood Supply

• The internal carotid artery supplies rostral telencephalic parts of the BG.
• The medial striate artery (recurrent artery of Heubner) supplies the head of the caudate (from the ACA).
• Lenticulostriate arteries supply the body of caudate, putamen, and GPe (from the MCA).
• The anterior choroidal artery (AChor) supplies the GPi.
• The vertebrobasilar system supplies caudal diencephalic and midbrain structures of the BG.
• The posterior communicating artery (PCom) supplies the rostral STN.
• The posterior choroidal artery (PChor) supplies the caudal STN and rostral SN, with caudal SN portions supplied by branches of the basilar artery.

BG Circuitry and Movement Control

• Lesions of the BG do not directly affect individual BG nuclei and muscles, nor do they connect to UMNs projecting to spinal cord or brainstem LMNs; instead, BG circuitry modulates afferents to UMN pathways.
• The BG influences 3 UMN systems: Corticostriatal/corticobulbar , Reticulospinal and Conjugate eye movement centers and tectospinal
• The BG affects 3 centers: Motor Thalamus, Pedunculopontine nucleus (PPN) and Superior Colliculus
• Motor Thalamus consists of the Ventral Anterior and Ventral Lateral Nuclei: they project directly to cortical neurons that form the corticospinal & corticobulbar pathways
• Pedunculopontine nucleus (PPN) is located in the caudal midbrain and rostral pons: it projects to pontine and medullary neurons that originate the medial and lateral reticulospinal tracts.
• Superior Colliculus is a control center for visual gaze: it influences both horizontal & vertical gaze centers as well as originates the tectospinal pathway.
• The Globus Pallidus Internus (GPi) and Substantia Nigra Pars Reticulata (SNr) are the main output nuclei that project to all 3 afferent centers.
• Striatum (STR) (caudate nucleus & putamen) is the main input nucleus.
• STR contains striatal neurons divided into two classes.
• STR D1 neurons express dopamine D1 receptors and project to the GPi-SNr, forming the striatal D1 DIRECT pathway, comprising roughly half of the STR neurons.
• STR D2 neurons express dopamine D2 receptors and project to the Globus Pallidus externus (GPe), forming the striatal D2 INDIRECT pathway, comprising roughly half of the STR neurons.
• The DIRECT pathway reaches the GPi-SNr in one synapse, while the INDIRECT pathway reaches the GPi-SNr in three synapses.
• The indirect pathway involves a loop involving the GPe and subthalamic nucleus (STN).
• Neurotransmission through the direct pathway reaches GPi-SNr in one synapse while the indirect pathway requires three
• The cerebral cortex (CTX) is the corticostriatal pathway. The STR receives input from all lobes of the cerebrum (frontal, parietal, temporal, occipital).
• The most important corticostriatal input arises from the collaterals of the corticospinal tract.
• Substantia nigra pars compacta (SNc) is the nigrostriatal pathway, which famously degenerates in Parkinson's disease.
• It is extremely important in balancing activity through striatal direct and indirect pathways.
• The motor thalamus, penduculopontine nucleus, and superior colliculus each use an excitatory neurotransmitter to stimulate each target.
• The GPi-SNr complex tonically fires at high frequency when the body is at rest: releasing the inhibitory neurotransmitter GABA into the thalamus, PPN, and SC inhibiting unwanted movements as a 'brake system'.
• Releasing the 'GPi-SNr brake' involves disinhibition, the overall mechanism of having 2 inhibitory synapses in a row.
• The striatal D2 Indirect pathway counters the effects of the striatal D1 with 3 synapses.
• More DA = more movement, direct pathway dominant and less DA = less movement, indirect pathway dominant.
• Dopammine (DA) nigrostriatal pathway is key to tipping the balance in favor of movement when the corticostriatal pathway is stimulated.
• Striatal neurons use DA D1 receptors (excitatory) and DA at D2 receptors expressed by striatal indirect pathway neurons, which suppress cAMP formation and is generally inhibitory.

Movement Disorders

• Damage to BG circuitry may result in movement disorders, classified as hypokinetic or hyperkinetic.
• Hypokinetic disorders cause suppressed movements, marked by a frozen, immobile appearance.
• Hyperkinetic disorders cause excessive movements indicating the patient is 'out of control'.
• Basal ganglia diseases may cause unilateral or bilateral symptoms.
• Unilateral symptoms with sudden onset indicate an ischemic event.
• Bilateral symptoms with gradual onset indicate BG disease affecting both hemispheres.
• Basal Ganglia circuitry in one hemisphere controls the musculature of the contralateral limbs.
• Unilateral BG damage primarily affects contralateral limbs, while bilateral damage causes bilateral symptoms.
• Subsequent sections focus on four movement disorders: Parkinsonism, Hemiballismus, Huntington's disease, and Wilson disease.
• Parkinsonism is the most common hypokinetic disorder; the other three are hyperkinetic.

Parkinson's Disease

• Hypokinetic disease refers to the akinetic, rigid syndrome often called Parkinsonism.
• Parkinsonism is typically responsive to treatment with the dopamine precursor L-DOPA administered orally.
• L-DOPA is converted to dopamine in cells as a treatment.
• Parkinsonism symptoms are: Tremors, Rigidity, Akinesia, and Postural disturbances
• Idiopathic Parkinson disease (PD) is of unknown origin, results from a progressive degeneration of dopamine neurons within the substantia nigra pars compacta.
• After 80% loss of dopamine neurons, patients begin to show the signs.
• The net effect of PD pathology is excessive STN activity, resulting in strong activation GPi/SNr inhibiting the excitatory stimulation.
• PD patients are commonly treated with L-DOPA administered with a peripheral inhibitor of dopa decarboxylase.
• Neurosurgical procedures include deep brain stimulation (DBS), in which probes are implanted into the overactive STN or GPi, with high-frequency pulses being delivered by a stimulator under the skin.

Hyperkinetic Disorders

• Hyperkinetic disorders produce several different types of abnormal movements: Chorea, Ballism, Athetosis, Dystonia.
• Hemiballismus (HB) is a stroke that damaged the posterior communicating artery or the posterior choroidal artery from the PCA
• HB is a unilateral damage to the STN with hyperkinesia in the contralateral limbs.
• Limb movements are sudden and powerful. Symptoms resolve spontaneously several weeks after the initial stroke, but many patients exhibit chorea over the long term.

Huntington’s disease

• Huntington's Disease (HD) is an autosomal dominant genetic disorder with complete penetrance that strikes in midlife usually after child-bearing age.
• Huntington's Disease presents as: Dementia, Chorea & athetosis.
• There will be hyperkinetic writhing movements of HD, which disrupts normal motor behavior; patients may attempt to mask by attempting to coincide with choreic bouts.
• At later stages of disease, patients transition to hypokinesia

Wilson's Disease

• Also called hepatolenticular degeneration, it is an autosomal recessive disorder affecting the ATP7B (adenosine triphosphate) gene involved in copper uptake.
• Damages the lenticular nucleus (putamen & globus pallidus).
• Neurologic manifestations include dysarthria, dystonia, rigidity, wing beating tremor, and choreoathetosis.

Recognizing BG Nuclei

• Recognizing changes in size, shape, or signal density in the BG nuclei in the medical images is essential as each may indicate disease.
• The head of the caudate is easy to spot just lateral to the slit-like anterior horn of the lateral ventricle and deep to the gray and white matter of the cerebral cortex

Overview of the basal ganglia's role in controlling movement through pathways to upper motor neurons. Focus on anatomical organization, including the striatum, caudate nucleus, and globus pallidus. Motor deficits are referred to as "extrapyramidal".