Basal Ganglia Anatomy and Function

• The basal ganglia are a group of deep gray matter nuclei in the brain that include the putamen, caudate nucleus, globus pallidus (GPe and GPi), subthalamic nucleus, and substantia nigra.
• These structures are critical for motor control, eye movements, cognitive functions, and emotional processing.
• The basal ganglia appear in coronal and horizontal brain sections as deep gray matter nuclei.
• The putamen is the most lateral structure and is separated from the caudate nucleus by the internal capsule.
• The globus pallidus is medial to the putamen and has two segments: the external segment (GPe) and the internal segment (GPi).
• The subthalamic nucleus lies below the thalamus.
• The substantia nigra is located in the midbrain within the cerebral peduncles, visible at the level of the superior colliculus.

Input and Output Pathways

• Input to the basal ganglia primarily comes via the striatum (caudate and putamen) from widespread cortical areas through the corticostriatal pathway.
• The striatum integrates cortical and subcortical inputs.
• Output from the basal ganglia is inhibitory (GABAergic), mainly from the GPi and substantia nigra pars reticulata (SNr), projecting to the ventral anterior (VA) and ventral lateral (VL) nuclei of the thalamus.
• These projections regulate motor cortex activity, influencing movement.

Internal Circuits and Motor Pathways

• The basal ganglia influence movement via two main internal circuits: the direct and indirect pathways, which have opposing effects.
• The direct pathway facilitates movement by reducing GPi-mediated inhibition of the thalamus.
  • The cortex excites the striatum, which inhibits the GPi, allowing the thalamus to activate the motor cortex.
• The indirect pathway suppresses unwanted movements.
  • The striatum inhibits the GPe, which normally inhibits the subthalamic nucleus (STN).
  • Inhibition of the GPe disinhibits the STN, allowing it to activate the GPi, which increases inhibition of the thalamus and reduces motor cortex activation.

Modulatory Pathways

• The nigrostriatal pathway, originating from the substantia nigra pars compacta (SNc), modulates both the direct and indirect pathways via dopamine.
  • Dopamine activates D1 receptors (excitatory) on the direct pathway and D2 receptors (inhibitory) on the indirect pathway, promoting movement overall.
• The STN communicates with GPi via the subthalamic fasciculus.
• The GPi sends output to the thalamus through the ansa lenticularis and lenticular fasciculus, collectively known as the thalamic fasciculus.
• Dysfunction in these circuits leads to various movement disorders:
  • Parkinson’s disease (SNc degeneration)
  • Hemiballismus (STN lesion)
  • Huntington’s disease (striatum atrophy)

Direct vs. Indirect Pathways

• The direct pathway facilitates movement.
  • Excitatory cortical input to the striatum inhibits the GPi/SNr.
  • GPi normally inhibits the thalamus, this "inhibition of inhibition" allows the thalamus to activate the cortex, promoting movement.
  • Dopamine from SNc enhances this via D1 receptors.
• The indirect pathway suppresses unwanted movement.
  • Involves inhibition of GPe, which disinhibits the subthalamic nucleus (STN).
  • The STN excites the GPi, which inhibits the thalamus more strongly, reducing motor output.
  • Dopamine inhibits this pathway via D2 receptors.

Parkinson's Disease (PD)

• Caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc).
• Reduces D1 stimulation (↓ direct pathway) and D2 inhibition (↑ indirect pathway), leading to less movement (hypokinesia or akinesia).
• The thalamus is over-inhibited, reducing cortical output.
• Treatment includes L-Dopa or deep brain stimulation, often targeting the subthalamic nucleus to reduce overactivity of the indirect pathway.

Huntington's Disease (HD)

• Involves degeneration of striatal neurons, particularly those projecting to the GPe.
• This weakens the indirect pathway, reducing STN activation of GPi.
• As a result, thalamic inhibition is lost, leading to excessive movement (chorea, hyperkinesia).

Functional Circuits of the Basal Ganglia

• Motor Circuit:
  • Integrates input from premotor, primary motor, and sensory cortex.
  • Regulates voluntary movement via thalamus (VA/VL).
• Oculomotor Circuit:
  • Regulates eye movements, especially saccades.
  • Links frontal eye fields → caudate → SNr → superior colliculus.
• Associative Circuit:
  • Governs cognitive and planning functions.
  • Connects prefrontal cortex → caudate/nucleus accumbens → VA/CM thalamus.
• Limbic Circuit:
  • Controls emotion and motivation.
  • Inputs from the amygdala, hippocampus, and orbitofrontal cortex project to the nucleus accumbens, influencing emotional expression and facial gestures.

Blood Supply to the Basal Ganglia

• Anterior choroidal artery (from internal carotid): supplies the posterior putamen and tail of the caudate.
• Anterior cerebral artery (ACA): supplies head of the caudate and anterior putamen/GP via medial lenticulostriate arteries.
• Middle cerebral artery (MCA): major supplier to the putamen and globus pallidus via lateral lenticulostriate arteries.
• Posterior cerebral artery (PCA): supplies the subthalamic nucleus and substantia nigra through deep penetrating branches.

Basal Ganglia Key Structures & Functions

• Globus Pallidus (GP):
  • Location: Medial to the putamen, lateral to the thalamus.
  • Subdivisions:
    • GPe (External Segment): part of the indirect pathway, modulates activity via the subthalamic nucleus.
    • GPi (Internal Segment): major output nucleus, sends inhibitory (GABAergic) signals to the thalamus.
  • Forms the lentiform nucleus along with the putamen.
• Nucleus Accumbens:
  • Location: Ventral/anterior fusion of the head of caudate and putamen.
  • Function: Central to limbic-motor integration, key role in reward circuitry and dopaminergic input.
  • Involved in addiction, motivation, and reward-seeking behavior.
• Subthalamic Nucleus (STN):
  • Location: Inferior to thalamus, superior to midbrain tegmentum.
  • Function: Excitatory output (glutamate) to GPi and SNr, helps time rhythmic motor output.
  • Lesions (e.g., in stroke) → hemiballismus (wild flinging movements).
  • Target for deep brain stimulation (DBS) in Parkinson’s disease.
• Substantia Nigra (SN):
  • Location: Rostral midbrain, part of cerebral peduncle.
  • Divisions:
    • Pars compacta (SNc): contains dopaminergic neurons projecting to striatum (caudate + putamen).
    • Pars reticulata (SNr): functionally similar to GPi, sends inhibitory output.
  • Function: Modulates the direct and indirect pathways via dopamine.
    • D1 receptors (excitatory) → stimulate direct pathway.
    • D2 receptors (inhibitory) → suppress indirect pathway.
  • Degeneration of SNc = hallmark of Parkinson’s disease.

Mnemonic

• GPi = "I" = Inhibits the thalamus directly
• GPe = "E" = Edits/modulates the indirect pathway via STN

Clinical Pearls

• GPi:
  • Target of deep brain stimulation (DBS) in Parkinson’s disease
  • Reducing its activity can increase movement
• GPe:
  • Degenerates in Huntington’s disease, leading to less inhibition of STN, disrupting motor control and causing involuntary movements (chorea)

Clinical Mnemonic

• “GAPS” for High-Yield Players:
  • G – Globus Pallidus (GPe/GPi)
  • A – Accumbens nucleus (emotion, reward)
  • P – Pars compacta (dopamine for movement)
  • S – Subthalamic nucleus (rhythmic inhibition, lesion → ballismus)