HUF 2-48 Basal ganglia functions and dysfunctions

Question 1

Disorders of basal ganglia

Answer 1

Hypokinetic: Parkinson’s disease

* also exhibits ‘release’ symptoms like resting tremor

Hyperkinetic:

Huntington’s disease

Ballism

Tardive dyskinesia

Question 2

Functions of basal ganglia

Answer 2

• Motor control (manifested by motor disorders)
• Higher order motor control: planning / execution of complex motor strategies
• Select the right motor program: facilitate certain movement / posture while suppress unwanted ones
• Non-motor, cognitive functions: decision-making

Question 3

Compositions of basal ganglia

Answer 3

5 extensively interconnected subcortical nuclei:

1. Caudate nu.
2. Putamen
3. Globus pallidus (ext. + int.)
4. Subthalamic nu.
5. Substantia nigra (pars compacta: dopamine; pars reticulate: GABA)

All nu. connections are GABAergic except STN (glutamate) and SNc (dopamine)

Input: Striatum (caudate + putamen)

Output: Globus pallidus int. + SNr

Question 4

Aff. connections of basal ganglia

Answer 4

Corticostriate projetion

Caudate nu.

• from cerebral cortex

Putamen

• from cerebral cortex; centromedian nu. of thalamus

Question 5

Eff. connections of basal ganglia

Answer 5

GPi

=> VA nu. + VL nu. + CM nu. of thalamus

=> Motor cortex

SNr

=> Superior colliculus

=> Eye movements

Question 6

Interconnections of basal ganglia nu.

Answer 6

Putamen

=> GPe, GPi, SNr

GPe

=> STN

STN

=> GPi, SNr

SNc

=> Putamen

Question 7

Parkinson’s disease

Answer 7

Pathophysiology:

• Degeneration of SN dopamine neurons
• ↓ dopamine in striatum
• Unknown cause

Clinical manifestations:

• Akinesia
• Bradykinesia
• Rigidity
• Resting tremor
• Slowly progressive; onset between 55-60

Treament:

• L-DOPA (precursor of dopamine)
• Anti-cholinergic agents
• Dopamine agonists e.g. Bromocriptine

Question 8

Huntington’s disease

Answer 8

Pathophysiology

• Degeneration of cholinergic and GABA neurons in striatum and cortex
• Autosomal dominant

Clinical manifestations:

• Chorea
• Dementia
• Onset at any age, but very rare

Treatment:

• No specific therapy for dementia
• Dopamine antagonists e.g. Phenothiazine (for chorea)

Question 9

Ballism

Answer 9

Pathophysiology:

• Lesion in one STN
• Vascular accident

Clinical manifestations:

• Chorea (severe)

Treatment:

• Dopamine antagonists e.g. Phenothiazine

Question 10

Tardive dyskinesia

Answer 10

Pathophysiology

• Dopamine receptor hypersensitivity
• Long term treatment of neuroleptics (dopamine antag.)

Clinical manifestations:

• Abnormal voluntary movements esp. in face

Treatment: - Stop offending drug

Question 11

Direct pathway of basal ganglia

Answer 11

Cortex

=> (+) Striatum

=> (-) SN / GPi

=> (-) Thalamus

(+)(-)(+) ∴ Facilitation

Question 12

Indirect pathway of basal ganglia

Answer 12

Cortex

=> (+) Striatum

=> (-) GPe

=> (-) STN

=> (+) SN / GPi

=> (-) Thalamus

(+)(-)(-)(+)(-) ∴ Inhibition

Question 13

Role of dopamine in basal ganglia

Answer 13

• SNc dopamine

=> facilitate movements *always*

• Excite striatum neurons of direct pathway (D1R)
• Inhibit neurons of indirect pathway (still facilitate movements)
• Loss of dopamine supply

=> Indirect pathway >> Direct pathway

Question 14

Malfunctions in Parkinson’s disease

Answer 14

Degeneration of nigrostriatal pathway

=> Indirect >> Direct

=> Hypokinetic symptoms

Question 15

Malfunctions in other basal ganglia disorders

Answer 15

Huntington’s disease: Cholinergic and GABA neurons of indirect pathways are selectively affected

Ballism: Damage to STN, which is in indirect pathway ONLY

Question 16

Surgical approach to Parkinson’s disease

Answer 16

Surgical lesions of STN and GPi

=> disrupt excessive inhibition from indirect pathway Deep brain stimulation of STN

• Avoids permanent lesion of STN
• Apply stimulus when needed
• Electrical stimulation inhibits or interferes STN output