180 Basal ganglia in brain………………………………….

Basal ganglia

1. The lady who wouldn’t
smile or frown

2. Mrs.P,60yearoldfemale,presentedwith
complaintsofdifficultyandslownessof
movement,andshakinessofhands.
Tremorsofhandswerenotedwhilehistory
wasbeingtaken.
Shewasfoundtospeakinamonotonousway,
withnofacialexpressions.
1.Whatistheprobablediagnosis?
2.Whichpartofthebrainisaffected?
3.Whatotherclinicalfeaturescanbe
expectedinthispatient?
4.Whatisthephysiologicalbasisof
treatment?

3. RoleofBasalGanglia
inMotorAct

4. Learning objectives
At the end of the session, learners should be able to:
1.List the constituent nuclei of “Basal ganglia”
2.Describe the afferent and efferent connections,
and internuclear circuits of basal ganglia
3.Explain the role of basal ganglia in motor activity
4.List the hypokinetic and hyperkinetic features of
basal ganglia lesion
5.Describe the pathophysiology, clinical features,
and the rationale of treatment of parkinsonism
6.Outline the features of other movement disorders
related to basal ganglia

5. Basal Ganglia

6. Basal Ganglia
Anatomy
Coronal section of the brain showing Basal ganglia
List the constituent nuclei of “Basal ganglia”

7. Basal Ganglia
Anatomy
Coronal section of the brain showing Basal ganglia
Striatum
List the constituent nuclei of “Basal ganglia”

8. Basal Ganglia
Anatomy
Coronal section of the brain showing Basal ganglia
Lenticular
nucleus
Pars compacta
Pars reticulata
List the constituent nuclei of “Basal ganglia”

9. Basal Ganglia
Anatomy
Coronal section of the brain showing Basal ganglia
Striatum
Pars compacta
Pars reticulata
List the constituent nuclei of “Basal ganglia”

10. Basal Ganglia
Anatomy
Lateral view of the brain showing Basal ganglia
List the constituent nuclei of “Basal ganglia”

11. Basal Ganglia
Neurotransmitters
GABA
Striatum
(Caudate &
Putamen)
GABA
Globus
Pallidus
Glutamate
Subthalamic
nucleus
Dopamine
Substantia
Nigra - PC
GABA
Substantia
Nigra - PR

12. Basal Ganglia
Major Connections
Basal ganglia
(Striatum)
Thalamus (IL)Cerebral cortex
Corticostriate pathway Thalamostriatal pathway
Globus Pallidus
Internus
Substantia Nigra
– Pars Reticulata
Thalamus
Pedunculopontine
nucleus
Cortical-basal ganglia-thalamic-cortical loop
Prefrontal and premotor cortex
Raphe
nucleus
Locus
coeruleus
List the connections of
“Basal ganglia”

13. Basal Ganglia
Major internal Connections
Three distinct biochemical pathways in the basal ganglia normally operate in a
balanced fashion:
1. Nigrostriatal dopaminergic system
2. Intrastriatal cholinergic system
Acetyl choline released by the interneurons within the caudate and
putamen nuclei
3. GABAergic system, which projects from the striatum to the globus pallidus and
substantia nigra.
Striatum
Substantia Nigra
- Pars compacta
List the connections of
“Basal ganglia”

14. Output
(GPi & SNr)
Thalamus Brainstem nuclei
Pedunculopontine
nucleus
Intralaminar
Ventrolateral
Ventroanterior
Superior colliculus
Gait & balance
Integrates
cerebellar
inputs
Head & eye
movements
Basal Ganglia
Major efferent Connections
CORTEX
Reticular formation
Red nucleus
Reticulo-
spinal tract
Rubro-spinal
tract
List the connections of
“Basal ganglia”

15. Striatum
Input
Globus pallidus
Internus
Output
Substantia Nigra
- Pars reticulata
Output
Globus pallidus
Externus
Globus pallidus
Internus
Output
Substantia Nigra
- Pars reticulata
Output
Pallidal fibres
Nigral fibres
Basal Ganglia
Major Connections
List the connections of
“Basal ganglia”

16. Input
Globus pallidus
Internus
Output
Substantia Nigra
- Pars reticulata
Output
Globus pallidus
Externus
Globus pallidus
Internus
Output
Subthalamic
nucleus
Substantia Nigra
- Pars reticulata
Output
Striatum
Basal Ganglia
Major Connections
List the connections of
“Basal ganglia”

17. DIRECT PATHWAY
Input
Globus pallidus
Internus
Output
Substantia Nigra
- Pars reticulata
Output
Globus pallidus
Externus
Globus pallidus
Internus
Output
Subthalamic
nucleus
Substantia Nigra
- Pars reticulata
Output
Striatum
Basal Ganglia
Major Connections
List the connections of
“Basal ganglia”

18. INDIRECT PATHWAY
Input
Globus pallidus
Internus
Output
Substantia Nigra
- Pars reticulata
Output
Globus pallidus
Externus
Globus pallidus
Internus
Output
Subthalamic
nucleus
Substantia Nigra
- Pars reticulata
Output
Striatum
Basal Ganglia
Major Connections
List the connections of
“Basal ganglia”

19. Pre & Supp
motor area
Globus pallidus
Internus
VA & VL
thalamus
Primary motor
area
Putamen
Basal Ganglia
Major Connections (Putamen circuit)
List the
connections of
“Basal ganglia”
Subthalamus
Globus pallidus
Externus
Substantia nigra
Somatosensory
area
Primary
circuit
Ancillary
circuit

20. Association areas
in different lobes
Globus pallidus
Internus
VA & VL
thalamus
Pre & Supp
motor areas
Caudate nucleus
Basal Ganglia
Major Connections (Caudate circuit)
List the
connections of
“Basal ganglia”
Somatosensory
area

21. Basal Ganglia
Functions
Role in motor activity
1. Cognitive control of motor activity
➢Formulation of appropriate motor response
➢Planning and programming of the movement
2. Execution of learned motor activity
Cutting paper with scissors, Hammering a nail, control of clutch and brake
while driving, etc.
Explain the functions of “Basal ganglia”
Caudate circuit
Putamen circuit

22. Basal Ganglia
Functions
Role in motor activity (contd…)
3. Timing and scaling of movement
➢Determine how rapidly the movement is to be performed
➢Control how large the movement will be
Explain the functions of “Basal ganglia”

23. Basal Ganglia
Functions
Role in motor activity (contd…)
4. Automatic & Associated movements
➢Swinging of arms while walking
➢Facial expressions that accompany speech
Control of reflex muscular activity
➢Inhibitory to spinal reflexes
➢Regulate activity of muscles which maintain posture
➢Co-ordinate visual & labyrinthine reflexes for maintenance of posture
Explain the functions of “Basal ganglia”

24. Basal Ganglia
Functions
Influence on muscle tone
Exerts inhibitory influence on muscle tone
By its effect on reticular formation (especially medullary RF)
(in lesion of BG, there is marked increase in muscle tone:
Lead-pipe Rigidity)
Role in arousal mechanism
By its connections with reticular formation
Explain the functions of “Basal ganglia”

25. Basal Ganglia
Clinical abnormalities
•Three distinct biochemical pathways in the basal ganglia normally operate in a
balanced fashion:
(1)Nigrostriatal dopaminergic system
(2)Intrastriatal cholinergic system
(3)GABAergic system, which projects from the striatum to the globus pallidus and
substantia nigra
•When one or more of these pathways become dysfunctional, characteristic motor
abnormalities occur

26. Basal Ganglia
Clinical abnormalities
•Diseases of the basal ganglia lead to two general types of disorders:
➢hyperkinetic
➢hypokinetic
•The hyperkinetic conditions are those in which movement is excessive and
abnormal, including chorea, athetosis, and ballism.
•Hypokinetic abnormalities include akinesia and bradykinesia.
List the hypokinetic and hyperkinetic features of basal ganglia lesion

27. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
•Also called Paralysis Agitans
•It was originally described in 1817 by James Parkinson and is
named after him.
•Pathogenesis: Degeneration of dopaminergic neurons of the
substantia nigra pars compacta.
➢Dopaminergic influence of Substantia nigra on striatum
decreases
➢Relative increase in cholinergic activity
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

28. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
Clinical features:
Hypokinetic features - akinesia and bradykinesia
➢Difficulty in initiation of voluntary movement
➢Decreased psychic drive for movement
➢Decrease in the normal, associated movements such as swinging of the arms
during walking,
➢Loss of Panorama of facial expressions related to the emotional content of
thought and speech- resulting in a fixed ‘Mask-like’ face
➢Postural instability caused by impaired postural reflexes, leading to poor
balance and falls
➢Gait disturbances (Festinant gait)
➢May include dysphagia, speech disorders, and fatigue
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

29. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
Clinical features (contd…)
Hyperkinetic features:
➢Rigidity
➢Due to increased tone in both agonists and antagonists
➢lead pipe rigidity (uniform resistance through out the range of motion)
➢cogwheel rigidity (series of catch-and-release resistance)
*Differentiate from Spasticity
➢Tremor
➢Present at rest and disappears with activity: Resting tremor
➢Due to regular, alternating 6-8 Hz contractions of antagonistic muscles
➢Typically described as pill-rolling movements of fingers
➢May also be seen in lips and tongue
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

30. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
Clinical features (recap)
Hypokinetic:
Akinesia and Bradykinesia
Decreased and slow voluntary activity
Decreased associated movements and facial expression
Festinant gait
Hyperkinetic:
Rigidity
Tremors
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

31. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
Treatment:
Restoration of dopamine activity (by providing a dopamine precursor like L-Dopa)
A combination of levodopa (L-dopa) and carbidopa, is the most commonly used
drug.
Why not give Dopamine directly?
Dopamine cannot cross blood-brain barrier, but L-dopa can. In the brain it gets
converted to dopamine.
What is the role of carbidopa?
The addition of carbidopa to L-dopa increases its effectiveness and prevents the
conversion of L-DOPA to dopamine in the periphery and thus reduces some of the
adverse side effects of L-dopa (nausea, vomiting, and cardiac rhythm disturbances).
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

32. Basal Ganglia
Clinical abnormalities – Parkinson’s disease
Other therapeutic interventions:
•Dopamine agonists - apomorphine , bromocriptine , pramipexole and
ropinirole
•MAO-B inhibitors - eg, selegiline also prevent the breakdown of
dopamine
•Anticholinergics
•Deep Brain Stimulation (DBS)
•Pallidotomy or Thalamotomy
•Implantion of dopamine-secreting tissue in or near the basal ganglia
Describe the pathophysiology, clinical features, and the rationale of treatment of parkinsonism

33. Basal Ganglia
Clinical abnormalities - HUNTINGTON’S DISEASE
•Inherited as an autosomal dominant disorder.
•Pathogenesis: The abnormal gene responsible for the disease is located near the
end of the short arm of chromosome 4.
➢It normally contains 11–34 cytosine-adenine-guanine (CAG) repeats, each
coding for glutamine.
➢In patients with Huntington disease, this number is increased to 42–86 or
more copies – abnormal protein HUNTINGTIN aggregates, which is toxic.
➢Damage to GABAergic and cholinergic neurons of striatum
Outline the features of other movement disorders related to basal ganglia

34. Basal Ganglia
Clinical abnormalities - Huntington’s disease
Clinical features:
•An early sign is a jerky trajectory of the hand when reaching to touch a spot,
especially toward the end of the reach.
•Later, hyperkinetic choreiform movements appear and gradually increase until
they incapacitate the patient.
•Speech becomes slurred and then incomprehensible,
•Progressive dementia is followed by death, usually within 10–15 years after the
onset of symptoms.
Outline the features of other movement disorders related to basal ganglia

35. Basal Ganglia
Clinical abnormalities – other HYPERKINETIC conditions
CHOREA
•Characterized by rapid, involuntary, jerky “dancing” movements
•Occurs due to damage to Caudate nucleus
ATHETOSIS
•Characterized by continuous, slow writhing movements of the extremities
•Due to damage to Putamen
HEMIBALLISM
•Ballism is characterized by involuntary flailing, intense, and violent movements
•Damage to Subthalamic nucleus produces Hemiballismic movements on one side
Outline the features of other movement disorders related to basal ganglia

36. Basal Ganglia
Clinical abnormalities – WILSON’S DISEASE
•A rare disorder of copper metabolism
•A genetic autosomal recessive disorder
•Effects are more pronounced on the liver and brain
•Pathogenesis: Mutation on the long arm of chromosome 13q
➢It affects the copper-transporting ATPase gene (ATP7B) in the liver, leading to
an accumulation of copper in the liver and resultant progressive liver
damage.
➢In affected individuals, copper accumulates in the periphery of the cornea in
the eye accounting for the characteristic yellow Kayser–Fleischer rings.
Outline the features of other movement disorders related to basal ganglia

37. Basal Ganglia
Clinical abnormalities – Wilson’s disease
Outline the features of other movement disorders related to basal ganglia

38. Basal Ganglia
Clinical abnormalities – Wilson’s disease
Pathophysiology: Degeneration of the putamen, a part of the lenticular
nucleus.
Motor disturbances:
•“wing-beating” tremor or asterixis
•dysarthria
•unsteady gait
•Rigidity
Treatment:
•Chelating agents (eg, penicillamine , trienthine ) are used to reduce the
copper in the body

Outline the features of other movement disorders related to basal ganglia

39. Basal Ganglia
Clinical abnormalities – TARDIVE DYSKINESIA
•Usually Iatrogenic in origin: Caused by medical treatment of another disorder
with neuroleptic drugs such as phenothiazides or haloperidol.
•Pathogenesis: Long-term use of these drugs may produce biochemical
abnormalities in the striatum.
➢The neuroleptic drugs act via blockade of dopaminergic transmission.
➢Prolonged drug use leads to hypersensitivity of D
3 dopaminergic
receptors and an imbalance in nigrostriatal influences on motor control.
•The motor disturbances include either temporary or permanent uncontrolled
involuntary movements of the face and tongue and cogwheel rigidity.
•Treatment: Tetrabenazine, Neuroleptic drug - Clozapine
Outline the features of other movement disorders related to basal ganglia

40. Basal Ganglia
Clinical abnormalities – KERNICTERUS
•Neurological complication of Haemolytic disease of newborn (usually due
to Rh incompatibility)
•Excess bilirubin in the blood can enter the brain tissue, as the blood-brain
barrier is not well established in the newborn
•Causes damage to brain tissue, especially Globus pallidus
•Fatal disease
•If the child survives, manifests with rigidity, chorea and mental retardation
Outline the features of other movement disorders related to basal ganglia

41. THANK YOU
Hand writing of a patient with Parkinsonism