basal ganglia anatomy connection pathways modulation loops defects Parkinsonism abnormal movement

1. Presented by
Dr Shashank Agrawal
Senior resident (DM neurology)
Basal ganglia
and its circuit

2. introduction
• Basal ganglia- basal nuclei
• Collection of mass of grey matter (subcortical
nuclei) situated at the base of fore brain and
top of midbrain within each cerebral
hemisphere
• The basal ganglia are a key part of the
network of brain cells and nerves that control
your body’s voluntary movements.
• They can approve or reject movement
signals that your brain sends, filtering out
unnecessary or incorrect signals.
• This lets you control certain muscles without
also using other muscles that are nearby

3. Embryology
• From the neural tube - 3 primary
vesicle is formed with in 4th week
Three primary brain vesicles:
• Forebrain (prosencephalon)
• Midbrain (mesencephalon)
• hindbrain(rhombencephalon)

5. Blood Supply
Artery From Supply
LENTICULOSTRIAT
E
MCA
Basal ganglia , internal
capsule
Anterior choroidal
Internal
carotid
Globus pallidus, putamen,
thalamus, posterior limb
internal capsule
Recurrent artery of
heubner
ACA
Head of caudate, anterior
putamen, globes pallidus,
internal capsule
Thalamoperforator PCA
Thalamus , posterior limb of
internal capsule

6. Neostraitum
• Caudate nucleus
• putamen
• Ventral straitum(nucleus accumbens)
Paleostriatum
• Globus pallidus external segment (GPe)
• Globus pallidus internal segment (GPi)
Substantia nigra
• Pars compacta(SNc)
• Par Reticulata(SNr)
Sub thalamic nucleus(STN)
Basal ganglia nuclei

7. Corpus Striatum
• .“striatum” - derived from the striated
appearance produced by the stands
of gray matter passing through the
internal capsule and connecting the
caudate nucleus to the putamen of
the lentiform nucleus
• Situated lateral to the thalamus and
is almost completely divided by a
band of nerve fiber (internal capsule)
into the caudate nucleus and
lentiform nucleus.

8. Caudate Nucleus
• The caudate nucleus is a large C-
shaped mass of gray matter that is
closely related to the lateral ventricle
and lies lateral to the thalamus
• The lateral surface of the nucleus is
related to the internal capsule, which
separates it from the lentiform nucleus.
• It can be divided into a head , body ,
and tail.

9. • The head of the caudate nucleus is
large and rounded and forms the
lateral wall of the anterior horn of
the lateral ventricle.
• The body of the caudate nucleus is
long and narrow and is continuous
with the head in the region of the
interventricular foramen and from
floor of lateral ventricle.
• The tail of the caudate nucleus is
long and slender and is continuous
with the body in region of the
posterior end of the thalamus.

10. Role of caudate nuclei
•several types of dementia
•obsessive-compulsive disorder (OCD)
•attention deficit hyperactivity disorder (ADHD)
•bipolar disorder
•schizophrenia
•Huntington’s disease
•Parkinson’s disease
•autism
•Tourette syndrome
•planning movement
•learning
•memory
•reward
•motivation
•emotion
•romantic exchanges
Dysfunction of caudate nuclei

11. Lenticular nucleus
• Biconvex lens
• Triangular in both coronal and
horizontal section
• Medially to internal capsule
• Separate caudate to thalamus
• Divide by external lamina of white
matter
• Putamen & Globus pallidus

12. Putamen
• Outer part of lenticular nucleus and it is
Quadrangular in shape
• Its lies medial to the insula.
• Bounded laterally by external capsule
• Medially by globes pallidus
• The putamen is a common site for
hypertensive bleed as well as infarction

13. Role of putamen nuclei
• Mixed motor and sensory
• Pure motor
• Pure sensory
• Ataxic hemiparesis
• Dysarthria with clumsy hands
• Hemiballism and hemichore
• Parkinson’s disease
• Learning
• Motor control
• Including speech articulation
• Language functions
• Reward
• Cognitive functioning
• Addiction
Dysfunction of putamen nuclei

14. Globus Pallidus
• Lighter in colour due to highly
concentric myelinated nerve fibre.
• lies beneath the insula
• The medial medullary lamina of the
white matter divides the GP into
globus pallidus internus (GPi) and
globus pallidus externus (GPe)

15. Role of globes pallidus
• he primary function of the globus pallidus is to control conscious and
proprioceptive movements.
• The GPe is the intrinsic nucleus, they act as a relay information
• whereas the GPi is the output nucleus, they primarily sends information to the
thalamus
dysfunction
• The dysfunction of the GP has been noted in (rare)ischemia, alcohol, and opiate
abuse.
• This dysfunction gives rise to various cognitive and motor problems like ADHD,
OCD, Tourette’s syndrome, acquired dystonia.

16. Substantia Nigra
• It is present in midbrain
• B/w the tegmentum & the basic peduncule
• Mesencephalic in origin
• Highest concentration of GABA in CNS
• Two component
• Pars compacta : dorsal cell- rich portion
• Pigmented (neuromelanin) neurons= contain
dopamine
• Principal source of striata dopamine
• Par reticulate: ventral cell-sparse portion
• Inhibitory neurotransmitter GABA

17. Subthalmic Nuclei
• The neurone of the sub thalamic nuclie
are glutaminergic and excitatory and
have many connections to the globes
pallidus and substantial nigra.
• It does not directly influence any
muscles, but it does play a role in
modulating movement with the other
components of the basal ganglia.
• Damage to the subthalamic nucleus
can result in a disorder of movement
called hemiballismus.

18. Function of basal ganglia
1. Control of muscle tone
2. Control of motor activity
• Regulation of voluntary movement
• Regulation of conscious movement
• Regulation of subconscious movement
3. Control of reflex muscular activity
4. control of automatic associated movements
5. Role in arousal mechanism

19. Limbic loop
• Cingulate , temporal, orbitofrontal,
hippocampus, amygdala are the main
input
• The limbic loop is likely to be involved in
giving motor expression to emotions, e.g.
through smiling or gesturing, or adoption
of aggressive or submissive posture.
• The loop is rich in dopaminergic nerve
endings , and their decline may account
for the mask like facies and absence of
spontaneous gesturing characterstics of
PD and later DEMENTIA

20. Cognitive loop(Prefrontal )
• Head of caudate nucleus receives a large
projection from the homolateral frontal cortex,
parietal , temporal, occipital cortex and it
participate in motor learning.
• The cortical connections of the caudate
suggest that it participates in planning ahead,
particularly with respect to complex motor
intentions.

21. motor loop
• They seem to be involved in scaling the
strength of muscle contraction and in organizing
the requisite sequence of excitation of cell
columns in the motor cortex.
• They come into action after the corticospinal
tract has already been activated by ‘ premotor ‘
area including the cerebellum.
• It is believed that the putamen provides a
reservoir of learned motor program which it is
able to assemble in appropriate sequence for
the movement , and transmit the code
information to Sensory Motor Area.

22. Oculomotor loop
• While the eye fixated , SNpr is tonically
active. Whenever a deliberate saccade is
about to be made toward another object,
the oculomotor loop is activated and the
superior colliculus is disinhibited.
• In PD oculomotor hypokinesia is due to
faulty disinhibition of the superior colliculus
following associated neuronal
degeneration within SNpr.

23. Basal ganglia circuit
• Two circuit important in regulation of
movement
• Direct pathway
• Indirect pathway
• Hyper direct pathway
• Direct pathway decrease inhibition
basal ganglia output
• Indirect pathway increase inhibitory
basal ganglia output
• Balancing of these two circuit
underlies regulation of movement
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C

24. Afferent fibre
From cerebral cortex arising primarily from the
pyramidal cells of the layer V, VI via corticostriate
fibres. These are glutaminergic
• Sensorimotor cortex——-> putamen
• Association region———> Caudate nucleus
• Prefrontal regions ———-> head of caudate.N
Thalamostriate fibres
• Intrealaminar nuclie of the thalamus —> caudate
& putamen

25. Afferent fibers
Nigrostriate fibers
• Substantia nigra ——> caudate &
putamen
• Likely dopamine at their terminal,
Inhibitory in function
Brainstem striatal fibres
• Brainstem —-> caudate and putamen
• Serotonine at the terminals , inhibitory
in function

26. Efferent fibres
• Striatopallidal fibers
• Caudate nucleus & putamen —->
globes pallidus (Gpe) and Gpi).
GABA (inhibitory) neurotransmitter
• Striatonigral fibres
• Caudate nucleus & putamen —->
Substantia nigra . GABA inhibitory
neurotransmitter

27. Connection to globes pallidus
• Afferent fibers- striatopallidial fibers.
• Efferent fibers- pallidofugal fibers.
Types……
• Ansa lenticularis —> thalamic nuclei
• Fascicles lenticularis—> sub-thalamus
• Pallidotegmental fibers —> caudal
tegmentum of the midbrain
• Pallidosubthalamic fibers—> subthalamic
nuclei

28. Direct pathway
• Direct pathway main function is to
initiation and maintenance of
movement
• Excitatory neuron from the cerebral
cortex to putamen
• From putamen to GPi and SNr
inhibitory projection
• From GPi /SNr to thalamus inhibitory
flow
• Disinhibition of thalamus cause
excitation of thalmocortical pathway
and activate the motor cortex

29. Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
direct
pathways

30. Indirect pathway
Main function to play role in suppression of
extraneous movement
• Excitatory neuron form cortex to
putamen
• Inhibitory neuron from putamen it
goes to GPe
• From GPe to substantial nigra
inhibitory neutron
• SBn to GPi excitatory neuron
• GPi to thalmus inhibitory neuron

31. Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Indirect
pathways
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
direct
pathways

32. Hyperdirect pathway
•substantia nigra receive strong
excitatory signals from the cortex
directly through STN and has a
shorter conduction time compared
to the direct and indirect pathways.
•cortex directly to the subthalamic
nucleus (STN), skipping the
striatum.
•Therefore, the glutamatergic
excitatory neurons of the STN can
then excite the GPi/SNr .
•thus suppressing thalamic activity
on the cerebral cortex.
Emergency brake

33. Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Hyperdirect
pathways

35. MODULATION OF THE BASAL GANGLIA
The neuronal circuits that modulate the function of the basal ganglia are:
•The Nigrostriatal Pathway
•The Cholinergic Pathway

36. Substantia nigra effect on direct pathway
• Substantia nigra release dopamine on Both pathway.
• Receptor on direct pathway is D1 , which is excitatory.
• So combine effect of glutamic and dopaminergic is always excitatory.
• Effect of dopamine is to initiate the movement and tuning of the movement

37. Without dopamine effect on indirect pathway

38. Dopamine effect on indirect pathway

39. Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
direct
pathways
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Indirect
pathways
D1
D2

40. Dopaminergic and cholinergic modulation
of direct and indirect pathways
• Dopamine produce y substantia nigra
par compacta
• Dopamine has an excitatory effect upon
Direct Pathway via D1 receptor
• Dopamine has an inhibitory effect on
indirect pathway via D2 receptors
• Both of these lead to increase motor
activity

41. Continue…
• Cholinergic (Ach) interneurons synapse
on the GABAergic striatal neurons that
project ti GPi and GPe.
• The cholinergic action s INHIBIT striatal
cells of the Direct Pathway and EXCITE
striatal cell of the Indirect Pathway
• Thus effect of ACH are opposite of
Dopamine on direct and indirect pathway
and decrease the motor activity

42. DOPAMINE
ACETYLECHOLINE
Substantia nigra and cholinergic cause tuning of the movement by controlling the indirect
pathway
GABA neuron fibers

43. Two type of disorder
• Hypertonic- hypo kinetic
• Hypotonic - hyperkinetic
Hypertonicity is an abnormal increase of the muscle tone in response to passive stretch. when
the indirect pathway of the basal ganglia is stimulated, it sends signals to the motor cortex and
brainstem, which ultimately inhibit muscle tone. when a lesion of the basal ganglia occur, this
inhibitory influence is lost and hypertonicity is manifested contralateral to the side of the lesion
Dyskinesia is a presence of the unintentional purposeless movements. Dyskinesias are
classified further as:
• Hypokinesia
• Hyperkinesia
Disorder of basal ganglia

44. Hypertonic-hypokinetic disorders
These disorders result from the degeneration of the neurons that form the direct pathway.
Since this is the pathway that serves for the planning of the movement, the problems that
patients will have been presented in two forms:
Bradykinesia represents a generalized slowness of movement and is the most
common hypokinesia.
Akinesia is presented with the inability to move at all because the individual is unable
to plan or to direct a movement toward a desired position or target.

45. Parkinson’s disease
Parkinson’s disease (PD) is a chronic
progressive nurodegenrative disorder
characterised by slowness in the initiation
and execution movement ( bradykinesia),
increase muscle tone ( rigidity), tremor at
rest, and gait changes.
Lack of dopaminergic response
Defect in Substantia Nigra

46. Parkinson disease
Hypokinesia- bradykinesia/akinesia
It is the result of the degeneration of the
dopaminergic neurons of the pars
compacta of the substantia nigra.
• direct pathway less excited
• Indirect pathway less inhibited
which lead to lost of the excitation of
the supplementary motor area
which cause loss pf planning and
execution of movement .
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Indirect
pathways

47. Rigidity
Rigidity means stiff or inflexible muscles. It
can stop your muscles from stretching and
relaxing, which can lead to pain and
muscle cramps and problems with balance.
Due to less excitation of the cortex , which
cause less stimulation of cortical reticular
fibre which lead to over excitation of or
reticulating system and cause in increase
of tone
Tone of both flexor and extensor increase
together and cause rigidity

48. Rigidity
•swinging your arms because your muscles are too tight and stiff.
•turning around, getting out of chairs, and turning over in bed.
•doing everyday tasks, such as writing or doing up buttons.
•chewing and swallowing. Stiff face muscles can make it harder to chew and
swallow.
•breathing and speaking clearly. Rigidity can also affect chest muscles and make
them weaker. This can lead to problems with breathing and issues like chest
infections.
•Breathing difficulties can also affect the tone and loudness of your voice, and make
pronounciation hard.
Action affected

49. Tremors
• Involuntary rhythmic oscillatory
movements of distal parts of limb
and head
• Resting tremors
• Absent at sleep and increase by
stress and excitement
• 4-6 times/sec
• Fill rolling movement

50. MANAGEMENT OF
PARKINSONISM
• Medical
• Surgical
• Deep brain stimulation

51. Surgical management
Ablative
• Thalamotomy
• Pallidotomy
• Subthalamotomy
Deep brain stimulation
• VIM thalamus (VIM)
• Globus pallidus internus(GPi)
• Subthalamic nucleus(STN)
Transplant
• Human fetal , xenotransplant, genetically engineered transplants

52. Deep brain stimulation
• Inroduced in the 1990s
• By Benavides ET AL
• neurosurgical procedure involve
ng the implantation of a
medical device called a
neurDstimulator
• sends electrical impulses, through
implanted electrodes, to specific
targets in the brain (brain nuclei) for
the treatment of movement and
neuropsychiatric disorders

53. Indication of DBS
1.Patients with uncontrollable tremor for
whom medications have not been effective.
2.Patients with symptoms that respond well to
medications but who, when the drugs wear
off, experience severe motor fluctuations
and dyskinesias, despite medication
adjustments.
3.Patients whose movement symptoms might
respond to higher or more frequent
medication doses, but who are limited to do
so because of side effects.
4. Essential tremor , dystonia
5.Psychiatric illness- OCD , Tourette disorder

54. Mechanism and target of DBS
Mechanism of action
• Inhibit of target
• Activation of target
• Combined effect
• Disruption of pathological oscillation to restore
rhythmic activity and synchronisation
Target site for stimulation
• Subthalmic nucleus
• Globus pallidus interna
• Thalamus

55. Component of DBS
•The LEAD or electrode : a thin, insulated
wire—is inserted through a small opening in
the skull and implanted in the brain. The tip
of the electrode is positioned within the
targeted brain area
•The EXTENSION Is an insulated wire that is
passed under the skin of the head, neck, and
shoulder, connecting the lead to the neuro
stimulator
•The NEUROSTIMULATOR : is the third
component and is usually implanted under
the skin near the collarbone.

56. Technique of DBS
• Targeted area Is located by ct or mri imaging
• Quadripolar leads are connected to stimulator and
to battery
• Once electrodes are implanted it is attached top
wires that run inside body from head down to
collar bone where battery operated stimulator are
implanted
• From stimulator electrical impulses are
continuously delivered over wire to electrode in
brain
• Reprogramming can be done with 3,4 months

57. Side effects of DBS
Confusion
Numbness and weakness of body
Difficulty in speech
Mood changes
Bleeding in brain
Movement disorder
Seizures
Lead - migration, fracture, erosion, malfunction

58. Hypotonic-hyperkinetic disorders
Disturbance of the indirect loop that causes a
loss of the inhibition of the thalamic neurons,
which ultimately results in excess cortical activity
and movement. They are presented as:
Tremor, that is a rhythmic, low amplitude
movement that may be manifested as the nodding
of the head, or in the hands and feet.
Dystonia is characterized by involuntary,
sustained muscle contraction that leads to
abnormal postures of the neck, toes, hands, or
other parts of the body.

59. Chorea
Chorea is a sequence of rapid
involuntary movements involving mostly
the hands and feet, the tongue, and
facial muscles.
In this many motor program are
abnormally release.
• Hunginton chorea
• Sydenhams chorea
• Chorea gravidum
• Wilsons disease ( hepatic lenticular)
Michael Jackson dance

60. Huntington’s
disease
• A rare inherited condition.
• Defect manifesting as a CAG repeat on chromosome 4p
on the HTT.
• Which leads to neuronal death in the caudate and the
putamen.
• The indirect pathway is interrupted and leads to a
hyperkinetic.
• Symptoms include involuntary movements such as
chorea, cognitive degeneration, and psychiatric
dysfunction.
• Tetrabenazine and reserpine are palliative medicines
that decrease the disease symptoms.
• Tetrabenazine which is a vesicular monoamine
transporter inhibitor. It inhibits monoamine (serotonin,
dopamine, norepinephrine) uptake into synaptic vesicles.
This reduces the intense stimulation of the striatum from
the nigrostriatal pathway.
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Indirect
pathways

61. Athetosis
Athetosis is a movement dysfunction.
It’s characterized by involuntary writhing
movements. These movements may be
continuous, slow, and rolling..
With athetosis, the same regions of the
body are repeatedly affected. These
typically include the hands, arms, and
feet. The neck, face, tongue, and trunk
can be involved, too.
Mostly distal part involve.

62. Hemiballismus
• A condition where the patient
exhibits involuntary ballistic (violent
striking) movements on only one
side of the body, that affect only the
proximal muscles of a limb.
• Lesion in the contralateral
subthalamic nuclei. Given that the
subthalamus is part of the indirect
pathway this lesion reduces or
eliminates indirect pathway signaling
• Leading to a relative overabundance
of activity in the direct pathway.
Cortex
P
GPe GPi
SN Pc
SN Pr
Thalamus
STN
C
Indirect
pathways

63. Ballismus is the equivalent to the hemiballismus,
with the difference that it affects the entire body. It
is the most extreme type of dyskinesia.
Tics are brief, stereotyped semi-voluntary
movements, which means that unlike other
movement disorders, they are partially
suppressible. Tics can be either motor (motor tics)
or sounds (vocal tics).These tics have been
associated with dysfunction of the GABAergic
projections from the striatum,
Myoclonus is a jerky, involuntary, and usually
Continue..
Tourette syndrome

64. Now use your limbic system to smile and get
arouse from the boring topic
And clap your hand by using motor pathway
Relax your ocolomotor loop as the seminar the end.

65. Zona increta and pedunculopontine nucleus pal a important
role in locomotion , muscle tone and akinesia
Gullian mollarate triangle- red nucleus, dentate nucleus,
inferior Oliver nucleus is involve and cause palatal
myoclonus and myothermia