The basal ganglia are clusters of grey matter in the brain that are involved in motor control and regulation. They consist of the striatum, globus pallidus, substantia nigra, and subthalamic nucleus. The basal ganglia have direct and indirect pathways that facilitate or inhibit movement through connections with the cortex and thalamus. Dopamine levels modulate these pathways. Diseases that impact the basal ganglia can cause either excessive or reduced movement. Parkinson's disease results from dopamine deficiency in the substantia nigra, leading to hypokinetic movements.

1. Basal ganglia anatomy

2.  The basal ganglia are the large masses of grey matter
situated within the white core of each cerebral
hemisphere and form essential constituents of the
extrapyramidal system

3.  The principal component of the extra pyramidal motor
system is the BG, the term extra pyramidal came to be
used to refer to the BG and their connections.
 It is not directly concerned with the production of
voluntary movement but is closely integrated with other
levels of the motor system to modulate and regulate the
motor activity that is carried out by way of the pyramidal
system

4.  Extra pyramidal disorders cause a category of
neurologic illness now more often referred to as
movement disorders.
Such conditions may :-
1)produce excessive movement (e.g., Huntington’s chorea),
2) poverty of movement (e.g., Parkinson’s disease),
3) disturbance of posture, tone, righting reflexes,
or other manifestations.

5. Other important structures involved in the
extrapyramidal motor control system include
 1)thalamus,
 2)red nucleus (RN),
 3) the brainstem reticular
formation (RF),
 4)the inferior olivary
nucleus in the medulla,
 5)the zona incerta (ZI),
 6)the vestibular nuclei,
 7)the pedunculopontine
nucleus (PPN), and
 8) the graymatter of the
quadrigeminal plate

6.  Several thalamic nuclei are involved, and these are
sometimes referred to as the motor thalamus
 1)ventralis lateralis (VL), pars oralis (VLo);
 2)ventralis lateralis, pars caudalis (VLc); ventralis posterior
lateralis,pars oralis (VPLo);
 3) ventralis anterior (VA)

7.  The RN is located in the tegmentum
of the midbrain at the level of the superior colliculi.
 It has magnocellular (large-celled) and parvocellular
(small-celled) portions.
 1)The caudal magnocellular part gives rise to the
rubrospinal tract, and
 2)the parvocellular part to the central tegmental tract

8.  The lateral and medial nuclear groups of the RF are
situated in the tegmentum of the midbrain, and other
constituents of the RF that either inhibit or facilitate
motor responses are placed caudally in the brainstem

9.  The PPN is a cholinergic nucleus that lies caudal to the
SN in the brainstem tegmentum, partially buried in the
superior cerebellar peduncle
 It receives afferents primarily fromGPi/SNr and sends
cholinergic projections to the dopaminergic neurons in
the SNc. It may be involved in locomotion

10.  Patients with Parkinson’s disease have significant loss of
PPN neurons, and dysfunction of the PPN may be
important in the pathophysiology of the locomotor and
postural disturbances of parkinsonism

11.  Anatomically, the term
basal ganglia include:
 • Corpus striatum,
 • Claustrum, and
 • Amygdaloid body
 Functionally, the term
basal ganglia also include
 substantia nigra and
subthalamus.Some
workers also
 include red nucleus..
 pedunculopontine nucleus
(PPN)

16.  Corpus Striatum
 Topographically it is almost completely divided into the
caudate nucleus and the lentiform nucleus by a band
of nerve fibres, the internal capsule

17.  However, antero-inferior ends of these nuclei remain
connected by a few bands of grey matter across the
anterior limb of internal capsule called as fundus striate
 These bands give it a striated appearance, hence the
name corpus striatum

18. Caudate Nucleus
 Caudate nucleus is a large comma-shaped mass of grey
matter, which surrounds the thalamus and is itself
surrounded by the lateral ventricle
 Its whole length of convexity projects into the cavity of
lateral ventricle.

20.  Anterior part of caudate nucleus in front of
inter ventricular foramen is called its head.The head
gradually tapers caudally into the body and then into
a tail which merges at its anterior extremity with
amygdaloid body
 The head is large and rounded, and forms the floor
and lateral wall of the anterior horn of lateral
ventricle.The bands of grey matter connect it to the
putamen across the anterior limb of internal capsule

21.  The body is long and narrow, and forms the floor of the
central part of lateral ventricle. It is separated from
thalamus by stria terminalis and thalamostriate vein.
 The tail is long and slender, and forms the roof of inferior
horn of lateral ventricle. It terminates anteriorly in the
amygdaloid body.

22. Lentiform nucleus
 Lentiform nucleus is a large lens-shaped mass of grey
matter beneath the insula forming the lateral boundary
of internal capsule
 It has three surfaces and divides into two parts :-
 The putamen
 The globus pallidus

23. Parts of lentiformnucleus
 A vertical plate of white matter the external medullary
lamina divides the lentiform nucleus into two parts, the
putamen and the globus pallidus.
 The putamen is larger lateral part, darker in colour,
consists of densely packed small cells.
 The globus pallidus is smaller medial part. It is lighter in
colour and consists of large cells.

24.  The globus pallidus is further subdivided by an internal
medullary lamina of white matter into outer and inner
segments

25. .

26. .
 Going caudually,the area
around junction of caudate
and putamen, we will see a
area called ventral striatum
where nucleus accumbens
is present
 Associated with reward
and pleasure seeking
behaviour

27. .
 Caudate nucleus continous
to get smaller
 Internal capsule gets larger
 Laterally we will see
putamen and globus
pallidus
 Anterior comissure
 Ventral pallidum

29. .
 Body of caudate nucleus
getting smaller
 Thalamus between internal
capsule and 3rd ventricle
 Lentiform nucleus
 Mamillary bodies

30. .

31. .

32. .

33. .

34. Connections of corpus striatum
 The BG have rich connections with
 1)one another
 2) brainstem structures,
 3) cerebral cortex and with lower centers

35.  In essence, the cerebral cortex projects to the striatum,
which in turn projects to the GP and SNr; efferents go to
the thalamus, which then projects back to cerebral
cortex, primarily to the motor areas.

36. Connections of corpus striatum
 The striatum (caudate nucleus and putamen) is the
receptive part
 while globus pallidus is the efferent part (outflow centre)
of the corpus striatum.

37. Striatal afferents and efferents

40. Striatal Afferents
 Cortex
The striatum receives topographically organized
glutaminergic axons that originate from small pyramidal cells
in layersV andVI of the entire ipsilateral neocortex
 1)The head of the caudate receives projections from the
frontal lobe
 2) the body from the parietal and occipital lobes
 3) the tail from the temporal lobe

41.  The massive input from the frontal lobe to the head is the
reason it is so much larger than the remainder of the
nucleus.These connections form the anatomical substrate
for the role of the caudate in cognition.
 The caudate also receives fibers from the dorsomedial
(DM) andVA nuclei of the thalamus (thalamostriate fibers)

42.  These connections from cortex and thalamus provide the
striatum with sensory and cognitive inputs
 The connections of the putamen are more focused; it receives
fibers from
 1)cortical areas 4 and6
 2) from the parietal lobe,
 3)the perirolandic motor centers, which are essentially the
same areas that give rise to the corticospinal tract
 putamen has a large connection with the caudate. It also receives
fibers from the SN by the comb bundle.

43. Striatal Efferents
 The caudate sends fi bers to the thalamus (striothalamic
fibers) and to the putamen and GP
 The primary efferent fibers from the striatum project to the
GP and SN
 1)The striatopallidal fi bers from the caudate
run directly through the anterior limb of internal capsule
 2)those from the putamen project medially
through the external medullary lamina into the GP

44. Pallidal Afferents

46.  The principal afferents to the GP are from the caudate and
putamen
 The STN also sends fibers to the GP in the subthalamic
fasciculus ; some pass throughthe internal capsule into the
medial segment of the GP, some cross in the supraoptic
commissure

47.  There are also fibers from the SNc to the GP
 The GP also receives impulses from DM and
VA, through thalamostriate fi bers in the inferior thalamic
peduncle, and from area 6 and possibly area 4 through
corticospinal collaterals

48. Pallidal Efferents

50.  The pallidal efferents are the principal outfl ow of the BG.
 There are four major bundles:
 (a) the fasciculus lenticularis;
 (b) the ansa lenticularis;
 (c) pallidotegmental fibers, which arise from GPi; and
 (d) pallidosubthalamic fibers, which arise from GPe

51. Subthalamic Nucleus
 The STN is reciprocally connected with the GP via
the subthalamic fasciculus, a bundle that runs
directly through the internal capsule
 The connection to the STN is the only pallidal
efferent to arise from GPe; all others come from Gpi
 The STN sends fibers back to GPe, as well as to GPi,
through the subthalamic fasciculus

53. Substantia Nigra
 The SN extends from the pons to the subthalamic region
and makes up the primary dopaminergic cell population
of the midbrain; cholinergic cells are also present
 The SNc of one side is continuous across the midline with
the SNc of the opposite side. Cells of the SNc contain
neuromelanin, a by-product of dopamine synthesis

54.  The striatonigral afferents from the striatum use GABA
and either SP or enkephalin as transmitters
 The SNr receives strionigral fibers from
the striatum, GP, and STN
 The primary efferents from the SN are to the striatum,
midbrain tectum, and thalamus

55.  The SNr is functionally related to the GPi; its efferents are
GABAergic.
 Dopaminergic nigrostriatal fi bers from SNc project to the
striatum
 The nigrothalamic tract runs toVA and DM.
 The nigrotectal tract connects the SN with the ipsilateral
superior colliculus and may be involved in the control of eye
movements

56.  There are also connections between the SN and the PPN
and RF

60. BASAL GANGLIA PHYSIOLOGY
 The connections of the motor system are complex.,
There are two major loops: the BG
and the cerebellar.
 The essential connections in the BG loop are cortex →
striatum → globus pallidus→ thalamus → cortex
 The projections of the thalamus, cortex, and STN are
excitatory

61.  The outputs of the striatum and pallidum are primarily
inhibitory
 The projections from the cortex to the striatum and from
the thalamus to the cortex are both
excitatory(glutaminergic)
 The pathway from the striatum to the thalamus may be
either excitatory or inhibitory depending on the route

62.  Current models of BG function include a direct and an
indirect loop or pathway for the connection between the
striatum and thalamus
 In brief, the direct loop is excitatory and the indirect loop is
inhibitory
 The indirect loop brings in GPe and STN, which are not
involved in the direct pathway

63.  The caudate, putamen, and STN make up the BG
Input nuclei
 The GPi and SNr are the output nuclei
 The input and output nuclei are connected by the
direct and indirect loops
 In essence, the output nuclei, GPi and SNr,
tonically inhibit the motor thalamus

64.  The input nuclei either facilitate cortical motor activity by
disinhibiting the thalamus, or inhibit motor activity by
increasing thalamic inhibition
 The direct pathway serves to facilitate cortical excitation
and carry out voluntary movement
 The indirect pathway serves to inhibit cortical excitation
and prevent unwanted movement

65.  Disease of the direct pathway produces hypokinesia,for
example, parkinsonism;
 Disease of the indirect pathway produces
hyperkinesias, for example, chorea or hemiballismus
 The SNc projects dopaminergic fi bers to the striatum,
causing excitation or inhibition depending on the
receptor

66.  There are five subtypes of dopamine receptor, D1
through D5
 The D1 and D2 receptors are the primary ones
involved in regulating movement.
 The dopamine effect on the D1 family of receptors
is excitatory; the effect on D2 receptors is
inhibitory

67.  The direct loop is routed through the D1 receptors, the
indirect loop through the D2 receptors
 Dopamine excitation of D1 receptors increases the inhibitory
effect of the striatum on the GPi/SNr through the direct
pathway, which results in a decrease of the inhibitory effect of
GPi/SNr on the thalamus and a net increase in
Thalamocortical excitation

68.  The net effect of dopamine on the D1 receptor is to
facilitate the direct loop and increase thalamocortical
excitation
 Dopamine inhibition of D2 receptors decreases the
inhibitory effect of the striatum on the GPe through the
indirect pathway, which results in a decrease of the
inhibitory effect of GPe on STN

69.  The disinhibition of STN causes an increase in its ability to excite
GPi/SNr, increasing the inhibitory output of GPi/SNr and causing a
net decrease in thalamocortical excitation
 The net result is that the nigrostriatal system facilitates activity in
the direct loop, which increases thalamocortical excitation and
inhibits activity in the inhibitory indirect loop, which also
increases thalamocortical excitation

70.  When there is dopamine deficiency, cortical activation is
decreased both because of decreased facilitation through the
excitatory direct loop and lack of inhibition of the inhibitory
indirect loop
 The inhibitory effect of the BG output neurons affects not
only the motor thalamus but the midbrain extrapyramidal
areas as well.The effects have been likened to a Brake

71.  Increased braking through increased activity from GPi/SNr
inhibits motor pattern generators in the cerebral cortex and
brainstem; decreased GPi/SNr activity decreases the braking
and results in a net facilitation of cortical and brainstem motor
activity.
 The STN increases the braking, whereas the striatum
decreases it

72.  The striatal input to GPi/SNr is organized to provide a
specific, focused inhibition (unbraking) in order to
selectively facilitate desired movements
 whereas the input from the STN causes a more global
excitation of GPi/SNr (braking), perhaps to inhibit
potentially competing movements

77. BASAL GANGLIA
PATHOPHYSIOLOGY or CLINICAL IMPORTANCE
 Hypokinetic movement disorders, such as parkinsonism,
are thought to result from an increase of the normal
inhibitory effects of the BG output neurons.
 Hyperkinetic movement disorders —such as chorea,
hemiballismus, and dystonia—presumably result from a
reduction in the normal inhibition

78.  The most common hypokinetic movement disorder is
Parkinson’s disease. Pathologically, there is loss of the
pigmented cells in the SNc, as well as loss of other
pigmented cells in the central nervous system, such as
the locus caeruleus

79.  The SNc cells are the origin of the nigrostriatal
dopaminergic pathway. Loss of dopamine input to the
striatum decreases thalamocortical activation by effects
mediated by both D1 and D2 receptors
 There is decreased activity in the direct loop, mediated
by the D1 receptor, causing loss of striatal inhibition of
GPi/SNr and increased inhibition of the motor thalamus,
resulting in decreased cortical activation. There is also
decreased inhibition of the indirect loop, mediated by
the D2 receptor

80.  The STN is released from the inhibitory control of
GPe, which causes increased activity of the STN; this
in turn increases the inhibitory effects of GPi/SNr.
Both of these effects decrease the thalamic drive to
the motor cortex, causing hypokinesia and bradykinesia
 There is a net increase in activity through the
indirect over the direct pathway, resulting in a net
hyperactivity of GPi/SNr and subsequent inhibition
or braking of the thalamocortical circuits

81.  In hyperkinetic movement disorders, the inhibition of the
motor thalamus by the GPi/SNr is impaired
 Hemiballismus results from a lesion of the contralateral
STN, usually infarction
 The damage to the STN removes its normal facilitation of
the inhibitory effects of GPi/SNr.
 The loss of facilitation of GPi/SNr output (less braking)
disinhibits the motor thalamus and the cortex, resulting in
hyperkinetic movements of the involved extremities

82.  In Huntington’s disease, there is loss of ENKergic spiny
neurons in the striatum, which project primarily to Gpe
 Loss of these neurons removes inhibition from GPe, the
effect of which is to profoundly inhibit STN, incapacitating
it.
 As with hemiballismus, without STN input, GPi/SNr
inhibition of the motor thalamus decreases, releasing the
brake, disinhibiting VL, and causing increased
thalamocortical activity and hyperkinesis

83.  Experimentally, chorea can be produced by lesioning
STN, disinhibition of GPe, or the administration of
dopaminergic agents

84. BLOOD SUPPLY

85. MRI IMAGES OF BASAL GANGLIA

87. Deep brain stimulation in parkinson’s
disease

88. Selection of patient
Inclusion criteria Exclusion criteria
 (1) clinically idiopathic PD
 (2) significant improvement
with regard to dopaminergic
medication (>30%) ( UPDRS)
 (3) refractory motor
fluctuations or tremor
 (4) only minor symptoms
during ON-state
 (1) biological age over 75 years
 (2)severe/malignant comorbidity
with considerably reduced life-
expectancy
 (3) chronic immunosuppression
 (4) distinct brain atrophy
 (5) severe psychiatric disorder

89. Target points
 1)Currently STN is the main target nucleus for DBS in PD.
 All cardinal symptoms that principally respond well to
levodopa, including akinesia,rigidity, tremor, and
postural instability can be effectively treated by STN-
DBS
 2) DBS of GPi shows an immediate and significant
reduction of levodopa-induced disabling dyskinesias

90.  3) In a majority of PD-patientsVIM-DBS leads
to an immediate and almost complete
suppression of tremor
 4)The pedunculopontine nucleus has recently
aroused interest as a new target for DBS in
PD

91. SPOTTER VEDIOS
.

96. Thank you