Basal ganglia

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Khushbu on Aug 14, 2012 Says :

nice set of information provided regarding basal ganglia.

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BASAL GANGLIA DR DAMODAR CHARI CHAIRED BY: DR PREETHI REBELLO

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Introduction The term basal ganglia refers to a group of subcortical nuclei that play an important role in the regulation and coordination of cortically originated movement They include corpus striatum,the amygdaloid nucleus and the claustrum These nuclei play important role in control of posture and voluntary movts

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They are phylogenetically derived from telencheplalon separated from diencephalon by Internal capsule. The term corpus striatum refers to the caudate, putamen, and globus pallidus. The terms striatum, dorsal striatum, and neostriatum refer to the caudate and putamen, the phylogenetically newer parts of the corpus striatum. Lentiform nucleus- Putamen & globus pallidus

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Terminology used to describe basal nuclei

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Corpus striatum Corpus striatum is situated lateral to thalamus Divided by internal capsule into the caudate nucleus and the lentiform nucleus These two nuclei are connected by band of grey matter- with stripped appearance- hence called striatum

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The lentiform nucleus lateral part- putamen medial part- the globus pallidus The caudate nucleus + putamen ( neostriatum) = striatum Globus pallidus ( paleostriatum) = pallidum

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caudate nucleus The caudate nucleus (a term derived from a Latin word that means "having a tail") is so named because it has a long extension or tail. It is a C-shaped structure that lies close to lateral ventricle and lateral to the thalamus Three parts- with an expanded rostral extremity, its head, which tapers down in size to form its body and tail

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The head forms a convexity into the anterior horn of the lateral ventricle. The body forms the lateral wall of the body of the lateral ventricle. The tail occupies a position in the roof of the inferior (temporal) horn of the lateral ventricle. In essence, it follows the curvature of the lateral ventricle and terminates in amygdaloid nucleus

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Lentiform nucleus Lens shaped nucleus, forms lateral boundary of int capsule Lies beneath the insula and the claustrum Divided into two parts Larger lateral part- the putamen Smaller medial part – the globus pallidus. Made up of large ( motor) cells

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Lentiform nucleus The putamen: is separated from the caudate by the anterior limb of the internal capsule. In their most rostral extents, the caudate and putamen are continuous around the anterior limb of the internal capsule. Largest part of the lentiform nucleus.

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The globus pallidus is a wedge-shaped structure between the putamen and posterior limb of the internal capsule. The putamen and globus pallidus are separated by the external pallidal lamina. The internal pallidal lamina separates a larger (lateral) and a smaller (medial) segments of globus pallidus

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Amygdaloid body Nuclear mass in temporal lobe, lying antero-superior to the inf horn of lat ventricle Structurally related to caudate nucleus, but functionally to stria terminalis – part of limbic system Afferents – from the olfactory tract Efferents – gives rise to stria terminalis, ending in ant commisure, the ant perforated substance & in hypothalamic nuclei

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Substatia Nigra and Subthalamic nuclei The substatia nigra of the midbrain and the subthalamic nuclei of the diencephelon are functionally closely related to the activities of the basal nuclei Neurons of substantia nigra are Dopaminergic and inhibitory, are linked to corpus striatum Neurons of STN are glutaminergic and are excitatory. They have many connections to the globus pallidus and substatia nigra

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claustrum Saucer shaped nucleus situated between putamen and insula It is thickest inferiorly and is continuous with the anterior perforated substance

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Blood supply Blood supply of the basal ganglia is provided from the internal carotid circulation via three arteries: 1) anterior choroidal, 2) middle cerebral (lateral striate branch), and 3) anterior cerebral (medial striate branch, of Huebner). The anterior choroidal artery supplies the tail of the caudate, caudal part of the putamen and all of globus pallidus. The head and body of the caudate, and the rostral part of the putamen are supplied by the lateral striate branch of the middle cerebral artery. The medial striate branch (Huebner's) of the anterior cerebral artery supplies the head of the caudate.

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Neuronal structures The neostriatum (caudate and putamen) contains two types of neurons: spiny (projection) and aspiny (interneurons). Spiny neurons - 90% of neostriatal neurons. Type1 & Type2 They contain GABA and a number of neuropeptides( Substance P, Enkephalin) .

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A spiny neurons are of two sizes. Large (Acetylcholine)and small(GABA). Based on acetylcholinesterase reactivity of its neurons the neostriatum is compartmentalized into weakly reactive patches (striosomes, 20 % of the striatum) interspersed between strongly reactive patches (matrix, 80% of the striatum). The two compartments differ in their input, output, neurotransmitters, and neuromodulators. Other mosaic-like compartments have also been identified. The GPi and SNr are morphologically and chemically similar. Most of their neurons are large multipolar projection neurons. Interneurons are infrequent. All neurons contain GABA.

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connections The caudate nucleus and the putamen form the main site to receive inputs for basal nuclei The globus pallidus forms major site for output from basal nuclei They don’t receive any direct input or output from spinal cord

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Input to the neostriatum originates in three main sites: 1) cerebral cortex, 2) thalamus, and 3) mesencephalic dopamine sites

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Cortical projections Cortical projections to the striatum are organized into three functional systems: 1) Sensorimotor, links sensory and motor cortical areas with the sensorimotor territory (putamen) of the neostriatum. 2) Association, links association cortices with the associative (caudate) neostriatal territory. 3) Limbic, links limbic and paralimbic cortical areas with the limbic (ventral striatum) neostriatal territory

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Cortical areas having reciprocal cortico-cortical association connections project to similar areas of the neostriatum and ventral striatum integrating both discrete functional areas of the cortex and cortical neural systems they participate in or contribute to. The sensorimotor projection is further subdivided somatotopically such that the arm, leg, and face areas of the sensorimotor cortex project to corresponding areas in the putamen. The neurotransmitter in corticostriate projections is glutamate.

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Thalamic projections: Originate from primarily two thalamic nuclei: 1) centromedian,2) parafascicular, and are topographically organized such that the centromedian nucleus projects to the sensorimotor (putamen) striatal territory, whereas the parafascicular nucleus projects to the associative (caudate) and the limbic (ventral striatum) striatal territories. The neurotransmitter in the thalamostriate projections is glutamate.

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Mesencephalostriate Input The principal mesencephalic projection to the striatum originates from the substantia nigra pars compacta. The neurotransmitter in this projection is dopamine. Dopamine exerts a facilitatory effect on striatal neurons that project to the internal segment of GP and SNr complex, and an inhibitory effect on striatal neurons that project to the GPe.

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Schematic diagram of nigrostriatal pathway showing the facilitatory action of dopamine on striatal neurons that project to SNr and GPi, and the inhibitory action of dopamine on striatal neurons that project to the GPe.

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Output of striatum The neostriatum projects to the following nuclei: globus pallidus (both segments), substantia nigra pars reticulata, and the ventral pallidum. The neurotransmitter is GABA. Several neuropeptides characterize striatal projections to the target nuclei. GABA/Substance P (SP) to GPI/SNr & GABA/ Enkephalin (ENK) to GPe/ STN Striatal projections to the GPi - SNr complex are both direct, as well as indirect via the GPe and the STN .

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INPUT TO Globus pallidus/Substantia nigra Both segments of GP and SNr receive inputs from the STN. In addition, the GP receives input from the putamen, whereas the SNr receives fibers from the caudate nucleus. The neurotransmitter of the neostriatal projection (caudate, putamen) is GABA. The neurotransmitter of the subthalamic projection is glutamate.

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OUTPUT OF Globus pallidus interna/Substatia nigra GPi and SNr constitute the major output structures of the basal ganglia. Their major projection is to the thalamus (ventral anterior, ventral lateral, dorsomedial, and intralaminar nuclei) via two pathways: the ansa lenticularis (around the internal capsule) and the lenticular fasciculus (through the internal capsule). The neurotransmitter of this output is GABA

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OUTPUT OF Globus pallidus externa The GPe is reciprocally connected with the STN. The neurotransmitter is GABA.

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Indirect pathway Direct pathway

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Subthalamic Nucleus The subthalamic nucleus is one of the subcortical nuclei that comprise the extrapyramidal system. It receives inputs from the cerebral cortex (areas 4 and 6), the external segment of globus pallidus, thalamus, and reticular formation. It projects to both segments of globus pallidus, and the substantia nigra pars reticulata. Lesions in the subthalamic nucleus result in a movement disorder known as hemiballismus. The neurotransmitter is Glutamate

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Ventral striatum The term ventral striatum refers to the ventral parts of caudate and putamen, the nucleus accumbens septi, and the striatal part of the olfactory tubercle thought to be phylogenetically older than the dorsal striatum.

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Connections of Ventral (Limbic) Striatum The ventral striatum, connected with a number of limbic structures, could as easily be named limbic striatum. It receives inputs from the hippocampus, amygdala, cingulate gyrus, temporal cortex, and orbitofrontal cortex. Dopaminergic input to the ventral striatum is substantial from the ventral tegmental nucleus of Tsai.

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Connections of Ventral (Limbic) Striatum The output from the ventral striatum is to the ventral pallidum. The output of the latter is not fully understood It send axons to the dorsomedial thalamic nucleus, an association nucleus with strong interconnections with the prefrontal cortex.

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Nucleus accumbens the area is the "pleasure center" of the brain nucleus accumbens has role in addiction it plays a role in processing many rewards such as food and sex the nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes

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Functions of corpus striatum Corpus striatum regulates muscle tone and helps smoothening muscle movts Controls automatic associated movts Controls coordinated movts of different parts of body for emotional expression Influences the precentral cortex to control the extrapyramidal activities of body

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Functions of corpus striatum Basal ganglia contributes to cognitive function of brain Help cortex in execution of learned pattern of behaviour Corpus striatum,cerebellum and motor areas are jointly responsible for planning, execution and control of movts

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Functions of corpus striatum Corpus striatum and cerebellum without sending fibers to spinal cord modify the effect on spinal cord through projections to motor cortex and extrapyramidal fibers Basal ganglia and cerebellum do not initiate movts but are able to adjust motor commands

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Disorders of Basal Ganglia

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Huntington’s disease AD, characterized by occurrence of choreoathetosis, dementia and behavioral syndrome Abnormality in trinucleotide repeats in huntigtin gene on chromosome 4 Bilateral atrophy of the head of the caudate nucleus and putamen Preferential loss of putamen GABA-nergic projecting to lateral Gobus pallidus ( Gpi) as the indirect pathway

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Increases GPi inhibition of STN and lowering activity of GPe thus increasing Ventrolateral thalamic excitation of motor cortex to produce choreoathetosis Cholinergic neurons are also affected in later stages Dopamine antagonist act by blocking inhibitary D2 receptors on GABA-nergic neuron of indirect pathway, thus improving inhibitory influence of GPi on VL

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Hemiballismus and hemichorea Hemiballismus & Hemichorea – produced by destructive lesions most commonly stroke Usual site subthalamic nucleus Glutaminergic STN neurones excite GPi/SNr which inhibit VL VA areas of the thalamus Abnormal movements occur when STN stimulation of the Pallidothalamic pathway is reduced

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DYSTONIA Abnormal co-contraction of the antagonistic muscles Not caused by simply increased or decreased activity in particular nucleus of the basal ganglia Dystonic co-contraction of the antagonistic muscles has multiple mechanisms Involvement of the cortical-basal ganglia-thalamocortical loop is implicated by most clinical & experimental studies

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Tardive dyskinesia Neuroleptic-induced tardive dyskinesia (TD) is a syndrome consisting of abnormal, involuntary movements caused by long-term treatment with antipsychotic medication Fine vermicular movements of the tongue is a common and early feature Lip smacking, puckering or pouting, chewing, jaw clenching or mouth opening, facial grimacing, blowing, blepharospasm and frowning are also common features Extremities & trunk movement is common in young patients, orofacial movements is common in older individuals

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Tardive dyskinesia Pathophysiology : Striatal dopamine receptor supersensitivity confirmed by PET among TD patients Degeneration of striatal cholinergic interneuron's and the resulting dopamine acetylcholine imbalance play a role in TD pathogenesis

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Parkinson’s disease Parkinson’s disease is a progressive disorder of nervous system characterized clinically by akinesia and bradykinesia,rigidity , rest tremors, postural and gait abnormalities Parkinsonism refers to the clinical features of PD when caused due to other types of lesion

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Clinical features General slowing up of movts, affecting fine hand movts, dexterity and general mobility There is slowness in starting and performing movement, as reflected by increased reaction time and movement time- independently affected. Program memory and retrieval of subprogram for execution is normal. Have defect in executing the motor plan and this increases with complexity of task.

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Particular difficulty in doing repetitive motor acts - switching from one program to another or doing 2 acts simultaneously. There is fundamental breakdown in capacity to run the sequence of motor movements that comprise motor plan. - “defect in kinetic melody”. The content, selection and assembly of simple motor programs not impaired, but there is break down of automatic execution of more complex multiprogram motor plans. The main culprit is Supplementary motor area.

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Pathophysiology In PD there is over-activity of projections from striatum (chiefly putamen) to GPE,resulting in decreased activity of GPE output upon STN excitatory neurons. The activity of STN upon both pallidal segment is increased, resulting in increased firing of GABAergic projections from GPI, thus suppression of neurons in the ventral thalamus

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long-loop reflexes originating in muscle spindles and running through cortical relays are at the basis of increased muscle tone electrophysiological studies have demonstrated that the activity of inhibitory interneurons at spinal levels are differentially altered in PD This may lead to tonic facilitation of alpha motor neurons. These processes can be reversed by administration of L-DOPA

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ADHD ADHD is a behavioral and neurocognitive condition characterized by developmentally inappropriate and impairing levels of gross motor overactivity, inattention, and impulsivity onset before age 7 years Characterized by easy distractibility, inability to sustain attention on task, failure to follow instruction, inability to complete tasks without constant supervision, and forgetfulness Also associated with increase in activity

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Pathophysiology functional and anatomical dysfunction in the brain's frontal cortex and basal ganglia segments of the cortico-basal ganglia-thalamo-cortical circuitry These areas are concerned with the regulation of attentional resources, the programming of complex motor behaviours, and the learning of responses to reinforcement

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review MRI, PET, single emission computed tomography (SPECT), and functional MRI studies -decreased volume and activity in prefrontal areas, anterior cingulate, globus pallidus, caudate, thalamus, hippocampus, and cerebellum in children with ADHD

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OCD OCD is represented by a diverse group of symptoms that include intrusive thoughts, rituals, preoccupations, and compulsions Symptoms of the disorder include excessive washing or cleaning, repeated checking, extreme hoarding, preoccupation with sexual, violent or religious thoughts These recurrent obsessions and compulsions cause distress to the patient

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Clinical descriptions of OCD associated with Sydenham's chorea (SC), tic disorders, traumatic brain injury, encephalitis, and Huntington's chorea have helped to solidify the broad concept of the disorder as brain based and presumably reflecting impaired striatal functioning. a recent study found reduced globus pallidus volume and grey matter volumetric abnormalities in the anterior cingulated gyrus in paediatric patients with OCD compared to healthy controls

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Dysfunction in the frontal cortical-striatal-thalamo-cortical networks has been suggested Imaging also suggests the frontal-limbic-basal ganglia system may mediate OCD symptom expression, demonstrating a wider interaction of cognitive and emotional circuits

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Athetosis Cerebral palsy Chorea Lesch nyhan syndrome Tourette's disorder Wilson's disease Anxiety disorders

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Summary The basal ganglia (or basal nuclei) are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas. The basal ganglia are associated with a variety of functions, including voluntary motor control, procedural learning relating to routine behaviors or "habits" such as eye movements, and cognitive, emotional functions

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Summary The basal ganglia play a central role in a number of neurological conditions, including several movement disorders The most notable are Parkinson's disease and Huntington's disease Further research on basal ganglia could provide researchers with newer ways of treating these conditions

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