L31Reg Post-part 4 Basal ganglia (2).pdf

Lecture 31: [PHY]: Regulation of posture & movement [PART 4] - Role of basal ganglia By Prof.Dr. Usha  Lecture 29: [PHY]: Regulation of posture & movement [PART 4] - Role of basal ganglia Topic Outcomes At the end of the lecture, students should be able to: 29.1 Describe th...

Lecture 31: [PHY]: Regulation of posture & movement [PART 4] - Role of basal ganglia By Prof.Dr. Usha  Lecture 29: [PHY]: Regulation of posture & movement [PART 4] - Role of basal ganglia Topic Outcomes At the end of the lecture, students should be able to: 29.1 Describe the components of basal ganglia. 29.2 Describe the functions of basal ganglia. 29.3 Describe the disorders of basal ganglia; Parkinson disease.  Basal Ganglia Subcortical Masses of gray matter found deep within the cortical white matter- Structure, Composed of: ۩ Caudate nucleus ۩ Subthalamic Striatum nucleus ۩ Putamen ۩ Substantia nigra ۩ Globus pallidus SNPR (pars GPe (external reticularis) segment) SNPC (pars GPi (internal segment) compacta) GPi & SNPR behave as a single functional entity Nuclei of Basal Ganglia ( Not a part of BG!)  Basal Ganglia Major input nucleus of BG is the striatum; inputs come from the cerebral cortex & the thalamus Globus pallidus (GPi) & SNPR form the major output nuclei of BG; send GABAergic, inhibitory projections to brainstem and thalamus. Independent neural circuits between cerebral cortex & putamen (putamen circuit) and cerebral cortex & caudate nucleus (caudate circuit) control voluntary movements Nigrostrial pathway is dopaminergic  Afferent Connections of Basal Ganglia Cortico-striate projection- from motor & other areas of cerebral cortex Thalamo-striate fibers – from centromedian nucleus of thalamus No afferents from spinal cord. Afferent Connections of Basal Ganglia  Circuitry of Basal Ganglia Direct pathway: StriatumGPi thalamus cortex Leads to less inhibition of the thalamus from GPi i.e. Striatum inhibits GPi, which in turn inhibits its normal (inhibitory) action on the thalamus (disinhibition). (Note: GPi actually inhibits thalamus) Thus leads to greater excitation from the thalamus to the cortex. Responsible for the ‘motor drive’ to initiate action Indirect pathway: StriatumGPe STN GPi thalamus cortex Excites the GPi, thereby increasing its inhibition of the thalamus. Responsible for suppression of unwanted movements Direct circuit- Excitatory Cerebral cortex (+) Gluta (+) Striatum ( - )GABA Globus pallidus IS ( - ) GABA Thalamus Disinhibition of thalamus by Gpi, thus greater excitation from the thalamus to the cortex. Responsible for the ‘motor drive’ to initiate action Indirect circuit- inhibitory Cerebral cortex (-) GABA Glut (+) Globus pallidus ES Striatum Dopamine GABA (-) SNPR, SNPC Globus pallidus IS GABA Subthalamic GABA (-) Thalamus nucleus Excites the GPi, thereby increasing its inhibition of the thalamus. Responsible for suppression of unwanted movements- red arrow loop  Circuitry of Basal Ganglia The circuitry involving SNPC & striatum involves 2 Neurotransmitters- Dopamine & Ach Dopamine acts as both excitatory NT (through D1 receptors) & inhibitory NT (through D2 receptors) at striatal interneurons These pathways are important in modulating the other circuits and in increasing the ‘motor drive’ & in suppression of unwanted movements Thus Damage to the ‘nigrostriatal pathway’ causes imbalance between excitation & inhibition & results in Parkinson’s disease.  Two Major Circuits (loops) of BG are involved in control of voluntary motor activity Caudate Circuit – All areas of the cortex (motor, sensory & association areas) → caudate N→ motor cortex – Major role in cognitive control of motor activity Putamen Circuit – Motor & premotor cortex→ putamen→ motor cortex – Programming of skilled motor activity – Timing & scaling the intensity of movements  Major neurotransmitters in the Basal Ganglia 1. Dopamine – In Striatum & SNPC at nigro-striatial fibers. 2. GABA - Intrinsic fibers of BG 3. ACh- Striatal neurons. 4. Glutamate - Cerebral cortical projection neurons to striatum  Roles of the Basal Ganglia The basal ganglia and cerebellum influence movement control through their effects on upper motor neurons. [UMN] Ultimately, all excitatory and inhibitory signals that control movement converge on the motor neurons that extend out of the brain stem and spinal cord to innervate skeletal muscles in the body  Role of the Basal Ganglia Neurons in four distinct but highly interactive neural circuits, collectively termed the somatic motor pathways, participate in control of movement by providing input to lower motor neurons. Local circuit neurons. Upper motor neurons. Basal ganglia neurons. Cerebellar neurons.  Basal ganglia neurons. Basal ganglia neurons assist movement by providing input to upper motor neurons. Neural circuits interconnect the basal ganglia with motor areas of the cerebral cortex (via the thalamus) and the brain stem. These circuits help initiate and terminate movements, suppress unwanted movements, and establish a normal level of muscle tone. The circuit—from cortex to basal ganglia to thalamus to cortex— appears to function in initiating and terminating movements. The basal ganglia suppress unwanted movements by their inhibitory effects on the thalamus Basal ganglia influences muscle tone. thus damage leads to generalized increase in muscle tone.  Neurons in the basal ganglia, discharge before movements begin. These observations, & analysis of the effects of diseases of the basal ganglion, and the effects of drugs that destroy dopaminergic neurons have led to the concept that, the basal ganglia are involved in the planning and programming of movement or, more broadly, in the processes by which an abstract thought is converted into voluntary action (initiating movemment) They discharge via the thalamus to areas related to the motor cortex, and the corticospinal pathways provide the final common pathway to the motor neurons.  Diseases of the Basal Ganglia in Humans Marked and characteristic abnormalities of motor function caused by disorders of basal ganglia. Disorders of movement associated with diseases of the basal ganglia are of two general types: hyperkinetic and hypokinetic. The hyperkinetic conditions, those in which there is excessive and abnormal movement, include chorea, athetosis, and ballism. Hypokinetic abnormalities include akinesia and bradykinesia  SUMMARY –FUNCTIONS BG Planning of movement: BG control the process by which an abstract thought is converted into voluntary action Control Of skilled voluntary movements Initiation of voluntary movement (motor drive) Timing & scaling of intensity of movements Cognitive Control Of Motor Activity. Subconscious execution of some movements Eg a) Control of clutch & brake while driving b) Swinging of arms while walking.  Diseases Associated With Basal Ganglia Dysfunction 1. Parkinson’s Disease 2. Chorea and Athetosis 3. Huntington’s Disease 4. Hemiballism 5. Wilson’s Disease 6. Kernicterus  Disorders Of Basal Ganglia 1) Parkinson’s disease (Paralysis agitans) Caused due to degeneration of dopaminergic neurons of nigrostriatal pathway & depletion of dopamine in SNPC & striatum (especially in putamen) Described by James Parkinson First disease identified that is caused by the deficiency of a specific neurotransmitter Has both hypokinetic & hyperkinetic features Usually affects middle-aged & elderly  Causes Idiopathic (unknown) degeneration of nigrostriatal system of dopaminergic neurons. Cerebral atherosclerosis Phenothiazine group drug toxicity- block D2 receptors Viral encephalitis  Pathogenesis There is imbalance between excitation and inhibition in the basal ganglia created by the loss of dopaminergic neurons. Results in decreased ‘motor drive’ for voluntary movements & decreased inhibition of unwanted, involuntary movements Symptoms appear when 60-80% dopaminergic neurons degenerate  Manifestations of Parkinsons’ Disease: 1. Hypokinetic features Akinesia, Hypokinesia, Bradykinesia: ❖ Difficulty in initiating voluntary movement. ❖ Poverty of movements-Loss of unconscious automatic movements, such as swinging arms while walking, facial expressions related to emotional content of speech & thought, multiple fidgety actions & gestures ❖ Slowness of movements  Manifestations of Parkinsons’ Disease: 2. Hyperkinetic features – Rigidity: abnormal increase in muscle tone consisting of stiffness Lead pipe & cogwheel types-explain? – Resting tremors: (4-7/sec), referred to as “pill rolling” when fingers are involved; may extend to hand- tremors disappear with activity  Rigidity Seen in both agonist and antagonist muscles. Large proximal group of muscles of limbs are affected. Uniform resistance throughout passive flexion- Lead- pipe rigidity. Series of catches during passive motion of the limbs- Cogwheel rigidity Cause of rigidity: Due to increased gamma efferent discharge.  Manifestations of Parkinsons’ Disease: Other manifestations – Postural instability: fixed, stooped posture – Gait disturbance: Shuffling gait walks with short, quick steps as if to catch his own center of gravity to prevent falling – Mask-like face- due to lack of facial expression & rigidity of facial muscles – Non-motor features may also occur- memory loss, emotional – PD develop dysarthria over the course of the diseasewith deviant perceptual characteristics including monopitch, monoloudness, variable rate, short rushes of speech, and imprecise consonants, As a result, the perceived intelligibility and naturalness of speech in individuals with PD can be negatively affected leading to social withdrawal and impaired work‐related performance  Treatment Medical L-dopa (Dopamine does not cross BBB) Carbidopa Anticholinergic drugs Surgical Surgical destruction of globus pallidium (pallidectomy) or ventral lateral nucleus of thalamus Introduction of dopamine secreting cells in or near BG Transplant of own/fetal adrenal medullary tissue  2) Chorea and Athetosis Chorea Rapid jerky involuntary movements (dancing movements) occur due to damage of caudate nucleus. Seen in children as a complication of rheumatic fever. Athetosis Characterized by slow rhythmic twisting worm-like (writhing) movements of extremities; affects finger and wrists Due to damage of putamen 3) Huntington’s Disease A hereditary disorder Caused by degeneration of the caudate nucleus, putamen & GP Cell loss involves GABA-secreting axons Increased glutamate neurosecretion Uncontrollable, jerky movements of the limbs 4) Hemiballism Cause: Damage to the Subthalamic Nucleus following hemorrhage into nucleus Characterized by spontaneous attacks of incoordinated movements affecting whole of opposite side of body – e.g. – Sudden flailing of arm of opposite side 5) Wilson’s Disease (Hepatolenticular Degeneration) Cause: Copper content of SN is high& Ceruloplasmin (plasma copper binding protein) levels are low Severe degeneration of lentiform nucleus with cirrhosis of liver Characterized by muscular rigidity, tremor and emotional disturbances  6) Kernicterus A hemolytic disease of the newborn due to Rh antibodies (Rh-ve mother/child incompatibility) The indirect bilirubin increases → crosses blood brain barrier → damages globus pallidus Manifests as rigidity, chorea, athetosis, mental deficiency or may cause death of newborn