2. Control of Posture and Movement- Part-IV Role of Basal Ganglia

3. Learning Outcomes At the end of lecture, students should be able to: Briefly explain the role of basal ganglia in regulation of posture and movement. Briefly explain the role of basal ganglia in regulation of posture and movement. Describe clinical features of Parkinson disease. Describe clinical features of Parkinson disease. Explain the underlying mechanism of defect and the physiological basis of treatment of Parkinson disease. Explain the underlying mechanism of defect and the physiological basis of treatment of Parkinson disease.

4. Basal ganglia One of the Accessory Motor system, associated with motor function. Work in association with Cerebral Cortex and cortico- spinal system Receive almost all inputs from Cerebral Cortex and provide its output to cortex Function not by itself but with association of Cortex

5. Basal Ganglia~ Structures Includes: The Striatum: putamen and caudate nucleus Globus pallidus: external segment of the globus pallidus (GPe), Internal segment of the globus pallidus (GPi), Subthalamic nuclei (STN), Substantia nigra (SN). substantia nigra pars compacta (SNc) substantia nigra pars reticulate (SNr).

7. Direct Pathway (promote movement) CORTEX PUTAMEN (GPe) (STN) GP interna VA/VL THALAMUS Glutamate (+) GABA (-)

8. Indirect Pathway (Inhibition of thalamus output) CORTEX PUTAMEN GP externa STN GP interna VA/VL THALAMUS Glutamate (+) GABA (-) Glutamate (+) GABA (-) Glutamate (+)

11. Direct and Indirect Pathways Direct pathway Disinhibits motor thalamus activates thalamo- cortical neurons Activates motor cortex Facilitates movement Indirect pathway Inhibits motor thalamus inhibits thalamo- cortical neurons Inhibits motor cortex Inhibits movement

12. Control complex patterns of motor activity performed subconsciously e.g. writing of letters of the alphabet. Other patterns of movements such as Other patterns of movements such as cutting paper with scissors, hammering nails, shooting cutting paper with scissors, hammering nails, shooting a basketball through a hoop, passing a football, throwing a baseball, a basketball through a hoop, passing a football, throwing a baseball, Most aspects of vocalization, controlled movements of the eyes, and virtually any other of our skilled movements. Most aspects of vocalization, controlled movements of the eyes, and virtually any other of our skilled movements.

13. Neural Pathways Signal originate in premotor and supplementary areas of the motor cortex and in the somatosensory areas of the sensory cortex. Putamen (bypassing the caudate nucleus internal portion of the globus pallidus ventroanterior and ventrolateral relay nuclei of the thalamus

14. Lesions in Putamen Circuit lesions in the globus pallidus frequently lead to spontaneous and often continuous writhing movements of a hand, an arm, the neck, or the face—movements called athetosis. A lesion in the subthalamus often leads to sudden flailing movements of an entire limb, a condition called hemiballismus. Multiple small lesions in the putamen lead to flicking movements in the hands, face, and other parts of the body, called chorea. Lesions of the substantia nigra lead to the common and extremely severe disease of Rigidity, Akinesia, and Tremors known as Parkinson’s disease,

15. Cognitive Control of Sequences of Motor Patterns Process of motor actions occur as a consequence of thoughts generated in the mind - cognitive control of motor activity determine the patterns of movement to be used together to achieve a complex goal subconsciously within seconds, e.g. person responding instantaneously & automatically, once he see a lion approaching him.

16. Timing and to Scale the Intensity of Movements Caudate circuit (in association with posterior parietal cortex) help to determine the rapidity & its range (scale) of movements. For instance, rapidity of writing “a” on a on a piece of paper or a large “a” on a chalkboard by maintaining proportional characteristics of the letter. Person lacking a left posterior parietal cortex, draw the proper proportions for the right side of the face but almost ignoring the left side

17. Neural Pathways Cerebral cortex to the caudate nucleus, Caudate nucleus transmit to the internal globus pallidus, GP (i) to relay nuclei of the ventroanterior and ventrolateral thalamus, Thalamus send the signals back to the prefrontal, premotor, and supplementary motor areas of the cerebral cortex concerned with sequential patterns of movement

18. Parkinson disease. Clinical features and underlying Defects

19. Parkinson disease Originally described by James Parkinson and named for him. Parkinson disease is the first disease identified as being due to a deficiency in a specific neurotransmitter. Featured with hypokinetic and hyperkinetic movements. In the 1960s, reported cause -- degeneration of dopaminergic neurons in the substantia nigra pars compacta.

20. Parkinson disease 1.Three distinct biochemical pathways in the basal ganglia normally operate in a balanced fashion: A.Nigrostriatal dopaminergic system, B.Intrastriatal cholinergic system, C.GABAergic system, 2.Abnormalility in any one or more results in motor abnormalities 3.Diseases of the basal ganglia lead to two general types of disorders ~ hyperkinetic and hypokinetic.

22. Hypokinetic disorders  result from over activity in the indirect pathway.  Exerting much more Inhibition to thalamus.  Movements are slow and difficult to initiate.  Causes: Decreased level of dopamine supply in nigrostriatal pathway results in  akinesia,  bradykinesia,  rigidity

23. Hyperkinetic disorders Hyperkinetic disorders result from under activity in the indirect pathway. Reduced degree of inhibition on thalamus Involuntary limb movements are excessive and abnormal Causes; Lesions of Subthlamic Nu. result in Ballism. Damage to the pathway from Putamen to GPe results in Chorea,.

24. Main features of Parkinsonism- Hyperkinetic 1.Tremors-occur due to due to alternating contraction of antagonists muscles, observed during rest but disappear once the movement is initiated- called Resting Tremors 2.Rigidity- resistance to passive bending of limbs through out the movement(lead pipe rigidity), some time series of catches (cogwheel rigidity)- due increased motor neuron discharge in both antagonists and agonists muscles

25. 1.Festinant Gate- 1.with increased rate of walking showing an automatic attempt by the body to overtake a displaced centre of gravity, 2.short and shuffling steps, 3.bend forward but does not fall, trying to catch the center of gravity Main features of Parkinsonism- Hyperkinetic

26. Main features of Parkinsonism- Hypokinetic Akinesia- difficulty in initiating movement and decreased spontaneous movements Bradykinesia- slowness of movement Decreased associated movements- such as loss of facial expression during talking, swinging of the arms during walking, expressionless face

27. HEMIBALLISMHEMIBALLISM - Usually results from CVA (Cerebrovascular Accident) (Cerebrovascular Accident) involving subthalamic nucleus involving subthalamic nucleus - sudden onset - Violent, writhing, involuntary movements of wide excursion movements of wide excursion confined to one half of the body confined to one half of the body - The movements are continuous and often exhausting but cease and often exhausting but cease during sleep during sleep - Sometimes fatal due to exhaustion - Could be controlled by phenothiazines and stereotaxic phenothiazines and stereotaxic surgery surgery Clinical Feature Lesion: Subthalamic Nucleus

28. Therapeutic Advances in Treatment Replacement of dopamine- L Dopa, a precursor of dopamine is the drug of choice, help to compensate for deficiency of dopamine. Other dopamine agonists like bromocryptine are also used. Antocholingeric agent- decrease concentration of ach in basal ganglia, thus restblish the ach-dopamine ration and improves the symptoms. experimental parkinsonism, neurotropic factors benefit the nigrostriatal neurons, local injection of GDNF attached to a lentivirus vector so that it penetrates cells has produced promising results