1. 7 The Control of Action 1

2. Muscles, Motor Neurons and the Spinal Cord 2

3. 3 Alpha motor neurons receive input from sensory fibers located in the muscles themselves Alpha motor neurons also receive input from the descending fibers of the spinal cord and interneurons within the spinal segment. The descending fibers originate in several subcortical and cortical structures. The signals can be either excitatory or inhibitory and are the basis for voluntary movements. Input sources of alpha motor neurons

4. 4 Mini-experiments: How do your hands respond to a pressure?

5. Subcortical motor structures 5

6. 6 Basal Ganglia A collection of five nuclei Input is restricted mainly to the two nuclei Output is almost exclusively by way of the internal segment of the globus pallidus and part of the substantia nigra. The output is primarily ascending: axons of the globus pallidus terminate in the thalamus, which in turn projects to motor and frontal regions of the cerebral cortex.

7. Subcortical motor structures 7

8. 8 Cortical motor areas

9. 9 Organization of motor areas Somatotopic representations of the body are found in primary and secondary motor areas The motor areas form a hierarchy with multiple levels of control: the motor control is a distributed process

10. 10 Think: Organization of a corporation

11. 11 Peripheral Control of Movement and the Role of Feedback The notion of hierarchical control implies that lower levels themselves can produce movements while the higher levels can modulate the lower levels. The central pattern generators can produce rhythmic walking movements without the input from the brain and the feedback from sensory neurons.

12. 12

13. 13 Content of Motor Plans Two possible ways to plan movements: Planning movement trajectory Specifying the motor commands that correspond to the target position Vote: which one is correct?

14. A simple reach experiment with deafferented monkeys showed results that were favoring the location hypothesis. 14 Emilio Bizzi and his colleagues (1984) at the MIT showed that central representations can be based primarily on a location code.

15. A follow-up study supported either predictions. The study demonstrated how movement can be viewed as a shift from one postural state to another. 15

16. Hierarchical representation of action sequences A model developed by Donald MacKay (1987) Useful in explaining the learning of new motor patterns 16 Think: Organization of a corporation (again)

17. Apostolos Georgopoulos (1995) 17

18. 18 Cells in motor cortex encoding movement direction The directional tuning is broad The problem of broad tuning can be solved by considering the population vector

19. 19

20. John Chapin experiment (Chapin et al. 1999)

21. 21 Internal Versus External Guidance of Movement What is the contribution of secondary and association areas for motor control? A dramatic demonstration was shown with TMS (Gerloff et al. 1997) on subjects trained to produce a complex sequence of finger movement TMS over the motor cortex: disturbed the next response. Subjects reported that finger suddenly seemed to jerk in the wrong direction TMS over SMA: the effect were delayed. The subjects reported that lost track of their place in the sequence

22. 22 The most significant functional aspect of the SMA is its role in coordinating voluntary movements. Electrical stimulation of the supplemental (as well as premotor) cortex requires higher currents for the elicitation of motor responses. The motor responses are of a more complex pattern than those elicited from the primary motor cortex. SMA is responsible for internally guided movement and motor plan.

25. 25 Patients who have lesions of the SMA display apraxia. Ideomotor apraxia. It refers to the inability to execute a movement upon request. An example is the failure of a patient to be able to brush his or her hair or tie his or her shoelaces. Ideational apraxia. It is the inability to conceptualize the movements, and the patient is unable to identify the sequences of movements that are necessary for carrying out the response in question. Apraxia -- Movement disorders associated with SMA

26. 26 The primary function of the basal ganglia is to provide a feedback mechanism to the cerebral cortex for the initiation and control of motor responses Much of the output of the basal ganglia, which is mediated through the thalamus, is to reduce or dampen the excitatory input to the cerebral cortex. The basal ganglia

29. 29 Connections of the Neostriatum with the Substantia nigra

30. 30 Fundamental Neuroscience. Squire et al Modulatory role of dopamine D1 receptors -> increases the excitability of MSNs and facilitate cortico-striatal synapses D2 receptors -> reduces the excitability of MSNs and depresses cortico-striatal synapses

32. 32 Parkinson’s disease Parkinson’s disease is characterized by a variety of symptoms. The patient displays involuntary movements at rest. The movements are typically rhythmic tremors at approximately 3 to 6 Hz, often appearing as a “pill-rolling” tremor involving the fingers, hands, and arm. Interestingly enough, the tremor disappears when the patient begins a voluntary movement. The patient also displays a reduced number of spontaneous movements (akinesia) as well as slowness of movement (bradykinesia). Parkinson’s disease is now known to result from a loss of the dopamine-containing neurons of the substantia nigra pars compacta.

33. 33 Parkinson’s disease might also exhibit reduced amounts of norepinephrine and serotonin elsewhere in the brain. Such observations indicate the heterogeneity of this disease with respect to behavioral and neurochemical variations present in different patients. Several lines of treatment therapies have been developed. 1.administration of the drug, L-3, 4-hydroxyphenylalanine (L- DOPA, a precursor of dopamine) 2.Transplantation of embryonic tissue containing dopamine neurons into the neostriatum. 3.To graft stem cells into regions where neurons have undergone degeneration as a result of a disease process. 4.Deep-brain stimulation in STN

34. 34 Huntington’s disease (Chorea) Characterized by wild, uncontrolled movements of the distal musculature. An inherited illness with the genetic defect located on the short arm of chromosome 4. The gene encodes a protein referred to as huntingtin. One hypothesis is that the huntingtinprotein causes an induction of apoptosis in the nucleus of the cell. Degeneration is extensive and involves the neostriatum, where there is significant loss of GABA The later progression also involves the cerebral cortex and, in particular, the frontal and prefrontal regions, as well as a number of other structures. The disease is progressive with an onset in the fifth and sixth decades of life. There is also a juvenile form of the disease, because of which patients usually die before the age of 21 years.