Faculty of Medicine Dr Zaïd Mansour Brain control of movement

1. Faculty of Medicine Dr Zaïd Mansour Brain control of movement

2. Motor control hierarchy • Strategy, sensory information generates a mental image of the body and its relationship to the environment. • Tactics, tactical decisions are based on the memory of sensory information from past movements. • Execution, sensory feedback is used to maintain posture, muscle length, and tension before and after each voluntary movement.

3. How does the brain communicate with the SC: • Lateral pathways • Ventromedial pathways

4. The lateral pathways -Corticospinal tract -Rubrospinal tract The rubrospinal tract facilitates motor neurons in the cervical spinal cord supplying the flexor muscles of the upper extremities.

5. The ventromedial pathways: • Vestibular tracts • Tectospinal tract • Reticulospinal tracts • Vestibulospinal tarcts: • Medial VST: bilateral connection to neck muscles (stability of the head) • Lateral VST: ipsilateral connection as far down as the lumbar region

7. The tectospinal tract The superior colliculus receives inputs from the retina, visual cortex, somatosensory and auditory information It constructs a map of the world around us for directing the head and eye movements towards the appropriate target

8. The reticulospinal tacts • The pontine (medial) RS tract: • Enhances the antigravity muscles • The medullary (lateral) RS tract: • Liberates the antigravity muscles • Both tracts are controlled by descending tracts from the cerebral cortex

9. Motor cortex • Area 4 (primary motor cortex, M1) • Area 6 • Premotor area (PMA) • Supplementary motor area (SMA) • Area 6 ------ Area 4 • What actions are desired ---- • how the actions will be carried out

10. Somatotopic map of the human motor cortex

11. Strategy - Motor area 6 - Posterior parietal cortex - Prefrontal cortex The posterior parietal cortex receives inputs from: -The primary somatosensory cortical areas -Visual cortex Per Roland: when the subjects were asked only to mentally rehearse the movement without actually moving the finger, area 6 remained active, but area 4 did not. Edward Evarts Cells in the SMA typically increase their discharge rates about a second before the execution of a movement in either hand.

12. The prefrotal cortex: -Abstract thinking -Decision making -Anticipation

13. Decorticate posture (decorticate rigidity, flexor posturing, mummy baby) Patients with decorticate posturing present with the arms flexed, or bent inward on the chest, the hands are clenched into fists, and the legs extended and feet turned inward. - Flexion in the UL: disinhibition of the red nucleus, the rubrospinal tract and medullary reticulospinal tract biased flexion outweighs the medial and lateral vestibulospinal and pontine reticulospinal tract biased extension in the upper extremities. - Extension in the LL: the pontine reticulospinal and the medial and lateral vestibulospinal biased extension tracts greatly overwhelm the medullary reticulospinal biased flexion tract.

14. Decerebrate posturing (decerebrate rigidity, or extensor posturing) It describes the involuntary extension of the upper extremities in response to external stimuli. In decerebrate posturing, the head is arched back, the arms are extended by the sides, and the legs are extended. A hallmark of decerebrate posturing is extended elbows. The arms and legs are extended and rotated internally. The patient is rigid, with the teeth clenched. Damage below the level of the red nucleus

15. The Basal Ganglia Loop: cortex BG thalamus cortex Function:selection and initiation of willed movements

16. Basal Ganglia Cortex ------Striatum ------Globus pallidus -------VLo -------Cortex (SMA)

17. Basal Ganglia Motor Loop: Putamen ---- (inhib) GP ---- (inhib) VLo ---- (excit) SMA Consequence: cortical activation of the putamen leads to excitation of the SMA How? At rest, neurons in the GP are spontaneously active and thus inhibit VLo Cortical activation(l) excites putamen neurons, which (2) inhibit globus pallidus neurons, which (3) release the cells in VLo from inhibition, allowing them to become active. (4) The activity in VLn boosts the activity of the SMA.

18. Basal Ganglia: • Function: facilitation of the initiation of willed movements • Hypokinesia: increased inhibition of the thalamus by the BG • Hyperkinesia: decreased inhibition of the thalamus by the BG • Substantia nigra is divided into SNr (reticulata) and SNc (compacta) • Direct pathway: • Cortex (stimulates) → Striatum (inhibits) → "SNr-GPi" complex (less inhibition of thalamus) → Thalamus (stimulates) → Cortex (stimulates) → Muscles → (hyperkinetic state) • Indirect pathway: • Cortex (stimulates) → Striatum (inhibits) → GPe (less inhibition of STN) → STN (stimulates) → "SNr-GPi" complex (inhibits) → Thalamus (is stimulating less) → Cortex (is stimulating less) → Muscles, etc. → (hypokinetic state)

19. Connectivity diagram showing excitatory glutamatergic pathways as red, inhibitory GABAergic pathways as blue, and modulatory dopaminergic as magenta

20. Parkinson’s disease: affects about 1 % of all people over age 50 Triad of : resting tremor, bradykinesia and rigidity Cause: degeneration of the substantia nigra The pathological hallmark of PD is a loss of the pigmented, dopaminergic neurons of the substantia nigra pars compacta, with the appearance of intracellular inclusions known as Lewy bodies

21. Parkinson’s disease: shuffling gait: short, uncertain steps, with minimal flexion and toes dragging

22. Normal situation: Substantia nigra (dopamine)----(excit) putamen----(inhib) GP----(inhib) VLo----(excit) SMA PD: bradykinesia

23. Treatment of PD: • -L Dopa ( (L-dihydroxyphenylalanine) • + carbidopa or benserazide • Dopamine-Receptor Agonists • bromocriptine (PARLODEL) and pergolide • (PERMAX); and two newer, more selective compounds, ropinirole (REQUIP) and pramipexole (MIRPEX). • Catechol-O-Methyltransferase (COMT) Inhibitors: tolcapone (TASMAR) and entacapone (COMTAN). • -Selective MAO-B Inhibitors: selegiline (ELDEPRYL), & rasagiline (Azilect) • Apomorphine (APOKYN) is a dopaminergic agonist that can be administered by subcutaneous injection

24. Huntington’s disease: • Is a fatal autosomal dominant disorder • Prevalence: 10 case per 100, 000 • Mutation in the Huntington’s gene on the short arm of chromosome 4 • (repeat codon CAG, CAG sequence encoding glutamine, exceeds a threshold value, 35) • Dyskinesia, dementia, mood & personality disorders • Degeneration in the BG (caudate, putamen, GP) and cortex • BG degeneration leads to chorea (spontaneous, uncontrollable and purposeless movements of various parts of the body) as a result of loss of the inhibitory output to the thalamus

25. HD Atrophy of BG & cortex

26. Hemiballismus: - violent, flinging movements of the extremities - it is caused by damage to the subthalamic nucleus - loss of excitatory drive to the globus pallidus facilitates VLn

27. Cerebellum 10% of the total volume of the brain 50% of the total number of neurons in the CNS Coordination of movement Vermis -------------- ventromedial descending pathways Cerebellar hemispheres --------- lateral pathways

28. The motor loop through the lateral cerebellum Cortex----Pons----Cerebellum----VLc----Motor Cortex The cortico-ponto-cerebellar projection contains about 20 million axons; that is 20 times more than in the pyramidal tract Execution of planned, voluntary, multijoint movements Practice makes perfect ! The cerebellum acts as the brain inside for skilled movements.

29. The motor loop through the lateral cerebellum

30. Tremor: • Physiological tremor • Resting tremor • Intention tremor

31. Resting tremor postural tremor intention tremor

32. Chorea Choreiform movements are brief, rapid, jerky, irregular, and unpredictable. They occur at rest or interrupt normal coordinated movements. Unlike tics, they seldom repeat themselves. The face, head, lower arms, and hands are often involved. Causes include Sydenham’s chorea (with rheumatic fever) and Huntington’s disease. Tics Tics are brief, repetitive, stereotyped, coordinated movements occurring at irregular intervals. Examples include repetitive winking, grimacing, and shoulder shrugging. Causes: drugs such as phenothiazines and amphetamines. Athetosis Athetoid movements are slower and more twisting and writhing than choreiform movements, and have a larger amplitude. They most commonly involve the face and the distal extremities. Athetosis is often associated with spasticity. Causes include cerebral palsy. Dystonia Dystonic movements are somewhat similar to athetoid movements, but often involve larger portions of the body, including the trunk. Twisted postures may result. Causes include drugs such as phenothiazines, spasmodic torticollis.