Organization of Motor Functions 4.

Transcription

1 Organization of Motor Functions 4. Dr. Attila Nagy 2018 Sensory-motor system Limbic cortex Structure Subcortical Motivational sub areas Frontal cortex Task Motivation Sequence Plan Tim e Ascending system Basal ganglia Cerebellum (vermis) Brainstem Interneuron g.v. Association cortex Thalamus Mot. nuclei Motor cortex Motoneuron (spinal) Cerebellum (hemispheres) Descending system Voluntary Posture Spinal motoric (Reflexes) Program 800 ms 50 ms Execution Receptor Muscle (effektor) Length, tension, position, joint relation (posture) Light, sound, temperature (environmental stimuli) 1

2 Cerebellum (Learning objective: 117) Cortex Basal ganglia Thalamus Cerebellum Brainstem Sensory events Spinal cord MOVEMENTS 2

3 Two major recurrent loops of the motor cortex: 1. cerebellar loop 2. basal ganglia loop A. cerebellar loop a. Cortical input runs to cerebellum from MI, SMA,PM, SI, 5 and 7 areas through pontine nuclei b. all sensory modalities provide input to cerebellum Feedback through motor nuclei of the thalamus B.basal ganglia loopfrom the cortex through basal ganglia and motor nuclei of the thalamus to the cortex Anatomy of the cerebellum 10% of the whole amount of the brain 2 hemispheres + vermis 10 lobes Cortex (gray matter) White matter (200 million input) Deep nuclei Dentate nucleus globosus + emboliformis nucleus (interpositus) Fastigial nucleus (Deiters nucleus) 3

4 Cerebellar functions: 1. postural function 2. Coordination of intention and actual movement. Comparison of afferent copy and efferent copy. 3. Coordination of muscles during movement (agonists, synergists, antagonists). Continuous, precise and coordinated activity of muscles. 4

5 Voluntary movements and postural functions 5

6 Somatotopy in the cerebellum: multiple mapping Somatotopy, homunculus Somatotopy in the cerebellum: multiple mapping 6

7 Cellular organization of the cerebellum 1. Molecular layer 2. Purkinje cell (ganglion) layer 3. Granule cell layer Purkinje cells Folia White matter PC Purkinje cell, GrC granule cell, GC Golgi cell, BC basket cell, SC stellate cell MF mossy fiber, CF climbing fiber, PF parallel fibers, CN cell in the deep nucleus 7

8 Neuron types in the cerebellum Inhibitory elements of the cerebellum: - purkinje cells - basket cells - stellate cells - Golgi cells - Lugaro cells Excitatory elements of the cerebellum: - mossy fibers - climbing fibers - granule cells - parallel fibres 8

9 The cerebellar module 1. Mossy fibers terminate at excitatory granule cells 2. Granule cells give parallel fibers that form synapses with many Purkinje cells 3. Parallel fibers also form synapses with inhibitory basket cells 4. Basket cells then form synapses with inhibitory Purkinje cells: inhibition of inhibition = release 5. Climbing fibers go to a single Purkinje cell - induction of complex spikes (multi-phase action potential) Golgi cell: inhibition of granule cells Purkinje cell s simple and complex spike (30-50 Hz spontaneous activity) Lugaro cell: feedback modulation of Golgi cells (Purkinje cells), serotonin sensitive Inhibition: GABA (gamma-aminobutyric acid) 9

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11 Functional organisation of the cerebellum: Output nuclei 1. archi(vestibulo) cerebellum Nucleus Deiters fastigial nucleus 2. paleo(spino)cerebellum interpositus nucleus fastigial nucleus 3. neo(cerebro)cerebellum dentate nucleus 1. Vestibulocerebellum (archicerebellum) Structure: flocculonodular lobe, vermis Afferent: vestibular, vision Efferent: Deiters nucleus, fastigial nucleus (formatio reticularis) Function: eye and head movement, gait and balance, postural functions 2. Spinocerebellum (paleocerebellum) Structure: paravermis Afferent: - spinocerebellar tract, vision, vestibular (consequence of motion) - cortex (motor program) Efferent: interpositus nucleus brainstem (red nucleus), spinal cord, thalamus - cortex Function: correction of movement patterns based on feedback (correction of muscle tone, power, coordination of flexors and extensors) 11

12 3. Cerebrocerebellum (neocerebellum, pontocerebellum) Structure: lateral hemispheres Afferent: sensory-motor cortex (BA 4,3,1,2,5,7), prefrontal cortex (via pons) Efferent: dentate nucleus 1. thalamus cortex (2. red nucleus oliva inferior cerebellum) Function: planning, initiation and termination of movements (timing), motor learning 12

13 vestibulocerebellum (archicerebellum) Flocculus Nodulus VERMIS Spinal and Brainstem (vestibular) relay nuclei Afferents spinocerebellar tr. Fastigium reticular formation Tr. reticulospinal med.lat. Deiters Tr. corticospinal Receptors MUSCLES Spinal cord Spinocerebellum (paleocerebellum) Pars intermedia Thalamus Motor cortex Pons Spinal cord Afferents tr. spinocerebellaris Climbing rfibers Oliva inf. Nucl. interpositus Nucl. ruber Rubrospinal tract Corticospinal tract Receptors MUSCLES Spinal cord 13

14 Cerebrocerebellum, Pontocerebellum (neocerebellum) Association cortex Pars intermedia Motor cortex Relay nuclei (Pons) Cerebellar hemisph. Climbing fibers Oliva inf. Thalamus Nucl. dentatus Nucl. ruber Tr. rubrospinal Tr. corticospinal MUSCLES Spinal cord Consequences of cerebellar damage: Cerebellar signs Charcot s triad: nystagmus, intention tremor, telegraphic speech Balance disorders (Romberg s test) Dizziness Nystagmus Ataxia (awkward movements) Hypotonia Co-ordination problems Dysmetria (Dimension problem between the goal and muscle performance (finger-to-nose test; heel-knee test) Dysdiadochokinesia (Supination and pronation of the hand is problematic) Star-like gait Rhythmic, monotonous speech Intention tremor (Closer to the target bigger the movement of the fingers) Rebound Disorder of weight approximation Signs are ipsilateral and NOT contralateral as in the pyramid tract! 14

15 The Basal Ganglia (Learning objective: 116) caudate nucleus thalamus brainstem amygdala hippocampus 15

16 NEOSTRIATUM n. caudatus VA ventralis anterior VL ventralis lateralis PALLIDUM putamen globus pallidus n. subthalamicus (Lewis) ARCHISTRIATUM ventral striatum (n. accumbens) - Amygdala central and medial nucleus - Claustrum substanita nigra pars compacta pars reticulata Basal ganglia Corpus striatum (Striatum) 1. N. caudatus, 2. Putamen 3. Globus pallidus (Pallidum) 4. Substantia nigra, 5. N. subthalamicus, 16

17 Inputs of the basal ganglia: 1) cortico-striatal 2) Nigro-striatal 3) Thalamo-striatal 17

18 Output of the basal ganglia 1) Globus pallidus pars interna to the thalamus - ventral-lateral nucleus - ventral-anterior nucleus - centro-median nucleus 2) Substantia nigra pars reticulata to the thalamus - ventral-lateral nucleus - ventral-anterior nucleus to the superior colliculus to the Pedunculopontine tegmental nucleus of the pons Main cell types of neostriatum: (ctx) Medium spiny neurons - receiving cortical tracts a. GABA + substance P/dynorphin D1 dopamine receptor b. GABA + encephalin D2 dopamine receptor Striatum (STR) (GP) (thal) Cholinergic interneurons (~10%, no spines) (SN) p.c. = pars compacta dopamine nigrostriatal pathway p.r. = pars reticularis, ext. = external, int. = internal 1. Direct ( go ) path (D1): ctx STR GPint thal ctx 2. Indirect ( no-go ) path (D2): ctx STR GPext SN GPint thal +ctx 3. Hyperdirect path: ctx SN GPint thal ctx p.r. ~ GPint - eye-movements: superior colliculus inhibited by p.r. - p.r. silence releases colliculus leading to eye movement +: excitatory (glutamate) -: inhibitory (GABA) 18

19 Indirect way direct way 19

20 From the thalamus to the cortex: 1) - sceletomotor loop (area 6) 2) - oculomotor loop (FEF) 3) - associative loop (prefrontal cortex) Hyperkinesia and hypokinesia and the basal ganglia 20

21 Parkinson s disease 1. Reduced and slow movements (hypo- and bradykinesia) 2. Muscle tone (cogwheel rigidity) 3. Resting tremor with low frequency 4. Disturbances of gait and posture 5. Blunted affect (mask-like face) 6. Disorder of planning and problem solving, slow thinking Pathogenesis: dopaminergic cell loss in substantia nigra pars compacta Alpha-synuclein: regulation of transmitter release in dopaminerg synapses + neuronal survival (aggregation in Parkinson s - Lewy-bodies) Treatment: - L-DOPA (dopamine s progenitor) - Dopamine receptor agonists - Deep brain stimulation Gowers, 1886 Normal substantia nigra Parkinson s Lewy-body: aggregated alpha-synuclein and other proteins Neuromelanine containing dopaminergic cells Reduced number of dopaminergic cells 21

22 Disorder of dopaminergic transmission: positron emission tomography (PET) Control Parkinson s Neuromelanine-sensitive magnetic resonance imaging (MRI) Decreased intensity in Parkinson s substantia nigra Deep brain stimulation (DBS) in Parkinson s disease 22

23 Disorders of the basal ganglia (formerly together with Parkinson s: extrapyramidal symptoms) Chorea: large amplitude dancing movements of extremities Huntington s disease: 4. chromosome, CAG-triplet expansion huntingtin protein (glutamine ), aggregation GABA-ergic spiny neurons severe cognitive disorder: disorganized thinking extreme swings of mood Ballism: involuntary flinging, swinging, and jerking movements of proximal extremities (n. subthalamicus lesion) Athetosis: slow, sinuous, writhing movements (putamen lesion) Tic: repetitive, nonrhythmic, stereotyped, circumscribed movement or vocalization (e.g. eye blinking, throat clearing) Tourette s disease Dystonia: tone in circumscribed muscles (e.g. torticollis); hereditary (torsin gene) or drug-induced (dopamine antagonists that also induce tardive dyskinesia [e.g. grimacing, tongue protrusion, lip smacking]) 23