2011.10.12.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY www.itk.ppke.hu By Imre Kalló Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erőss, Róbert Gábriel, Kisvárdai Zoltán Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu Movement disordersImre Kalló & Anita KamondiPázmány Péter Catholic University, Faculty of Information Technology I. Brain regions and pathways involved in motor control. II. Disturbance of motor control at the level of -basal ganglia (Parkinson’s disease) -cerebellum (Spinocerebellar ataxia and essential tremor) -cerebral cortex (Apraxia) Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu Elements of voluntarymovements 1. Decisionofmovement 2. Activationoftheadequatemotorpattern 3. Planningofmovement 4. Startingthemovement 5. Executionofmovement Continuousadaptationofthemuscletonetothemovement Continuoussensorycontrolofthemovement 6.Terminationofmovement Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu Structures of the nervous system controlling movement Organizationofmovement motorcortex(supplementary,premotor) systemofthebasalganglia cerebellum Executionofmovement ”upper”motoneuronsintheprimarymotorcortex cortico-spinalpathway(pyramidaltract) ”lower”motoneuronsinthespinalcord peripheralnerves neuro-musculartransmissionoftheimpulse Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu Major cortical areas participating in motor control Agy_motor.tif Premotor Primary motor Supplementary Cingulate Posterior parietal Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu Representation of different regions of the body in the primary motor cortex homunculus.gif notorhomunculus Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu Functions of the various cortical motor areas Agy_motor2.tif 1. Primary motor cortex-It coordinates muscle contractions -It determines the temporal process of muscular activation -Downstream information of motor centers about the planned movement 2. Premotor cortex-It controls movements triggered by visual and auditory stimuli -Postural settings neccessary to carry out movements -It facilitates the subsequent motor response-Lesions in this brain region results in akinetic mutism 3. Supplementary motor cortex-It transfers sensory informations triggered by movements to the primary motor cortex -It ensures coordinated muscle actions during complex movements-It prevents mirror movements-It influences motor control of the spinal cord Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu Functions of the various motor cortical areas Agy_motor2.tif 4. Cingular motor cortex-It plays role in the planning and initiation of movements-It integrates motor actions related to emotions 5. Posterior parietal cortex -It provides important environmental information to carry out movements-It collects visual, auditory and somatosensory informations about -the position of different body parts -the position of external objects -It transfers information to the dorsolateral prefrontal cortex and the frontal eye field Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu Emotions trigger similar motor patterns in humans and primates majom.jpg Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu Anger, surprise, disgust, joy, despair, fear–different emotions evoke similar motor patterns in individuals anger.jpg disgust.jpg dispair.jpg fear.jpg surprise.jpg joy.jpg Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu The most important executive motor system is the pyramidal tract upper motoneuron pyramidal tract lower motoneuron Its lesion results in reduction (paresis) or complete loss (paralysis) of muscle power. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu The pyramidal tract can be visualised in MR scans (tractography programs) Tractogram1.jpg Tractogram2.jpg Motor cortex Internal capsule Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu Subcortical structures of movement control: the basal ganglia BASALGG2 basgan1 Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 www.itk.ppke.hu Cerebellar system of the movement control cerebellum cerebelhomun 1. Spinocerebellum (vermis, intermedier zone): balance, gait2. Cerebrocerebellum (cerebellar hemispheres): accuracy of goal-directed fast movement 3. Vestibulocerebellum (flocculonodular): spatial organization of movement Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Descending motor patways in the brainstem rubrospinal 1. Vestibulo-spinal tract: It originates from brainstem vestibular nuclei, affects lower motoneurons via interneurons in the spinal cord. It mediates postural reactions; activates extensor and inhibits flexor motoneurons. 2. Cortico-reticular and reticulospinal pathways: They regulate muscle tone (supplementary motor cortex -reticular system –spinal cord .and .motoneurons). 3. Tecto-spinal and rubro-spinal pathways: They regulate muscle tone via spinal cord interneurons, and maintain head position and balance when fixing gaze. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu Neuronal circuits regulating movement 1. Striatal circuit cerebral cortex (motor, sensory) -striatum -thalamus (VA, VL) -supplementary, premotor and primary motor cortex It regulates the direction and extent of movement. 2. Cerebellar circuit motor cortex –pons –cerebellar cortex -deep cerebellar nuclei -thalamus VL –motor cortical areas It regulates initiation of movement and coordination of co-acting muscles. CORTEX …………….. THALAMUS CORTEX Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 www.itk.ppke.hu Examination of the motor system Muscle tone:the normal state of balanced tension in the relaxed muscle. The appropriate muscle tone is the prerequisite of precise motor control. Muscle volume(trophy):it is influenced by several undetermined factors, any disturbance in the neuro-muscular transmissionresults in a reduction of muscle mass. Muscle power (strenght):the extent of work that can be carried out by a given muscle.Stretch reflexes:muscles contract in response to stretch. The stretch reflex may exaggerate or vanish underpathological conditions. Symptoms of pyramidal tract injury:various pathological reflexes, such as Babinski’s sign, indicating a lesionof the pyramidal tract.Coordination of movement:capability to carry out goal-directed movements, which is ensured by the collaboration of motor, sensory and association systems. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu Middle cerebral artery stroke in the left hemisphere causes right sided hemiparesis Right Left Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 www.itk.ppke.hu Symptoms of the patient Negative deficits: In response to the order of the examiner: -the patient is unable to move the right extremities (arms, legs) -the patient is unable to smile symmetrically (mouth is pulled to the left) Positive deficits: In response to the examiner’s action: -the patient exhibits spastic muscle tone (fingers and elbow on the right side are flexed) -the patient exhibits pathological reflexes (Babinski reflex, clasp-knife phenomenon) Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 www.itk.ppke.hu Disorders of the basal ganglia: Parkinson’s disease A neurodegenerative disease with unknown etiology. Main pathological characteristic is the loss of dopaminergic neurons in the substantia nigra. The dopaminergic, noradrenergic, serotoninergic and cholinergic neurotransmisson is disturbed. Serious motor and non-motor symptoms emerge. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 www.itk.ppke.hu Pathological changes in the brain substnigra SNeg_1.jpg SNbe_1.jpg Normal substantia nigra Loss of dopaminergic cells in the substantia nigra in Parkinson’s disease Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 www.itk.ppke.hu Indirect Direct Primary mot. cortex Suppl.mot. cortex STRIATUM Thalamus STN PPN SNc SNr GPe GPi D2 D1 GABA GABA SP Glu DA Glu Primary mot. cortex Suppl.mot. cortex STRIATUM Thalamus STN PPN SNc SNr GPe GPi D2 D1 GABA GABA SP Glu DA Glu + - Healthy Parkinson’s Disease Changes in excitatory and inhibitory inputs in PD Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 www.itk.ppke.hu Motorsymptoms Tremor (resting) Muscle rigidity Disturbance of posture Disturbance of movement initiation (akinesia) Slowing of movement (bradykinesia) Irott copy.jpg PDTART Charcot’s“vibratory chair” Charcot_Chair.jpg Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 www.itk.ppke.hu Pathways participating in tremor genezis Cerebral ctx Striatum GPe GPi SNr STN Voa NuR SNc OI Spinal cord Limbs Cerebellum NuD NuIP Aspartate DA GABA Acetylcholine Glutamate GPe: globus pallidus ext. GPi: globus pallidus int. SNc: subst. nigra p. comp. SNr: subst. nigra p. ret. VLa: nucl.ventrolat. thal. VLp: nucl.ventropost. thal. STN: nucl. subthalamicus NuR: nucl. ruber OI: oliva inferior NuD: nucl. dentatus NuIP: nucl. interpositus Midline Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu dopaminerg Ascending monoaminergic pathways Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu Non-motor symptoms (cognitive disturbances) REY Rey-complex test Working memory Problem solving Planning Execution Attention Emotional life Speech Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu Recall of the Rey-complex in Parkinson’s Disease REY3 Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu Disorder of the cerebellar motor system 1. Spinocerebellar ataxia It is genetically determined group of diseases (9thchromosome). Degeneration of the posterior bundle of the spinal cord, the spinocerebellar and the cortico-spinal pathways. Symptoms: limb-and trunk ataxia, ataxic gait, paresthesia, ocular movement disorder etc. 2. Essential tremor Its etiology is not known. Very likely that it is caused by the functional disturbance of both the brainstem and cerebellar motor control systems. Symptoms: postural and intention tremor, tremor of the head and vocal cords. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 www.itk.ppke.hu The „cognitive” movement disorder:Apraxia The goal-directed motor actsare the result of the synthesis of elementary movement patterns. Execution of complex movements requires sufficient muscle force, muscle tone, intact coordination and sensory systems. Preceding the motor actions it is necessary to design a motor plan. Apraxia is the result of a brain injury, which makes patients incapable to carry out goal-directed movements, to execute learned complex movements, to coordinate the movements of the limbs, while they do not exhibit any muscle weakness, functional disturbance of coordination or the sensory system, and they do understand the task. Introduction to functional neurobiology: Movement disorders 2011.10.12. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu Types of apraxia Ideomotor:the patient is unable to imitate the action without the presence of the corresponding objects Ideator:the patient is unable to plan complex movements, consequently the execution is often interrupted Kinetic:the patient is unable to carry out fine movements Constructive:the patient is unable to execute tasks requiring spatial recognition even usingeye control Dressingapraxia: the patient is unable to properly dress up. The end