The Basal Ganglia SMA Posterior S1 M1 Anterior Posterior PMA parietal Prefrontal Basal Ganglia Loop Ganglia Basal Thalamus VLc VLo Pons Overview 1 Caudate Putamen N. Accumbens Red Globus pallidus Cerebellum Cerebellar Loop Cerebellar Nuc. Substantia nigra Subthalamic nuc. Inf. Sup. & Inf. Olive Colliculi Vest. Retic. Nuc. Form. Spinocerebellar Tr. Spinocerebellar Vest. Retic. Rubro Cortico- Tecto- Spinal Spinal Spinal Spinal Spinal Tr. Tr. Tr. Tr. Tr. Anterior Posterior 1 SMA Posterior S1 M1 Posterior PMA parietal Prefrontal Basal Ganglia Loop Ganglia Basal Thalamus VLc VLo Pons Overview 1 Caudate Putamen N. Accumbens Red Globus pallidus Cerebellum Cerebellar Loop Cerebellar Nuc. Substantia nigra Subthalamic nuc. Inf. Sup. & Inf. Olive Colliculi Vest. Retic. Nuc. Form. Spinocerebellar Tr. Spinocerebellar Vest. Retic. Rubro Cortico- Tecto- Spinal Spinal Spinal Spinal Spinal Tr. Tr. Tr. Tr. Tr. Areas of the Nervous System Involved in Movement Upper Motor Neuron Association Cortex Association Cortex Thalamus Thalamus Basal Ganglia Cerebellum Lower Motor Neuron Muscle 2 Motor loop of the basal ganglia Nuclei of the Basal Ganglia Input Intrinsic Output Caudate nucleus Putamen Globus pallidus – Nucleus accumbens external segment Subthalamic nucleus Globus pallidus – Substantia nigra pars internal segment compacta Substantia nigra pars Ventral tegmentum reticulata Ventral pallidum Ventricles Thalamus Caudate Putamen Globus Pallidus 3 Coronal Section Corpus Callosum Cingulate Gyrus Lateral Ventricle Caudate (head) Septum Pellucidum Internal Capsule Claustrum Putamen Nucleus Accumbens Optic Chiasm 4 Coronal Section Caudate Nucleus Putamen Internal Capsule Thalamus Globus Pallidus Pars Externa Pars Interna Amygdala BCP p.479 5 Simplified box diagram of basal ganglia loop Substantia nigra pars compacta Ventral tegmental area Output nuclei Input nuclei Thalamus Globus pallidus Cerebral cortex Caudate n. pars interna Ventral lateral n. (all lobes) BasalPutamen Ganglia CircuitryVentral pallidum Ventral anterior n. N. accumbens Substania nigra Medial dorsal n. pars reticulata Direct route Globus pallidus Subthalamic Frontal lobe pars externa nucleus Indirect route Corticospinal / Corticobulbar Tract General Circuitry of the Basal Ganglia Direct and Indirect Pathways Substantia Nigra Direct route Cerebral cortex (all lobes) Input nuclei Output nuclei Thalamus Indirect route Globus pallidus Subthalamic Frontal lobe pars externa nucleus The Direct Pathway (Skeletomotor) Substantia nigra pars compacta D1 Cortex Thalamus E I Globus pallidus I M1, S1 pars interna Premotor Putamen VA, VL Substania nigra cortex pars reticulata Low Spontaneous High Spontaneous M1, SMA, PMA E E I I E: Sign Preserving – “disinhibitory” 6 The Indirect Pathway (Skeletomotor) Substantia nigra pars compacta Cortex D2 Thalamus Globus pallidus M1, S1 E I pars interna Premotor Putamen VA, VL Substania nigra cortex pars reticulata I E I Globus pallidus Subthalamic M1, SMA, PMA pars externa nucleus E E I I E I E: Sign Inverting – “inhibitory” Skeletomotor Loop Substantia nigra Inhibition Excitation pars compacta Dopamine Thalamus Globus pallidus M1, S1 pars interna Premotor Putamen VA, VL Substania nigra cortex pars reticulata Direct pathway Globus pallidus Subthalamic M1, SMA, PMA pars externa nucleus Corticospinal/corticobulbar tract Direct path excites thalamic target neurons Indirect path inhibits thalamic target neurons DopamineX (SNc) ? Direct path Indirect path Dopamine is thought to facilitate movement by both exciting direct path and inhibiting indirect path 7 Normal Diseased SNc Parkinson’s disease (Paralysis Agitans) Loss of dopaminergic SN pars compacta (SNc) inputs to the basal ganglia increases inhibition of voluntary movement Hypokinetic signs (impoverished movement) Major impairment initiating movements – akinesia Reduction in the extent and speed of movements – bradykinesia Postural deficits Resting tremor (shaking palsy, resembles pill rolling) Expressionless face, infrequent blinking – mask facies Characteristic limb stiffness – lead pipe or cogwheel rigidity Disorders of the basal ganglia: disturbances of tone: dystonia abnormalities of movements: dyskinesia Upper Motor Neuron signs Extrapyramidal signs •Increased tone in specific •General increased tone across muscle groups all muscles •Clasp-knife response •Cogwheel rigidity •Hyperreflexia •Reflexes ~normal •Weakness (paresis) •Slowed/limited movement, but not particularly weak •Positive signs (tremor, ballism, chorea, athetosis) 8 Ballismus / hemiballismus “Releases” Indirect pathway thalamus Cortex Thalamus Globus pallidus M1, S1 E Putamen pars interna I Premotor Substania nigra VA, VL cortex pars reticulata I E Globus pallidus I Subthalamic M1, SMA, PMA pars externa nucleus E Caused by vascular accidents affecting the subthalmamic nucleus Loss of excitatory influence of subthalamic nucleus reduces output of GPi, which in turn releases thalamus of inhibition Leads to exaggerated, large amplitude movements: hyperkinesis Dyskinesias due to degeneration of the striatum (Huntington’s disease) Substantia Nigra Cerebral cortex (all lobes) Input nuclei Output nuclei Thalamus Direct route X Globus pallidus Subthalamic Frontal lobe pars externa nucleus Indirect route Normal Diseased Chorea / Choreiform Movements Involuntary, sudden, frequent, and purposeless jerks of the extremities, head, and trunk 9 Athetosis / Athetoid Movements Combination of symptoms characterized chiefly by a more or less constant mobility of the extremities and an inability to retain them in any fixed position Treatment of basal ganglia disorders such as PD Dopamine replacement (levodopa) MAO inhibitors (e.g. selegiline) prolong action of dopamine Surgical lesions: pallidotomy (reduces rigitidy) thalamotomy (relieves tremor) Fetal nigral transplantation Drug MPTP, a heroin like compound, destroys DA neurons, and has been used to develop a experimental model of Parkinsonism 10 Implantable Components Patient Component System Start-up Requirements Cortical origin Input nucleus Output nuclei Thalamus / SC Posterior M1 SMA parietal PosteriorCaudate S1 SN, reticulata VA nucleus PMA Prefrontal parietal GP, interna Prefrontal MD Additional loops Loop Ganglia Basal Frontal & Oculomotor loop Suppl. eye fields Thalamus VLc VLo Posterior Pons SN, reticulata parietal Caudate Caudate VA GP, interna Premotor nucleus Putamen MD N. Accumbens Red Globus pallidus Cerebellum Cerebellar Loop Cerebellar Nuc. Association loop Substantia nigra Prefrontal Subthalamic nuc. Inf. Sup. & Inf. Olive Colliculi Vest. Retic. Nuc. Form. Ventral pallidum Temporal Ventral striatum SN, reticulata MD Hippocampus (n. accumbens) Spinocerebellar Tr. Spinocerebellar GP, interna VA Vest. Retic. Rubro Cortico- Tecto- Ant. cingulateSpinal Spinal Spinal SpinalLimbic loopSpinal OrbitofrontalTr. Tr. Tr. Tr. Tr. Overview 1 11.