Basal Ganglia PDF

Basal Ganglia Anne K. Galgon PT, PhD, NCS Eric S. Pelletier PT, DPT, PCS Department of Physical Therapy DPT - Neuroscience Objectives Identify the structures of the basal ganglia system Identify and understand the interaction of the basal ganglia system with other cortical and subc...

Basal Ganglia Anne K. Galgon PT, PhD, NCS Eric S. Pelletier PT, DPT, PCS Department of Physical Therapy DPT - Neuroscience Objectives Identify the structures of the basal ganglia system Identify and understand the interaction of the basal ganglia system with other cortical and subcortical structures Compare and contrast the direct and indirect pathways of basal ganglia transmission Describe how the basal ganglia has an influence on motor control and relate this information to how injury/disease to basal ganglia structures will have an impact on motor control in patients.  Compare and Contrast Basal Ganglia vs. Cerebellar influences on Motor Control  Leonard 1998 Fig. 7-1 Motor learning Early: Cognitive Big Concept Motor learning Late: Automatic Basal Ganglia Refers to a group of closely related nuclei: Corpus Striatum (caudate and putamen) Globus Pallidus Substantia Nigra Subthalamic Nuclei The Basal Ganglia participate in complex networks that influence the descending motor systems Modulate the output of these systems Basal Ganglia Basal Ganglia Anatomy Basal Ganglia Function Govern the initiation and cessation of movement Regulation of muscle contraction Regulation of muscle force Regulation of multi-joint movements Sequencing of movements Creating and executing motor plans Output of the basal ganglia is conveyed to UMNs via Ventral lateral nucleus of the thalamus to the cerebral cortex and via the pedunculopontine nucleus in brainstem Structures of the Basal Ganglia Structures of the BG Striatum (Neostriatum) Caudate Nucleus and Putamen Principally involved in the control of movement Receive virtually all inputs to BG Important connections with the thalamus and subthalamic nucleus of diencephalon  Caudate Nucleus Important in learning and memory functions Feedback Processing Highly innervated by dopamine neurons Consists of a large, globular head; a tapering body; and a long thin tail Putamen Disk shaped nucleus on the lateral border of the basal ganglia Receives input from the premotor and sensorimotor cortex  Caudate and Putamen Function Caudate and Putamen contain similar neuronal circuitry Both receive fibers from the ipsilateral neocortex GABAergic fibers from the caudate-putamen innervate the ipsilateral globus pallidus GABA (Gamma AminoButyric Acid) Rostral/Anterior caudate related to the prefrontal cortex – Controls behavioral and cognitive function Putamen connects to premotor and motor cortex Influences the motor operation of limb musculature Caudate and Putamen Function Caudate Nucleus Evaluates a movements appropriateness Motor planning – via connections to frontal lobe Inhibitory control of movement Brakes Putamen Activating automated mechanism of motor control  Caudate and Putamen Neurons Principal Neurons Medium Spiny Neurons Make up 96% of space dendrites have smooth surfaces up to or near their first branches, at which point they become profusely covered in spines. The axons are observed to emit several collaterals before the primary branch extends beyond the striatum. Local Circuit Neurons Medium Spiny Neurons Giant Spiny Neurons GABA Caudate and Putamen Impairment Lesions or degeneration of neurons Leads to hyperkinetic states such as chorea, athetosis, and dystonia Chorea is a rapid, jerky, aimless and constant motion of limbs https://www.youtube.com/watch?v=yRFi01fIeeM Athetosis is a slow sinous motion of the limbs https://www.youtube.com/watch?v=J_wIDm1_ax4 Dystonia is a slow sustained contorting of the body https://www.youtube.com/watch?v=9WH3HPTChkQ Behavioral changes Cognitive changes Lesions restricted to Putamen result in motor dysfunction in contralateral limbs Putamen connects to the premotor and motor cortex Lesions restricted to the caudate lead to behavioral defects characterized by apathy, disinhibition, and/or major affective disturbance. Tics Tardive dyskinesias (tongue protrusions, facial grimacing, lip smacking) Globus Pallidus Wedge shaped structure between Putamen and Internal Capsule Consists of two segments: medial (internal) and lateral (external)  Globus Pallidus – Medial/Internal Output region of the corpus striatum. Projects primarily to the thalamus (ventral anterior (VA)), ventrolateral (VL)and centromedian (CM) nuclei) Receives GABAergic projections from caudate and putamen Part of direct pathway through the basal ganglia  Globus Pallidus – Lateral/External Projects to the subthalamic nucleus (STN) Receives GABAergic projections from caudate and putamen Part of an indirect pathway through the basal ganglia  Globus Pallidus Impairment Lesions lead to profound hypokinesia Similar to Parkinsonian rigidity Without Tremor Surgeons have used carefully placed lesions to reduce unwanted movements Carbon dioxide or carbon disulfide intoxication Causes profound rigidity and catatonic posture Substantia Nigra Located in Anterior midbrain, just dorsal to the cerebral peduncles. Composed of two nuclei Pars reticulata (Output Nucleus of BG) Pars compacta Contains melanin – byproduct of dopamine metabolism Axons from S.N. innervate the ipsilateral caudate and putamen Substantia Nigra Impairment Destruction of dopamine containing cells in pars compacta Results in Parkinsonian signs and symptoms in the contralateral side of the body. Synthetic heroin containing MPTP caused significant parkinsonism in young users.  Subthalamic Nuclei Thin elongated wedge of gray matter Part of indirect pathway Receives inhibitory fibers (GABAergic) from external Globus Pallidus (GP) Excitatory projections to internal GP Source of excitation to the internal GP that can be modulated by the external GP. Connections to/from BG INPUT - all regions of cerebral cortex project to the basal ganglia (black) OUTPUT of basal ganglia is directed towards the frontal lobe, particularly pre-motor and supplementary motor cortex (Blue-grey), via the thalamus Basal Ganglia Inputs Striatum (Caudate and Putamen) main recipient of input to BG From Cerebral Cortex Frontal Lobe to Caudate head and Putamen Parietal/Occipital Lobes to Caudate Body Temporal Lobe to Caudate Tail Primary Motor Cortex and Primary Somatosensory Cortex project to Putamen Premotor cortex and supplementary motor areas to caudate head Intralaminar nuclei of thalamus to Putamen Substantial Nigra pars Compacta! dopamine INPUTs of BG Basal Ganglia Outputs Arise from two structures: Globus Pallidus Interna Body output EXCEPT head and neck Substantia Nigra pars reticulata Outputs for head and neck Output pathways are either excitatory or inhibitory Smooth motor function depends on a balance of both Using GABA Pathway is through the VL and VA nuclei of the thalamus Thalamic nuclei convey information to entire frontal cortex (mainly the premotor cortex, supplementary motor area, and primary motor cortex) Intrinsic Basal Ganglia Pathways Neurotransmitters in Basal Ganglia Circuit SN = substantia Nigra Glutamate (Glu) Gpe globus pallidus external GPI globus pallidus internal Excitatory STN= subthalamic Nucleus Released by cortical motor areas Gamma-aminobutyric acid (GABA) Inhibitory Dopamine (DA) Excitatory in Direct Pathway Inhibitory in Indirect Pathway Why would dopamine have excitatory and inhibitory effects on the striatum?  Direct Pathway Excitatory (less inhibition oF the thalamus) Indirect Pathway Inhibitory (more inhibition of the thalamus)  This is just a different representation of the direct pathway Direct Pathway CORTEX VA/VL PUTAMEN GPi Direct Motor Loop This is meant to show who firing patterns are effected by the excitatory and inhibitory influences.  Direct Pathway Cortex – Movement is desired- (Initiated) Excitation of Direct Inhibitory Pathway of Putamen and Globus Pallidus (Striatum) Disinhibition of Thalamus Facilitation of Cortex Movement Occurs Indirect Pathway Corticostriatal system Causes Subthalamus to Stimulated activate GP, suppressing Subthalamic Nuclei (STN) thalamic activation releases input into Globus Pallidus (GP) Suppressing unwanted Increased inhibition of movements thalamic nuclei Reduces Thalamo- cortical output Indirect Pathway Indirect Motor Loop  Direct vs. Indirect Cortical Excitation Cortical Inhibition Initiation and Control of Volitional Movement Motivation Higher order Basal I will sign my name association cortex Ganglia Context Where? Sensory/Motor Motor How Big? Association Execution of How Fast? Cortex Cortex Signature Sitting or Standing? Legibly? Status How fast is hand moving? Vestibular System Cerebellum Where is my wrist etc? Visual Somatosensory How much resistance from pen Spinal Cord and paper? S?M Association Looking at paper or elsewhere? Four Parallel Channels Through Basal Ganglia Parallel circuits Somatosensory Orientation Cognitive Emotional Somatomotor & Gaze & visceral Motor Channel Cortical Inputs Travel to Putamen Outputs from Globus Pallidus and Substantia Nigra to reach VA and VL of Thalamus From Thalamus to SMA, Premotor cortex and primary motor cortex Control of facial, limb and trunk musculature. Oculomotor Channel Input from body of caudate nucleus Output is to frontal eye fields and supplementary eye fields (for eye movement) Prefrontal Channel Important in cognitive processes involving frontal lobes Input from head of caudate Output reaches prefrontal cortex Strategic planning of behavior Limbic Channel Regulation of emotions and motivation Inputs from limbic cortex, hippocampus, amygdala Outputs to anterior cingulate and orbital frontal cortex. Appear to play an important role in psychiatric disorders Clinical Application Basal Ganglia Impairment Basal Ganglia Inhibits the Thalamus typically Hypokinetic Disorders Too Little Movement Parkinson’s Disease Excessive inhibition from Basal Ganglia Hyperkinetic Disorders Excessive Movement Huntington’s Disease Dystonia Some Types of Cerebral Palsy Inadequate inhibition from Basal Ganglia Parkinson’s Disease Characterized by: Muscular Rigidity Shuffling Gait Stooped Posture Rhythmical Muscular Tremors Masklike Facial Expression Functional Impairments Poor transitions from standing to sitting Gait with flexed posture, shuffling of feet, decreased/absent arm swing Rigidity Increased resistance to movement in all muscles Caused by direct upper motor neuron facilitation of alpha motor neurons without appropriate inhibition from basal ganglia circuit Parkinson’s Pathology Degeneration of Dopamine Neurons in the substantia nigra One can lose about 80% of of Dopaminergic cells in the substantia nigra without symptoms  Decreased dopamine results in Parkinson’s Disease Circuit Less disinhibition (direct root) and more inhibition (indirect root) Cerebral Cortex Blue= inhibition of the thalamus White excitation Resulting in Hypokinetic movement Striatum Globus Pallidus e Substantia Nigra c Thalamus Subthalamic Globus pallidus i nucleus Substantia Nigra r Adapted from (Pfann, 1997) Pedunculopontine nuclei Provide activation of muscle tension The Basal ganglia dampens the muscle tension for purpose full movements Loss of BS input results in rigid muscles Huntington’s Chorea Characterized by increase in choreiform movements (Also results in cognitive and behavioral deficits) Involuntary continuous movements of the body Lose striatal inhibition of the Gpe (indirect pathway) Subthalamic nuclei no longer facilitate GPi and SN Ultimately disinhibition of the thalamus occurs  Huntington Disease affect on Basal Ganglia Circuit Cerebral Cortex Indirect pathway Loss of inhibition Resulting in Hyperkinetic movement Striatum Problem. X Globus Pallidus e Substantia Nigra c Thalamus Subthalamic Globus pallidus i nucleus Substantia Nigra r Adapted from (Pfann 1997) dark arrows inhibits/ white arrow excitation Clinical Application Leisman et al. (2014) suggest that the basal ganglia also function in some cognitive and affective processes such as timing of verbal interaction in groups and in the ability to delay impulsive behaviors. Theories exist that suggest that pathology of the basal ganglia could be involved in ADHD and autism spectrum disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923298/ Clinical Case and Questions The physical therapist examines a 74 year old male in the skilled nursing facility. The examination reveals the following: Tremors in all four extremities Decreased volitional movement Muscle Rigidity Visual Perceptual Impairments Poor postural stability Clinical Case and Questions The physical therapist examines a 74 year old male in the skilled nursing facility. The examinations reveals the following: Tremors in all four extremities Decreased volitional movement Muscle Rigidity Visual Perceptual Impairments Poor postural stability What is the most likely diagnosis for the patient? A) Alzheimers Disease B) Huntington’s Chorea C) Middle Cerebral Artery Infarction D) Parkinson’s Disease Clinical Case and Questions The physical therapist examines a 74 year old male in the skilled nursing facility. The examinations reveals the following: Tremors in all four extremities Decreased volitional movement Muscle Rigidity Visual Perceptual Impairments Poor postural stability What structure is most likely involved in this case? A) Caudate Nucleus B) Globus Pallidus C) Substantia Nigra D) Thalamus Clinical Case and Questions The physical therapist examines a 74 year old male in the skilled nursing facility. The examinations reveals the following: Tremors in all four extremities Decreased volitional movement Muscle Rigidity Visual Perceptual Impairments Poor postural stability Which of the following neurotransmitters is deficient? A) Acetylcholine B) Dopamine C) Gamma Aminobutyric Acid D) Glutamate