From Ch. 38 “Principles of Neural Science”, 4th Ed. Kandel et al Voluntary Movement From Ch. 38 “Principles of Neural Science”, 4th Ed. Kandel et al May 13, 2009

Voluntary movement Voluntary movements are organized in cortex Sensory feed back Visual information Proprioceptive information Sounds and somatosensory information Goal of movement Vary in response to the same stimulus depending on behavioral task (precision vs. power grip) Improves with learning/ experience Can be generated in response to external stimuli or internally May 13, 2009

Cortical organization Hierarchical organization of motor control and task features Populations of neurons encode motor parameters e.g. force, direction, spatial patterns The summed activity in a population determines kinematic details of movement Voluntary movement is highly adaptable Novel behavior requires processing in several motor and parietal areas as it is continuously monitored for errors and then modified Primary motor cortex Fires shortly before and during movement Fires only with certain tasks and patterns of muscle activation Premotor areas encode global features of movement Set-related neurons Sensorimotor transformations (external environment integrated into motor programs) Delayed response

Motor cortex Primary motor cortex Activated directly by peripheral stimulation Executes movements Adapt movements to new conditions Premotor areas (different aspects of motor planning) Dorsal premotor area (dPMA) Selection of action; Sensorimotor transformations; Externally triggered movements; external cues that do not contain spatial information Ventral premotor area (vPMA) Conforming the hand to shape of objects; Mirror neurons; Selection of action; Sensorimotor transformations; Externally triggered movements Supplementary motor area (SMA) Preparation of motor sequence from memory (internally not in response to external information) Pre-supplementary motor area (pre-SMA) Motor sequence learning Cingulate motor area (CMA) Dorsal and ventral portions of caudal and roastral CMA (along the cingulate sulcus) Functions: to be determined

Somatotopical organization Sequence in human and monkey M1 similar Face and finger representations are much bigger than others Greater motor control required for face and fingers May 13, 2009

Motor cortex stimulation Historical perspective 1870 Discovery of electrical excitability of cortex in the dog; first brain maps (Fritsh and Hitzig) 1875 First motor map of the primate brain (Ferrier) 1926 Recording of extracellular spike activity of a nerve fiber (Adrian) 1937 First experimentally derived human motor map (Penfield and Boldrey) 1957 Microelectrode recordings to map primary somatosensory area (Mountcastle et al.) 1958 First recordings from neurons in awake monkeys (Jasper) 1967 Intracortical microstimulation for mapping of cortical motor output (Asanuma) 1985 TMS is used to activate motor cortex noninvasively (Barker et al.) 1870 electrical stimulation of the cerebral cortex evoked movement in the periphery; Movements were ordered e.g. stimulation of cortical areas next to each other could evoke movement of fingers in the order they were placed on the hand 1937 Stimulating the human brain with weak electrical shocks in conscious patients during surgery. They later constructed the homunculus showing the real cortical extend of representation of the body. 1985 barker et al developed a new stimulator with the movable hand held coil we know today

Transcranial stimulation TES – transcranial electrical stimulation (Merton and Morton 1980): High voltage (1-2kV), short duration pulses (10-50us), low resistance electrodes. Direct stimulation occurs at the anode Current passes through skin and scalp (resistance) before reaching cortex. TMS – transcranial magnetic stimulation (Barker 1985) Discharge of large capacitive currents (5-10kA, 2-300us) through a coil producing high magnetic field (1-2T). Stimulus site depends on coil design, coil orientation and stimulus intensity Non-invasive techniques to study Structure-function relationship (e.g. rTMS virtual lesion) Map brain motor output (typically averaged EMG as output =MEP) Measure conduction velocity TMS has advantages over TES No discomfort (no current passes through skin and high current densities can be avoided) No attenuation of field when passing through tissue No skin preparation (conduction gel) TES: short duration reduces discomfort of electroshock Big electrodes (5-10cm) ensures no tissue damage by creating low current densities Anode should be placed over the site to be stimulated. Cathode indifferent site

Transcranial magnetic stimulation Principles of TMS Coil design B Field decays as the square of distance from coil Faraday’s law B field induces am electric field E which induces a current in cortex Current is parallel to the place of the coil and flowing in opposite direction of the current in the coil The electric field affects the membrane potential which depolarizes mostly at axon curvatures. May evoke muscle contractions, sensory perceptions, or behavioural changes e.g. antidepressant COIL: figure-8 coil most commonly used because it produces a more focal area of stimulation

Motor cortex stimulation Movements can be evoked by direct stimulation of motor cortex Activates corticospinal fibers Direct from motor cortex to spinal motor neurons or interneurons Evokes a short latency EMG response in contralateral muscles Latency depends on corticospinal distance impulses have to travel Latency difference May 13, 2009

Cortex-muscle connections Shoulder muscle Wrist muscle Maps can be generated by intracortical microstimulation Sites controlling individual muscles are distributed over a wide area of motor cortex Muscle representations overlap in cortex Stimulation of single sites activates several muscles (diverging innervation) Many motor cortical neurons contribute to multijointed movements May 13, 2009

Motor cortex Primary motor cortex Activated directly by peripheral stimulation Executes movements Adapt movements to new conditions Premotor areas (different aspects of motor planning) Dorsal premotor area (dPMA) Selection of action; Sensorimotor transformations; Externally triggered movements; external cues that do not contain spatial information Ventral premotor area (vPMA) Conforming the hand to shape of objects; Mirror neurons; Selection of action; Sensorimotor transformations; Externally triggered movements Supplementary motor area (SMA) Preparation of motor sequence from memory (internally not in response to external information) Pre-supplementary motor area (pre-SMA) Motor sequence learning Cingulate motor area (CMA) Dorsal and ventral portions of caudal and roastral CMA (along the cingulate sulcus) Functions: to be determined

Cortical projections Premotor cortex and primary motor cortex has reciprocal connections Parietal projections to premotor areas (sensorimotor transformations) Prefrontal projections to some premotor areas (cognitive-affective control and learning) Premotor areas and primary motor areas have direct projections to spinal motor neurons May 13, 2009

Other projections Inputs from cerebellum Inputs from basal ganglia Do not project directly to spinal cord Inputs from basal ganglia Cortico-striatal pathways Motor loops Motor cortex => striatum => globus pallidus => Thalamus => motor cortex May 13, 2009

Motor cortex plasticity The functional organization of M1 changes after transection of facial nerve May 13, 2009

Practiced movements PET data M1 representation becomes more dense with practice PET data May 13, 2009

Pyramidal tract Successive cortical stimuli result in progressively larger EPSP in spinal motor neurons Make it possible to make individual movement of digits and isolated movements of proximal joints Direct corticospinal control is necessary for fine control of digits Bilateral sectioning of the pyramidal tract removes the ability if fine movements May 13, 2009

Ia spinal circuits Spinal Ia neurons are inhibitory interneurons Can respond directly to changes in somatosensory input Cortical centers do not need to respond to minor changes The Ia inhibitory neurons in the spinal cord sends inhibitory signals to antagonist motor neurons when muscle spindles in the agonist muscle are activated Ia neurons also inhibits spinal reflexes Spinal circuits are used as components of complex behaviors May 13, 2009

Direction of movement Increased activity with load Wrist displacement constant but load is different Activity in individual neurons in M1 is related to muscle force and not direction May 13, 2009

Postspike facilitation Spike-triggered averaging May 13, 2009

M1 and force Linear relationship between M1 firing rate and force generation Two types of motor cortical neurons Phasic-tonic: initial dynamic burst Tonic: tonic high level May 13, 2009

Direction of movement Single neuron Population vector Predicted from vector Actual movement Direction of movement is encoded by a population of neurons Motor cortical neurons are broadly tuned to directions but have a preferred direction May 13, 2009

Direction of movement M1 encoding of force required to maintain a direction Single Arm movements without and with external loads Unloaded: preferred direction to the upper left Loaded: opposite, preferred direction to the lower right A cells firing rate increases if a load opposes movement in preferred direction and decreases if load pulls in preferred direction May 13, 2009

Activity depends on motor task Precision grip: same activity whether force is light or heavy Power grip: No activity, but EMG activity the same May 13, 2009

Complexity of movement May 13, 2009

Internal and external information Influence on visual cue and prior training in motor cortex May 13, 2009

Motor preparation Dorsal premotor area is active during preparation Fires according to different delay times Fires during the whole period of anticipation May 13, 2009

Visuomotor transformations Separate but parallel fronto-parietal projections May 13, 2009

Ventral premotor cortex Specific hand tasks activate vPMC May 13, 2009

Mirror neurons Precision grip Observed movement Ventral premotor area Precision grip Observed movement Observed human movement Self-performed movement May 13, 2009

Summary Hierarchical organization of motor control and task features Populations of neurons encode motor parameters e.g. force, direction, spatial patterns The summed activity in a population determines kinematic details of movement Voluntary movement is highly adaptable Novel behavior requires processing in several motor and parietal areas as it is continuously monitored for errors and then modified Primary motor cortex Fires shortly before and during movement Fires only with certain tasks and patterns of muscle activation Premotor areas encode global features of movement Set-related neurons Sensorimotor transformations (external environment integrated into motor programs) Delayed response