Eberhard E. Fetz - US grants

[unreadable] DESCRIPTION (provided by applicant): We will investigate the neural mechanisms controlling voluntary hand and arm movement in primates. The functional roles of neurons in primary motor cortex and spinal cord will be directly compared. The activity of premotor (PreM) cells (identified by correlational linkages to forelimb motoneurons) and multiple muscles will be documented during multidirectional wrist movements and grip. This repertoire of movements will activate muscles in different synergistic combinations and test the degree to which PreM cells and non-PreM cells are organized in terms of muscles and movement parameters. Spinal interneurons will be identified by their synaptic inputs from different forelimb muscles and from functionally identified cortical sites. The results should reveal significant differences between motor cortex cells and spinal interneurons. We will further investigate the involvement of spinal cord interneurons in preparation and execution of voluntary movements in a two-dimensional instructed delay task. We will also investigate the movements of arm and hand evoked by electrical stimulation of spinal cord sites; the modulations of these responses during an instructed delay task will reveal the interaction of intraspinally evoked responses with preparation and execution of voluntary movements. To obtain information important for the use of neural activity to control brain-computer interfaces [BCI] we will systematically investigate the volitional control of identified neurons in different cortical areas using biofeedback training. The correlated responses in other cortical cells and muscles will be documented to determine the extent and variability of correlated activity. A novel chronically implanted recurrent BCI will be used to investigate the consequences of directly linking cortical cell activity to stimuli delivered in motor cortex, spinal cord and muscles. .An implanted computer chip will allow long-term monitoring of cell and muscle activity during unrestrained behavior and will test the monkeys' adaptation to continuous operation of recurrent circuits. The recurrent BCI will be used to test the feasibility of directly controlling functional electrical stimulation of muscles with activity of motor cortex cells. These studies of the primate motor system will provide unique information essential to understanding and effectively treating clinical motor disorders, like cerebral palsy, stroke and spinal cord injury. Results with the implanted recurrent BCI will have significant consequences for development of prosthetic applications. [unreadable] [unreadable] [unreadable]

nervous system; Primates; Mammalia;

Coordination of limb movements requires continuous interactions between cortical neurons in separate regions representing different components of the movements. The neural mechanisms mediating these interactions remain unknown. A testable hypothesis proposes that intracortical "binding" may be mediated by some form of temporal synchrony between the firing of neurons, in the form of either coincidences between aperiodic cell spikes or periodic oscillatory activity. Our previous studies have documented the appearance of widespread oscillatory activity in sensorimotor cortex during finely controlled reaching movements. To investigate these mechanisms further, we documented the activity of arm-related neurons in left and right motor cortex in two pigtailed macaques while they performed a coordinated bimanual task. The monkeys controlled the two-dimensional position of a cursor on a video screen by operating two joysticks separately with the left and right hands. Each joystick controlled one axis of the cursor position (x or y position). Both monkeys performed well in tracking a randomly moving target. In addition to cell activity we recorded local field potentials in premotor and supplementary motor areas; these field potentials provide robust measures of synchronous activity in local populations. Sometimes the relation between the joystick deflection and cursor coordinates was altered unexpectedly so that we could analyze the neural concomitants of learning new motor strategies. The recordings are being analyzed to determine whether synchrony is increased preferentially during the coordinated task, and when this synchrony occurs with respect to changes in target position. The results will elucidate the long-range cortical interactions that mediate coordinated sensorimotor activity.

nervous system; Primates; Mammalia;

Spinal neurons play a critical role in coordinating limb movements, but since they have usually been studied in anesthetized animals, little is known about their activity during normal voluntary movements. Moreover, they usually have been characterized with respect to sensory input, so virtually nothing is known about their output effects on different muscles. To investigate these issues, we recorded the activity of task-related interneurons in the C7-T1 cervical spinal cord of monkeys generating isometric flexion-extension torques about the wrist. Premotor (PreM) interneurons were identified by post-spike output effects in spike-triggered averages of EMG of forearm muscles. Most PreM interneurons fired during wrist responses in proportion to active torque. In contrast to corticomotoneuronal (CM) cells, which fire during either flexion or extension. but never both, most spinal interneurons showed some activity with both directions. CM cells tend to have larger muscle fields than spinal PreM interneurons, and more often exert reciprocal inhibitory effects on antagonists of their facilitated muscles. Thus cortical output neurons tend to control larger and more complex muscle fields. To determine whether interneurons were related to preparation for movement as well as to generation of muscle activity, interneurons were recorded during a task involving an instructed delay period between a cue that indicated the direction of the next movement and a "go" signal that indicated the time to begin the movement. A significant number of interneurons changed their firing rates during the delay period. Sometimes the delay period activity occurred in the same direction as the activity associated with movement, which may simply represent a form of subthreshold preparatory activation. However, in many other cases the instructed delay period activity was distinctly different from their changes in rate during movement. Thus, spinal interneurons can show the same evidence of involvement in preparation to move as do cortical neurons.

neuroregulation; limb movement; neurons; Primates; animal colony; cerebellum; clinical research;

neuroregulation; limb movement; clinical research;

neuroregulation; wrist; limb movement; interneurons; spinal cord; clinical research;

implant; nervous system prosthesis; computers; Primates; animal colony; medical implant science; clinical research;

limb movement; neurophysiology; spinal cord; interneurons; clinical research;

ALS; Action Potentials; Amyotrophic Lateral Sclerosis; Arm; Behavior; CRISP; Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Computers; Corticospinal Tracts; Distal; EMG; Electric Stimulation; Electrical Stimulation; Electrodes; Electromyography; Extremities; Feedback; Forearm; Funding; Gehrig's Disease; Grant; Home; Home environment; Implant; Institution; Investigators; Left; Lesion; Limb structure; Limbs; Lou Gehrig Disease; Mammalia; Mammals; Mammals, General; Mammals, Primates; Memory; Monkeys; Motor; Motor Cortex; Motor Neuron Disease, Amyotrophic Lateral Sclerosis; Movement; Muscle; Muscle Tissue; Myelopathy, Traumatic; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nerve Block; Nerve Cells; Nerve Unit; Nervous; Neural Block; Neural Blockade; Neural Cell; Neurocyte; Neurons; Non-Trunk; Operation; Operative Procedures; Operative Surgical Procedures; Output; Palsy; Paralysed; Patients; Pattern; Performance; Physiologic pulse; Play; Plegia; Primates; Pulse; Pulse taking; Records; Recurrence; Recurrent; Research; Research Personnel; Research Resources; Researchers; Resources; Role; Site; Source; Spinal Cord Trauma; Spinal Injuries; Spinal Trauma; Spinal cord injured; Spinal cord injuries; Spinal cord injury; Stimulus; Surgical; Surgical Interventions; Surgical Procedure; Testing; Torque; Training; United States National Institutes of Health; Upper arm; body movement; brain computer interface; free behavior; limb movement; motor control; neural; neuronal; paralysis; paralytic; relating to nervous system; social role; spine injury; surgery; vertebral injury

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Spinal neurons play a crucial role in generating voluntary limb movements. We are continuing to investigate the way that spinal interneurons are engaged in controlling muscle synergies by documenting their responses in monkeys performing a repertoire of movements about the wrist (flexion-extension, radial-ulnar deviation, pronation-supination and grip). Most interneurons in cervical segments were modulated during one or more of these hand movements, showing preferential relationships to particular muscle patterns. We have also been documenting the response patterns of motor cortical cells during the same response repertoire to compare the tuning properties of cortical and spinal neurons. We also documented the output effects on muscles evoked by intraspinal stimulation at different cervical sites. In behaving monkeys the excitatory and inhibitory post-stimulus effects evoked by single intraspinal stimuli in upper and lower cervical segments were investigated by stimulus-triggered averages of muscle EMG. At most spinal sites the stimuli evoked responses in multiple muscles indicating that intraspinal sites could be useful for evoking synergistic muscle responses. Recent experiments showed that a monkey could control intraspinal stimulation by modulating the high-frequency power in the cortical field potential. The intraspinal stimulation evoked EMG activity that was converted to movement of a cursor into a target, demonstrating for the first time that volitional control of cortical potentials can be used to generate goal-directed output from spinal stimulation.