Roles of monkey premotor neuron classes in movement preparation and execution.

Dorsal premotor cortex (PMd) is known to be involved in the planning and execution of reaching movements. However, it is not understood how PMd plan activity-often present in the very same neurons that respond during movement-is prevented from itself producing movement. We investigated whether inhibitory interneurons might "gate" output from PMd, by maintaining high levels of inhibition during planning and reducing inhibition during execution. Recently developed methods permit distinguishing interneurons from pyramidal neurons using extracellular recordings. We extend these methods here for use with chronically implanted multi-electrode arrays. We then applied these methods to single- and multi-electrode recordings in PMd of two monkeys performing delayed-reach tasks. Responses of putative interneurons were not generally in agreement with the hypothesis that they act to gate output from the area: in particular it was not the case that interneurons tended to reduce their firing rates around the time of movement. In fact, interneurons increased their rates more than putative pyramidal neurons during both the planning and movement epochs. The two classes of neurons also differed in a number of other ways, including greater modulation across conditions for interneurons, and interneurons more frequently exhibiting increases in firing rate during movement planning and execution. These findings provide novel information about the greater responsiveness of putative PMd interneurons in motor planning and execution and suggest that we may need to consider new possibilities for how planning activity is structured such that it does not itself produce movement.

[1]  S. Wise,et al.  Effects of hand movement path on motor cortical activity in awake, behaving rhesus monkeys , 2004, Experimental Brain Research.

[2]  S. Scott Inconvenient Truths about neural processing in primary motor cortex , 2008, The Journal of physiology.

[3]  A. Nieder,et al.  Complementary Contributions of Prefrontal Neuron Classes in Abstract Numerical Categorization , 2008, The Journal of Neuroscience.

[4]  T J Ebner,et al.  Visuomotor processing as reflected in the directional discharge of premotor and primary motor cortex neurons. , 1999, Journal of neurophysiology.

[5]  Stefan Everling,et al.  Monkey Prefrontal Cortical Pyramidal and Putative Interneurons Exhibit Differential Patterns of Activity Between Prosaccade and Antisaccade Tasks , 2009, The Journal of Neuroscience.

[6]  Jude F. Mitchell,et al.  Differential Attention-Dependent Response Modulation across Cell Classes in Macaque Visual Area V4 , 2007, Neuron.

[7]  Y. Amit,et al.  Encoding of Movement Fragments in the Motor Cortex , 2007, The Journal of Neuroscience.

[8]  W. Newsome,et al.  The Variable Discharge of Cortical Neurons: Implications for Connectivity, Computation, and Information Coding , 1998, The Journal of Neuroscience.

[9]  P S Goldman-Rakic,et al.  Functional synergism between putative gamma-aminobutyrate-containing neurons and pyramidal neurons in prefrontal cortex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  L. Craighero,et al.  Modulation of spinal excitability during observation of hand actions in humans , 2001, The European journal of neuroscience.

[11]  H. Sompolinsky,et al.  Chaos in Neuronal Networks with Balanced Excitatory and Inhibitory Activity , 1996, Science.

[12]  Tomoki Fukai,et al.  Microcircuitry coordination of cortical motor information in self-initiation of voluntary movements , 2009, Nature Neuroscience.

[13]  H. Swadlow Fast-spike interneurons and feedforward inhibition in awake sensory neocortex. , 2003, Cerebral cortex.

[14]  Michael I. Jordan,et al.  Optimal feedback control as a theory of motor coordination , 2002, Nature Neuroscience.

[15]  RP Dum,et al.  The origin of corticospinal projections from the premotor areas in the frontal lobe , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  S. Royer,et al.  Cell-type-specific GABA responses and chloride homeostasis in the cortex and amygdala. , 2001, Journal of neurophysiology.

[17]  Byron M. Yu,et al.  Techniques for extracting single-trial activity patterns from large-scale neural recordings , 2007, Current Opinion in Neurobiology.

[18]  Joo-Hyun Song,et al.  Roles of narrow- and broad-spiking dorsal premotor area neurons in reach target selection and movement production. , 2010, Journal of neurophysiology.

[19]  A Keller,et al.  Intrinsic synaptic organization of the motor cortex. , 1993, Cerebral cortex.

[20]  Thomas Naselaris,et al.  Dynamic Sculpting of Directional Tuning in the Primate Motor Cortex during Three-Dimensional Reaching , 2008, The Journal of Neuroscience.

[21]  K. Shenoy,et al.  A Central Source of Movement Variability , 2006, Neuron.

[22]  G. Rizzolatti,et al.  The mirror neuron system. , 2009, Archives of neurology.

[23]  A. Fuchs,et al.  Brainstem control of saccadic eye movements. , 1985, Annual review of neuroscience.

[24]  R Porter,et al.  Corticocortical synaptic influences on morphologically identified pyramidal neurones in the motor cortex of the monkey. , 1988, The Journal of physiology.

[25]  P. Goldman-Rakic,et al.  Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC. , 1999, Journal of neurophysiology.

[26]  S. Grossberg,et al.  Neural dynamics of planned arm movements: emergent invariants and speed-accuracy properties during trajectory formation. , 1988, Psychological review.

[27]  D. McCormick,et al.  Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. , 1985, Journal of neurophysiology.

[28]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[29]  T. Sawaguchi,et al.  Application of the GABA antagonist bicuculline to the premotor cortex reduces the ability to withhold reaching movements by well-trained monkeys in visually guided reaching task. , 1996, Journal of neurophysiology.

[30]  Paul Cisek,et al.  Preparing for speed. Focus on "Preparatory activity in premotor and motor cortex reflects the speed of the upcoming reach". , 2006, Journal of neurophysiology.

[31]  Asaf Keller,et al.  Synaptic relationships involving local axon collaterals of pyramidal neurons in the cat motor cortex , 1993, The Journal of comparative neurology.

[32]  C. Sherrington,et al.  OBSERVATIONS ON THE EXCITABLE CORTEX OF THE CHIMPANZEE, ORANG‐UTAN, AND GORILLA , 1917 .

[33]  Kevin Staras,et al.  What Roles Do Tonic Inhibition and Disinhibition Play in the Control of Motor Programs? , 2010, Front. Behav. Neurosci..

[34]  S P Wise,et al.  Movement-related activity in the premotor cortex of rhesus macaques. , 1986, Progress in brain research.

[35]  A. Riehle,et al.  Monkey primary motor and premotor cortex: single-cell activity related to prior information about direction and extent of an intended movement. , 1989, Journal of neurophysiology.

[36]  J. A. Pruszynski,et al.  The long-latency reflex is composed of at least two functionally independent processes. , 2011, Journal of neurophysiology.

[37]  R. Lemon,et al.  The involvement of monkey premotor cortex neurones in preparation of visually cued arm movements , 1985, Behavioural Brain Research.

[38]  V. Okhotin Cytophysiology of spiny stellate cells in the striate cortex and their role in the excitatory mechanisms of intracortical synaptic circulation. , 2006, Neuroscience and behavioral physiology.

[39]  D. Lewis,et al.  Cluster analysis-based physiological classification and morphological properties of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex. , 2005, Journal of neurophysiology.

[40]  Alexander Kraskov,et al.  Large Identified Pyramidal Cells in Macaque Motor and Premotor Cortex Exhibit “Thin Spikes”: Implications for Cell Type Classification , 2011, The Journal of Neuroscience.

[41]  H. Kuypers,et al.  Premotor cortical ablations in monkeys: contralateral changes in visually guided reaching behavior. , 1977, Science.

[42]  Alexa Riehle,et al.  Cancellation of a planned movement in monkey motor cortex , 2006, Neuroreport.

[43]  Julie Duque,et al.  Role of corticospinal suppression during motor preparation. , 2009, Cerebral cortex.

[44]  S.I. Ryu,et al.  An extensible infrastructure for fully automated spike sorting during online experiments , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[45]  Y. Kubota,et al.  GABAergic cell subtypes and their synaptic connections in rat frontal cortex. , 1997, Cerebral cortex.

[46]  J. Hartigan,et al.  The Dip Test of Unimodality , 1985 .

[47]  J. Csicsvari,et al.  Intracellular features predicted by extracellular recordings in the hippocampus in vivo. , 2000, Journal of neurophysiology.

[48]  Byron M. Yu,et al.  Single-Trial Neural Correlates of Arm Movement Preparation , 2011, Neuron.

[49]  John P. Cunningham,et al.  Gaussian-process factor analysis for low-dimensional single-trial analysis of neural population activity , 2008, NIPS.

[50]  Gopal Santhanam,et al.  Preparatory activity in premotor and motor cortex reflects the speed of the upcoming reach. , 2006, Journal of neurophysiology.

[51]  S. Wise,et al.  The premotor cortex of the monkey , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  E. Fetz,et al.  Primate spinal interneurons show pre-movement instructed delay activity , 1999, Nature.

[53]  S. Votaw,et al.  Roles of primate spinal interneurons in preparation and execution of voluntary hand movement , 2002, Brain Research Reviews.

[54]  J. Kalaska,et al.  Prior information in motor and premotor cortex: activity during the delay period and effect on pre-movement activity. , 2000, Journal of neurophysiology.

[55]  G. Rizzolatti,et al.  Motor facilitation during action observation: a magnetic stimulation study. , 1995, Journal of neurophysiology.

[56]  K. Shenoy,et al.  Delay of movement caused by disruption of cortical preparatory activity. , 2007, Journal of neurophysiology.

[57]  P. Strick,et al.  Motor areas in the frontal lobe of the primate , 2002, Physiology & Behavior.

[58]  G. Buzsáki,et al.  Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. , 2004, Journal of neurophysiology.

[59]  P. Cisek Integrated Neural Processes for Defining Potential Actions and Deciding between Them: A Computational Model , 2006, The Journal of Neuroscience.

[60]  J. Kalaska,et al.  Learning to Move Machines with the Mind , 2022 .

[61]  J. Kalaska,et al.  Covariation of primate dorsal premotor cell activity with direction and amplitude during a memorized-delay reaching task. , 2000, Journal of neurophysiology.

[62]  Byron M. Yu,et al.  Neural Variability in Premotor Cortex Provides a Signature of Motor Preparation , 2006, The Journal of Neuroscience.

[63]  A. Nambu,et al.  Organization of nonprimary motor cortical inputs on pyramidal and nonpyramidal tract neurons of primary motor cortex: An electrophysiological study in the macaque monkey. , 2000, Cerebral cortex.

[64]  A. Riehle,et al.  The predictive value for performance speed of preparatory changes in neuronal activity of the monkey motor and premotor cortex , 1993, Behavioural Brain Research.

[65]  K.V. Shenoy,et al.  Power feasibility of implantable digital spike sorting circuits for neural prosthetic systems , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[66]  S. Scott Optimal feedback control and the neural basis of volitional motor control , 2004, Nature Reviews Neuroscience.

[67]  Henry Szechtman,et al.  Longlasting consequences of chronic treatment with the dopamine agonist quinpirole for the undrugged behavior of rats , 1993, Behavioural Brain Research.

[68]  A L Towe,et al.  Extracellular microelectrode sampling bias. , 1970, Experimental neurology.

[69]  T. Ebner,et al.  Temporal encoding of movement kinematics in the discharge of primate primary motor and premotor neurons. , 1995, Journal of neurophysiology.

[70]  S. Wise,et al.  Oscillations in the premotor cortex: single-unit activity from awake, behaving monkeys , 2000, Experimental Brain Research.

[71]  A. Fuchs,et al.  Activity of omnipause neurons in alert cats during saccadic eye movements and visual stimuli. , 1982, Journal of neurophysiology.

[72]  C. Koch,et al.  On the origin of the extracellular action potential waveform: A modeling study. , 2006, Journal of neurophysiology.

[73]  J. Tanji,et al.  Anticipatory activity of motor cortex neurons in relation to direction of an intended movement. , 1976, Journal of neurophysiology.

[74]  Marie-Hélène Boudrias,et al.  Output properties and organization of the forelimb representation of motor areas on the lateral aspect of the hemisphere in rhesus macaques. , 2010, Cerebral cortex.

[75]  D. Simons Response properties of vibrissa units in rat SI somatosensory neocortex. , 1978, Journal of neurophysiology.

[76]  Matthew T. Kaufman,et al.  Cortical Preparatory Activity: Representation of Movement or First Cog in a Dynamical Machine? , 2010, Neuron.

[77]  G. Tucker,et al.  Testing for bimodality in frequency distributions of data suggesting polymorphisms of drug metabolism--hypothesis testing. , 1989, British journal of clinical pharmacology.

[78]  B. Cohen,et al.  Unit activity in the pontine reticular formation associated with eye movements , 1972 .

[79]  David A Lewis,et al.  Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex. , 2005, Journal of neurophysiology.

[80]  D. Humphrey,et al.  Properties of pyramidal tract neuron system within a functionally defined subregion of primate motor cortex. , 1978, Journal of neurophysiology.

[81]  E. Evarts Pyramidal tract activity associated with a conditioned hand movement in the monkey. , 1966, Journal of neurophysiology.

[82]  Daniel Bullock,et al.  Neural dynamics of planned arm movements: emergent invariants and speed-accuracy properties during trajectory formation , 1988 .

[83]  B. Connors,et al.  Intrinsic firing patterns of diverse neocortical neurons , 1990, Trends in Neurosciences.

[84]  Richard P. Heitz,et al.  Biophysical support for functionally distinct cell types in the frontal eye field. , 2009, Journal of neurophysiology.

[85]  E. Fetz Movement control: Are movement parameters recognizably coded in the activity of single neurons? , 1992 .

[86]  J. Huguenard,et al.  Robust Short-Latency Perisomatic Inhibition onto Neocortical Pyramidal Cells Detected by Laser-Scanning Photostimulation , 2009, The Journal of Neuroscience.

[87]  Maneesh Sahani,et al.  A dynamical systems view of motor preparation: implications for neural prosthetic system design. , 2011, Progress in brain research.

[88]  D. Ringach,et al.  On the classification of simple and complex cells , 2002, Vision Research.