Spinal Mechanisms

Bizzi, E., M. C. Tresch, P. Saltiel, and A. d'Avella. "New Perspectives on Spinal Motor Systems." Nature Reviews/Neuroscience 1 (2000): 101-108.

PubMed abstract:  The production and control of complex motor functions are usually attributed to central brain structures such as cortex, basal ganglia and cerebellum. In traditional schemes the spinal cord is assigned a subservient function during the production of movement, playing a predominantly passive role by relaying the commands dictated to it by supraspinal systems. This review challenges this idea by presenting evidence that the spinal motor system is an active participant in several aspects of the production of movement, contributing to functions normally ascribed to 'higher' brain regions.

Mussa-Ivaldi, F. A., and E. Bizzi. "Motor Learning Through the Combination of Primitives." Philosophical Transactions of the Royal Society Lond.: Biological Sciences 355 (2000): 1755-1769.

PubMed abstract:  In this paper we discuss a new perspective on how the central nervous system (CNS) represents and solves some of the most fundamental computational problems of motor control. In particular, we consider the task of transforming a planned limb movement into an adequate set of motor commands. To carry out this task the CNS must solve a complex inverse dynamic problem. This problem involves the transformation from a desired motion to the forces that are needed to drive the limb. The inverse dynamic problem is a hard computational challenge because of the need to coordinate multiple limb segments and because of the continuous changes in the mechanical properties of the limbs and of the environment with which they come in contact. A number of studies of motor learning have provided support for the idea that the CNS creates, updates and exploits internal representations of limb dynamics in order to deal with the complexity of inverse dynamics. Here we discuss how such internal representations are likely to be built by combining the modular primitives in the spinal cord as well as other building blocks found in higher brain structures. Experimental studies on spinalized frogs and rats have led to the conclusion that the premotor circuits within the spinal cord are organized into a set of discrete modules. Each module, when activated, induces a specific force field and the simultaneous activation of multiple modules leads to the vectorial combination of the corresponding fields. We regard these force fields as computational primitives that are used by the CNS for generating a rich grammar of motor behaviours.

Kargo, William J., and Simon F. Giszter. "Rapid Correction of Aimed Movements by Summation of Force-Field Primitives." J. Neurosci. 20 (2000): 409-426.

PubMed abstract:  Spinal circuits form building blocks for movement construction. In the frog, such building blocks have been described as isometric force fields. Microstimulation studies showed that individual force fields can be combined by vector summation. Summation and scaling of a few force-field types can, in theory, produce a large range of dynamic force-field structures associated with limb behaviors. We tested for the first time whether force-field summation underlies the construction of real limb behavior in the frog. We examined the organization of correction responses that circumvent path obstacles during hindlimb wiping trajectories. Correction responses were triggered on-line during wiping by cutaneous feedback signaling obstacle collision. The correction response activated a force field that summed with an ongoing sequence of force fields activated during wiping. Both impact force and time of impact within the wiping motor pattern scaled the evoked correction response amplitude. However, the duration of the correction response was constant and similar to the duration of other muscles activated in different phases of wiping. Thus, our results confirm that both force-field summation and scaling occur during real limb behavior, that force fields represent fixed-timing motor elements, and that these motor elements are combined in chains and in combination contingent on the interaction of feedback and central motor programs.

Tresch, Mathew C., Philippe Saltiel, and Emilio Bizzi. "The Construction of Movement by the Spinal Cord." Nature Neuroscience 2 (1999): 162-167.

PubMed abstract:   We used a computational analysis to identify the basic elements with which the vertebrate spinal cord constructs one complex behavior. This analysis extracted a small set of muscle synergies from the range of muscle activations generated by cutaneous stimulation of the frog hindlimb. The flexible combination of these synergies was able to account for the large number of different motor patterns produced by different animals. These results therefore demonstrate one strategy used by the vertebrate nervous system to produce movement in a computationally simple manner.

PubMed abstract:   1. Although reaching movements are characterized by hand paths that tend to follow roughly straight lines in Cartesian space, a fundamental issue is whether this reflects constraints associated with perception or movement production. 2. To address this issue, we examined two-joint planar reaching movements in which we manipulated the mapping between actual and visually perceived motion. In particular, we used a nonlinear transformation such that straight line hand paths in Cartesian space would result in curved paths in perceived space and vice versa. 3. Under these conditions, subjects learned to make straight line paths in perceived space even though the paths of the hand in Cartesian space were markedly curved. In contrast, when the motion was perceived in Cartesian space (i.e., in the absence of a nonlinear distortion), straight line hand paths were observed. 4. These findings suggest that visually guided reaching movements are planned in a perceptual frame of reference. Reaching movements in the horizontal plane are adapted so as to produce straight lines in visually perceived space. 

Hiebert, G. W., and K. G. Pearson. "Contribution of Sensory Feedback to the Generation of Extensor Activity During Walking in the Decerebrate Cat." J. Neurophysiol 81 (1999): 758-770. (0022-3077/99 The American Physiological Society.)

PubMed abstract:   In this investigation we have estimated the afferent contribution to the generation of activity in the knee and ankle extensor muscles during walking in decerebrate cats by loading and unloading extensor muscles, and by unilateral deafferentation of a hind leg. The total contribution of afferent feedback to extensor burst generation was estimated by allowing one hind leg to step into a hole in the treadmill belt on which the animal was walking. In the absence of ground support the level of activity in knee and ankle extensor muscles was reduced to approximately 70% of normal. Activity in the ankle extensors could be restored during the "foot-in-hole" trials by selectively resisting extension at the ankle. Thus feedback from proprioceptors in the ankle extensor muscles probably makes a large contribution to burst generation in these muscles during weight-bearing steps. Similarly, feedback from proprioceptors in knee extensor appears to contribute substantially to the activation of knee extensor muscles because unloading and loading these muscles, by lifting and dropping the hindquarters, strongly reduced and increased, respectively, the level of activity in the knee extensors. This conclusion was supported by the finding that partial deafferentation of one hind leg by transection of the L4-L6 dorsal roots reduced the level of activity in the knee extensors by approximately 50%, but did not noticeably influence the activity in ankle extensor muscles. However, extending the deafferentation to include the L7-S2 dorsal roots decreased the ankle extensor activity. We conclude that afferent feedback contributes to more than one-half of the input to knee and ankle extensor motoneurons during the stance phase of walking in decerebrate cats. The continuous contribution of afferent feedback to the generation of extensor activity could function to automatically adjust the intensity of activity to meet external demands.

Kandel, Schwartz, and Jessell. "Locomotion." 
 
Kjaerulff, O., and O. Kiehn. "Distribution of Networks Generating and Coordinating Locomotor Activity in the Neonatal Rat Spinal Cord in Vitro: A Lesion Study." The Journal of Neuroscience 16, 18 (1996): 5777-5794.

PubMed abstract:   The isolated spinal cord of the newborn rat contains networks that are able to create a patterned motor output resembling normal locomotor movements. In this study, we sought to localize the regions of primary importance for rhythm and pattern generation using specific mechanical lesions. We used ventral root recordings to monitor neuronal activity and tested the ability of various isolated parts of the caudal thoraciclumbar cord to generate rhythmic bursting in a combination of 5-HT and NMDA. In addition, pathways mediating left/right and rostrocaudal burst alternation were localized. We found that the isolated ventral third of the spinal cord can generate normally coordinated rhythmic activity, whereas lateral fragments resulting from sagittal sections showed little or no rhythmogenic capability compared with intact control preparations. The ability to generate fast and regular rhythmic activity decreased in the caudal direction, but the rhythm-generating network was found to be distributed over the entire lumbar region and to extend into the caudal thoracic region. The pathways mediating left/ right alternation exist primarily in the ventral commissure. As with the rhythmogenic ability, these pathways were distributed along the lumbar enlargement. Both lateral and ventral funiculi were sufficient to coordinate activity in the rostral and caudal regions. We conclude that the networks organizing locomotor-related activity in the spinal cord of the newborn rat are distributed.

Vallbo, A. B., and J. Wessberg. "Organization of Motor Output in Slow Finger Movements in Man." Journal of Physiology 469 (1993): 673-691.

PubMed abstract:   1. Slow finger movements were analysed in normal human subjects with regard to kinematics and EMG activity of the long finger muscles. Surface EMG from the finger extensor and flexor muscles on the forearm was recorded along with angular position and angular velocity during voluntary ramp movements at single metacarpophalangeal joints. Angular acceleration was computed from the velocity record. 2. It was found that movements were not smooth but characterized by steps or discontinuities, often recurring at intervals of 100-125 ms, yielding velocity and acceleration profiles dominated by 8-10 Hz cycles. The discontinuities were manifest from the very first trial and thus not dependent on training. Their amplitude and amount varied between subjects but were relatively stable for the individual subject. 3. The 8-10 Hz cycles were seen with voluntary ramp movements of widely varying velocities, higher velocities being associated with larger steps recurring with the same repetition rate as the small steps of slow voluntary ramps. Maximal step amplitude observed was more than one order of magnitude larger than physiological tremor. 4. The individual 8-10 Hz cycle was asymmetrical in that decelerations usually reached higher peaks than the preceding acceleration, suggesting that the antagonist contributed with a braking action. Moreover, in very slow voluntary ramps, the movement cycles were often interspaced by periods of zero velocity, providing a highly non-sinusoidal velocity profile. 5. The EMG of the agonist and the antagonist muscles was modulated in close relation to the accelerations and decelerations respectively of the individual movement cycle. These modulations were present in both extensor and flexor muscles, although they were more consistent and usually more prominent in the former. 6. The findings indicate that a feature of slow finger movements was an 8-10 Hz periodic output to the muscular system, suggesting that slow finger movements are implemented by a series of biphasic force pulses, involving not only the shortening agonist muscle propelling the movement, but the antagonist muscle as well whose activity increased shortly after the agonist and contributed to a sharp deceleration of the individual step of movement. 7. It is proposed, as a hypothesis, that this biphasic motor output may reflect a similar organization of the descending motor command for slow finger movements. Hence, this command would include a series of biphasic pulses, concatenated at a rate of 8-10 per second and a pulse-height regulator capable of setting the size of the pulse and thus the overall speed of the movement.

PubMed abstract:  This is the third in a series of studies of the neural representation of tactile spatial form in somatosensory cortical area 3b of the alert monkey. We previously studied the spatial structure of >350 fingerpad receptive fields (RFs) with random-dot patterns scanned in one direction () and at varying velocities (). Those studies showed that area 3b RFs have a wide range of spatial structures that are virtually unaffected by changes in scanning velocity. In this study, 62 area 3b neurons were studied with three to eight scanning directions (58 with four or more directions). The data from all three studies are described accurately by an RF model with three components: (1) a single, central excitatory region of short duration, (2) one or more inhibitory regions, also of short duration, that are adjacent to and nearly synchronous with the excitation, and (3) a region of inhibition that overlaps the excitation partially or totally and is temporally delayed with respect to the first two components. The mean correlation between the observed RFs and the RFs predicted by this three-component model was 0.81. The three-component RFs also predicted orientation sensitivity and preferred orientation to a scanned bar accurately. The orientation sensitivity was determined most strongly by the intensity of the coincident RF inhibition in relation to the excitation. Both orientation sensitivity and this ratio were stronger in the supragranular and infragranular layers than in layer IV.

DiCarlo, J. J., K. O. Johnson, and S. S. Hsiao. "Structure of Receptive Fields in Area 3B of Primary Somatosensory Cortex in the Alert Monkey." J. Neurosci. 18, 7 (1998): 2626-2645.

PubMed abstract:  We investigated the two-dimensional structure of area 3b neuronal receptive fields (RFs) in three alert monkeys. Three hundred thirty neurons with RFs on the distal fingerpads were studied with scanned, random dot stimuli. Each neuron was stimulated continuously for 14 min, yielding 20,000 response data points. Excitatory and inhibitory components of each RF were determined with a modified linear regression algorithm. Analyses assessing goodness-of-fit, repeatability, and generality of the RFs were developed. Two hundred forty-seven neurons yielded highly repeatable RF estimates, and most RFs accounted for a large fraction of the explainable response of each neuron. Although the area 3b RF structures appeared to be continuously distributed, certain structural generalities were apparent. Most RFs (94%) contained a single, central region of excitation and one or more regions of inhibition located on one, two, three, or all four sides of the excitatory center. The shape, area, and strength of excitatory and inhibitory RF regions ranged widely. Half the RFs contained almost evenly balanced excitation and inhibition. The findings indicate that area 3b neurons act as local spatiotemporal filters that are maximally excited by the presence of particular stimulus features. We believe that form and texture perception are based on high-level representations and that area 3b is an intermediate stage in the processes leading to these representations. Two possibilities are considered: (1) that these high-level representations are basically somatotopic and that area 3b neurons amplify some features and suppress others, or (2) that these representations are highly transformed and that area 3b effects a step in the transformation.

Florence, S. L., N. Jain, M. W. Pospichal, P. D. Beck, D. L. Sly, and J. H. Kaas. "Central Reorganization of Sensory Pathways Following Peripheral Nerve Regeneration in Fetal Monkeys." Nature 381 (1996): 69-71.

PubMed abstract:  Transection of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children. The basis for this superior recovery in children was unknown. Here we show that there is little or no topographic order in the median nerve to the hand after median nerve section and surgical repair in immature macaque monkeys. Remarkably, however, in the same animals the representation of the reinnervated hand in primary somatosensory cortex area (area 3b) is quite orderly. This indicates that there are mechanisms in the developing brain that can create cortical topography, despite disordered sensory inputs. Presumably the superior recovery of perceptual abilities after peripheral nerve transection in children depends on this restoration of somatotopy in the central sensory maps.

Johnson, K. O. "Neural Coding." Neuron 26 (2000): 563-566.

Kaas, J. H. "Plasticity of Sensory and Motor Maps in Adult Mammals." Annu. Rev. of Neurosci. 14 (1991): 137-67.

Moore, C. I., S. B. Nelson, and M. Sur. "Dynamics of Neuronal Processing in Rat Somatosensory Cortex." Trends in Neurosciences 22 (1999): 513-520.

PubMed abstract:  Recently, the study of sensory cortex has focused on the context-dependent evolution of receptive fields and cortical maps over millisecond to second time-scales. This article reviews advances in our understanding of these processes in the rat primary somatosensory cortex (SI). Subthreshold input to individual rat SI neurons is extensive, spanning several vibrissae from the center of the receptive field, and arrives within 25 ms of vibrissa deflection. These large subthreshold receptive fields provide a broad substrate for rapid excitatory and inhibitory multi-vibrissa interactions. The 'whisking' behavior, an approximately 8 Hz ellipsoid movement of the vibrissae, introduces a context-dependent change in the pattern of vibrissa movement during tactile exploration. Stimulation of vibrissae over this frequency range modulates the pattern of activity in thalamic and cortical neurons, and, at the level of the cortical map, focuses the extent of the vibrissa representation relative to lower frequency stimulation (1 Hz). These findings suggest that one function of whisking is to reset cortical organization to improve tactile discrimination. Recent discoveries in primary visual cortex (VI) demonstrate parallel non-linearities in center-surround interactions in rat SI and VI, and provide a model for the rapid integration of multi-vibrissa input. The studies discussed in this article suggest that, despite its original conception as a uniquely segregated cortex, rat SI has a wide array of dynamic interactions, and that the study of this region will provide insight into the general mechanisms of cortical dynamics engaged by sensory systems.

Nicolelis, M. A. L., A. A. Ghazanfar, C. R. Stambaugh, L. M. O. Oliveira, M. Laubach, J. K. Chapin, R. J. Nelson, and J. H. Kaas. "Simultaneous Encoding of Tactile Information by Three Primate Cortical Areas." Nature Neuroscience 7 (1998): 621-630.

PubMed abstract:  We used simultaneous multi-site neural ensemble recordings to investigate the representation of tactile information in three areas of the primate somatosensory cortex (areas 3b, SII and 2). Small neural ensembles (30-40 neurons) of broadly tuned somatosensory neurons were able to identify correctly the location of a single tactile stimulus on a single trial, almost simultaneously. Furthermore, each of these cortical areas could use different combinations of encoding strategies, such as mean firing rate (areas 3b and 2) or temporal patterns of ensemble firing (area SII), to represent the location of a tactile stimulus. Based on these results, we propose that ensembles of broadly tuned neurons, located in three distinct areas of the primate somatosensory cortex, obtain information about the location of a tactile stimulus almost concurrently.

Racanzone, G. H., M. M. Merzenich, and C. E. Schreiner. "Changes in the Distributed Temporal Response Properties of SI Cortical Neurons Reflect Improvements in Performance on a Temporally Based Tactile Discrimination Task." J. Neurophys. 67 (1992): 1071-1091.

PubMed abstract:  1. Temporal response characteristics of neurons were sampled in fine spatial grain throughout the hand representations in cortical areas 3a and 3b in adult owl monkeys. These monkeys had been trained to detect small differences in tactile stimulus frequencies in the range of 20-30 Hz. Stimuli were presented to an invariant, restricted spot on a single digit. 2. The absolute numbers of cortical locations and the cortical area over which neurons showed entrained frequency-following responses to behaviorally important stimuli were significantly greater when stimulation was applied to the trained skin, as compared with stimulation on an adjacent control digit, or at corresponding skin sites in passively stimulated control animals. 3. Representational maps defined with sinusoidal stimuli were not identical to maps defined with just-visible tapping stimuli. Receptive-field/frequency-following response site mismatches were recorded in every trained monkey. Mismatches were less frequently recorded in the representations of control skin surfaces. 4. At cortical locations with entrained responses, neither the absolute firing rates of neurons nor the degree of the entrainment of the response were correlated with behavioral discrimination performance. 5. All area 3b cortical locations with entrained responses evoked by stimulation at trained or untrained skin sites were combined to create population peristimulus time and cycle histograms. In all cases, stimulation of the trained skin resulted in 1) larger-amplitude responses, 2) peak responses earlier in the stimulus cycle, and 3) temporally sharper responses, than did stimulation applied to control skin sites. 6. The sharpening of the response of cortical area 3b neurons relative to the period of the stimulus could be accounted for by a large subpopulation of neurons that had highly coherent responses. 7. Analysis of cycle histograms for area 3b neuron responses revealed that the decreased variance in the representation of each stimulus cycle could account for behaviorally measured frequency discrimination performance. A strong correlation between these temporal response distributions and the discriminative performances for stimuli applied at all studied skin surfaces was even stronger (r = 0.98) if only the rising phases of cycle histogram were considered in the analysis. 8. The responses of neurons in area 3a could not account for measured differences in frequency discrimination performance. 9. These representational changes did not occur in monkeys that were stimulated on the same schedule but were performing an auditory discrimination task during skin stimulation. 10. It is concluded that by behaviorally training adult owl monkeys to discriminate the temporal features of a tactile stimulus, distributed spatial and temporal response properties of cortical neurons are altered.

Romo, R., A. Hernandez, A. Zainos, and E. Salinas. "Somatosensory Discrimination Based on Cortical Microstimulation." Nature 392 (1998): 387-390.

PubMed abstract:  The sensation of flutter is produced when mechanical vibrations in the range of 5-50Hz are applied to the skin. A flutter stimulus activates neurons in the primary somatosensory cortex (S1) that somatotopically map to the site of stimulation. A subset of these neurons-those with quickly adapting properties, associated with Meissner's corpuscles-are strongly entrained by periodic flutter vibrations, firing with a probability that oscillates at the input frequency. Hence, quickly adapting neurons provide a dynamic representation of such flutter stimuli. However, are these neurons directly involved in the perception of flutter? Here we investigate this in monkeys trained to discriminate the difference in frequency between two flutter stimuli delivered sequentially on the fingertips. Microelectrodes were inserted into area 3b of S1 and the second stimulus was substituted with a train of injected current pulses. Animals reliably indicated whether the frequency of the second (electrical) signal was higher or lower than that of the first (mechanical) signal, even though both frequencies changed from trial to trial. Almost identical results were obtained with periodic and aperiodic stimuli of equal average frequencies. Thus, the quickly adapting neurons in area 3b activate the circuit leading to the perception of flutter. Furthermore, as far as can be psychophysically quantified during discrimination, the neural code underlying the sensation of flutter can be finely manipulated, to the extent that the behavioural responses produced by natural and artificial stimuli are indistinguishable.

Romo, R., and E. Salinas. "Touch and Go: Decision-Making Mechanisms in Somatosensation." Annu. Rev. Neurosci. 24 (2001): 107-37.

PubMed abstract:  A complex sequence of neural events unfolds between sensory receptor activation and motor activity. To understand the underlying decision-making mechanisms linking somatic sensation and action, we ask what components of the neural activity evoked by a stimulus are directly related to psychophysical performance, and how are they related. We find that single-neuron responses in primary and secondary somatosensory cortices account for the observed performance of monkeys in vibrotactile discrimination tasks, and that neuronal and behavioral responses covary in single trials. This sensory activity, which provides input to memory and decision-making mechanisms, is modulated by attention and behavioral context, and microstimulation experiments indicate that it may trigger normal perceptual experiences. Responses recorded in motor areas seem to reflect the output of decision-making operations, which suggests that the ability to make decisions occurs at the sensory-motor interface.

Sheth, B., C. I. Moore, and M. Sur. "Temporal Modulation of Spatial Borders in Rat Barrel Cortex." J.Neurophys. 79 (1998): 464-470.

PubMed abstract:  We examined the effects of varying vibrissa stimulation frequency on intrinsic signal and neuronal responses in rat barrel cortex. Optical imaging of intrinsic signals demonstrated that the region of cortex activated by deflection of a single vibrissa at 1 Hz is more diffuse and more widespread than the territory activated at 5 or 10 Hz. With the use of two different paradigms, constant time of stimulation and constant number of vibrissa deflections, we showed that the optically imaged spread of activity is more discrete at higher stimulation frequencies. We combined optical imaging with multiple electrode recording and confirmed that the neuronal response to individual vibrissa stimulation at the optically imaged center of activity is greater than the response away from the imaged center. Consistent with the imaging data, these recordings also showed no response to a second vibrissa deflection at 5 Hz at a peripheral recording site, though there was a significant response to a second vibrissa deflection at 1 Hz at the same peripheral site. These findings demonstrate that vibrissa stimulation at higher frequencies leads to more focused physiological responses in cortex. Thus the spread of activation in rat barrel cortex is modulated in a dynamic fashion by the frequency of vibrissa stimulation.

Steinmetz, P. N., A. Roy, P. J. Fitzgerald, S. S. Hsiao, K. O. Johnson , and E. Niebur. "Attention Modulates Synchronized Neuronal Firing in Primate Somatosensory Cortex." Nature 404 (2000): 187-190.

PubMed abstract:  A potentially powerful information processing strategy in the brain is to take advantage of the temporal structure of neuronal spike trains. An increase in synchrony within the neural representation of an object or location increases the efficacy of that neural representation at the next synaptic stage in the brain; thus, increasing synchrony is a candidate for the neural correlate of attentional selection. We investigated the synchronous firing of pairs of neurons in the secondary somatosensory cortex (SII) of three monkeys trained to switch attention between a visual task and a tactile discrimination task. We found that most neuron pairs in SII cortex fired synchronously and, furthermore, that the degree of synchrony was affected by the monkey's attentional state. In the monkey performing the most difficult task, 35% of neuron pairs that fired synchronously changed their degree of synchrony when the monkey switched attention between the tactile and visual tasks. Synchrony increased in 80% and decreased in 20% of neuron pairs affected by attention.

Sur, M. "Somatosensory Cortex. Maps of Time and Space." Nature 378 (1995): 13-14.

Wang, X., M. M. Merzenich, K. Sameshima, and W. M. Jenkins. "Remodeling of Hand Representation in Adult Cortex Determined by Timing of Tactile Stimulation." Nature 378 (1995): 71-75. (With commentary.)

PubMed abstract:  The primate somatosensory cortex, which processes tactile stimuli, contains a topographic representation of the signals it receives, but the way in which such maps are maintained is poorly understood. Previous studies of cortical plasticity indicated that changes in cortical representation during learning arise largely as a result of hebbian synaptic change mechanisms. Here we show, using owl monkeys trained to respond to specific stimulus sequence events, that serial application of stimuli to the fingers results in changes to the neuronal response specificity and maps of the hand surfaces in the true primary somatosensory cortical field (S1 area 3b). In this representational remodelling stimuli applied asychronously to the fingers resulted in these fingers being integrated in their representation, whereas fingers to which stimuli were applied asynchronously were segregated in their representation. Ventroposterior thalamus response maps derived in these monkeys were not equivalently reorganized. This representational plasticity appears to be cortical in origin.

PubMed abstract:  Learning a motor skill sets in motion neural processes that continue to evolve after practice has ended, a phenomenon known as consolidation. Here we present psychophysical evidence for this, and show that consolidation of a motor skill was disrupted when a second motor task was learned immediately after the first. There was no disruption if four hours elapsed between learning the two motor skills, with consolidation occurring gradually over this period. Previous studies in humans and other primates have found this time-dependent disruption of consolidation only in explicit memory tasks, which rely on brain structures in the medial temporal lobe. Our results indicate that motor memories, which do not depend on the medial temporal lobe, can be transformed by a similar process of consolidation. By extending the phenomenon of consolidation to motor memory, our results indicate that distinct neural systems share similar characteristics when encoding and storing new information.

Gandolfo, F., C. S. R. Li, B. J. Benda, C. P. Schioppa, and E. Bizzi. "Cortical Correlates of Learning in Monkeys Adapting to a New Dynamical Environment." PNAS 97 (2000): 2259-2263.

PubMed abstract:  In this paper, we describe the neural changes observed in the primary motor cortex of two monkeys while they learned a new motor skill. The monkeys had to adapt their reaching movements to external forces that interfered with the execution of their arm movements. We found a sizable population of cells that changed their tuning properties during exposure to the force field. These cells took on the properties of neurons that are involved in the control of movement. Furthermore, the cells maintained the acquired activity as the monkey readapted to the no-force condition. Recent imaging studies in humans have reported the effects of motor learning in the primary motor cortex. Our results are consistent with the findings of these studies and provide evidence for single-cell plasticity in the primary motor cortex of primates.

Georgopoulos, A. P., A. B. Schwartz, and R. E. Kettner. "Neuronal Population Coding of Movement Direction." Science 233 (1986): 1416-1419.

PubMed abstract:  Although individual neurons in the arm area of the primate motor cortex are only broadly tuned to a particular direction in three-dimensional space, the animal can very precisely control the movement of its arm. The direction of movement was found to be uniquely predicted by the action of a population of motor cortical neurons. When individual cells were represented as vectors that make weighted contributions along the axis of their preferred direction (according to changes in their activity during the movement under consideration) the resulting vector sum of all cell vectors (population vector) was in a direction congruent with the direction of movement. This population vector can be monitored during various tasks, and similar measures in other neuronal populations could be of heuristic value where there is a neural representation of variables with vectorial attributes.

Georgopoulos, A. P., J. F. Kalaska, R. Caminiti, and J. T. Massey. "On the Relations Between the Direction of Two-Dimensional Arm Movements and Cell Discharge in Primate Motor Cortex." J. Neurosci. 2 (1982): 1527-1537.

PubMed abstract:  The activity of single cells in the motor cortex was recorded while monkeys made arm movements in eight directions (at 45 degrees intervals) in a two-dimensional apparatus. These movements started from the same point and were of the same amplitude. The activity of 606 cells related to proximal arm movements was examined in the task; 323 of the 606 cells were active in that task and were studied in detail. The frequency of discharge of 241 of the 323 cells (74.6%) varied in an orderly fashion with the direction of movement. Discharge was most intense with movements in a preferred direction and was reduced gradually when movements were made in directions farther and farther away from the preferred one. This resulted in a bell-shaped directional tuning curve. These relations were observed for cell discharge during the reaction time, the movement time, and the period that preceded the earliest changes in the electromyographic activity (approximately 80 msec before movement onset). In about 75% of the 241 directionally tuned cells, the frequency of discharge, D, was a sinusoidal function of the direction of movement, theta: D = b0 + b1 sin theta + b2cos theta, or, in terms of the preferred direction, theta 0: D = b0 + c1cos (theta - theta0), where b0, b1, b2, and c1 are regression coefficients. Preferred directions differed for different cells so that the tuning curves partially overlapped. The orderly variation of cell discharge with the direction of movement and the fact that cells related to only one of the eight directions of movement tested were rarely observed indicate that movements in a particular direction are not subserved by motor cortical cells uniquely related to that movement. It is suggested, instead, that a movement trajectory in a desired direction might be generated by the cooperation of cells with overlapping tuning curves. The nature of this hypothetical population code for movement direction remains to be elucidated.

Grafton, S.T., E. Hazeltine, and R. B. Ibry. "Abstract and Effector-Specific Representations of Motor Sequences Identified with PET." J. Neurosci. 18 (1998): 9420-9428.

PubMed abstract:  Positron emission tomography was used to identify neural systems involved in the acquisition and expression of sequential movements produced by different effectors. Subjects were tested on the serial reaction time task under implicit learning conditions. In the initial acquisition phase, subjects responded to the stimuli with keypresses using the four fingers of the right hand. During this phase, the stimuli followed a fixed sequence for one group of subjects (group A) and were randomly selected for another group (group B). In the transfer phase, arm movements were used to press keys on a substantially larger keyboard, and for both groups, the stimuli followed the sequence. Behavioral indices provided clear evidence of learning during the acquisition phase for group A and transfer when switched to the large keyboard. Sequence acquisition was associated with learning-related increases in regional cerebral blood flow (rCBF) in a network of areas in the contralateral left hemisphere, including sensorimotor cortex, supplementary motor area, and rostral inferior parietal cortex. After transfer, activity in inferior parietal cortex remained high, suggesting that this area had encoded the sequence at an abstract level independent of the particular effectors used to perform the task. In contrast, activity in sensorimotor cortex shifted to a more dorsal locus, consistent with motor cortex somatotopy. Thus, activity here was effector-specific. An increase in rCBF was also observed in the cingulate motor area at transfer, suggesting a role linking the abstract sequential representations with the task-relevant effector system. These results highlight a network of areas involved in sequence encoding and retrieval.

Grafton, S.T., J. Salidis, and D. B. Willingham. "Motor Learning of Compatible and Incompatible Visuomotor Maps." J. Cog. Neurosci. 13 (2001): 217-231.

PubMed abstract:  Brain imaging studies demonstrate increasing activity in limb motor areas during early motor skill learning, consistent with functional reorganization occurring at the motor output level. Nevertheless, behavioral studies reveal that visually guided skills can also be learned with respect to target location or possibly eye movements. The current experiments examined motor learning under compatible and incompatible perceptual/motor conditions to identify brain areas involved in different perceptual-motor transformations. Subjects tracked a continuously moving target with a joystick-controlled cursor. The target moved in a repeating sequence embedded within random movements to block sequence awareness. Psychophysical studies of behavioral transfer from incompatible (joystick and cursor moving in opposite directions) to compatible tracking established that incompatible learning was occurring with respect to target location. Positron emission tomography (PET) functional imaging of compatible learning identified increasing activity throughout the precentral gyrus, maximal in the arm area. Incompatible learning also led to increasing activity in the precentral gyrus, maximal in the putative frontal eye fields. When the incompatible task was switched to a compatible response and the previously learned sequence was reintroduced, there was an increase in arm motor cortex. The results show that learning-related increases of brain activity are dynamic, with recruitment of multiple motor output areas, contingent on task demands. Visually guided motor sequences can be linked to either oculomotor or arm motor areas. Rather than identifying changes of motor output maps, the data from imaging experiments may better reflect modulation of inputs to multiple motor areas.

Graziano, M. S. A., and C. G. Gross. "Spatial Maps for the Control of Movement." Curr. Opin. Neurobiol. 8 (1998): 195-201.

PubMed abstract:  Neurons in the ventral premotor cortex of the monkey encode the locations of visual, tactile, auditory and remembered stimuli. Some of these neurons encode the locations of stimuli with respect to the arm, and may be useful for guiding movements of the arm. Others encode the locations of stimuli with respect to the head, and may be useful for guiding movements of the head. We suggest that a general principle of sensory-motor integration is that the space surrounding the body is represented in body-part-centered coordinates. That is, there are multiple coordinate systems used to guide movement, each one attached to a different part of the body. This and other recent evidence from both monkeys and humans suggest that the formation of spatial maps in the brain and the guidance of limb and body movements do not proceed in separate stages but are closely integrated in both the parietal and frontal lobes.

Kakei, S., D. S. Hoffman, and P. L. Strick. "Muscle and Movement Representations in the Primary Motor Cortex." Science 285 (1999): 2136-2139.

PubMed abstract:  What aspects of movement are represented in the primary motor cortex (M1): relatively low-level parameters like muscle force, or more abstract parameters like handpath? To examine this issue, the activity of neurons in M1 was recorded in a monkey trained to perform a task that dissociates three major variables of wrist movement: muscle activity, direction of movement at the wrist joint, and direction of movement in space. A substantial group of neurons in M1 (28 out of 88) displayed changes in activity that were muscle-like. Unexpectedly, an even larger group of neurons in M1 (44 out of 88) displayed changes in activity that were related to the direction of wrist movement in space independent of the pattern of muscle activity that generated the movement. Thus, both "muscles" and "movements" appear to be strongly represented in M1.

Kalaska, J. F., S. H. Scott, P. Cisek, and L. Sergio. "Cortical Control of Reaching Movements." Curr. Opin. Neurobiol. 7 (1997): 849-859.

PubMed abstract:  Recent studies provide further support for the hypothesis that spatial representations of limb position, target locations, and potential motor actions are expressed in the neuronal activity in parietal cortex. In contrast, precentral cortical activity more strongly expresses processes involved in the selection and execution of motor actions. As a general conceptual framework, these processes may be interpreted in terms of such formalisms as sensorimotor transformations and 'internal models'.

Kandel, R., J. H. Schwartz, and T. M. Jessell, eds. "Voluntary Movement." In Principles of Neural Science, 4th ed. New York: McGraw-Hill, 2000, pp. 756-781.

Kleim, J. A., S. Barbay, and R. J. Nudo. "Functional Reorganization of the Rat Motor Cortex Following Motor Skill Learning." J. Neurophysiol. 80 (1998): 3321-3325.

PubMed abstract:  Functional reorganization of the rat motor cortex following motor skill learning. J. Neurophysiol. 80: 3321-3325, 1998. Adult rats were allocated to either a skilled or unskilled reaching condition (SRC and URC, respectively). SRC animals were trained for 10 days on a skilled reaching task while URC animals were trained on a simple bar pressing task. After training, microelectrode stimulation was used to derive high resolution maps of the forelimb and hindlimb representations within the motor cortex. In comparison with URC animals, SRC animals exhibited a significant increase in mean area of the wrist and digit representations but a decrease in elbow/shoulder representation within the caudal forelimb area. No between-group differences in areal representation were found in either the hindlimb or rostral forelimb areas. These results demonstrate that motor skill learning is associated with a reorganization of movement representations within the rodent motor cortex.

Li, C. S. R., C. Padoa-Schioppa, and E. Bizzi. "Neuronal Correlates of Motor Performance and Motor Learning in the Primary Motor Cortex of Monkeys Adapting to an External Force Field." Neuron 30 (2001): 593-607.

PubMed abstract:  The primary motor cortex (M1) is known to control motor performance. Recent findings have also implicated M1 in motor learning, as neurons in this area show learning-related plasticity. In the present study, we analyzed the neuronal activity recorded in M1 in a force field adaptation task. Our goal was to investigate the neuronal reorganization across behavioral epochs (before, during, and after adaptation). Here we report two main findings. First, memory cells were present in two classes. With respect to the changes of preferred direction (Pd), these two classes complemented each other after readaptation. Second, for the entire neuronal population, the shift of Pd matched the shift observed for muscles. These results provide a framework whereby the activity of distinct neuronal subpopulations combines to subserve both functions of motor performance and motor learning.

Muellbacher, W., U. Ziemann, J. Wissel, N. Dang, M. Kofler, S. Facchini, B. Boroojerdi, W. Poewe, and M. Hallett. "Early Consolidation in Human Primary Motor Cortex." Nature 415 (2002): 640-644.

PubMed abstract:  Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.

Rioult-Pedotti, M. S., D. Friedman, G. Hess, and J. P. Donoghue. "Strengthening of Horizontal Cortical Connections Following Skill Learning." Nat. Neurosci. 1 (1998): 230-234.

PubMed abstract:  Learning a new motor skill requires an alteration in the spatiotemporal pattern of muscle activation. Motor areas of cerebral neocortex are thought to be involved in this type of learning, possibly by functional reorganization of cortical connections. Here we show that skill learning is accompanied by changes in the strength of connections within adult rat primary motor cortex (M1). Rats were trained for three or five days in a skilled reaching task with one forelimb, after which slices of motor cortex were examined to determine the effect of training on the strength of horizontal intracortical connections in layer II/III. The amplitude of field potentials in the forelimb region contralateral to the trained limb was significantly increased relative to the opposite 'untrained' hemisphere. No differences were seen in the hindlimb region. Moreover, the amount of long-term potentiation (LTP) that could be induced in trained M1 was less than in controls, suggesting that the effect of training was at least partly due to LTP-like mechanisms. These data represent the first direct evidence that plasticity of intracortical connections is associated with learning a new motor skill.

Rioult-Pedotti, M. S., F. Friedman, and J. P. Donoghue. "Learning-Induced LTP in Neocortex." Science 290 (2000): 533-536.

PubMed abstract:  The hypothesis that learning occurs through long-term potentiation (LTP)- and long-term depression (LTD)-like mechanisms is widely held but unproven. This hypothesis makes three assumptions: Synapses are modifiable, they modify with learning, and they strengthen through an LTP-like mechanism. We previously established the ability for synaptic modification and a synaptic strengthening with motor skill learning in horizontal connections of the rat motor cortex (MI). Here we investigated whether learning strengthened these connections through LTP. We demonstrated that synapses in the trained MI were near the ceiling of their modification range, compared with the untrained MI, but the range of synaptic modification was not affected by learning. In the trained MI, LTP was markedly reduced and LTD was enhanced. These results are consistent with the use of LTP to strengthen synapses during learning.

Rizzolatti, G., L. Fadiga, V. Gallese, and L. Fogassi. "Premotor Cortex and the Recognition of Motor Actions." Cog. Br. Res. 3 (1996): 131-141.

PubMed abstract:  In area F5 of the monkey premotor cortex there are neurons that discharge both when the monkey performs an action and when he observes a similar action made by another monkey or by the experimenter. We report here some of the properties of these 'mirror' neurons and we propose that their activity 'represents' the observed action. We posit, then, that this motor representation is at the basis of the understanding of motor events. Finally, on the basis of some recent data showing that, in man, the observation of motor actions activate the posterior part of inferior frontal gyrus, we suggest that the development of the lateral verbal communication system in man derives from a more ancient communication system based on recognition of hand and face gestures.

Rizzolatti, G., L. Fogassi, and V. Gallese. "Parietal Cortex: From Sight to Action." Curr. Opin. Neurobiol. 7 (1997): 562-567.

PubMed abstract:  Recent findings have altered radically our thinking about the functional role of the parietal cortex. According to this view, the parietal lobe consists of a multiplicity of areas with specific connections to the frontal lobe. These areas, together with the frontal areas to which they are connected, mediate distinct sensorimotor transformations related to the control of hand, arm, eye or head movements. Space perception is not unitary, but derives from the joint activity of the fronto-parietal circuits that control actions requiring space computation.

Sanes, J. N., and J. P. Donoghue. "Plasticity and Primary Motor Cortex." Annu. Rev. Neurosci. 23 (2000): 393-415.

PubMed abstract:  One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

Schieber, M. H. "Constraints on Somatotopic Organization in the Primary Motor Cortex." J. Neurophysiol. 86 (2001): 2125-2143.

PubMed abstract:  Since the 1870s, the primary motor cortex (M1) has been known to have a somatotopic organization, with different regions of cortex participating in control of face, arm, and leg movements. Through the middle of the 20th century, it seemed possible that the principle of somatotopic organization extended to the detailed representation of different body parts within each of the three major representations. The arm region of M1, for example, was thought to contain a well-ordered, point-to-point representation of the movements or muscles of the thumb, index, middle, ring, and little fingers, the wrist, elbow, and shoulder, as conveyed by the iconic homunculus and simiusculus. In the last quarter of the 20th century, however, experimental evidence has accumulated indicating that within-limb somatotopy in M1 is not spatially discrete nor sequentially ordered. Rather, beneath gradual somatotopic gradients of representation, the representations of different smaller body parts or muscles each are distributed widely within the face, arm, or leg representation, such that the representations of any two smaller parts overlap extensively. Appreciation of this underlying organization will be essential to further understanding of the contribution to control of movement made by M1. Because no single experiment disproves a well-ordered within-limb somatotopic organization in M1, here I review the accumulated evidence, using a framework of six major features that constrain the somatotopic organization of M1: convergence of output, divergence of output, horizontal interconnections, distributed activation, effects of lesions, and ability to reorganize. Review of the classic experiments that led to development of the homunculus and simiusculus shows that these data too were consistent with distributed within-limb somatotopy. I conclude with speculations on what the constrained somatotopy of M1 might tell us about its contribution to control of movement.

Scott, S. H., P. L. Gribble, K. M. Graham, and D. W. Cabel. "Dissociation Between Hand Motion and Population Vectors from Neural Activity in Motor Cortex." Nature 413 (2001): 161-165.

PubMed abstract:  The population vector hypothesis was introduced almost twenty years ago to illustrate that a population vector constructed from neural activity in primary motor cortex (MI) of non-human primates could predict the direction of hand movement during reaching. Alternative explanations for this population signal have been suggested but could not be tested experimentally owing to movement complexity in the standard reaching model. We re-examined this issue by recording the activity of neurons in contralateral MI of monkeys while they made reaching movements with their right arms oriented in the horizontal plane-where the mechanics of limb motion are measurable and anisotropic. Here we found systematic biases between the population vector and the direction of hand movement. These errors were attributed to a non-uniform distribution of preferred directions of neurons and the non-uniformity covaried with peak joint power at the shoulder and elbow. These observations contradict the population vector hypothesis and show that non-human primates are capable of generating reaching movements to spatial targets even though population vectors based on MI activity do not point in the direction of hand motion.

Shima, K., and J. Tanji. "Role for Cingulate Motor Area Cells in Voluntary Movement Selection Based on Reward." Science 282 (1998): 1335-1338.

PubMed abstract:  Most natural actions are chosen voluntarily from many possible choices. An action is often chosen based on the reward that it is expected to produce. What kind of cellular activity in which area of the cerebral cortex is involved in selecting an action according to the expected reward value? Results of an analysis in monkeys of cellular activity during the performance of reward-based motor selection and the effects of chemical inactivation are presented. We suggest that cells in the rostral cingulate motor area, one of the higher order motor areas in the cortex, play a part in processing the reward information for motor selection.

Wessberg, J., C. R. Stambaugh, J. D. Kralik, P. D. Beck, M. Laubach, J. K. Chapin, J. Kim, S. J. Biggs, M. A. Srinivasan, and M. A. L. Nicolelis. "Real-Time Prediction of Hand Trajectory by Ensembles of Cortical Neurons in Primates." Nature 408 (2000): 361-365.

PubMed abstract:  Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Wise, S. P., S. L. Moody, K. J. Blomstrom, and A. R. Mitz. "Changes in Motor Cortical Activity During Visuomotor Adaptation." Exp. Brain Res. 121 (1998): 285-299.

PubMed abstract:  We examined neuronal activity in three motor cortical areas while a rhesus monkey adapted to novel visuomotor transforms. The monkey moved a joystick that controlled a cursor on a video screen. Each trial began with the joystick centered. Next, the cursor appeared in one of eight positions, arranged in a circle around a target stimulus at the center of the screen. To receive reinforcement, the monkey moved the joystick so that the cursor contacted the target continuously for Is. The video monitor provided continuous visual feedback of both cursor and target position. With those elements of the task constant, we modified the transform between joystick movement and that of the cursor at the beginning of a block of trials. Neuronal activity was studied as the monkey adapted to these novel joystick-cursor transforms. Some novel tasks included spatial transforms such as single-axis inversions, asymmetric double-axis inversions and angular deviations (also known as rotations). Other tasks involved changes in the spatiotemporal pattern and magnitude of joystick movement. As the monkey adapted to various visuomotor tasks, 209 task-related neurons (selected for stable background activity) showed significant changes in their task-related activity: 88 neurons in the primary motor cortex (M1), 32 in the supplementary motor cortex (M2), and 89 in the caudal part of the dorsal premotor cortex (PMdc). Slightly more than half of the sample in each area showed significant changes in the magnitude of activity modulation during adaptation, with the number of increases approximately equaling the number of decreases. These data support the prediction that changes in task-related neuronal activity can be observed in M1 during motor adaptation, but fail to support the hypothesis that M1 and PMdc differ in this regard. When viewed in population averages, motor cortex continued to change its activity for at least dozens of trials after performance reached a plateau. This slow, apparently continuing change in the pattern and magnitude of task-related activity may reflect the initial phases of consolidating the motor memory for preparing and executing visuomotor skills.

PubMed abstract:  1. Although reaching movements are characterized by hand paths that tend to follow roughly straight lines in Cartesian space, a fundamental issue is whether this reflects constraints associated with perception or movement production. 2. To address this issue, we examined two-joint planar reaching movements in which we manipulated the mapping between actual and visually perceived motion. In particular, we used a nonlinear transformation such that straight line hand paths in Cartesian space would result in curved paths in perceived space and vice versa. 3. Under these conditions, subjects learned to make straight line paths in perceived space even though the paths of the hand in Cartesian space were markedly curved. In contrast, when the motion was perceived in Cartesian space (i.e., in the absence of a nonlinear distortion), straight line hand paths were observed. 4. These findings suggest that visually guided reaching movements are planned in a perceptual frame of reference. Reaching movements in the horizontal plane are adapted so as to produce straight lines in visually perceived space.

Vallbo A. B., and J. Wessberg. "Organization of Motor Output in Slow Finger Movements in Man." Journal of Physiology 469 (1992): 673-691.

PubMed abstract:  1. Slow finger movements were analysed in normal human subjects with regard to kinematics and EMG activity of the long finger muscles. Surface EMG from the finger extensor and flexor muscles on the forearm was recorded along with angular position and angular velocity during voluntary ramp movements at single metacarpophalangeal joints. Angular acceleration was computed from the velocity record. 2. It was found that movements were not smooth but characterized by steps or discontinuities, often recurring at intervals of 100-125 ms, yielding velocity and acceleration profiles dominated by 8-10 Hz cycles. The discontinuities were manifest from the very first trial and thus not dependent on training. Their amplitude and amount varied between subjects but were relatively stable for the individual subject. 3. The 8-10 Hz cycles were seen with voluntary ramp movements of widely varying velocities, higher velocities being associated with larger steps recurring with the same repetition rate as the small steps of slow voluntary ramps. Maximal step amplitude observed was more than one order of magnitude larger than physiological tremor. 4. The individual 8-10 Hz cycle was asymmetrical in that decelerations usually reached higher peaks than the preceding acceleration, suggesting that the antagonist contributed with a braking action. Moreover, in very slow voluntary ramps, the movement cycles were often interspaced by periods of zero velocity, providing a highly non-sinusoidal velocity profile. 5. The EMG of the agonist and the antagonist muscles was modulated in close relation to the accelerations and decelerations respectively of the individual movement cycle. These modulations were present in both extensor and flexor muscles, although they were more consistent and usually more prominent in the former. 6. The findings indicate that a feature of slow finger movements was an 8-10 Hz periodic output to the muscular system, suggesting that slow finger movements are implemented by a series of biphasic force pulses, involving not only the shortening agonist muscle propelling the movement, but the antagonist muscle as well whose activity increased shortly after the agonist and contributed to a sharp deceleration of the individual step of movement. 7. It is proposed, as a hypothesis, that this biphasic motor output may reflect a similar organization of the descending motor command for slow finger movements. Hence, this command would include a series of biphasic pulses, concatenated at a rate of 8-10 per second and a pulse-height regulator capable of setting the size of the pulse and thus the overall speed of the movement.

PubMed abstract:  Our previous observations led to the hypothesis that cells in the substantia nigra pars reticulata (SNr) tonically inhibit saccade-related cells in the intermediate layers of the superior colliculus (SC). Before saccades to visual or remembered targets, cells in SNr briefly reduce that inhibition, allowing a burst of spikes of SC cells that, in turn, leads to the initiation of a saccadic eye movement. Since this inhibition is likely to be mediated by gamma-aminobutyric acid (GABA), we tested this hypothesis by injecting a GABA agonist (muscimol) or a GABA antagonist (bicuculline) into the superior colliculus and measured the effects on saccadic eye movements made to visual or remembered targets. An injection of muscimol selectively suppressed saccades to the movement field of the cells near the injection site. The affected area expanded over time, thus suggesting the diffusion of muscimol in the SC; the area never included the other hemifield, suggesting that the diffusion was limited to one SC. One of the monkeys became unable to make any saccades to the affected area. Saccades to visual targets following injection of muscimol had longer latency and slightly shorter amplitudes that were corrected by subsequent saccades. The most striking change was a decrease in the peak velocity of the saccade, frequently to less than half the preinjection value. Saccades to remembered targets following injection of muscimol also showed an increase in latency and decrease in velocity, but in addition, showed a striking decrease in the accuracy of the saccades. The trajectories of saccades became distorted as if they were deflected away from the affected area. After muscimol injection, the area over which spontaneous eye movements were made shifted toward the side ipsilateral to the injection. Saccades toward the contralateral side were less frequent and slower. In nystagmus, which developed later, the slow phase was toward the contralateral side. In contrast to muscimol, injection of bicuculline facilitated the initiation of saccades. Injection was followed almost immediately by stereotyped and apparently irrepressible saccades made toward the center of the movement field of the SC cells at the injection site. The monkeys became unable to fixate during the tasks; the fixation was interrupted by saccadic jerks made to the affected area of the visual field and then back to the fixation point.

Schiller, P. H. "The Neural Control of Visually Guided Eye Movements." In Cognitive Neuroscience of Attention. Edited by J. Richards. NJ: Erlbaum, 1998.

Schiller, P. H., and J. E. Tehovnik. "Look and See: How the brain moves your eyes about." Chap. 9 in Vision: from Neurons to Cognition. Edited by C. Casanova and M. Ptito. M.A. (Progress in Brain Research. Vol. 134. Amsterdam, Elsevier, 2001.)

PubMed abstract:  Two major cortical streams are involved in the generation of visually guided saccadic eye movements: the anterior and the posterior. The anterior stream from the frontal and medial eye fields has direct access to brainstem oculomotor centers. The posterior stream from the occipital cortices reaches brainstem oculomotor centers through the superior colliculus. The parietal cortex interconnects with both streams. Our findings suggest that the posterior stream plays an unique role in the execution of rapid, short-latency eye movements called 'express saccades'. Both the anterior and posterior streams play a role in the selection of targets to which saccades are to be generated, but do so in different ways. Areas V1, V2 and LIP contribute to decisions involved in where to look as well as where not to look. In addition, area LIP is involved in decisions about how long to maintain fixation prior to the execution of a saccade. Area V4 does not appear to be directly involved in eye-movement generation. In the anterior stream, the frontal eye fields, and to a lesser extent the medial eye fields, are involved in the correct execution of saccades subsequent to decisions made about where to look and where not to look.

Tehovnik, E. J., M. A. Sommer, I. Chou, W. M. Slocum, and P. H. Schiller. "Eye Fields in the Frontal Lobes of Primates." Brain Research Reviews 32 (2000): 413-448.

PubMed abstract:  Two eye fields have been identified in the frontal lobes of primates: one is situated dorsomedially within the frontal cortex and will be referred to as the eye field within the dorsomedial frontal cortex (DMFC); the other resides dorsolaterally within the frontal cortex and is commonly referred to as the frontal eye field (FEF). This review documents the similarities and differences between these eye fields. Although the DMFC and FEF are both active during the execution of saccadic and smooth pursuit eye movements, the FEF is more dedicated to these functions. Lesions of DMFC minimally affect the production of most types of saccadic eye movements and have no effect on the execution of smooth pursuit eye movements. In contrast, lesions of the FEF produce deficits in generating saccades to briefly presented targets, in the production of saccades to two or more sequentially presented targets, in the selection of simultaneously presented targets, and in the execution of smooth pursuit eye movements. For the most part, these deficits are prevalent in both monkeys and humans. Single-unit recording experiments have shown that the DMFC contains neurons that mediate both limb and eye movements, whereas the FEF seems to be involved in the execution of eye movements only. Imaging experiments conducted on humans have corroborated these findings. A feature that distinguishes the DMFC from the FEF is that the DMFC contains a somatotopic map with eyes represented rostrally and hindlimbs represented caudally; the FEF has no such topography. Furthermore, experiments have revealed that the DMFC tends to contain a craniotopic (i.e., head-centered) code for the execution of saccadic eye movements, whereas the FEF contains a retinotopic (i.e., eye-centered) code for the elicitation of saccades. Imaging and unit recording data suggest that the DMFC is more involved in the learning of new tasks than is the FEF. Also with continued training on behavioural tasks the responsivity of the DMFC tends to drop. Accordingly, the DMFC is more involved in learning operations whereas the FEF is more specialized for the execution of saccadic and smooth pursuit eye movements.

PubMed abstract:  The Albin-DeLong 'box and arrow' model has long been the accepted standard model for the basal ganglia network. However, advances in physiological and anatomical research have enabled a more detailed neural network approach. Recent computational models hold that the basal ganglia use reinforcement signals and local competitive learning rules to reduce the dimensionality of sparse cortical information. These models predict a steady-state situation with diminished efficacy of lateral inhibition and low synchronization. In this framework, Parkinson's disease can be characterized as a persistent state of negative reinforcement, inefficient dimensionality reduction, and abnormally synchronized basal ganglia activity.

Beiser, D. G., and J. C. Houk. "Model of Cortico-Basal Ganglionic Processing: Encoding the Serial Order of Sensory Events." J. Neurophysiol. 79 (1998): 3168-3188.

PubMed abstract:  Several lines of evidence suggest that the prefrontal (PF) cortex and basal ganglia are important in cognitive aspects of serial order in behavior. We present a modular neural network model of these areas that encodes the serial order of events into spatial patterns of PF activity. The model is based on the topographically specific circuits linking the PF with the basal ganglia. Each module traces a pathway from the PF, through the basal ganglia and thalamus, and back to the PF. The complete model consists of an array of modules interacting through recurrent corticostriatal projections and collateral inhibition between striatal spiny units. The model's architecture positions spiny units for the classification of cortical contexts and events and provides bistable cortical-thalamic loops for sustaining a representation of these contextual events in working memory activations. The model was tested with a simulated version of a delayed-sequencing task. In single-unit studies, the task begins with the presentation of a sequence of target lights. After a short delay, the monkey must touch the targets in the order in which they were presented. When instantiated with randomly distributed corticostriatal weights, the model produces different patterns of PF activation in response to different target sequences. These patterns represent an unambiguous and spatially distributed encoding of the sequence. Parameter studies of these random networks were used to compare the computational consequences of collateral and feed-forward inhibition within the striatum. In addition, we studied the receptive fields of 20,640 model units and uncovered an interesting set of cue-, rank- and sequence-related responses that qualitatively resemble responses reported in single unit studies of the PF. The majority of units respond to more than one sequence of stimuli. A method for analyzing serial receptive fields is presented and utilized for comparing the model units to single-unit data.

Blazquez, P., N. Fujii, J. Kojima, and A. M. Graybiel. "A Network Representation Of Response Probability in the Striatum." Neuron 33 (2002): 973-982.

PubMed abstract:  The striatum of the basal ganglia is considered a key structure in the learning circuitry of the brain. To analyze neural signals that underlie striatal plasticity, we recorded from an identifiable class of striatal interneurons as macaque monkeys underwent training in a range of conditioning and non-associative learning paradigms, and recorded eyeblink electromyographs as the measure of behavioral response. We found that the responses of these striatal interneurons were modifiable under all training conditions and that their population responses were tightly correlated with the probability that a given stimulus would evoke a behavioral response. Such a network signal, proportional to current response probability, could be crucial to the learning and decision functions of the basal ganglia.

DeLong, M. R. "The Basal Ganglia." In Principles of Neural Science. 4th ed. Edited by E. R. Kandel, J. H. Schwartz, and T. M. Jessell. New York: McGraw-Hill, 2000, pp. 853-867.

Doya, K. "Complementary Roles of Basal Ganglia and Cerebellum in Learning and Motor Control." Curr. Opin. Neurobiol. 10 (2000): 732-739.

PubMed abstract:  The classical notion that the basal ganglia and the cerebellum are dedicated to motor control has been challenged by the accumulation of evidence revealing their involvement in non-motor, cognitive functions. From a computational viewpoint, it has been suggested that the cerebellum, the basal ganglia, and the cerebral cortex are specialized for different types of learning: namely, supervised learning, reinforcement learning and unsupervised learning, respectively. This idea of learning-oriented specialization is helpful in understanding the complementary roles of the basal ganglia and the cerebellum in motor control and cognitive functions.

Graybiel, A. M. "The Basal Ganglia and Chunking of Action Repertoires." Neurobiol. Learn. Mem. 70 (1998): 119-136.

PubMed abstract:  The basal ganglia have been shown to contribute to habit and stimulus-response (S-R) learning. These forms of learning have the property of slow acquisition and, in humans, can occur without conscious awareness. This paper proposes that one aspect of basal ganglia-based learning is the recoding of cortically derived information within the striatum. Modular corticostriatal projection patterns, demonstrated experimentally, are viewed as producing recoded templates suitable for the gradual selection of new input-output relations in cortico-basal ganglia loops. Recordings from striatal projection neurons and interneurons show that activity patterns in the striatum are modified gradually during the course of S-R learning. It is proposed that this recoding within the striatum can chunk the representations of motor and cognitive action sequences so that they can be implemented as performance units. This scheme generalizes Miller's notion of information chunking to action control. The formation and the efficient implementation of action chunks are viewed as being based on predictive signals. It is suggested that information chunking provides a mechanism for the acquisition and the expression of action repertoires that, without such information compression would be biologically unwieldy or difficult to implement. The learning and memory functions of the basal ganglia are thus seen as core features of the basal ganglia's influence on motor and cognitive pattern generators. Copyright 1998 Academic Press.

Gurney, K., T. J. Prescott, and P. Redgrave. "A Computational Model of Action Selection in the Basal Ganglia. I. A New Functional Anatomy." Biol. Cybern. 84 (2001): 401-410.

PubMed abstract:  In a companion paper a new functional architecture was proposed for the basal ganglia based on the premise that these brain structures play a central role in behavioural action selection. The current paper quantitatively describes the properties of the model using analysis and simulation. The decomposition of the basal ganglia into selection and control pathways is supported in several ways. First, several elegant features are exposed--capacity scaling, enhanced selectivity and synergistic dopamine modulation--which might be expected to exist in a well designed action selection mechanism. The discovery of these features also lends support to the computational premise of selection that underpins our model. Second, good matches between model globus pallidus external segment output and globus pallidus internal segment and substantia nigra reticulata area output, and neurophysiological data, have been found which are indicative of common architectural features in the model and biological basal ganglia. Third, the behaviour of the model as a signal selection mechanism has parallels with some kinds of action selection observed in animals under various levels of dopaminergic modulation.

------. "A Computational Model of Action Selection in the Basal Ganglia. II. Analysis and Simulation of Behaviour." Biol. Cybern. 84 (2001): 411-423.

PubMed abstract:  We present a biologically plausible model of processing intrinsic to the basal ganglia based on the computational premise that action selection is a primary role of these central brain structures. By encoding the propensity for selecting a given action in a scalar value (the salience), it is shown that action selection may be recast in terms of signal selection. The generic properties of signal selection are defined and neural networks for this type of computation examined. A comparison between these networks and basal ganglia anatomy leads to a novel functional decomposition of the basal ganglia architecture into 'selection' and 'control' pathways. The former pathway performs the selection per se via a feedforward off-centre on-surround network. The control pathway regulates the action of the selection pathway to ensure its effective operation, and synergistically complements its dopaminergic modulation. The model contrasts with the prevailing functional segregation of basal ganglia into 'direct' and 'indirect' pathways.

Jog, M., Y. Kubota, C. I. Connolly, V. Hillegaart, and A. M. Graybiel. "Building Neural Representations of Habits." Science 285 (1999): 1745-1749.

PubMed abstract:  Memories for habits and skills ("implicit or procedural memory") and memories for facts ("explicit or episodic memory") are built up in different brain systems and are vulnerable to different neurodegenerative disorders in humans. So that the striatum-based mechanisms underlying habit formation could be studied, chronic recordings from ensembles of striatal neurons were made with multiple tetrodes as rats learned a T-maze procedural task. Large and widely distributed changes in the neuronal activity patterns occurred in the sensorimotor striatum during behavioral acquisition, culminating in task-related activity emphasizing the beginning and end of the automatized procedure. The new ensemble patterns remained stable during weeks of subsequent performance of the same task. These results suggest that the encoding of action in the sensorimotor striatum undergoes dynamic reorganization as habit learning proceeds.

Kawagoe, R., Y. Takikawa, and O. Hikosaka. "Expectation of Reward Modulates Cognitive Signals in the Basal Ganglia." Nature Neuroscience 1 (1998): 411-416.

PubMed abstract:  Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neuron's preferred direction often changed with the change in the rewarded direction. The subsequent saccade to the target was earlier and faster for the rewarded direction. Our results indicate that the caudate contributes to the determination of oculomotor outputs by connecting motivational values (for example, expectation of reward) to visual information.

Mink, J. W. "The Basal Ganglia: Focused Selection and Inhibition of Competing Motor Programs." Prog. Neurobiol 50 (1996): 381-425.

PubMed abstract:  The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these a abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity.

Nakahara, H., K. Doya, and O. Hikosaka. "Parallel Cortico-Basal Ganglia Mechanisms for Acquisition and Execution of Visuomotor Sequences - A Computational Approach." J. Cogn. Neurosci. 13 (2001): 626-647.

PubMed abstract:  Experimental studies have suggested that many brain areas, including the basal ganglia (BG), contribute to procedural learning. Focusing on the basal ganglia-thalamocortical (BG-TC) system, we propose a computational model to explain how different brain areas work together in procedural learning. The BG-TC system is composed of multiple separate loop circuits. According to our model, two separate BG-TC loops learn a visuomotor sequence concurrently but using different coordinates, one visual, and the other motor. The visual loop includes the dorsolateral prefrontal (DLPF) cortex and the anterior part of the BG, while the motor loop includes the supplementary motor area (SMA) and the posterior BG. The concurrent learning in these loops is based on reinforcement signals carried by dopaminergic (DA) neurons that project divergently to the anterior ("visual") and posterior ("motor") parts of the striatum. It is expected, however, that the visual loop learns a sequence faster than the motor loop due to their different coordinates. The difference in learning speed may lead to inconsistent outputs from the visual and motor loops, and this problem is solved by a mechanism called a "coordinator," which adjusts the contribution of the visual and motor loops to a final motor output. The coordinator is assumed to be in the presupplementary motor area (pre-SMA). We hypothesize that the visual and motor loops, with the help of the coordinator, achieve both the quick acquisition of novel sequences and the robust execution of well-learned sequences. A computational model based on the hypothesis is examined in a series of computer simulations, referring to the results of the 2 x 5 task experiments that have been used on both monkeys and humans. We found that the dual mechanism with the coordinator was superior to the single (visual or motor) mechanism. The model replicated the following essential features of the experimental results: (1) the time course of learning, (2) the effect of opposite hand use, (3) the effect of sequence reversal, and (4) the effects of localized brain inactivations. Our model may account for a common feature of procedural learning: A spatial sequence of discrete actions (subserved by the visual loop) is gradually replaced by a robust motor skill (subserved by the motor loop).

Poldrack, R. A., J. Clark, E. J. Pare-Blagoev, D. Shohamy, J. C. Moyano, C. Myers, and M. A. Gluck. "Interactive Memory Systems in the Human Brain." Nature 414 (2001): 546-550.

PubMed abstract:  Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.

Schultz, W., and A. Dickinson. "Neuronal Coding of Prediction Errors." Annu. Rev. Neurosci. 23 (2000): 473-500.

PubMed abstract:  Associative learning enables animals to anticipate the occurrence of important outcomes. Learning occurs when the actual outcome differs from the predicted outcome, resulting in a prediction error. Neurons in several brain structures appear to code prediction errors in relation to rewards, punishments, external stimuli, and behavioral reactions. In one form, dopamine neurons, norepinephrine neurons, and nucleus basalis neurons broadcast prediction errors as global reinforcement or teaching signals to large postsynaptic structures. In other cases, error signals are coded by selected neurons in the cerebellum, superior colliculus, frontal eye fields, parietal cortex, striatum, and visual system, where they influence specific subgroups of neurons. Prediction errors can be used in postsynaptic structures for the immediate selection of behavior or for synaptic changes underlying behavioral learning. The coding of prediction errors may represent a basic mode of brain function that may also contribute to the processing of sensory information and the short-term control of behavior.

Schultz, W., P. Dayan, and P. R. Montague. "A Neural Substrate of Prediction and Reward." Science 275 (1997): 1593-1599.

PubMed abstract:  The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

Zheng, T., and C. J. Wilson "Corticostriatal Combinatorics: The Implications of Corticostriatal Axonal Arborizations." J Neurophysiol 87 (2002): 1007-1017.

PubMed abstract:  The complete striatal axonal arborizations of 16 juxtacellularly stained cortical pyramidal cells were analyzed. Corticostriatal neurons were located in the medial agranular or anterior cingulate cortex of rats. All axons were of the extended type and formed synaptic contacts in both the striosomal and matrix compartments as determined by counterstaining for the mu-opiate receptor. Six axonal arborizations were from collaterals of brain stem-projecting cells and the other 10 from bilaterally projecting cells with no brain stem projections. The distribution of synaptic boutons along the axons were convolved with the average dendritic tree volume of spiny projection neurons to obtain an axonal innervation volume and innervation density map for each axon. Innervation volumes varied widely, with single axons occupying between 0.4 and 14.2% of the striatum (average = 4%). The total number of boutons formed by individual axons ranged from 25 to 2,900 (average = 879). Within the innervation volume, the density of innervation was extremely sparse but inhomogeneous. The pattern of innervation resembled matrisomes, as defined by bulk labeling and functional mapping experiments, superimposed on a low background innervation. Using this sample as representative of all corticostriatal axons, the total number of corticostriatal neurons was estimated to be 17 million, about 10 times the number of striatal projection neurons.

PubMed abstract:  Plasticity of representational maps in adult cerebral cortex has been documented in both sensory and motor cortex, but the anatomical basis for cortical plasticity remains poorly understood. To investigate horizontal connectivity in primary motor cortex (M1) as a putative anatomical substrate for short-term, functional plasticity of adult motor cortical representations, a combination of electrical stimulation and biocytin labeling was used to examine pre-existing patterns of intrinsic connections in adult rat M1 in relationship to the pattern of reorganization of the motor movement may induced by transection of the contralateral facial nerve. Two hours after nerve cut, small, circumscribed regions of the forelimb representation expanded medially into territory previously devoted to the vibrissae representation. Outside of this novel, expanded forelimb region, no forelimb movement could be evoked from the former vibrissae representation at any time over the period of hours tested, thus representing silent cortex. Injections placed into vibrissae cortex representing the newly expanded forelimb representation gave rise to labeled axons and dense terminal fiber labeling which crossed the forelimb/vibrissae border and extended up to 1.2 mm within the low-threshold forelimb representation. In contrast, injections placed into silent vibrissae cortex gave rise to labeled axons and terminal boutons which remained mostly restricted to the original vibrissae representation, with only sparse projections that crossed into the low-threshold forelimb representation. Thus, these results suggest that the extent of short-term, functional reorganization of M1 induced within the first several hours following peripheral nerve cut is mediated, and constrained, by an anatomical framework of pre-existing, horizontal projections which traverse representation borders.

Jacobs, K. M., and J. P. Donoghue. "Reshaping the Cortical Motor Map by Unmasking Latent Intracortical Connections." Science 251 (1991): 944-947.

PubMed abstract:  The primary motor cortex (MI) contains a map organized so that contralateral limb or facial movements are elicited by electrical stimulation within separate medial to lateral MI regions. Within hours of a peripheral nerve transection in adult rats, movements represented in neighboring MI areas are evoked from the cortical territory of the affected body part. One potential mechanism for reorganization is that adjacent cortical regions expand when preexisting lateral excitatory connections are unmasked by decreased intracortical inhibition. During pharmacological blockade of cortical inhibition in one part of the MI representation, movements of neighboring representations were evoked by stimulation in adjacent MI areas. These results suggest that intracortical connections form a substrate for reorganization of cortical maps and that inhibitory circuits are critically placed to maintain or readjust the form of cortical motor representations.

Karni, A., G. Meyer, P. Jezzard, M. M. Adams, R. Turner, and L. G. Ungerleider. "Functional MRI Evidence for Adult Motor Cortex Plasticity During Motor Skill Learning." Nature 377 (1995): 155-158.

PubMed abstract:  Performance of complex motor tasks, such as rapid sequences of finger movements, can be improved in terms of speed and accuracy over several weeks by daily practice sessions. This improvement does not generalize to a matched sequence of identical component movements, nor to the contralateral hand. Here we report a study of the neural changes underlying this learning using functional magnetic resonance imaging (MRI) of local blood oxygenation level-dependent (BOLD) signals evoked in primary motor cortex (M1). Before training, a comparable extent of M1 was activated by both sequences. However, two ordering effects were observed: repeating a sequence within a brief time window initially resulted in a smaller area of activation (habituation), but later in larger area of activation (enhancement), suggesting a switch in M1 processing mode within the first session (fast learning). By week 4 of training, concurrent with asymptotic performance, the extent of cortex activated by the practised sequence enlarged compared with the unpractised sequence, irrespective of order (slow learning). These changes persisted for several months. The results suggest a slowly evolving, long-term, experience-dependent reorganization of the adult M1, which may underlie the acquisition and retention of the motor skill.

Karni, A., G. Myer, C. Rey-Hipolito, P. Jezzard, M. M. Adams, R. Turner, and L. G. Ungerleider. "The Acquisition Of Skilled Motor Performance: Fast and Slow Experience-Driven Changes in Primary Motor Cortex." Proc. Natl. Acad. Sci. 95 (1998): 861-868.

PubMed abstract:  Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Nudo, R. J. "Recovery After Damage to Motor Cortical Areas." Current Opinion in Neurobiology 9 (1999): 740-747.

PubMed abstract:  Until recently, the neural bases underlying recovery of function after damage to the cerebral cortex were largely unknown. Recent results from neuroanatomical and neurophysiological studies in animal models have demonstrated that after cortical damage, long-term and widespread structural and functional alterations take place in the spared cortical tissue. These presumably adaptive changes may play an important role in functional recovery.

Nudo, R. J., G.W. Milliken, W. M. Jenkins, and M. M. Merzenich. "Use-Dependent Alterations of Movement Representations in Primary Motor Cortex of Adult Squirrel Monkeys." J. Neurosci. 16 (1996): 785-807.

PubMed abstract:  This study was undertaken to document plastic changes in the functional topography of primary motor cortex (M1) that are generated in motor skill learning in the normal, intact primate. Intracortical microstimulation mapping techniques were used to derive detailed maps of the representation of movements in the distal forelimb zone of M1 of squirrel monkeys, before and after behavioral training on two different tasks that differentially encouraged specific sets of forelimb movements. After training on a small-object retrieval task, which required skilled use of the digits, their evoked-movement digit representations expanded, whereas their evoked-movement wrist/forearm representational zones contracted. These changes were progressive and reversible. In a second motor skill exercise, a monkey pronated and supinated the forearm in a key (eyebolt)-turning task. In this case, the representation of the forearm expanded, whereas the digit representational zones contracted. These results show that M1 is alterable by use throughout the life of an animal. These studies also revealed that after digit training there was an areal expansion of dual-response representations, that is, cortical sectors over which stimulation produced movements about two or more joints. Movement combinations that were used more frequently after training were selectively magnified in their cortical representations. This close correspondence between changes in behavioral performance and electrophysiologically defined motor representations indicates that a neurophysiological correlate of a motor skill resides in M1 for at least several days after acquisition. The finding that cocontracting muscles in the behavior come to be represented together in the cortex argues that, as in sensory cortices, temporal correlations drive emergent changes in distributed motor cortex representations.

Pascual-Leone, A., J. Grafman, and M. Hallett. "Modulation of Cortical Motor Output Maps During Development of Implicit and Explicit Knowledge." Science 263 (1994): 1287-1289.

PubMed abstract:  The excitability of the human motor cortex during the development of implicit and declarative knowledge of a motor task was examined. During a serial reaction time test, subjects developed implicit knowledge of the test sequence, which was reflected by diminishing response times. Motor cortical mapping with transcranial magnetic stimulation revealed that the cortical output maps to the muscles involved in the task became progressively larger until explicit knowledge was achieved, after which they returned to their baseline topography. These results illustrate the rapid functional plasticity of cortical outputs associated with learning and with the transfer of knowledge from an implicit to explicit state.

Pascual-Leone, A., N. Dang, L. G. Cohen, J. P. Barsil-Neto, A. Cammorota, and M. Hallett. "Modulation of Muscle Responses Evoked by Transcranial Magnetic Stimulation During the Acquisition of New Fine Motor Skills." J. Neurophysiol. 74 (1995): 1037-1045.

PubMed abstract:  1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill.

Rioult-Pedotti, S. Mengia, D. Friedman, and J. P. Donoghue. "Learning-Induced LTP in Neocortex." Science 290 (2000): 533-536.

PubMed abstract:  The hypothesis that learning occurs through long-term potentiation (LTP)- and long-term depression (LTD)-like mechanisms is widely held but unproven. This hypothesis makes three assumptions: Synapses are modifiable, they modify with learning, and they strengthen through an LTP-like mechanism. We previously established the ability for synaptic modification and a synaptic strengthening with motor skill learning in horizontal connections of the rat motor cortex (MI). Here we investigated whether learning strengthened these connections through LTP. We demonstrated that synapses in the trained MI were near the ceiling of their modification range, compared with the untrained MI, but the range of synaptic modification was not affected by learning. In the trained MI, LTP was markedly reduced and LTD was enhanced. These results are consistent with the use of LTP to strengthen synapses during learning.

Rioult-Pedotti, S. Mengia, D. Friedman, G. Hess, and J. P. Donoghue. "Strengthening of Horizontal Cortical Connections Following Skill Learning." Nature Neuroscience 1 (1998): 230-234.

PubMed abstract:  Learning a new motor skill requires an alteration in the spatiotemporal pattern of muscle activation. Motor areas of cerebral neocortex are thought to be involved in this type of learning, possibly by functional reorganization of cortical connections. Here we show that skill learning is accompanied by changes in the strength of connections within adult rat primary motor cortex (M1). Rats were trained for three or five days in a skilled reaching task with one forelimb, after which slices of motor cortex were examined to determine the effect of training on the strength of horizontal intracortical connections in layer II/III. The amplitude of field potentials in the forelimb region contralateral to the trained limb was significantly increased relative to the opposite 'untrained' hemisphere. No differences were seen in the hindlimb region. Moreover, the amount of long-term potentiation (LTP) that could be induced in trained M1 was less than in controls, suggesting that the effect of training was at least partly due to LTP-like mechanisms. These data represent the first direct evidence that plasticity of intracortical connections is associated with learning a new motor skill.

Sanes, J. N., and J. P. Donoghue. "Plasticity and Primary Motor Cortex." Annu. Rev. Neurosci. 23 (2000): 393-415.

PubMed abstract:  One fundamental function of primary motor cortex (MI) is to control voluntary movements. Recent evidence suggests that this role emerges from distributed networks rather than discrete representations and that in adult mammals these networks are capable of modification. Neuronal recordings and activation patterns revealed with neuroimaging methods have shown considerable plasticity of MI representations and cell properties following pathological or traumatic changes and in relation to everyday experience, including motor-skill learning and cognitive motor actions. The intrinsic horizontal neuronal connections in MI are a strong candidate substrate for map reorganization: They interconnect large regions of MI, they show activity-dependent plasticity, and they modify in association with skill learning. These findings suggest that MI cortex is not simply a static motor control structure. It also contains a dynamic substrate that participates in motor learning and possibly in cognitive events as well.

Shadmehr, R., and H. H. Holcomb. "Neural Correlates of Motor Memory Consolidation." Science 277 (1997): 821- 825.

PubMed abstract:  Computational studies suggest that acquisition of a motor skill involves learning an internal model of the dynamics of the task, which enables the brain to predict and compensate for mechanical behavior. During the hours that follow completion of practice, representation of the internal model gradually changes, becoming less fragile with respect to behavioral interference. Here, functional imaging of the brain demonstrates that within 6 hours after completion of practice, while performance remains unchanged, the brain engages new regions to perform the task; there is a shift from prefrontal regions of the cortex to the premotor, posterior parietal, and cerebellar cortex structures. This shift is specific to recall of an established motor skill and suggests that with the passage of time, there is a change in the neural representation of the internal model and that this change may underlie its increased functional stability.

Ziemann, Ulf, M. Hallett, and L. G. Cohen. "Mechanisms of Deafferentation-Induced Plasticity in Human Motor Cortex." J. Neurosci. 18 (1998): 7000-7007.

PubMed abstract:  Deafferentation induces rapid plastic changes in the cerebral cortex, probably via unmasking of pre-existent connections. Several mechanisms may contribute, such as changes in neuronal membrane excitability, removal of local inhibition, or various forms of short- or long-term synaptic plasticity. To understand further the mechanisms involved in cortical plasticity, we tested the effects of CNS-active drugs in a plasticity model, in which forearm ischemic nerve block (INB) was combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) of the deafferented human motor cortex. rTMS was used to upregulate the plastic changes caused by INB. We studied six healthy subjects. In two control sessions without drug application, INB plus rTMS increased the motor-evoked potential (MEP) size and decreased intracortical inhibition (ICI) measured with single- and paired-pulse TMS in the biceps brachii muscle proximal to INB. A single oral dose of the benzodiazepine lorazepam (2 mg) or the voltage-gated Na+ and Ca2+ channel blocker lamotrigine (300 mg) abolished these changes. The NMDA receptor blocker dextromethorphan (150 mg) suppressed the reduction in ICI but not the increase in MEP size. With sleep deprivation, used to eliminate sedation as a major factor of these drug effects, INB plus rTMS induced changes similar to that seen in the control sessions. The findings suggest that (1) the INB plus rTMS-induced increase in MEP size involves rapid removal of GABA-related cortical inhibition and short-term changes in synaptic efficacy dependent on Na+ or Ca2+ channels and that (2) the long-lasting (>60 min) reduction in ICI is related to long-term potentiation-like mechanisms given its duration and the involvement of NMDA receptor activation.

Massaquoi, S. G., and J-J. E. Slotine. "The Intermediate Cerebellum May Function as a Wave-Variable Processor." Neurosci. Letters 215 (1996): 60-64.

PubMed abstract:  A newly developed model suggests that the intermediate cerebellum and spinal cord gray matter may contribute to movement control by processing control signals as wave variables. Within specialized communication systems, wave variables are combinations of forward and return signals that ensure stable exchange between two sites despite transmission delays. The composition of signals transmitted in the ventral spinocerebellar tract appears to be consistent with that of a wave variable, and computer simulations of the model yield signals similar to those observed in the monkey interpositus nucleus. Wave-variable communication may enable the animal motor system to maintain stable, high-performance feedback control in the presence of potentially destabilizing signal transmission delays.

Massaquoi, S. G., and M. Hallett. "Ataxia and Other Cerebellar Syndromes." In Parkinson's Disease and Movement Disorders. 3rd ed. Edited by J. Jankovic and E. Tolosa. Baltimore: Williams & Wilkins, 1998, pp. 623-686.

------. "Kinematics of Initiating a Two-Joint Arm Movement in Patients with Cerebellar Ataxia." Can. J. Neurol Sci. 23 (1996): 3-14.

PubMed abstract:  OBJECTIVE: To characterize kinematically any systematic aberration in multi-joint movements in cerebellar ataxia. METHODS: Nine patients with cerebellar degeneration and nine normal subjects, mobile only at the shoulder and elbow of the right arm, were required to produce left-to-right cross-body linear hand trajectories on the horizontal surface of a digitizing tablet. Nonlinearity indicated failure of precise coordination of the two joints. A wide range of hand speeds was studied. Data analysis was restricted primarily to the first 130 ms of movement. RESULTS: As hand velocities increased, normal subjects and, especially, patients produced misdirected, curved paths. Normal subjects had significant curvature when peak speeds exceeded 100 cm/s and a trend toward significant bi-directional angular deviation at velocities greater than 300 cm/s. In patients, peak path curvature was significantly greater than normal at peak velocities of 50 to 200 cm/s. By 3.3 cm, their paths deviated significantly outward at all but the slowest speeds. Overall, patients' maximal hand velocities and shoulder angular velocities, as well as maximal angular accelerations at both joints, were significantly lower than normal. CONCLUSIONS: The patients' trajectory aberrations were attributed to a deficient rate of rotation at the shoulder relative to that at the elbow. Relative to task requirements, their rate of torque development was apparently deficient at both joints. but to a greater degree at the shoulder. Joint torque-rate impairment may contribute to the ataxia in both multi- and single-joint movements of patients with cerebellar disorders. A similar, but smaller impairment may produce milder nonlinearity in high-velocity movements of normal subjects.

Schweighofer, N., M. A. Arbib, and M. Kawato. "Role of the Cerebellum in Reaching Movements in Humans I and II." Eur. J. Neurosci. 10 (1998): 86-105.

PubMed abstract:  This study focuses on the role of the motor cortex, the spinal cord and the cerebellum in the dynamics stage of the control of arm movement. Currently, two classes of models have been proposed for the neural control of movements, namely the virtual trajectory control hypothesis and the acquisition of internal models of the motor apparatus hypothesis. In the present study, we expand the virtual trajectory model to whole arm reaching movements. This expanded model accurately reproduced slow movements, but faster reaching movements deviated significantly from the planned trajectories, indicating that for fast movements, this model was not sufficient. These results led us to propose a new distributed functional model consistent with behavioural, anatomical and neurophysiological data, which takes into account arm muscles, spinal cord, motor cortex and cerebellum and is consistent with the view that the central nervous system acquires a distributed inverse dynamics model of the arm. Previous studies indicated that the cerebellum compensates for the interaction forces that arise during reaching movements. We show here how the cerebellum may increase the accuracy of reaching movements by compensating for the interaction torques by learning a portion of an inverse dynamics model that refines a basic inverse model in the motor cortex and spinal cord.

Wolpert, D. M., R. C. Miall, and M. Kawato. "Internal Models in the Cerebellum." Trend in Cog. Sci. 2, 9 (1998): 338-347.

PubMed abstract:  The activity of 176 individual cells in the arm area of motor cortex (areas 4 and 6) was studied while monkeys made arm movements of similar direction within different parts of extrapersonal space. The behavioral paradigm used was a 3-dimensional reaction-time task aimed at dissociating the direction of movement, which remained similar across the work space, from the patterns of muscular activity and the angular joint excursions necessary to perform these movements. In agreement with other studies (Georgopoulos et al., 1982; Schwartz et al., 1988), we found that, within a given part of space, the activity of 169 (96.0%) cells studied increased most for a given preferred direction and less for other directions of movement. This change was graded in an orderly fashion. We further analyzed the orientation in space of the cells' preferred directions under the differing conditions of the task. We found that, as movements with similar trajectories were made within different parts of space, the cells' preferred directions changed spatial orientation. This change was of different magnitudes for different cells, but at the level of the population, it followed closely the changes in orientation of the arm necessary to perform the movements required by the task. Movement population vectors (Georgopoulos et al., 1983, 1986, 1988) computed from cell activity proved to be good predictors of movement direction regardless of where in space the movements were performed. These results indicate that motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space. The data are discussed in relation to the existence of mechanisms which facilitate the transformation between extrinsic and intrinsic coordinates. These transformations are necessary to perform arm movements to visual targets in space.

Evarts, E. V. "Relation of Pyramidal Tract Activity to Force Exerted During Voluntary Movement." J. Neurophysiol. 31 (1968): 14-27.

Georgopoulos, A. P., J. F. Kalaska, R. Caminiti, and J. T. Massey. "On the Relations Between the Direction of Two-Dimensional Arm Movements and Cell Discharge in Primate Motor Cortex." J. Neurosci. 2 (1982): 1527-1537.

PubMed abstract:  The activity of single cells in the motor cortex was recorded while monkeys made arm movements in eight directions (at 45 degrees intervals) in a two-dimensional apparatus. These movements started from the same point and were of the same amplitude. The activity of 606 cells related to proximal arm movements was examined in the task; 323 of the 606 cells were active in that task and were studied in detail. The frequency of discharge of 241 of the 323 cells (74.6%) varied in an orderly fashion with the direction of movement. Discharge was most intense with movements in a preferred direction and was reduced gradually when movements were made in directions farther and farther away from the preferred one. This resulted in a bell-shaped directional tuning curve. These relations were observed for cell discharge during the reaction time, the movement time, and the period that preceded the earliest changes in the electromyographic activity (approximately 80 msec before movement onset). In about 75% of the 241 directionally tuned cells, the frequency of discharge, D, was a sinusoidal function of the direction of movement, theta: D = b0 + b1 sin theta + b2cos theta, or, in terms of the preferred direction, theta 0: D = b0 + c1cos (theta - theta0), where b0, b1, b2, and c1 are regression coefficients. Preferred directions differed for different cells so that the tuning curves partially overlapped. The orderly variation of cell discharge with the direction of movement and the fact that cells related to only one of the eight directions of movement tested were rarely observed indicate that movements in a particular direction are not subserved by motor cortical cells uniquely related to that movement. It is suggested, instead, that a movement trajectory in a desired direction might be generated by the cooperation of cells with overlapping tuning curves. The nature of this hypothetical population code for movement direction remains to be elucidated.

Georgopoulos, A. P., R. E. Kettner, and A. B. Schwartz. "Primate Motor Cortex and Free Arm Movements to Visual Targets in Three-Dimensional Space. II. Coding of the Direction of Movement by a Neuronal Population." J. Neurosci. 8 (1988): 2928-2937.

PubMed abstract:  We describe a code by which a population of motor cortical neurons could determine uniquely the direction of reaching movements in three-dimensional space. The population consisted of 475 directionally tuned cells whose functional properties are described in the preceding paper (Schwartz et al., 1988). Each cell discharged at the highest rate with movements in its "preferred direction" and at progressively lower rates with movements in directions away from the preferred one. The neuronal population code assumes that for a particular movement direction each cell makes a vectorial contribution ("votes") with direction in the cell's preferred direction and magnitude proportional to the change in the cell's discharge rate associated with the particular direction of movement. The vector sum of these contributions is the outcome of the population code (the "neuronal population vector") and points in the direction of movement in space well before the movement begins.

Ghez., C., and J. Krakauer. "The Organization of Movement." In Principles of Neural Science. 4th ed. Edited by E. R. Kandel, J. H. Schwartz, and T. M. Jessell. New York: McGraw-Hill, 2000, pp. 653-673.

Johnson, M. T., C. R. Mason, and T. J. Ebner. "Central Processes for the Multiparametric Control Of Arm Movements in Primates." Curr Opin Neurobiol. 11 (2001): 684-688.

PubMed abstract:  Recent single-unit recording studies have clarified how multiple parameters of movement are signaled by individual cortical and cerebellar neurons, and also that multiple coordinate frames are utilized. Cognitive processes also modulate the firing of these neurons. The various signals and coordinate systems vary in time and evolve throughout a behavioral sequence, consistent with the demands of the task and the required sensorimotor transforma.

Kakei, S., D. S. Hoffman, and P. L. Strick. "Direction of Action is Represented in the Ventral Premotor Cortex." Nat Neurosci. 4 (2001): 1020-1025.

PubMed abstract:  The ventral premotor area (PMv) is a major source of input to the primary motor cortex (M1). To examine the potential hierarchical processing between these motor areas, we recorded the activity of PMv neurons in a monkey trained to perform wrist movements in different directions with the wrist in three different postures. The task dissociated three major variables of wrist movement: muscle activity, direction of joint movement and direction of movement in space. Many PMv neurons were directionally tuned. Nearly all of these neurons (61/65, 94%) were 'extrinsic-like'; they seemed to encode the direction of movement in space independent of forearm posture. These results are strikingly different from results from M1 of the same animal, and suggest that intracortical processing between PMv and M1 may contribute to a sensorimotor transformation between extrinsic and intrinsic coordinate frames.

------. "Muscle and Movement Representations in the Primary Motor Cortex." Science 285 (1999): 2136-2139.

PubMed abstract:  What aspects of movement are represented in the primary motor cortex (M1): relatively low-level parameters like muscle force, or more abstract parameters like handpath? To examine this issue, the activity of neurons in M1 was recorded in a monkey trained to perform a task that dissociates three major variables of wrist movement: muscle activity, direction of movement at the wrist joint, and direction of movement in space. A substantial group of neurons in M1 (28 out of 88) displayed changes in activity that were muscle-like. Unexpectedly, an even larger group of neurons in M1 (44 out of 88) displayed changes in activity that were related to the direction of wrist movement in space independent of the pattern of muscle activity that generated the movement. Thus, both "muscles" and "movements" appear to be strongly represented in M1.

Kalaska, J. F., D. A. D. Cohen, M. L. Hyde, and M. Prud'homme. "A Comparison of Movement Direction-Related Versus Load Direction-Related Activity in Primate Motor Cortex, Using a Two-Dimensional Reaching Task." J. Neurosci. 9 (1989): 2080-2102.

PubMed abstract:  Shoulder joint-related motor cortex cells show continuously graded changes in activity, centered on a preferred movement direction, during active arm movements in 8 directions away from a central starting position (Georgopoulos et al., 1982). We demonstrate here that many of these cells show similar large continuously graded changes in discharge when the monkey compensates for inertial loads which pull the arm in 8 different directions. These load-dependent discharge variations are typically unimodal, centered on one load direction called the cell's load axis, and are often sufficiently continuous, symmetric, and broad as to show a good fit to a sinusoidal curve. A vectorial representation of cell activity indicates that the pattern of load-dependent activity changes in the population forms a signal whose direction is appropriate to compensate for the loads. The responses of single cells to different combinations of movement and load direction are often complex. Nevertheless, the mean activity of the sample population under any condition of movement direction and load direction can be described reasonably well by a simple linear summation of the movement-related discharge without any loads, and the change in tonic activity of the population caused by the load, measured prior to movement. The strength of the load-dependent discharge variation differs among cells. Cells can be sorted into 2 phasic and 2 tonic groups that show differing degrees of sensitivity to loads. In particular, it was found that the greater the degree of cell discharge variation associated with different actively maintained limb postures, the greater the activity changes caused by loads. No similar correlation was found for the degree of discharge variation during movement. Preliminary evidence suggests that phasic and tonic cell groups may be spatially segregated in the motor cortex. These observations are consistent with the idea that there exists in the motor cortex activity encoding aspects of movement kinematics, as well as movement dynamics. These observations are in agreement with studies of more distal arm joints, showing that the activity of certain motor cortex cells varies with the patterns of muscle activity and output forces required to produce a movement. These experiments extend the description of the control of the direction of movement of a multiple degree-of-freedom joint into the spatial (direction) domain to a greater extent than previously achieved.

Kalaska, J. F., S. H. Scott, P. E. Cisek, and L. Sergio. "Cortical Control of Reaching Movements." Curr. Opin. in Neurobiol. 7 (1997): 849-859.

PubMed abstract:  Recent studies provide further support for the hypothesis that spatial representations of limb position, target locations, and potential motor actions are expressed in the neuronal activity in parietal cortex. In contrast, precentral cortical activity more strongly expresses processes involved in the selection and execution of motor actions. As a general conceptual framework, these processes may be interpreted in terms of such formalisms as sensorimotor transformations and 'internal models'.

Krakauer, J. and C. Ghez. "Voluntary Movement." In Principles of Neural Science. 4th ed. Edited by E. R. Kandel, J. H. Schwartz, and T. M. Jessell. New York: McGraw-Hill, 2000, pp. 756-781.

Moran, D. W., and A. B. Schwartz. "Motor Cortical Activity During Drawing Movements: Population Representation During Spiral Tracing." J. Neurophysiol. 82 (1999): 2693-2704.

PubMed abstract:  Monkeys traced spirals on a planar surface as unitary activity was recorded from either premotor or primary motor cortex. Using the population vector algorithm, the hand's trajectory could be accurately visualized with the cortical activity throughout the task. The time interval between this prediction and the corresponding movement varied linearly with the instantaneous radius of curvature; the prediction interval was longer when the path of the finger was more curved (smaller radius). The intervals in the premotor cortex fell into two groups, whereas those in the primary motor cortex formed a single group. This suggests that the change in prediction interval is a property of a single population in primary motor cortex, with the possibility that this outcome is due to the different properties generated by the simultaneous action of separate subpopulations in premotor cortex. Electromyographic (EMG) activity and joint kinematics were also measured in this task. These parameters varied harmonically throughout the task with many of the same characteristics as those of single cortical cells. Neither the lags between joint-angular velocities and hand velocity nor the lags between EMG and hand velocity could explain the changes in prediction interval between cortical activity and hand velocity. The simple spatial and temporal relationship between cortical activity and finger trajectory suggests that the figural aspects of this task are major components of cortical activity.

Reina, G. A., D. W. Moran, and A. B. Schwartz. "On the Relationship Between Joint Angular Velocity and Motor Cortical Discharge During Reaching." J. Neurophysiol. 85 (2001): 2576-2589.

PubMed abstract:  Single-unit activity in area M1 was recorded in awake, behaving monkeys during a three-dimensional (3D) reaching task performed in a virtual reality environment. This study compares motor cortical discharge rate to both the hand's velocity and the arm's joint angular velocities. Hand velocity is considered a parameter of extrinsic space because it is measured in the Cartesian coordinate system of the monkey's workspace. Joint angular velocity is considered a parameter of intrinsic space because it is measured relative to adjacent arm/body segments. In the initial analysis, velocity was measured as the difference in hand position or joint posture between the beginning and ending of the reach. Cortical discharge rate was taken as the mean activity between these two times. This discharge rate was compared through a regression analysis to either an extrinsic-coordinate model based on the three components of hand velocity or to an intrinsic-coordinate model based on seven joint angular velocities. The model showed that velocities about four degrees-of-freedom (elbow flexion/extension, shoulder flexion/extension, shoulder internal/external rotation, and shoulder adduction/abduction) were those best represented in the sampled population of recorded activity. Patterns of activity recorded across the cortical population at each point in time throughout the task were used in a second analysis to predict the temporal profiles of joint angular velocity and hand velocity. The population of cortical units from area M1 matched the hand velocity and three of the four major joint angular velocities. However, shoulder adduction/abduction could not be predicted even though individual cells showed good correlation to movement on this axis. This was also the only major degree-of-freedom not well correlated to hand velocity, suggesting that the other apparent relations between joint angular velocity and neuronal activity may be due to intrinsic-extrinsic correlations inherent in reaching movements.

Sabes, P. "The Planning and Control Of Reaching Movements." Curr Opin Neurobiol. 10 (2000): 740-746.

PubMed abstract:  The notion of internal models has become central to the study of visually guided reaching. Armed with this theoretical framework, researchers are gleaning insights into long-standing problems in the field, such as the ability to respond rapidly to changes in the location of a reach target and the fine control of the multi-joint dynamics of the arm. A key factor in these advances is our increased understanding of how the brain integrates feedforward control signals, sensory feedback, and predictions based on internal models of the arm.

Scott, S. H., and J. F. Kalaska. "Reaching Movements With Similar Hand Paths But Different Arm Orientations. I. Activity Of Individual Cells In Motor Cortex." J. Neurophysiol. 77 (1997): 826-852.

PubMed abstract:  This study shows that the discharge of many motor cortical cells is strongly influenced by attributes of movement related to the geometry and mechanics of the arm and not only by spatial attributes of the hand trajectory. The activity of 619 directionally tuned cells was recorded from the motor cortex of two monkeys during reaching movements with the use of similar hand paths but two different arm orientations, in the natural parasagittal plane and abducted into the horizontal plane. Nearly all cells (588 of 619, 95%) showed statistically significant changes in activity between the two arm orientations [analysis of variance (ANOVA). P < 0.01]. A majority of cells showed a significant change in their overall level of activity (ANOVA, main effect of task, P < 0.01) between arm orientations before, during, and after movement. Many cells (433 of 619, 70%) also showed a significant change in the relation of their discharge with movement direction (ANOVA, task x direction interaction term, P < 0.01) during movement, including changes in the dynamic range of discharge with movement and changes in the directional preference of cells that were directionally tuned in both arm orientations. Similar effects were seen for the discharge of cells while the monkey maintained constant arm postures over the different peripheral targets with the use of different arm orientations. Repeated data files from the same cell with the use of the same arm orientation showed only small changes in the level of discharge or in directional tuning, suggesting that changes in cell discharge between arm orientations cannot be explained by random temporal variations in cell activity. The distribution of movement-related preferred directions of the whole sample differed between arm orientations, and also differed strongly between cells receiving passive input predominantly from the shoulder or elbow. The electromyographic activity of most prime mover muscles at the shoulder and elbow was also strongly affected by arm orientation, resulting in changes in overall level of activity and/or directional tuning that often resembled those of the proximal arm-related motor cortical cells. A mathematical model that represented movements in terms of movement direction centered on the hand could not account for any of the arm-orientation-related response changes seen in this task, whereas models in intrinsic parameter spaces of joint kinematics and joint torques predicted many of the effects.

Scott, S. H., L. E. Sergio, and J. F. Kalaska. "Reaching Movements With Similar Handpaths But Different Arm Orientations. II. Activity of Individual Cells in Dorsal Premotor Cortex and Parietal Area 5." J. Neurophysiol. 78 (1997): 2413-2426.

PubMed abstract:  Reaching movements with similar hand paths but different arm orientations. II. Activity of individual cells in dorsal premotor cortex and parietal area 5. J. Neurophysiol. 78: 2413-2426, 1997. Neuronal activity in primary motor cortex (MI) is altered when monkeys make reaching movements along similar handpaths at shoulder level with two different arm orientations, either in the natural orientation with the elbow positioned below the level of the shoulder and hand or in an abducted orientation with the elbow abducted nearly to shoulder level. The present study examines to what degree two other cortical areas, the dorsal premotor (PMd) and parietal area 5, also show modulation of cell activity related to arm geometry during reaching. The activity of most (89%) of the 207 cells in PMd recorded while monkeys made reaching movements showed a statistically significant change in activity between orientations [analysis of variation (ANOVA), P < 0.01]. A common effect of arm orientation on cell activity was a change in the overall level of discharge either before, during, and/or after movement (67%, ANOVA, task main effect, P < 0.01). Many cells (76%) showed a statistical change in their response to movement direction (ANOVA, task x direction interaction term, P < 0.01), including changes in dynamic range and changes in the preferred direction of cells that were directionally tuned in both arm orientations. Overall, these effects were similar qualitatively but not as strong quantitatively as those observed in MI. A sample of cells was recorded in area 5 of one monkey. Most (95%) of the 79 area 5 cells showed a change in activity when reaching movements were performed using different arm orientations (ANOVA, P < 0.01). As in PMd and MI, many area 5 cells (56, 71%) showed changes in their tonic discharge before, during, and/or after movement, and 70 cells (89%) showed changes in their response to movement direction (ANOVA, task x direction interaction term, P < 0.01). The observed changes in neuronal activity related to posture and movement in MI, PMd and area 5 demonstrate that single-cell activity in these cortical areas is not simply related to the spatial attributes of hand trajectory but is also strongly influenced by attributes of movement related to arm geometry.

Sergio, L. E., and J. F. Kalaska. "Changes in the Temporal Pattern of Primary Motor Cortex Activity in a Directional Isometric Force Versus Limb Movement Task." J. Neurophysiol. 80 (1998): 1577-1583.

PubMed abstract:  We recorded the activity of 75 proximal-arm-related cells in caudal primary motor cortex (MI) while a monkey generated either isometric forces or limb movements against an inertial load. The forces and movements were in eight directions in a horizontal plane. The isometric force generated at the hand increased monotonically in the direction of the target force level. The force exerted against the load in the movement task was more complex, including a transient decelerative phase during the movement as the hand approached the target. Electromyographic (EMG) activity of proximal-arm muscles reflected the task-dependent changes in dynamics, showing a ramp increase in activity during the isometric task and a reciprocal triphasic burst pattern in the movement task. A sliding 50-ms window analysis showed that the directionality of the EMG, when expressed in hand-centered spatial coordinates, remained stable throughout the isometric ramp but often showed a significant transient shift during the limb movements. Many cells in M1 showed corresponding significant changes in activity pattern and instantaneous directionality between the two tasks. This momentary dissociation of discharge from the directional kinematics of hand displacement is evidence that the activity of many single proximal-arm related M1 cells is not coupled only to the direction and velocity of hand motion.

------. "Systematic Changes in Directional Tuning of Motor Cortex Cell Activity With Hand Location in the Workspace While Generating Static Isometric Forces in Constant Spatial Directions." J. Neurophysiol. 78 (1997): 1170-1174.

PubMed abstract:  We examined the activity of 46 proximal-arm-related cells in the primary motor cortex (MI) during a task in which a monkey uses the arm to exert isometric forces at the hand in constant spatial directions while the hand is in one of nine different spatial locations on a plane. The discharge rate of all 46 cells was significantly affected by both hand location and by the direction of static force during the final static-force phase of the task. In addition, all cells showed a significant interaction between force direction and hand location. That is, there was a significant modulation in the relationship between cell activity and the direction of exerted force as a function of hand location. For many cells, this modulation was expressed in part as a systematic arclike shift in the cell's directional tuning at the different hand locations, even though the direction of static force output at the hand remained constant. These effects of hand location in the workspace indicate that the discharge of single MI cells does not covary exclusively with the level and direction of force output at the hand. Sixteen proximal-arm-related muscles showed similar effects in the task, reflecting their dependence on various mechanical factors that varied with hand location. The parallel changes found for both MI cell activity and muscle activity for static force production at different hand locations are further evidence that MI contributes to the transformation between extrinsic and intrinsic representations of limb movement.

Thach, W. T. "Correlation of Neural Discharge with Pattern and Force of Muscular Activity, Joint Position, and Direction of Intended Next Movement in Motor Cortex and Cerebellum." J. Neurophysiol. 41 (1978): 654-676.

PubMed abstract:  . Monkeys were trained to grasp a rod movable in a horizontal arc (Fig. 1), and to hold the rod by angulation of the wrist in each of three positions (A,B, C). A maintained load was placed on the rod alternately to oppose flexion and extension. At a light signal, the monkey had to move to the next position in a prescribed sequence (ABCBABCBA, ETC.). The task was designed to dissociate, while holding in position, the following variables: 1) pattern of muscular activity in the forearm required to hold the wrist in position, determined by the direction of the load (flexor or extensor muscles); 2) position of the rod, and thus angulation of the wrist joint (A, B, and C); and 3) set for the direction of the intended next movement (flexor or extensor). These variables are subsequently referred to as MPAT, JPOS, and DSET, respectively. 2. After training, recordings were made of the EMG activity of muscles used in the task and of the discharge of single neurons in the motor cortex of the cerebrum and the interposed and dentate nuclei of the cerebellum. 3. While holding the wrist in position, EMG and interpositus behaved uniformly, with higher discharge frequency under load in one direction and lower discharge frequency under load in the opposite direction. This relation was relatively independent of the position held and of the direction of the intended next movement. Thus, interpositus and EMG both seemed best related to the MPAT variable, as opposed to JPOS and DSET variables. By contrast, neurons in motor cortex and in dentate fell into three categories: one category discharged in relation to the pattern of muscular activity (MPAT), a second to the position of the wrist (JPOS), and a third to the direction of the intended next movement (DSET). While MPAT neurons formed a distinct dissociated group, neurons that were best related to JPOS were often related to DSET, and vice versa. 4. A few of the MPAT neurons in interpositus and motor cortex were further studied by varying the magnitude (as well as the direction) of the loads. Both interpositus and motor cortex MPAT neurons changed firing frequency in relation to the magnitude of load, and though few neurons were thus studied, the relation seemed clearer for interpositus than for motor cortex. 5. Anatomically, the three types of neurons thus classified by firing pattern during the hold periods were intermixed in the arm area of motor cortex. In dentate and interpositus, those neurons thus related to the performance were localized to a narrow strip across the posterior part of both nuclei. Neurons apparently related to eye and drinking movements were located more posteriorly still, suggesting somatotopic representation.