Interactions between motor commands and somatic perception in sensorimotor cortex

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Interactions between motor commands and somatic perception in sensorimotor cortex Randall J Nelson For many years, it has been postulated that interactions between motor commands and somatic perception in the sensorimotor cortices exist, but they have been difficult to demonstrate. Recent studies have made demonstration of this interaction easier and suggest that cortical activity related to somatic sensation and perception is modified by movement-generating mechanisms. Corollary discharge and efference copy may also play a role in motor behavior.

Addresses Department of Anatomy and Neurobiology, University of Tennessee, 875 Monroe Avenue, Memphis, Tennessee 38163, USA; e-mail: rnelson@utmeml .utmem.edu Abbreviations cingulate motor cortex CM fMRI functional magnetic resonance imaging GABA ~aminobutyric acid primary motor cortex MI parietal cortex PA premotor cortex PM regional cerebral blood flow rCBF SI primary somatosensory cortex somatosensory evoked potential SEP supplementary motor area SMA transcranial magnetic stimulation TMS

Current Opinion in Neurobiology 1996, 6:801-810 © Current Biology Ltd ISSN 0959-4388

Introduction "We assume that each voluntary movement, or change of posture, involves not only the downward discharge to the peripheral effectors, but a simultaneous central discharge from motor to sensory systems preparing the latter for those changes that will occur as a result of the intended movement" [1]. This statement, made by Teuber in the mid 1960s, illustrates the need to realize the inextricable relationship between the central control of m o v e m e n t and the peripheral re-afference generated by them. Using terms previously defined in the literature [2,3], the simultaneous central discharge can be called efference copy, as the term was used by von Hoist and Mittelstaedt [4]. T h e comparison of efference copy with sensory information results in corollary discharge, as suggested by Sperry [5]. Efference copy and corollary discharge in the oculomotor [6°° ] and electrosensory processing [7] systems have recently been discussed in extensive reviews. Here, consideration of these concepts will be limited to what might occur in the primary motor cortex (MI) and primary somatosensow cortex (SI),

portions of the parietal cortex (PA), the premotor cortex (PM), and the cingulate motor cortex (CM), along with the supplementary motor area (SMA); see Figure 1. Most of the recent studies mentioned below have been concerned with effects localized to these regions. Matthews [8] suggests that efference copy results in corollary discharges that modulate sensory responsiveness, thus improving motor control. Paraphrasing his thoughts on these processes, regions involved should receive signals upon the issuance of motor commands. Thus, the effects of corollary discharges should be evident at about the same time as initiation of movement. In this scenario, corollary discharges are produced only if the motor commands must interact with unwanted (n.b. here interpreted to be redundant or competitive) sensory inputs and may vary with the properties of the sensory inputs. Finally, multiple types of corollary discharges may occur simultaneously. When a corollary discharge interacts with afferent inputs, some sensations leading to perceptions may be suppressed, whereas others may be facilitated. Evidence for the influence of motor commands over sensory responsiveness has been somewhat indirect, although recent technological and conceptual advances have provided further clarification of this issue. In this review, I consider the modulation of cortical activity during actual or imagined m o v e m e n t and the mimicry of motor commands by stimulation, which I will do in light'of recent clinical and experimental observations. Activity at 'about the same time' as initiation of movement If motor commands interact with sensory inputs at the cortical level, then both motor and sensory cortical neurons should show activity changes when these commands are i s s u e d - - t h a t is, just before movement. Non-primary and primary motor cortices are activated before movement. In monkeys, the firing rate of CM neurons increases before the animal increases its grip force or isometric pinching [9"]. In humans, the SMA is not active during simple repetitive movements or during median nerve stimulation, but it is active when subjects suppress a pre-cued but invalid and moderately complex m o v e m e n t sequence before it occurs [10"]. Activity changes in the SMA typically occur about lOOms after go-cues, thus preceding movement by as much as several hundred milliseconds. PM and SMA neurons respond to transitions in the phases of tasks involving m o v e m e n t preparation and execution. Transitional responses are more c o m m o n in PM than in the SMA [11].

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Figure 1 Schematic diagram of some of the telencephalic connections of the sensorimotor regions of the cortex and basal ganglia. (Compiled from [g°,22,23,24°,78].) In general, on the horizontal face of each block is the designation(s) commonly given to the region based on physiology. On the vertical faces are designations based on anatomy. The numbers represent cortical areas. In the upper tier, the non-primary somatosensory and motor cortices discussed within the text are depicted to the right and left of the dotted line representing the central sulcus. These regions are reciprocally interconnected with each other and with the corresponding primary cortical region. MI and SI are also reciprocally interconnected, although the connection from MI to area 3b is species-dependent [22]. Area 2 and the area 5 portions of PA provide a major input to MI (area 4). PM and CM, along with SMA, make up the non-primary motor cortices. Below, the striatum (STR; primarily the putamen in this instance), the subthalamic nucleus (STN) and the pallidum, consisting of internal (i) and external (e) globus pallidus (GP) segments (see [Tg]), are depicted. Circles containing crosses represent routes by which sensory and motor signals may converge, Convergence sites include each non-primary cortical region by virtue of interconnections with one another, primary cortices by the same interconnection scheme and the non-primary cortices with the primary cortex on the opposite side of the central sulcus. Other possible sites of interaction are the STR, because the massive convergence of sensory and motor cortical inputs occurring there [78], and the STN, although the contribution from the sensory cortices is still debated (light gray arrow).

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MI neuronal activity precedes movement, in keeping with its major contribution to the corticospinal tract, and this activity varies in polarity and amplitude as a function of intended response direction [12 °°] and current limb posture [13]. MI activity also varies with the behavioral requirements for, and knowledge of, the direction, extent and force of the intended m o v e m e n t [13,14",15,16°]. Multiple activation foci in MI are often found for a given movement, suggesting a distributed network representing each movement [17°']. This distributed m o v e m e n t representation, however, could indicate that one region controls movement while another funnels suppression to other sites. Ipsilateral, as well as contralateral, MI is activated with hand and finger manipulations [18]. T h e activity of precentral neurons, as was shown previously for SI neurons [19], is shaped by intracortical GABAergic transmission [20,21]. T h e

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precentral cortical regions have abundant interconnections with postcentral cortices [22,23,24 °] (Figure 1). In addition to their subcortical connections, precentral regions receive information about task-related sensory events from the sensory cortices. Therefore, precentral regions have the capacity to modulate the activity of neurons in postcentral cortices after having received sensory information. Recent studies do not provide a consensus about how frequently SI and PA neurons fire preceding movement. SI neuronal responses to sustained peripheral inputs change before initiation of m o v e m e n t [25,26°,27°]; some changes occur well before electromyographic activity (EMG) onset, whereas others happen close enough to it that re-afference from the periphery cannot be ekcluded. SI neurons with forelimb tactile receptive fields may show 'proprioceptive-like' activity during visually cued active

Motor commands and sensorimotor cortex Nelson

movements, even when direct contact of the receptive fields with external surfaces is avoided [28]. Under some conditions, however, a few SI neurons are active before the first measurable limb displacement, suggesting that it is unlikely that there is a central source for task-related activity changes [29]. Under these conditions, the activity of area 3b, which receives sparse precentral connections, is commonly greater than in area 1, which receives input from MI, although areas 3b and 1 receive very similar thalamic input. This activity may indicate that area 1 neurons are more likely than area 3b neurons to be suppressed by motor commands issued before movements are made. PA neurons and, to some extent, SI neurons receive information about both complex stimuli and impending movements. Romo and co-workers [30*] suggest that SI neurons represent the direction of moving stimuli in their population code. Groups of PA neurons appear to maintain representations of possible motor responses to external stimuli [31**,32°]. PA activity 'develops' selectivity to movement parameters after go-cues but before the initiation of movement [16"]. This selectivity may be regulated by the MI because ablation of area 4 causes a substantial increase in the number of neurons showing early premovement activity changes in area 5 [33]. T h e balance of excitatory/inhibitory input has been shown to differ for different somatosensory cortical regions while subjects await peripheral stimuli [34°°]. The SI displays increases in magnetically recorded potentials following intermittent stimuli when compared with standards, but no further increases when intermittent stimuli are presented without intervening standards. T h e PA displays increases in the first instance and a further activity enhancement when the intermittent stimuli are given by themselves. Several functional roles for sensorimotor cortical neurons have recently been suggested or reiterated. T h e CM may participate in motor control by facilitating the execution of appropriate responses and/or suppressing the execution of inappropriate ones [35]. T h e responses to instruction stimuli and sequences of impending movements are more common in the SMA than in the CM [11]. Sadato and colleagues [36*°,37] have shown that regional cerebral blood flow (rCBF) in the SMA and CM is at the highest level at the slowest performance rates, and it decreases as performance rates increase. T h e y suggest that the rCBF decrease in the SMA/CM may indicate a change from reactive to predictive performance. Since the SMA is selectively activate when previously programmed movements must be aborted, the SMA may inhibit motor activity [10*°]. PM neurons display both tonic and phasic activity patterns that co-vary with movement preparation rather than with sustained postures [14°°,15,16°,31°°]. Precentral and PA neuronal activity commonly precedes movement execution, in keeping with the role of the former in movement generation, but also suggesting

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that motor commands transmitted to the PA at the same time could alter sensory responses and perceptions. Simultaneous activation of MI and SI occurs during most behaviors and during sensorimotor ideation [38*]. T h e selective activation of the precentral sensorimotor cortices before movements, and their connections with postcentral cortices suggest they could play a role in early modification of preprogrammed behaviors and modulation of sensory inputs in unpredictable situations. T h e effect of motor commands on SI neurons, however, have not been demonstrated unequivocally. Multiple activation loci and resolution limitations of imaging techniques make precise localization of cortical representations of motor commands and their effects on representations of sensations in humans difficult. Relatively good correspondence exists, however, between functional magnetic resonance imaging (fMRI) and electrophysiological localization of the hand region of sensorimotor cortex [39°]. This correspondence facilitates comparison between clinical and experimental studies. Thus, we must look to clinical observations as well as other animal studies for additional evidence that alterations in cortical activity at about the time of movement accompany changes in somatic perception. This consideration is reasonable in light of the homology between the sensorimotor cortices in macaques and humans [40]. Modulation of somatic sensation and perception Simultaneous stimulation of regions of the sensory periphery by behavior may result in attenuation of somatic sensation and perception. The same is true for experimentally induced stimulation. Within a step cycle, somatic perception is facilitated during the middle and late parts of the swing phase, whereas it is attenuated during the stance phase [41°°]. Schnitzler et al. [42 °°] have demonstrated that active exploration reduces the amplitude of early components of somatosensory evoked fields recorded magnetically. T h e y have also shown that active movement around imaginary objects attenuates somatosensory evoked fields. These authors suggest that attenuation results when a motor command is issued and movements are made even though the movements do not cause significant tactile stimulation. Tactile interference alone (stimulation of other than the target digit) was ineffective in attenuating some somatosensory evoked potential (SEP) components. Moreover, they suggested that alterations of parietal P27 (equivalent to P25 of [43°]) and frontal P22 and N30 components resulted from gating of SI by MI.

Cohen et al. [44] have shown that simultaneous stimulation of two adjacent, as compared with two separated, fingers results in significant attenuation of certain SEP components. These authors describe the attenuation of a patient's tactile perceptions for one digit when the cortical representation of an adjacent finger is electrically

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stimulated. Hsieh and co-workers [43"] have demonstrated that the N20 (area 3b) component of the SEP is not attenuated by simultaneous stimulation of adjacent digits, whereas P25 (area 1) shows the largest attenuation. Some attenuation of P22 (MI) and P17 (thalamus) was observed in this study. However, the cuneate N16 and P35 potentials were not significantly altered. These authors provide convincing evidence that the modulation of SEPs during exploratory finger movements occurs predominantly in SI. Transcranial magnetic stimulation (TMS) may mimic motor commands by activating MI output neurons. TMS delivered over the cortex from 200ms before until just after a peripheral stimulus attenuates its detection [44]. The effect is maximal 0-20ms after peripheral stimulus presentation and is optimal if located over the precentral cortical region that produces very small but reproducible contractions of muscles in the target finger. TMS can block detection of peripheral inputs when delivered at about the time or slightly after electrical stimulation of a finger [45]; the block is still present 50 ms post-stimulus. Peripheral stimulation just before TMS activates the motor cortex and causes facilitation of motor cortical activity, as measured by facilitation of the H-reflex [46"]. This facilitation may also indicate the need for a premovement suppression mechanism. If movements of appropriate extent and direction are to be made, inputs that would non-selectively facilitate MI output may be unwanted and, thus, need to be eliminated. MI excitability to TMS increases when subjects observe actions performed by another [47"]. The pattern of muscle activation evoked by TMS during observation is similar to that occurring when the subjects execute the same action. However, MI excitability to TMS is suppressed by TMS stimulation of the dentato-thalamo-cortical pathway [48]. Attenuation of somatic perception and/or cortical activity occurs when tested with natural (tactile) stimuli. In areas 3b and 1, evoked potentials to air puffs are reduced in a non-specific manner during isometric and isotonic contractions [49]. However, isometric compared with isotonic muscular contractions may actually have a relatively minor effect on the perceived intensity of peripheral stimuli [50]. Decreases evoked potentials to air puffs were observed in areas 3b and 1 following intracortical microstimulation in quiescent monkeys [51]. $I neuronal responses to air puffs are 'gated out', on average, at about 66ms before movement [52]. Thus, under certain conditions, sensory inputs are attenuated before and during motor outputs, independent of whether or not movements are actually executed in conjunction with the issuance of motor commands.

Facilitation and s u p p r e s s i o n Directing attention toward or away from the location of somatic stimuli alters perception. Attention directed toward an expected vibrotactile stimulus results in a

significant increase in SI rCBF [53]. Decreases in rCBF occur in the ipsilateral SI representation of the same body part where the stimulus is expected. Contralaterally, decreases occur in SI representations of peripheral sensory surface where behaviorally important stimuli are not expected [54°°]. Rhythmic cortical activity may underlie distributed information processing of multiple sensory attributes in groups of neurons [55]. Disruption of rhythmic activity, therefore, could indicate gating of perceptions. Recent work by Salmelin and Hari [56] has demonstrated that reductions in rhythmic activity are greater during voluntary movements than during those triggered by external sources. On the basis of timing and recording location, these authors suggest that the 10 Hz component of human cortical rhythmic (mu) activity represents a true somatosensory rhythm, whereas the 20 Hz component may be somatomotor in origin. The 10 Hz and 20 Hz components are thought to occur when subjects are ready to receive new sensory inputs. During thumb movements, the 10 Hz and 20 Hz components are strongly suppressed. Another study has shown that PA mu rhythm amplitude in the below 20Hz range drops before reaching movements [57]. PM is the source of the greatest power in the 20Hz spectrum and is thought to drive MI and PA into rhythmic activity via cortico-cortical connections. Rhythms in the 20-25 Hz range, which have maximal amplitude during motor preparation, become minimal with movement execution. Motor preparation and focused attention on the periphery, independent of whether movements are actually made, cause increases in 30 Hz to 50 Hz synchronous activity in the hand region of SI contralateral to the attended peripheral location [58]. Recordings made simultaneously at several levels of the somatosensory system have led to new interpretations of rhythmic activity and its relationship to sensory perception [59"']. Using rat whisker movements as a model, Nicolelis et al. [59"'] have suggested that mu-like rhythmic activity cannot be caused by re-afference. This is because mu rhythms occur before whisker movements and after whisker removal, and they are not present in the first-order or primary second-order sensory relays. Rhythmic activity does, however, predict the imminent onset of low amplitude whisker twitches and mimics a motor output function. A transient sensory facilitation accompanies these rhythms as well as whisker protractions. Thalamic neurons and dorsal column nuclei neurons temporally lag the cortex in developing rhythmicity. SI and MI rhythms occur at about the same time (MA Nicolelis, personal communication). The observations discussed above suggest that both facilitation and suppression of sensation and perception occur before expected sensory events and the motor responses to them. Missing from the literature are demonstrations from single-cell recordings that unwanted or redundant sensations are suppressed while, at the same

Motor commands and sensorimotor cortex Nelson

time, behaviorally significant ones are facilitated before movement. Two bits of evidence from our laboratory suggest that facilitation and suppression occur. First, the fidelity with which SI neurons represent sustained vibrotactile stimuli decreases, although mean firing rates increase before movement [25]. Peripheral vibration can interfere with movement accuracy by activating proprioceptors. Second, some, but not all, neurons having both sensory-related and motor-related premovement activity show a decrease of the latter activity when sustained vibrotactile stimuli are presented but an increase when it is not [33,60]. This suppression varies with movement direction and receptive field type (cutaneous or deep) for area 1 but not for area 3b neurons. Thus, sensory inputs that might interfere with proprioceptive monitoring of movement are suppressed just before movement. This suppression might happen especially for movements made in the predictive versus the reactive mode, although this prediction was not tested. In predictive mode, comparisons are probably made between motor commands and internal signals rather than externally generated sensations when assessing outcome (see below).

Deficits resulting from altered comparisons of motor commands and sensations Recent reports demonstrate that proprioceptive information is important, but not absolutely essential, for initiating movement, assessing outcome, and determining errors. Deafferented patients use visual cues to update their reference about current limb position [61]; without visual cues, performance suffers. It has been suggested that patients perhaps cannot generate corrective signals resulting from the comparison of afferent and efferent signals [62",63",64]. Aglioti et al. [62"] have shown that when patients are deafferented as a result of cortical lesions, they may use mental imagery to compensate for the lack of sensory inputs to compare with motor commands. In a structured environment with predictable outcomes, patients can reduce the need for proprioceptive updating [63"].

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of the feedforward motor command is dependent on the brevity of the visuo-motor memory, however, the accuracy in the control of amplitude and end position of wrist movements is soon compromised as the memory requirements for the movements increase [68]. Strategies that patients adopt to ameliorate deficits accompanying Parkinson's disease and deafferentation are similar. There is an unusually heavy reliance on visual information. Active and imposed movements without visual guidance are equally hypometric, which suggests that kinesthesia rather than corollary discharge is deficient in Parkinson's disease [69"]. Parkinson's disease results in decreased intracortical inhibition, which can be improved with pharmacological agents. Decreased intracortical inhibition may result in a loss of selectivity of cortical discharges during movement [70]. SMA and CM are involved in selecting which movements are to be made next. In Parkinson's disease, akinesia may result from SMA and CM not receiving appropriate input from the basal ganglia [71]. Cheron et al. [72] demonstrated that patients with Parkinson's disease exhibit a reduced SEP N30 that can be elevated by apomorphine. N30 is thought to reflect the activity of modulatory loop control exerted by the basal ganglia on the SMA, frontal lobes and MI. However, under some conditions, patients with Parkinson's disease still exhibit SEP gating comparable to normal subjects. T h e authors discuss a number of other studies in which gating is significantly reduced. Focal dystonia is correlated with a reduction of sensorimotor cortical SEPs during the premotor period [73]. T h e motor cortical potential is abnormally low, whereas the N30 of the SEP is enhanced. Moreover, this study also suggests that abnormal MI activation may result in abnormal co-contraction and an overflow of muscle activation, as is typical in dystonia. It remains unclear whether the basal ganglia participate in sensory gating via their influence over the motor cortices. Basal ganglia output is unlikely to be the source of the initial command to move but is more likely involved in preparing motor areas for forthcoming movements [74]. One type of preparation may be to regulate sensory information inflow.

Compensation may occur rapidly if patients are given sufficient 'Knowledge of Results' (i.e. feedback about performance) [65], which suggests that efference copy can be linked with inputs from other modalities to produce error signals (corollary discharge). Compromised 'Knowledge of Results' without proprioception jeopardizes the effectiveness of the efference copy [66]. This same group of authors [63 °] found that improved spatial accuracy in pointing is correlated with sparing of more posterior regions of SI, suggesting a site of action.

Future directions- models for actions and sites of comparison between motor commands and sensations

However, no significant increases in rCBF in sensorimotor cortex, as a whole, accompany movement made during transient deafferentation when compared with pre-deafferentation measurements [67"]. T h e lack of a net change could result from increased MI activation accompanying decreases SI activation. If the utilization

Recently, models of sensorimotor integration have been proposed or reviewed that incorporate corollary discharge and efference copy ([75-77]; see also [14"']). Several of the features of these models have been compiled in Figure 2. One general feature is a mechanism for comparing 'intended' and 'actual' behavioral outcome that generates an error signal if there is a mismatch. Other

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Figure 2 Graphic representation of some common features of recent models of sensorimotor Proprioceptive/tactile integration. Most models postulate that an error signal is generated by a comparator (circle containing cross), having as its inputs a signal representing the 'intended movement' (motor command) and a signal representing the 'actual movement' that is either being made or the probability that if made, it can be executed according to plan [75,76]. The output of the comparator provides an error signal when there is a mismatch between the two inputs. The 'actual movement' signal may be provided by proprioceptive/tactile input from the periphery. This sensory signal is summed (T_.)with internal feedback (e.g. from visual information [75] and/or central representations of impending movements [31 °°,32"]) when control is in 'closed-loop' mode [76] or reactive mode [36"]. In predictive mode, the gain (g) of the sensory input signal may be lowered so that internal signals provide the majority of the 'actual movement' signal. The gain of peripheral input signals © 1996CurrentOpinion in Neurobiology may also be modulated by attentional mechanisms (see e.g. [53,54°°]). In predictive mode, sensory signals may be gated in or out depending on whether they are behaviorally relevant. Sensory inputs may also modulate the gain of motor commands [46°]. Deficits in external signal utilization may be overcome if conditions are predictable [63 °] and adequate 'Knowledge of Results' [65], as a type of internal feedback, is provided.

feature are switching between reactive and predictive modes and attentional control of sensory input gain. For new behaviors, the 'actual' outcome signal results from comparing peripheral feedback and motor commands; this may be indicative of reactive mode. Once behaviors are internalized and outcome is predictive, peripheral feedback may be replaced by internal signals or signals from other modalities such as vision. Most models take into consideration the general notions of differential reliance on sensations and their suppression or facilitation at cortical levels as behavioral constraints allow. T h e s e models also consider neuronal activity representing parameters of intended movements that exist before movements are initiated (e.g. [75]). This latter activity may serve as another form of internally generated feedback that can be substituted for proprioceptive or tactile inputs during movement. Also included in Figure 2 is an attention component that may modulate the gain of sensory inputs to the 'actual m o v e m e n t ' summing junction and the motor command component.

Future studies are needed to establish where and under which conditions the switch is made from relying on proprioception/tactile inputs to internal signals to provide the input to be compared with motor commands. This switching may be seen either as the imposition of, or release from, sensory suppression at different times during

behavior or as correlated activity at sites of sensorimotor convergence. Salinas and Abbott [77] have suggested in their model that information that is not important to network output is eliminated if it is not correlated w i t h the activity of that network. Furthermore, they state that a system may develop invariant responses to combinations of sensory information that are most correlated with its functional role. Demonstrating these phenomena experimentally is one challenge for future work. Another challenge is to determine which of the possible sites of sensorimotor interaction regulate which functions. T h e r e are several sites within the sensorimotor cortices where comparisons between motor commands and sensory inputs may take place (Figure 1). In addition to the sensorimotor cortices, the basal ganglia may be one place where a corollary discharge might occur because there are large regions of overlap between the somatosensory and motor corticostriate projections [78]. T h e basal ganglia may also participate in complex forms of sensorimotor integration (see [79] for a brief review).

Conclusions Returning to the suggestions of Matthews [8] paraphrased earlier, it appears that a diverse group of studies, described briefly above, provides new evidence that motor commands influence somatic perception. Activity changes in sensory cortices occur at about the same time as

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movement-related activity in motor centers. It is possible that these activity changes represent corollary discharges that could be produced from motor commands interacting with unwanted sensory inputs. Certainly, regions of the cortex hold traces of impending movements and receive input from the ascending somatosensory system or the sensory cortices. Sensory responsiveness varies as a function of the location of stimulation with respect to other stimulation sites and attended locations. Motor commands can facilitate or suppress sensory responsiveness and, thus, probably perception, depending on temporal and behavioral constraints. T h e studies mentioned above provide new evidence for the interaction of motor commands and somatic sensations. However, much remains to be done to determine the sites of interactions between motor commands and sensory responses, and the crucial times during movement planning, initiation and execution when these interactions shape perceptions.

Acknowledgements Supported by United States Air Force Grant AFOSR 91-0333.

References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as:

Cadoret G, Smith AM: Input-output properties of handrelated cells in the ventral cingulate cortex in the monkey. J Neurophysio11995, 73:2584-9590. Describes single-unit recordings in monkeys taught to make pinching and gripping movements. The ventral cingulate cortex receives afferent input about 45 ms after it is delivered and shows movement-related activity before a number of behaviors. The role of this region in movement initiation is discussed in light of its connections with the SI and area 5 of the PA. 9. ,

Vidal F, Bonnet M, Macar F: Programming the duration of a motor sequence: role of the primary and supplementary motor areas in man. Exp Brain Res 1995, 106:339-350. The authors recorded event-related potentials in human senso6motor cortex while subjects responded to preparatory information that was either validated or invalidated by subsequent response-generating cues. Their results indicate that the SMA is involved in imposing inhibition on MI when actions must be deprogrammed through response selection. It is reasonable to speculate that the suppression of SI by this mechanism could occur simultaneously. The discussion includes a table listing several articles dealing with the activation of the SMA (or lack thereof) in humans, which was recorded during several tasks. The authors provide arguments for the timing of the onset of motor commands as related to the onset of SMA and MI activity. 10. ••

11.

Teuber H-L: Alterations of perception after brain injury. In Brain and Conscious Experience. Edited by Eccles JC. New York: Springer-Verlag; 1966:182-216.

2.

Evarts EV: Feedback and corollary discharge: a merging of the concepts. In Central Control of Movement. Neurosciences Research Program Bulletin, vol 9, no 1. Edited by Bishop DW, LeBlanc CM. Brookline, Massachusetts: Neuroscienoes Research Program; 1971:86-112.

3.

Miles FA, Evarts EV: Concepts of motor organization. Annu Rev Psycho/1979, 30:327-362.

4.

Von Hoist E, Mittelstaedt H: Das Reafferenzprinzip. Wechselwirkungen zwischen zentralnervensystem und peripherie. Naturwissenschaften 1950, 37:464-476. [Title translation: The reafference principle. Interactions between the central nervous system and the periphery.] [English translation in Zur Verhaltensphysio/ogie bei Tieren und Menschen. The Behavioral Physiology of Animals and Man. The Selected Papers of Erich yon Hoist. Translated by Martin R. London: Methuen; 1973:139-173.]

5.

Sperry RW: Neural basis of the spontaneous optokinetic response produced by visual inversion. J Comp Physiol Psycho/ 1950, 43:482-489.

Bridgeman B: A review of the role of efference copy in sensory and oculomotor control systems. Ann Biomed Eng 1995, 23:409-422. A thorough and insightful review of the control of eye movements by central outflow. Beginning with descriptions of efferenoe copy from a historical perspective, the author delivers nine 'commandments' of efference copy. He then provides evidence for each. One important concept discussed here, but rarely elsewhere, is the notion that cognitively based motor control may only be 'pressed into service' when efference copy is unavailable. Another important concept is the idea that the efference copy system may operate only at low frequencies, which may be why it fails to compensate for changes that occur at faster rates. 5. •.

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Meek J, Grant K: The role of motor command feedback in electrosensory processing. Eur J Morphol 1994, 32:225-234.

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Matthews PBC: Proprioceptors and their contribution to somatosensory mapping: complex messages require complex processing. Can J Physiol Pharmaco11988, 66:430-438.

Mushiake H, Inase M, Tanji J: Neuronal activity in the primate premotor, supplementary motor and precentral motor during visually guided and internally determined sequential movements. J Neurophysiol 1991, 66:705-718.

12. Georgopoulos AP: Current issues in directional motor control. •. TrendsNeurosci 1995, 18:506-510. The author presents a review of the work conducted over the past 15 years that has shaped the thinking about where representations of intended movement directions reside, in what forms they are available, and how this infor* mation may be used by movement-generating mechanisms. The review takes what are at times difficult concepts and presents them in a manner that is both easy to follow and instructive. Of note is the consideration of MI as the crossroad for several different but interactive motor control circuits. 13.

• of special interest == of outstanding interest 1.

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Scott SH, Kalaska JF: Changes in motor cortex activity during reaching movements with similar hand paths but different arm postures. J Neurophysiol 1995, 73:2563-2567.

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Crammond DJ, Kalaska JF: Differential relation of discharge in primary motor cortex and premotor cortex to movements versus actively maintained postures during a reaching task. Exp Brain Res 1996, 108:45-61. The results obtained from recordings made in the PM and MI of monkeys suggest that phasic bursts of PM activity occur mostly before movements but not when postural adjustments are made. MI activity is about equal for both. These findings suggest a major role for the PM in selecting and planning visually guided movements. The discussion includes an extremely well focused evaluation of some current models of motor control. The authors suggest that MI is not functionally homogeneous, but that it is part of a larger rostrocaudal precentral cortical motor control gradient within which multiple aspects of limb movements are processed in parallel. See [17"'] for evidence from imaging studies that several cortical sites are active during the same movement. 15.

Riehle A, MacKay WA, Requin J: Are extent and force independent movement parameters? Preparation- and movement-related neuronal activity in the monkey cortex. Exp Brain Res 1994, 99:56-74.

Riehle A, Requin J: Neuronal correlates of the specification of movement direction and force in four cortical areas of the monkey. Behav Brain Res 1995, 70:1-13. Single-neuron activity recorded in monkey PM, MI, PA, and SI suggests that these regions are activated sequentially as behaviors progress from planning to initiation to execution. Interestingly, for both PA and SI, about half of the neurons had activity changes related to impending movements during the time between the issuance of the movement cue and the start of the movement. 16. •

17. ••

Sanes .IN, Donoghue JP, Thangaral V, Edelman RR, Warach S: Shared neural substrates controlling hand movements in human motor cortex. Science 1995, 268:1775-1777. Using fMRI to measure rCBF, these authors demonstrate in humans that there are multiple sites of activation within MI for all movements tested. When the sites for different movements are compared, some of the sites overlap. This Overlap may mediate multiple motor and cognitive functions, which occur almost simultaneously, suggesting distributed rather than discrete processing during movements. Thus, multiple sites in the sensory cortices may also be influenced via cortical interconnections. 18.

Kim S, Ashe J, Georgopoulos AP, Merkle H, Ellermann JM, Menon RS, Ogawa S, Ugurbil K: Functional imaging of human motor cortex at high magnetic field. J Neurophysiol 1993, 69:297-302.

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19.

Dykes RW, Landry P, Metherate R, Hicks TP: Functional role of GABA in cat primary somatosensory cortex: shaping receptive fields of cortical neurons. J Neurophysiol 1984, 52:1066-1093.

generated corollary discharges "...to interpret the re-afferent input from the limb as movement unfolds." As is typical of these authors, the discussion is thorough, detailed, and extremely thought-provoking.

20.

Matsumura M, Sawaguchi T, Kubota K: GABAergic inhibition of neuronal activity in the primate motor and premotor cortex during voluntary movements. J Neurophysio/1992, 68:692-702.

32. •

21.

Jacobs KM, Donoghue JP: Reshaping the cortical motor map by unmasking latent intracortical connections. Science 1991, 251:944-942

22.

Stepniewska I, Preuss TM, Kaas JH: Architectonics, somatotopic organization, and ipsilateral cortical connections of the primary motor area (M1) of owl monkeys. J Comp Neuro11993, 330:238-271.

23.

Jones EG, Coulter JD, Hendry SHC: Intracortical connectivity of architectonic fields in the somatic sensory, motor and parietal cortex of monkeys. J Comp Neurol 1978, 181:291-348.

24. •

He SQ, Dum RP, Strick PL: Topographic organization of corticospinal projections from the frontal lobe: motor areas on the medial surface of the hemisphere. J Neurosci 1995, 15:3284-3306. This paper describes the organization and connections of the non-primary motor cortices in monkeys. The report describes the contribution of these areas to the corticospinal tract. This article is important for its discussion of these regions in the descending control of movements. 25.

Lebedev MA, Denton JM, Nelson RJ: Vibration-entrained and premovement activity in monkey primary somatosensory cortex. J Neurophysiol 1994, 72:1654-1673.

26. •

Lebedev MA, Nelson R.I: Rhythmically firing (20-50 Hz) neurons in monkey primary somatosensory cortex: activity patterns during initiation of vibratory-cued hand movements. J Comput Neurosci 1995, 2:313-334. Rhythmic activity of presumptive SI interneurons is complementary to quickly adapting SI neurons [60] recorded in monkeys performing vibratory-triggered wrist movements. A model is provided in which phasic and tonic interneurons are involved in tonically inhibiting the output of SI neurons. This model assumes that SI receives direct excitatory inputs from other regions related to changes in phases of behavioral tasks. The input to the circuit proposed was suggested to be from subcortical sources. However, cortico-cortical inputs with similar characteristics, such as those from MI and PA, could provide the necessary input to result in task phase dependent modulation of sensory responsiveness. 27. •

Lebedev MA, Nelson RJ: High-frequency vibratory sensitive neurons in monkey primary somatosensory cortex: entrained and nonentrained responses to vibration during the performance of vibratory-cued hand movements. Exp Brain Res 1996, 111:313-325. These authors describe monkey Sl neurons that fire preferentially to higher frequency stimuli. About half of these neurons decreased firing before movement if peripheral vibratory stimuli were sustained until after movements began. When vibration was not present, the vast majority showed premovement activity increases. This result suggests that although vibratory stimuli activate these neurons, their activity is suppressed before movements. 28.

Cohen DA, Prud'homme MJ, Kalaska JF: Tactile activity in primate somatosensory cortex during active arm movements: correlation with receptive field properties. J Neurophysio/1994, 71:161-172.

29.

Prud'homme MJ, Cohen DA, Kalaska .IF: Tactile activity in primate somatosensory cortex during active arm movements: cytoarchitectonic distribution. J Neurophysio/1994, 71:173-181.

30. •

Ruiz S, Crespo P, Romo R: Representation of moving tactile stimuli in the somatic sensory cortex of awake monkeys. J Neurophysio/1995, 73:525-537. These authors present evidence that the activity of groups of monkey SI neurons can represent the direction of moving tactile stimuli. The magnitude of the population vector varies with stimulus speed. The results suggest that there are dynamically maintained internal representations of the sensory environment that are necessary for higher-order processing. 31. ••

Kalaska JF, Crammond DJ: Deciding not to go: neuronal correlates of response selection in a go/nogo task in primate premotor and parietal cortex. Cereb Cortex 1995, 5:410-428. The authors make several extremely important observations based on their recordings from area 5 in monkeys taught to execute or withhold movements in an instructed delay task. They hypothesize that part of the PA processes somatic and visual information about the location and environmental conditions of behaviorally salient body parts. They suggest that representations of motor responses to external cues reside in PA, whereas representations of intended movements are located in PM. They also suggest that these representations may be accessed when it is necessary to consult centrally

Colby LC, Duhamel JR, Goldberg ME: Oculocantric spatial representation in parietal cortex. Cereb Cortex 1995, 5:470-481. The monkey lateral intraparietal (LIP) cortex undergoes anticipatory remapping, allowing neurons to respond to visual stimuli even before a saccade is made to bring the stimulus into the neuron's receptive field. They also respond to the memory trace of recently flashed stimuli when saccades are made to the location where the stimulus had been. Thus, internal representations of impending movements and remembered stimuli shape LIP neuronal responses. It is probable that the same types of mechanism are functioning in the more somatic sensory part of the PA [31°°]. 33.

Biolac B, Burbaud P, Varoqueaux D: Activity of area 5 neurons in monkeys during arm movements: effects of dentate nucleus lesion and motor cortex ablation. Neurosci Lett 1995, 192:189-192.

34. •.

Fores N, Jousm&ki V, Hari R: Interaction between afferent input from fingers in human somatosensory cortex. Brain Res 1995, 685:68-76. Using a 122-channel magnetometer, these authors recorded somatosensory evoked magnetic fields resulting from expected and intermittent stimuli. Their findings suggest that, in agreement with animal experiments [19], the different excitatory/inhibitory balances are maintained in sensorimotor cortices. This study illustrates the vast potential of this technique because its spatial and temporal resolution is better than other non-invasive methods of recording human evoked potentials. (See also [56].) 35.

Paus T, Petrides M, Evans AC, Meyer E: Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. J Neurophysio/1993, 70:453-469.

36. ••

Sadato N, IbaSez V, Deiber MP, Campbell G, Leonardo M, Hallett M: Frequency-dependent changes of regional cerebral blood flow during finger movements. J Cereb B/ood Flow Metab 1996, 16:23-33. This study describes rCBF measurements made while subjects performed finger movements at various rates. The SMA and anterior cingulate codex display the highest activation at slow rates and a decrease with faster movements. In general, the opposite is true for SI. The authors suggest that these changes in activation reflect progressive changes in performance from reactive to predictive modes. There is an intriguing possibility suggested here, although not directly by the authors. The opposite activation patterns of the SMA and SI and the postulated roles of SMA in response selection and motor inhibition [10 °.] suggest that the SMA could be involved in modulating activity in SI. It is difficult to reconcile these observations with the hypothesis of suppression of sensation during predictive movements, however, unless it is assumed that increased SI rCBF represents increased suppression of inputs. 3?.

Ibahez V, Deiber MP, Sadato N, Toro C, Grissom J, Woods RP, Mazziotta JC, Hallett M: Effects of stimulus rate on regional cerebral blood flow after median nerve stimulation. Brain 1995, 118:1339-1351.

38. •

Sabbah P, Simond G, Levrier O, Habib M, Trabaud V, Murayama N, Mazoyer BM, Briant JF, Raybaud C, Salamon G: Functional magnetic resonance at 1.5 T during sensorimotor and cognitive task. Fur Neurol 1995, 35:131-136. Although the authors consider the results presented in this study to be preliminary, they provide an indication that 'sensorimotor ideation' causes substantial activation of the sensorimotor codices when viewed using fMRI techniques. They also note that mental imagery of visual stimuli activates the primary visual codex. It appears, therefore, that central activation of mechanisms that process stimuli or generate movement results in increased activation as far backward in the processing chain as the primary cortices. This is true even though the stimuli themselves are not present and the movements are not made. One possibility is that this activation represents the imposition of central signals such as those hypothesized to convey the information about intended movements or expected stimuli. This may represent efference copy issued without corresponding afference. 39. •

Puce A, Constable RT, Luby ML, McCarthy G, Nobre AC, Spencer DD, Gore JC, Allison T: Functional magnetic resonance imaging of sensory and motor cortex: comparison with electrophysiological localization. J Neurosurg 1995, 83:262-2?0. These authors present outstanding fMRI plates of human sensorimotor cortices and their activation during some but not all behavioral tasks tested. They note that there is good correspondence between these images and alectrophysiological maps of the hand region in the sensorimotor codices. 40.

Zilles K, Schlaug G, Matelli M, Luppino G, Schleicher A: Mapping of human and macaque sensorimotor areas by integrating

Motor commands and sensorimotor cortex Nelson

architectonic, transmitter receptor, MRI and PET data. J Anat 1995, 187:515-537. Altenm(JllerE, Berger W, Prokop T, Trippel M, Dietz V: Modulation of sural nerve somatosensory evoked potentials during stance and different phases of the step cycle. E/ectroencepha/ogrC/in Neurophysio11995, 96:516-525. This study describes human evoked potential recordings localized to several cortical and subcortical regions. A major finding is that the responses to peripheral electrical stimulation of the moving limb during locomotion are modulated at cortical but not subcortical levels. A second major finding is that this modulation may be in the form of attenuation or facilitation, depending upon the phase of the step cycle. Responses are facilitated during part of the cycle in which the limb is not in contact with the ground, and they are suppressed during the support phase when the limb contacts the floor. This work is reminiscent of earlier experimental work in animals (see the discussion section of their article) and suggests that sensations and perceptions are gated in or out depending upon their importance for the current behavior. 41. •*

42. ••

Schnitzler A, Witte OW, Cheyne D, Haid G, Vrba J, Freund HJ: Modulation of somatosensory evoked magnetic fields by sensory and motor interferences. Neuroreport 1995, 6:1653-1658. The authors used magnetic field recording techniques and then superimposed the results on MRI images of the human subjects from which they were recorded. The major findings include a demonstration that during continuous exploratory behavior and exploration without object contact, somatic evoked fields resulting from electrical stimulation of the hand are markedly reduced. Most notable is the fact that the number of fields attributed to the SI region are reduced by half in comparison to those present when the subject is stimulated and is at rest. Passive (experimenter-moved) exploration results in a much smaller reduction. This implies that active movements, whether they contact objects or not, are accompanied by attenuations in stimulusrelated fields. The authors suggest that efference copy from area 4 is the cause. 43. •

Hsieh CL, Shima F, Tobimatsu S, Sun SJ, Kato M: The interaction of the somatosensory evoked potentials to simultaneous finger stimuli in the human central nervous system. A study using direct recordings. Electroencephalogr C/in Neurophysiol 1995, 96:135-142. Interaction ratios that gauge the attenuation in SEP magnitudes of simultaneous finger stimulation versus the sum of the SEPs for stimulation of the single fingers alone are described. The attenuation is greatest in the somatosensory cortex, followed by the thalamus and the cuneate region. Their findings suggest that area 3b modulates later-occurring activity in the cuneate nucleus. 44.

Cohen LG, Bandinelli S, Sato S, Kufta C, Hallett M: Attenuation in detection for somatosensory stimuli by transcranial magnetic stimulation. Electroencephalogr C/in Neurophysiol 1991,81:366-376.

45.

PascucaI-Leone A, Torres F: Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. Brain 1993, 116:39-52.

Baldissera F, Leocani L: Afferent excitation of human motor cortex as revealed by enhancement of direct cortico-spinal actions in motoneurones. Electroencephalogr C/in Neurophysiol 1995, 97:394-401. This study shows that peripheral stimulation preceding a motor volley caused by transcranial magnetic stimulation of MI causes facilitation of the corticospinal effect of the MI stimulation. This is an extremely thorough study, which indirectly suggests that one role of efference copy may be to keep peripheral stimuli from influencing corticospinal neurons just before and during movements. 46. •

Fadiga L, Fogassi G, Pavesi G, Rizzolatti G: Motor facilitation during action observation: a magnetic stimulation study. J Neurophysio/1995, 73:2608-2611. The authors used transcranial magnetic stimulation to stimulate normal subjects while they observed someone else grasping an object, looked at the same object, watched the experimenter trace figures in the air, and detected a light dimming. Motor-evoked potentials increased when subjects observed actions. These increases reflected the patterns of muscle activity that were recorded when the subjects themselves performed the actions. The authors suggest that these results illustrate the linkage between observational and executional systems and discuss these findings in light of their recent electrophysiological studies using monkeys.

50.

Milne RJ, Aniss AM, Kay NE, Gandevia SC: Reduction in perceived intensity of cutaneous stimuli during movement: a quantitative study. Exp Brain Res 1988, 70:569-576.

51.

Jiang W, Chapman CE, Lamarre Y: Modulation of somatosensory evoked responses in the primary somatosensory cortex produced by intracortical microstimulation of the motor cortex in the monkey. Exp Brain Res 1990, 80:333-344.

52.

Jiang W, Chapman CE, Lamarre Y: Modulation of the cutaneous responsiveness of neurones in the primary somatosensory cortex during conditioned arm movements in the monkey. Exp Brain Res 1991, 84:342-354.

53.

Meyer E, Ferguson SS, Zatorre RJ, Alivisatos B, Marrett S, Evans AC, Hakim AM: Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography. Ann Neuro/1991, 29:440-443.

54. *-,

Drevets WC, Burton H, Videen TO, Snyder AZ, Simpson JR, Raichle ME: Blood flow changes in human somatosensory cortex during anticipated stimulation. Nature 1995, 373:249-252. This study is extremely important because it addresses several unanswered questions. Using positron emission tomography to measure rCBF, the authors determined that there were increases and decreases in somatosensory cortical regions during the same behaviors. There were decreases in rCBF in regions representing body parts other than those where stimuli were expected. These included the ipsilateral cortical representation, which subserves the same body part on the opposite side of the body, and the contralateral representations immediately adjacent to that representing the target body part. The authors observed no significant net change in rCBF in the codex representing the skin field where the stimulus was expected. However, they suggest that this is because within that region, there is simultaneous enhancement of the responsiveness of the representation of the target skin locus and suppression of the representations of a circumscribed peripheral zone. The report, while brief, is thorough. It considers several classes of peripheral stimuli and their effects on rCBF. 55.

K~nig P, Engel AK: Correlated firing in sensory-motor systems. Curr Opin Neurobiol 1995, 5:511-519.

56.

Salmelin R, Had R: Spatiotemporal characteristics of sensorimotor neuromagnetic rhythms related to thumb movement. Neuroscience 1994, 60:537-550.

57.

MacKay WA, Mendon~a AJ: Field potential oscillatory bursts in parietal cortex before and during reach. Brain Res 1995, 704:167-174.

56.

Nashmi R, Mendon~a AJ, MacKay WA: EEG rhythms of the sensorimotor region during hand movements. E/ectroencepha/ogr Clin Neurophysio/1994, 91:456-467.

Nicolelis MA, Baccala LA, Lin RC, Chapin JK: Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system. Science 1995, 268:1353-1358. The major findings of this paper are mentioned in the text of this review. The importance of simultaneous electrophysiological recording at several sites in a pathway cannot be stressed too much. The technical advances that this paper outlines will lead to answers about how distributed networks function in real-time during behavior. In this manner, questions of relative timing of effects at multiple cortical and subcortical locations can be directly answered. Moreover, synchronous activity in spatially separated populations of neurons, which waxes and wanes depending upon behavior contingencies, can be demonstrated. 59. ..

60.

Nelson PJ, Smith BN, Douglas VD: Relationships between sensory responsiveness and premovement activity of quickly adapting neurons in areas 3b and 1 of monkey primary somatosensory cortex. Exp Brain Res 1991, 84:75-90.

61.

Gordon AM, Soechting JF: Use of tactile afferent information in sequential finger movements. Exp Brain Res 1995, 107:281-292.

47. •

48.

Saito Y, Yokata T, Yuasa T: Suppression of motor cortical excitability by magnetic stimulation of the cerebellum. Brain Res 1995, 691:200-206.

49.

Jiang W, Lamarre Y, Chapman CE: Modulation of cutaneous cortical evoked potentials during isometric and isotonic contractions in the monkey. Brain Res 1990, 536:69-78.

809

62. •

Aglioti S, Beltramello A, Bonazzi A, Corbetta M: Thumb pointing in humans after damage to somatic sensory cortex. Exp Brain Res 1996, 109:92-100. This study documents changes in movement accuracy in humans who do not have access to proprioceptive information about performance. The discussion is especially good because it considers not only performance aspects, but what factors improve movement accuracy. 63. •

Bard C, Fleury M, Teasdale N, Paillard J, Nougier V: Contribution of proprioception for calibrating and updating the motor space. Can J Physiol Pharmacol 1995, 73:246-254. Perhaps the best in a series of papers [63",65,66] on the behavior of patients for which proprioceptive afference is unavailable to act in the dynamic

810

Neural control

updating of movement conditions. Various strategies for compensation are discussed in detail. The findings lead to the conclusion that, provided enough feedback from visual and internal sources, behaviors can be adapted to fit task needs. 64.

65.

66.

that this is due to decreased excitability of intrinsic inhibitory cortical circuits and may underlie decreases in the selectivity of motor cortical discharges. 70.

Ghez C, Gordon J, Ghilardi MF: Impairments of reaching movements in patients without proprioception. II. Effects of visual information on accuracy. J Neurophysiol 1995, 73:361-372.

Ridding MC, Inzelberg R, Rothwell JC: Changes in excitability of motor cortical circuitry in patients with Parkinson's disease. Ann Neuro/1995, 37:181-188.

71.

FleuryM, Macar F, Bard C, Teasdale N, Cole J, Lamarre Y, Forget R: Production of short timing responses: a comparative study with a deafferented patient. Neuropsychologia 1994, 32:1435-1440.

Touge T, Werhahn KJ, Rothwell JC, Marsden CD: Movementrelated cortical potentials preceding repeUtive and randomchoice hand movements in Parkinson's disease, Ann Neurol 1995, 37:791-799.

72.

Cheron G, Piette T, Thiriaux A, Jacquy J, Godaux E: Somatosensory evoked potentials at rest and during movement in Parkinson's disease: evidence for a specific apomorphine effect on the frontal N30 wave. E/ectroencepha/ogr C/in Neurophysiol 1994, 92:491-501.

73.

Deuschl G, Toro C, Matsumoto J, Hallett M: Movement-related cortical potentials in writers cramp. Ann Neuro11995, 38:381-392.

74.

Marsden CD, Obeso JA: The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson's disease. Brain 1994, 117:877-89'7.

75.

Bullock D, Grossberg S, Guenther FH: A self-organizing neural model of motor equivalent reaching and tool use by a multijoint arm. J Cogn Neurosci 1993, 5:408-435.

76.

Prochazka A: Comparison of natural and artificial control of movement. IEEE Trans Rehab Eng 1993, 1:7-16.

77.

Salinas E, Abbott LF: Transfer of coded information from sensory to motor networks. J Neurosci 1995, 15:6461-6474.

78,

FlahertyAW, Graybiel AM: Motor and somatosensory corticocortical projection magnifications in the squirrel monkey. J Neurophysiol 1995, 74:2638-2648.

79.

Mink JW, Thach WT: Basal ganglia intrinsic circuits and their role in behavior. Curt Opin Neurobiol 1993, 3:950-957.

La Rue J, Bard C, Fleury M, Teasdale N, Paillard J, Forget R, Lamarre Y: Is propriocepUon important for the timing of motor activities? Can J Physiol Pharmacol 1995, 73:255-261.

67.

Sadato N, Zeffiro TA, Campbell G, Konishi J, Shibasaki H, • Hallet M: Regional cerebral blood flow changes in motor cortical areas after transient anesthesia of the forearm. Ann Neuro11995, 37:74-81. The most interesting suggestion made in this study is that rCBF levels in the sensorimotor cortices measured during movements, as a whole, do not increase with temporary deafferentation. The authors suggest that this may be due to deafferentation-induced disinhibition of MI by the reduction of input to SI. 68.

69. •

Miall RC, Haggard PN, Cole JD: Evidence of a limited visuomotor memory used in programming wrist movements. Exp Brain Res 1995, 107:267-280.

Klockgether T, Borutta M, Rapp H, Spieker S, Dichgans J: A defect of kinesthesia in Parkinson's disease. Motor Disorders 1995, 10:460-465. This study indicates that there is a significant decrease in cortico-cortical inhibition in patients with Parkinson's disease, as compared to controls, that can be ameliorated when the patients are given L-dopa. The authors suggest