Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Montreal, Quebec H3C 3T8, Canada
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Boudreau, Marie-Josée and Allan M. Smith. Activity in Rostral Motor Cortex in Response to Predictable Force-Pulse Perturbations in a Precision Grip Task. J. Neurophysiol. 86: 1079-1085, 2001. The purpose of this investigation was to characterize the discharge of neurons in the rostral area 4 motor cortex (MI) during performance of a precision grip task. Three monkeys were trained to grasp an object between the thumb and index finger and to lift and hold it stationary for 2-2.5 s within a narrow position window. The grip and load forces and the vertical displacement of the object were recorded on each trial. On some trials a downward force-pulse perturbation generating a shear force and slip on the skin was applied to the object after 1.5 s of static holding. In total, 72 neurons were recorded near the rostral limit of the hand area of the motor cortex, located close to the premotor areas. Of these, 30 neurons were examined for receptive fields, and all 30 were found to receive proprioceptive inputs from finger muscles. Intracortical microstimulation applied to 38 recording sites evoked brief hand movements, most frequently involving the thumb and index finger with an average threshold of 12 µA. Slightly more than one-half of the neurons (38/72) demonstrated significant increases in firing rate that on average began 284 ± 186 ms before grip onset. Of 54 neurons tested with predictable force-pulse perturbations, 29 (53.7%) responded with a reflexlike reaction at a mean latency of 54.2 ± 16.8 ms. This latency was 16 ms longer than the mean latency of reflexlike activity evoked in neurons with proprioceptive receptive fields in the more caudal motor cortex. No neurons exhibited anticipatory activity that preceded the perturbation even when the perturbations were delivered randomly and signaled by a warning stimulus. The results indicate the presence of a strong proprioceptive input to the rostral motor cortex, but raise the possibility that the afferent pathway or intracortical processing may be different because of the slightly longer latency.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The cortical control of natural
precision grasping movements has been investigated for more than 30 yr
(Hepp-Reymond and Wiesendanger 1972; Lawrence and
Kuypers 1968
; Smith et al. 1975
). It is now clear that precision grasping is the result of a distributed control process involving both central sensorimotor structures (Cadoret and Smith 1997
; Dugas and Smith 1992
;
Hepp-Reymond et al. 1978
, 1989
,
1994
; Lemon 1993
; Picard and Smith
1992a
,b
; Salimi et al. 1999
) and peripheral
afferents (Johansson and Westling 1984
; Westling and
Johansson 1984
). However, the execution of the precision
grip seems to be critically dependent on the primary motor cortex
(Brochier et al. 1999
; Lawrence and Kuypers
1968
; Schieber and Poliakov 1998
). Through its
direct projections to motoneurons supplying the intrinsic and extrinsic
muscles of the hand, the primary motor cortex (MI or Brodmann's area
4) can directly influence all the muscles involved in grasping
(Lemon 1993
). The important contribution of motor cortex
to the control of relatively independent finger movements has been well
supported by the combined contribution of electrophysiological studies
in primates (Clough et al. 1968
; Lemon
1993
; Muir and Lemon 1983
), clinical
observations on the effects of lesions (Lawrence and Hopkins
1976
; Lawrence and Kuypers 1968
;
Passingham 1988
; Penfield and Rasmussen
1950
) and from more recent reversible cortical inactivation
experiments in primates (Brochier et al. 1999
;
Schieber and Poliakov 1998
). The direct supraspinal
action on the spinal motoneurons is essential for the ability to move
the fingers independently (Lawrence and Kuypers 1968
), a
characteristic feature of almost all hand skills. The initiation of a
precision grip involves establishing a finger configuration that
accurately matches the size of the object (Jeannerod 1984
, 1986
), but that ultimately requires the
fine control of the grip forces between thumb and index finger.
Johansson and Westling (1984)
demonstrated the
importance of this fine control in the grasping, lifting, and holding
of small objects. These authors (Johansson and Westling
1984
; Westling and Johansson 1984
) and others
(Cadoret and Smith 1996
) have shown that the grip force used during a grasping task is accurately scaled to the weight and
frictional properties of the hand-held object. The precise control of
finger forces is most likely exerted by the primary motor cortex since
the contribution of this area to the production of pinch force has been
repeatedly found in a variety of neurophysiological studies in awake
monkeys and for different tasks (Bennett and Lemon 1996
;
Hepp-Reymond et al. 1978
; Lemon et al.
1996
; Maier et al. 1993
; Muir and Lemon
1983
; Picard and Smith 1992a
,b
; Smith et
al. 1975
).
According to Strick and Preston (1982a,b
), the motor
cortex in new world primates (squirrel monkeys) contains two spatially separate motor representations of the digits and wrist that can be
defined on the basis of their somatosensory afferent input. These
authors observed that the cutaneous inputs were located in the caudal
part of the hand representation in motor cortex, whereas the
proprioceptive inputs were located in the rostral part of the hand
representation area. Picard and Smith (1992a
,b
), in
their studies of awake old world monkeys, reported that a high proportion of neurons in caudal motor cortex responded to cutaneous stimulation from the glabrous skin of the hand, and they suggested that
this region was important for adjusting grip forces to the digit/surface friction of grasped objects. These authors mainly recorded from the caudal motor cortex in the bank of the central sulcus
where a preponderance of cutaneous afferents from the volar fingers and
palm are found. However, they implied that the more rostral regions on
the surface near the lip of the central sulcus with a higher percentage
of proprioceptive afferents might also be important. The present
experiment was designed to supplement the study of Picard and
Smith (1992b)
and to further characterize the neurons of the
most rostral part of the primary motor cortex during the precision grip
task. Particular attention was given to the dominant presence of
proprioceptive afferents to neurons in this area. The input-output
properties of neurons were carefully examined, and the modulation of
the neuronal activity in response to a readily predictable perturbation
during the task performance was studied.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Subjects and motor task
Three female monkeys (macaca fascicularis) weighing
between 2.8 and 3.5 kg were used in these experiments. Although the
area 6, premotor cortex (PM) was also explored in two animals, in this paper we will focus only on motor cortex. One of the three animals was
also a subject in a muscimol inactivation experiment (Brochier et al. 1999). The experimental procedures and the task were the same as in the preceding paper (Boudreau et al.
2001
). Briefly the monkeys were trained to grasp a metal tab
between the thumb and index finger that was attached to the
instrumented armature of a linear motor. The animal was required to
hold the object within a vertical position window of 12-25 mm. The
linear motor generated a force of 0.6 N to simulate an object weighting
approximately 60 g. Occasionally some neurons were tested with
object weight simulations of 30, 60, and 100 g. The
computer-controlled object measured both the horizontal force exerted
by the fingers (grip force) and the vertical lifting (load force) and
the movement of the object in the vertical axis.
Force-pulse perturbations
On separate blocks of trials, a brief (100-ms) downward force-pulse perturbation was applied to the object during the stationary holding phase to produce an additional downward shear force on the fingers. This perturbation was usually delivered 1.5 s after the onset of the tone indicating that the object had entered the position window and was therefore predictable after the first trial. The force of the perturbation was 1.0 N for two monkeys and 3.5 N for the other monkey. The perturbation force was adjusted to produce a downward object displacement of several millimeters. If unopposed, the perturbations were strong enough to displace the manipulandum from the position window, resulting in a loss of reward for the monkey. The monkey had to resist the perturbation by stiffening the wrist and fingers to maintain the metal tab within the boundaries of the position window. For two monkeys, the testing procedures began with a block of unperturbed control trials followed by a block of consecutively perturbed trials and then followed by a second block of unperturbed control trials to extinguish the behavioral expectancy of the perturbation in subsequent conditions. On some occasions, for the third monkey, an additional block of trials consisting of random combinations of 75% perturbed and 25% unperturbed trials were presented. In this condition, a warning flash delivered 800 ms prior to the perturbation preceded all force-pulse perturbation trials. Both the control and perturbed conditions were always applied to a tonic resistive force of 0.6 N and a grasping surface covered with 329 grit sandpaper.
Surgical preparation
Following previously published procedures (Espinoza and
Smith 1990; Evarts 1965
), a circular stainless
steel recording chamber 18 mm diam was implanted stereotaxically over
the hand representation of the primary motor and premotor cortices
contralateral to the trained hand under sterile surgical conditions.
Recording procedures
After a postoperative recovery period, recording sessions were conducted on a daily basis while the monkey performed the grasping task. If the activity of a cell was judged to be task related, the cell discharge was recorded in different conditions. Whenever possible after data collection, each cell was carefully examined to identify the receptive field (RF) by stimulating the skin with air puffs or a camel hair bush or by passively moving the hand or digits about different joints when the monkey was as quiescent and relaxed as possible. Moreover, for almost every recording site, intracortical microstimulation (ICMS) was carried out to identify the output property of the region. The ICMS consisted of a 100-ms train of 0.2-ms cathodal pulses delivered at 300 Hz through a constant-current isolation unit. The maximum applied intensity was 45 µA. The ICMS threshold corresponded to the lowest current intensity required to evoke a discrete visible movement of the fingers or wrist. The RF and ICMS were also used to map the extent of the thumb and index finger representation in the recorded area.
Histological analysis and reconstruction of recording sites
To confirm the location of the recorded cells, electrolytic
lesions were made in the three monkeys by passing current through the
recording microelectrode sites (25-50 µA for 20 s). These electrolytic marking lesions were produced at three stereotaxically chosen penetrations within the recording chamber. At the conclusion of
experimentation, the animals were killed with an overdose of pentobarbital sodium and perfused transcardially with 0.9%
saline followed by 4% paraformaldehyde. After the brains had been
removed, visible markers were applied to the cortical surface at the
penetration sites, and the brains were photographed. The brains were
immersed in a solution of sucrose (20%, 4°C) for 24 h for
cryoprotection before freezing (80°C). Frozen sections (40 µm
thick) were cut in a parasagittal plane and were stained with cresyl
violet. The location of electrode penetrations and the recording sites
were reconstructed from the lesion coordinates.
Statistical analysis
The cellular discharge, grip force, load force, and vertical
displacement of the object were recorded in blocks of 25-35 trials under both perturbed and unperturbed conditions. The onset time of
neuronal activity related to the task was defined as a 100-ms change in
discharge that was at least 2 SDs greater than the mean activity,
calculated during a similar 100-ms control period occurring 0.8 s
before the grip onset. Either a t-test or an ANOVA was used to determine whether the prehensile force and neuronal discharge frequency were significantly altered by the test conditions. The reflexlike responses to the perturbation were determined by comparing the mean firing frequency during the 100 ms before and after the perturbation onset with a t-test (P 0.05).
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
A total of 72 motor cortical neurons in 3 monkeys were found to be active in the grasping task. This rather low yield was due to the fact that the primary purpose of the study was to examine the activity of neurons of the ventral and dorsal premotor area. Fifty-four of the 72 neurons were tested for responses to the perturbation, and the receptive fields were identified for 30 of 30 neurons tested.
Location of the recorded neurons
The histological analysis, based on the electrolytic marking
lesions and electrode tracks in the cortex, indicated that these neurons were clustered in the rostral hand representation of area 4 motor cortex at a distance of about 3.0 mm from the central sulcus
close to the ventral premotor cortex. The boundary between the motor
cortex and the premotor cortex was established on the basis of
cytoarchitectonic criteria distinguishing area 4 from area 6 (Sessle and Wiesendanger 1982). These included the
higher density of large pyramidal cells in layer V of primary motor
cortex area and the low current threshold required for eliciting
movements with ICMS in this area compared with the relatively lower
incidence of motor reactions to ICMS in the premotor cortex. This
region was nevertheless rostral to the area explored by Rosen
and Asanuma (1972)
. The rostral recording zone did not appear
to overlap even the most rostral region recorded by Picard and
Smith (1992a
,b
), which was either within the central sulcus or
close to it. Figure 1 shows the
approximate surface location of task-modulated cells for the three
monkeys. All cells were recorded at an estimated depth of 0.5-2.5 mm
below the cortical surface.
|
Responses to microstimulation and identification of receptive fields
ICMS performed at 38 penetration sites within the recording area evoked movements from 37 sites at thresholds varying from 4 to 30 µA (average threshold of 12 ± 7 µA, mean ± SD). These clear ICMS responses contrast with a lower incidence in adjacent premotor areas. Most of the responses were brief, unambiguous, short-latency movements frequently involving the thumb and forefinger rather than the wrist. At 23 sites, independent movements of the thumb were observed, whereas 13 sites yielded movements in the other fingers. Only one stimulation site evoked movement of the wrist.
The responses to cutaneous and proprioceptive stimuli were examined for
a total of 30 neurons. All of these 30 neurons were responsive to
proprioceptive stimulation, which involved a displacement of the
digits, particularly the thumb as well as tapping and stretching intrinsic and extrinsic hand muscles. Movements of the thumb activated 19/30 neurons, whereas only 5 were related to the displacement of the
index finger, and the remaining 6 neurons were related to the movement
of several fingers. No RFs were associated with either wrist or elbow
movements. As reported by Picard and Smith (1992a),
passive movement in a single direction activated most of these cells
(26/30) with proprioceptive RFs. However, four cells responded to
stimulation applied in two opposite directions such as either
flexion/extension (3/4) or adduction/abduction (1/4).
Input-output relationship
The relationship between the input-output properties of the motor
cortex cells examined in this experiment was derived from 30 neurons
that had well-defined RFs recorded in a region from which a clear ICMS
response could be evoked. For 13 neurons the ICMS evoked movements in
the same location on the hand as the proprioceptive receptive field.
Seven neurons received their input from muscle groups acting in one
direction and ICMS-produced activity in the opposite direction. In the
10 remaining neurons the afferent input came from groups of muscles
concurrently active during the task performance, but acting at
different fingers than the muscles activated by ICMS (Espinoza
and Smith 1990). These results generally extend the close
relation between afferent input and efferent cortical output described
by Rosen and Asanuma (1972)
to the rostral limit of area 4.
Activation patterns
The discharge of neurons active during the task were examined for
common features and grouped into the three categories, phasic, phasic-tonic, and tonic, on the basis of established patterns observed
earlier in motor cortex (Hepp-Reymond et al. 1978;
Smith et al. 1975
). The relative proportion of each
activation pattern in the rostral motor cortex was similar to the
caudal zone according to unpublished data from Picard and Smith. In
both zones most task-related neurons were active during the dynamic
phase of the task and the proportion of phasic, phasic-tonic, and tonic
neurons was similar (61, 29, and 10% for the rostral zone compared
with 52, 23, and 11.2% for the caudal zone, respectively).
Pregrip activity
A substantial number of the rostral motor cortex neurons (38/72 or
52.7%) demonstrated a significant increase in their activity before
the grip onset. Some neurons (7/72, or 9.7%) also showed an activity
change even before the hand began moving toward the grasping tab. The
onset of neuronal activity change was on average 284 ± 186 ms
before grip onset. This pregrip activity onset in the rostral motor
cortex was later than the pregrip activity for neurons found in
premotor areas that on average show activity changes 392 ms in the
ventral PM and 378 ms in the dorsal PM (Boudreau et al.
2001). Figure 2
illustrates a rostral motor cortex cell with an activity change prior
to the grip onset. As seen from the raster, the onset and duration of
pregrip activity in this particular cell varied from trial to trial and
appeared to be related to the opening of the hand in preparation for
grasping.
|
Responses to the perturbation
Of 72 task-modulated cells, 54 were tested with the perturbation. From these, 53/54 cells were tested with consecutive unsignaled perturbations, and 9 were also tested with a warning stimulus signaling the impending perturbation. One cell was tested in the signaled condition only.
TRIGGERED REACTIONS. All three monkeys demonstrated a stereotyped, reflexlike, grip force increase and upward movement generated at the wrist to maintain the object within the position window. These triggered reactions were immediately and invariably present after the perturbation at a latency of 50-100 ms, and they disappeared as soon as the perturbation was withdrawn.
More than one-half of the cells (29/54) responded to the perturbation with reflexlike responses. In 26 cells the perturbation resulted in an increased discharge frequency. In the majority of these cells, the increase in firing frequency was of sharp onset and could be accurately measured from a peristimulus activity histogram. An example of these reflexlike reactions is illustrated in Fig. 3. Figure 3 also shows the activity histogram both for signaled and unsignaled perturbations. As observed in the caudal motor cortex (Picard and Smith 1992b
|
|
PREPARATORY RESPONSES. The force-pulse perturbations were always applied at the same time on each trial and therefore were highly predictable, allowing the animals to develop an appropriate preparatory strategy. In anticipation of the forthcoming perturbation, two strategies emerged. One consisted of either increasing the grip force before the perturbation onset to attenuate the object slip, and the second was simply to hold the object higher within the position window. Frequently the animal opted for a combination of both strategies. The animals generally started their anticipatory grip force increase once the object position was stabilized in the holding phase of the task. Unfortunately the warning stimulus used to assist the animal in discriminating perturbed from unperturbed trials did not appear to have any additional effect on either the anticipatory grip forces or object displacement strategies.
Despite a preparatory grip force increase associated with the perturbations, no neurons showed any change in discharge frequency prior to the force-pulse perturbation. Moreover, the warning stimulus did not produce any observable enhancement of the neuronal activity in the rostral motor cortex. ![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The present study examined the modulation of the neurons in the rostral hand region of the primary motor cortex during performance of a precision grip task. Two main observations were reported. The first observation was that all 30 hand-related cells tested for receptive fields in this region had proprioceptive inputs from hand muscles. The second observation was that more than one-half the neurons in the rostral motor cortex responded to the perturbation but at a longer latency than neurons with proprioceptive receptive fields in the caudal motor cortex. No neurons showed any preparatory activity in anticipation of the perturbation.
Proprioceptive afferents
All task-modulated cells examined for receptive fields in this
study were responsive to proprioceptive inputs from intrinsic and
extrinsic hand muscles. Moreover the rostral motor cortex from which
these cells were recorded was more anterior than the region recorded by
Picard and Smith (1992a). However, this area appeared to
be a pure hand representation region as indicated by the fact that the
responses to ICMS were limited to the fingers. The predominance of
proprioceptive afferents to this area is in agreement with earlier
observations by Strick and Preston (1982b)
on rostral
area 4 in Saimiri sciureus monkeys. If the results of the
present study are combined with those of Picard and Smith (1992a
,b
), there is clear evidence of a rostrocaudal gradient in afferent submodality as suggested by Strick and Preston
(1982a
,b
). Even within the rostral zone of Picard and Smith, a
minority of neurons with cutaneous receptive fields were found, whereas
the present study found no cutaneous fields further rostrally. These data further support the notion that cutaneous and proprioceptive afferents are segregated within motor cortex.
Modulation of neuronal activity related to the perturbation
TRIGGERED REACTIONS.
The downward force-pulse perturbation elicited short-latency responses
in some rostral motor cortex neurons similar to those reported for
caudal motor cortex by Picard and Smith (1992b). Moreover, like observations have also been reported by other authors (Evarts 1973
; Evarts and Fromm 1981
;
Johansson et al. 1988
) for perturbations applied during
wrist movements. In addition, like the neurons in the caudal motor
cortex (Picard and Smith 1992b
), the response latency of
the rostral motor cortex neurons was short enough to suggest their
participation in long-latency reflexes (Evarts 1973
;
Evarts and Fromm 1981
; Evarts and Tanji
1976
; Lee and Tatton 1982
; Macefield et
al. 1996a
). It has been proposed that motor cortical neurons,
activated by feedback from cutaneous and proprioceptive receptors in
response to the perturbations contribute, directly or indirectly, to
the reflex grip force increases observed 50-100 ms after object slip
or load increase (Cole and Abbs 1988
; Dugas and
Smith 1992
; Johansson and Westling 1984
, 1988
; Picard and Smith 1992b
). However,
Macefield and colleagues (1996b)
suggested that tactile
afferents of the skin were the only receptors in the hand responding at
a latency early enough to trigger a grip force change at a latency of
<100 ms. In contrast, our results suggest that the proprioceptive
afferents could play a role in these triggered responses. The fact that
a substantial number of the cells in the present study had
proprioceptive RFs and responded to the perturbation within 100 ms
supports this view. However, the mean response latency of neurons
receiving proprioceptive afferents in the rostral motor cortex was
significantly longer (P < 0.005) than the mean
response latency of neurons receiving proprioceptive afferents in the
caudal motor cortex. These results suggest that there might be two
pathways to the primary motor cortex or possibly an additional
intracortical relay for proprioceptive afferents to the rostral cortex.
Otherwise, the proportion of responsive neurons in the rostral zone
(53.7%) was not significantly lower than the proportion of responsive
neurons found in the caudal zone (61%) of the primary motor cortex
(Picard and Smith 1992b
). That is, cells receiving
cutaneous afferents were not more responsive to the force-pulse
perturbation than cells receiving proprioceptive afferents, suggesting
that both sensory afferents could make an important contribution to the
grip force adjustments following sudden load force changes.
![]() |
ACKNOWLEDGMENTS |
---|
We gratefully acknowledge Dr. T. Brochier and M. Paré for assistance in some experiments. We also thank L. Lessard, J. Jodoin, C. Gauthier, C. Valiquette, and G. Messier for technical assistance.
This research was supported by a grant to Groupe de Recherche en Sciences Neurologiques from Medical Research Council of Canada and fellowships from the Fonds pour la Formation des Chercheurs et l'Aide à la Recherche.
![]() |
FOOTNOTES |
---|
Address for reprint requests: A. M. Smith, Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, C. P. 6128 Succ. A, Montreal, Quebec H3C 3T8, Canada (E-mail: allan.smith{at}umontreal.ca).
Received 29 November 2000; accepted in final form 3 May 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|