Effects on Muscle Activity From Microstimuli Applied to Somatosensory and Motor Cortex During Voluntary Movement in the Monkey

Gail L. Widener and Paul D. Cheney

Department of Physiology and Smith Mental Retardation and Human Development Research Center, University of Kansas Medical Center, Kansas City, Kansas 66160

    ABSTRACT
Abstract
Introduction
Methods
Results
Discussion
References

Widener, Gail L. and Paul D. Cheney. Effects on muscle activity from microstimuli applied to somatosensory and motor cortex during voluntary movement in the monkey. J. Neurophysiol. 77: 2446-2465, 1997. It is well known that electrical stimulation of primary somatosensory cortex (SI) evokes movements that resemble those evoked from primary motor cortex. These findings have led to the concept that SI may possess motor capabilities paralleling those of motor cortex and speculation that SI could function as a robust relay mediating motor responses from central and peripheral inputs. The purpose of this study was to rigorously examine the motor output capabilities of SI areas with the use of the techniques of spike- and stimulus-triggered averaging of electromyographic (EMG) activity in awake monkeys. Unit recordings were obtained from primary motor cortex and SI areas 3a, 3b, 1, and 2 in three rhesus monkeys. Spike-triggered averaging was used to assess the output linkage between individual cells and motoneurons of the recorded muscles. Cells in motor cortex producing postspike facilitation (PSpF) in spike-triggered averages of rectified EMG activity were designated corticomotoneuronal (CM) cells. Motor output efficacy was also assessed by applying stimuli through the microelectrode and computing stimulus-triggered averages of rectified EMG activity. One hundred seventy-one sites in motor cortex and 68 sites in SI were characterized functionally and tested for motor output effects on muscle activity. The incidence, character, and magnitude of motor output effects from SI areas were in sharp contrast to effects from CM cell sites in primary motor cortex. Of 68 SI cells tested with spike-triggered averaging, only one area 3a cell produced significant PSpF in spike-triggered averages of EMG activity. In comparison, 20 of 171 (12%) motor cortex cells tested produced significant postspike effects. Single-pulse intracortical microstimulation produced effects at all CM cell sites in motor cortex but at only 14% of SI sites. The large fraction of SI effects that was inhibitory represented yet another marked difference between CM cell sites in motor cortex and SI sites (25% vs 93%). The fact that motor output effects from SI were frequently absent or very weak and predominantly inhibitory emphasizes the differing motor capabilities of SI compared with primary motor cortex.

    INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References

Many studies dating back to the pioneering work of Schaefer (1900) have demonstrated that electrical stimulation of postcentral cortex in primates can evoke movements of the limbs. Similar findings were reported for humans by Penfield and colleagues (Penfield and Boldrey 1937; Penfield and Rasmussen 1952). Woolsey (1958) produced detailed maps of motor output from the postcentral gyrus in monkeys and first showed that the motor output maps and sensory input maps were in register. Movements evoked from postcentral cortex resemble in almost every respect those from stimulation of primary motor cortex (MI), with the exception that thresholds are greater than those for MI (Doetsch and Gardner 1972; Woolsey 1958). The pathway by which effects from primary somatosensory cortex (SI) are mediated is not clear. Linkages from SI areas to MI are well documented and seem to be the most likely route by which SI-evoked motor responses could occur (Avendano et al. 1992; Ghosh and Porter 1988; Ichikawa et al. 1987; Jones et al. 1978; Zarzecki et al. 1978). Areas 3a and 2 make particularly dense projections to MI (Jones and Porter 1980; Phillips and Porter 1977; Pons and Kaas 1985). In fact, some SI neurons can be shown to terminate directly on pyramidal neurons in motor cortex (Ghosh and Porter 1988; Zarzecki et al. 1978), suggesting the existence of a direct and potentially powerful linkage between some SI areas and motor cortical output.

However, movements can be evoked by surface stimulation of SI even after ablation of areas 4 and 6 of MI, suggesting the existence of a functional linkage to motoneurons that is not dependent on precentral cortex (Kennard and McCulloch 1943; Woolsey et al. 1953). It is well known that SI areas contain large numbers of corticospinal neurons (Bentivoglio and Rustoni 1986; Coulter and Jones 1977; Coulter et al. 1976; Galea and Darian-Smith 1994; Harting and Noback 1970; Jones and Wise 1977; Murray and Coulter 1981; Nudo and Masterton 1990; Ralston and Ralston 1985; Sessle and Wiesendanger 1982; Toyoshima and Sakai 1982). Many of these neurons terminate in the spinal cord dorsal horn and seem to influence transmission of sensory information to higher levels (Fetz 1968). However, labeling studies have shown that some SI corticospinal neurons terminate in laminae V, VI, and VII of the spinal cord (Casale and Light 1991; Cheema et al. 1984; Ralston and Ralston 1985). The dendrites of motoneurons can extend well beyond the boundaries of the motor nuclei, raising the possibility that some SI corticospinal neurons could terminate directly on the dendrites of motoneurons (Keirstead and Rose 1983; Liang et al. 1991; Rose and Richmond 1981). Of course, the possibility of nonmonosynaptic effects on motoneurons from SI corticospinal neurons also exists.

Possible functions of the motor output linkage from SI are not well understood. Injection of the gamma -aminobutyric acid agonist muscimol into postcentral cortex is known to produce hand movements that are clumsy and discoordinated, although this is mainly for movements involving tactile exploration with the hand rather than visually guided movements (Hikosaka et al. 1985). The fact that the discharge of some SI neurons precedes the onset of movement and that the pattern of discharge in some cases closely resembles that of MI neurons suggests that SI could receive central commands for the initiation and execution of movement that are then transmitted to motor cortex. Yet another proposal directly involving SI in motor output is that SI may be a critical link in a transcortical circuit that mediates long-latency reflex responses of muscle, such as the M2 component of the electromyographic (EMG) response to muscle stretch (Phillips 1969; Tatton et al. 1975). SI areas 3a and 2 seem to be the best candidates to mediate this type of function, because both receive strong input from muscle receptors and both project heavily to motor cortex (Hore et al. 1976; Jones and Porter 1980; Phillips and Porter 1977; Pons and Kaas 1985). However, to perform effectively in either of these functions, SI would need to be capable of brisk, powerful excitatory control over muscle activity. Another hypothesis has been proposed by Asanuma and colleagues to explain the motor function of SI (Favorov et al. 1988; Iriki et al. 1989; Pavlides et al. 1993; Sakamoto et al. 1987). This hypothesis does not require the robust, direct control over muscle activity implicated by the functions of mediating central commands for movement initiation or peripheral afferent reflex responses for movement correction. Rather, this hypothesis is based on the finding of long-term potentiation in motor cortex neurons following tetanic stimulation of sensory cortex. Sensory cortex is postulated to be involved in facilitating the acquisition of new motor skills by strengthening, with use, transmission through specific corticoperipheral loop circuits.

The purpose of this study was to evaluate the strength of coupling between motor output and SI areas 3a, 3b, 1, and 2 using spike- and stimulus-triggered averaging of EMG activity (Cheney and Fetz 1985; Fetz and Cheney 1980). These methods provide a highly sensitive means of detecting and quantifying both excitatory and inhibitory effects from the site of stimulation. Comparing the sign and magnitude of output effects on muscle activity from SI areas with output effects from identified CM cell sites in motor cortex provides a means of assessing the characteristics of the neural linkage from SI to motoneurons.

The results show that the excitatory output effects on muscle activity from all SI areas are extremely weak compared with those from CM cell sites in motor cortex. Moreover, the effects from SI are predominantly inhibitory. We conclude that the motor output capabilities of SI contrast sharply with those of MI. Furthermore, the nature of the output coupling from SI areas to motoneurons is not consistent with the notion of a robust functional linkage to motoneurons capable of vigorous control of muscle activity.

    METHODS
Abstract
Introduction
Methods
Results
Discussion
References

Training procedures

Three adolescent rhesus macaques (Macaca mulatta) weighing between 5 and 9 kg were used for these studies. Each monkey was trained to make self-paced ramp-and-hold wrist movements alternating between flexion and extension target zones. Monkeys were seated in a primate chair and placed in a sound-attenuating chamber. Both arms were restrained. The right hand was held between padded plates with fingers extended. A torque motor was used to generate springlike loads opposing movements away from the zero position (hand aligned with the forearm). Wrist position was monitored by a potentiometer connected to the axle of the torque motor. Applesauce rewards were administered for holding within the target zone for the required minimum amount of time, generally 0.8-1 s. Both visual and auditory cues were used to indicate entry into the target zone. A microcomputer was used to set the position zones, hold time requirements, and feeding schedule (Mewes et al. 1985). Training continued until the monkey consistently performed >= 3,000 responses per session against a wide range of torque loads.

Surgical procedures

A stainless steel chamber allowing exploration of a 22-mm diam area of MI and SI hand cortex was stereotaxically anchored to the skull at anterior 12.0, lateral 18.0 mm as described in previous work (Kasser and Cheney 1985).

Intramuscular EMG electrodes were implanted under sterile surgical conditions. Electrode pairs were placed in 12 forearm muscles (6 flexors and 6 extensors) that were directly involved in the wrist movement task. The muscles implanted were flexor digitorum superficialis, flexor digitorum profundus, flexor carpi ulnaris, palmaris longus, flexor carpi radialis, pronator teres, extensor digitorum 2 and 3 (ED2,3), extensor carpi ulnaris (ECU), extensor digitorum 4 and 5 (ED4,5), extensor digitorum communis (EDC), extensor carpi radialis-brevis (ECR-B), and extensor carpi radialis-longus (ECR-L). EMG electrodes were multistranded stainless steel wires with ~2 mm of exposure at the tip. Pairs of electrodeswere inserted percutaneously into each muscle 5-7 mm apart (Loeb and Gans 1986). Muscle location was determined with the use of surface anatomic landmarks. Proper EMG electrode placement was confirmed by observing appropriate movements of the wrist or digits from repetitive stimulation through the electrodes (Fetz and Cheney 1980). Electrodes were secured to the arm with the use of medical adhesive tape. To protect the implant, monkeys wore custom-fitted, long sleeved nylon jackets while in the home cage. EMG implants remained stable and in good condition for 4-8 wk.

Recording procedures

Single units and clusters of units were recorded with the use of conventional extracellular techniques. The five cortical areas investigated were Broadman's areas 4, 3a, 3b, 1, and 2. Each SI area receives specific afferent information from peripheral sensory receptors. The sensory properties coupled with distance from the central sulcus and depth within the cortex allowed initial identification of cells as belonging to SI area 3a, 3b, 1, or 2. Identification of a cell's physiological properties was based on responses to sensory stimulation including light touch, deep pressure (muscle palpation), and joint manipulation. Responses to active and passive wrist movements and torque pulse perturbations were also tested. Figure 1 illustrates the electrode penetration sites for each of the three monkeys.


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FIG. 1. Map illustrating sites of electrode penetrations in pre- and postcentral cortex in 3 monkeys (B, J, and R) used in this study. AS, arcuate sulcus; CS, central sulcus; IPS, intraparietal sulcus.

Single-unit and multiunit activity, position, velocity, torque, rate of torque change (dT/dt), and 12 EMGs were amplified and led to a PDP 11/73 computer for on-line averaging and analysis. These same signals were recorded on a 15-channel Vetter analog tape recorder.

Spike- and stimulus-triggered averaging procedures

As previously described by Cheney and Fetz (1980), spike-triggered averaging can be used to identify cells producing significant postspike facilitation (PSpF) of EMG activity. Motor cortex cells producing PSpF are termed corticomotoneuronal (CM) cells (Fetz and Cheney 1980). Kasser and Cheney (1985) showed that spike-triggered averaging could also be used to identify postspike suppression of average EMG activity. Neuronal and EMG activity was monitored on an oscilloscope and single-unit spikes were isolated with two Bak spike discriminators connected in series. EMG trials were collected separately for the extensor and flexor muscles by gating the spike triggers from the wrist position signal. The analysis period for averaging was generally 30 ms, with a 5-ms pretrigger period and a 25-ms posttrigger period. All spike-triggered averages were based on a minimum of 2,000 trigger events.

Stimulus-triggered averaging of rectified EMG activity can be used to evaluate the motor output effects of a group of neurons in the vicinity of the electrode tip (Cheney and Fetz 1985). Two forms of stimulus-triggered averaging were used to assess motor output effects on EMG activity---repetitive and single-pulse intracortical microstimulation (ICMS) (Cheney et al. 1985). Repetitive ICMS (R-ICMS) consisted of a train of 10 biphasic stimulus pulses delivered at a rate of 330 Hz (Asanuma and Rosén 1972). The computer was triggered from the onset of each stimulus train. Averages were generally based on 40 trains of stimuli. Single-pulse ICMS (S-ICMS), on the other hand, consisted of the same biphasic stimulus pulses but applied at a much lower frequency (10-20 Hz). In this case the computer was triggered from each individual stimulus. Effects from R-ICMS are generally stronger than those from S-ICMS because of temporal summation of excitatory postsynaptic potentials at the motoneuron and possible physiological spread of stimulation beyond the sphere of direct activation by the current pulse (Fetz and Cheney 1980; Jankowska et al. 1975; Lemon et al. 1987). For this reason, S-ICMS is assumed to be a more discrete and localized method of brain stimulation than R-ICMS. Averages were collected separately for flexor and extensor muscles and stimuli were only applied for the movement direction of the muscles being tested. Stimulation intensities ranged from 1.5 to 60 µA.

EMG recordings were tested for cross talk by computing EMG-triggered averages as described in previous work (Kasser and Cheney 1985). Each muscle was tested against all other muscles. Any nontrigger muscle showing cross talk of >= 15% was eliminated from the data base (Fetz and Cheney 1980).


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FIG. 2. Parasagittal section through the wrist-hand area of the pre- and postcentral cortex from one of the experimental monkeys. Cortical areas are indicated by their respective numbers. Arrows: cytoarchitectonic boundaries between areas. Electrode tracts are visible running through area 4 and several locations in areas 1 and 2 and the white matter of the postcentral gyrus. A small microlesion is present in the middle of area 3b, located next to the hole left by a blood vessel.


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FIG. 3. Functional properties of an area 3a cell and output effects obtained from same site. This was the only primary somatosensory cortex (SI) cell that produced significant postspike effects in spike-triggered averages of rectified electromyographic (EMG) activity. Postspike facilitation (PSpF) was present in multiple extensor muscles including extensor digitorum 4 and 5 (ED4,5), extensor digitorum 2 and 3 (ED2,3), extensor carpi ulnaris (ECU), and extensor digitorum communis (EDC). PSpF was superimposed on synchrony facilitation in 2 muscles, ED4,5 and EDC (Flament et al. 1992). Arrowheads: onset of PSpF. The 4 records with PSpF are summed in the bottom record of the group of spike-triggered averages. Matching poststimulus facilitation (PStF) was obtained in 3 of these muscles (ED4,5, ED2,3, and EDC). No effects were observed in the flexor muscles. The active movement response average shows a strong unidirectional, phasic-tonic discharge pattern during active wrist extension against an intermediate load (firing rate-torque relationship). Comparing the firing rate of the cell with 6 different levels of torque shows that the discharge of this cell did not vary significantly as a function of wrist torque and in this respect was fundamentally different than corticomotoneuronal (CM) cells. Filled triangle located on the parasagittal section through the pre- and postcentral cortex shows that the cell was located well into area 3a and not on the boundary between 3a and 4. Values in parentheses: number of sweeps averaged. Vertical dashed lines: time 0; these lines coincide with the onset and offset of the stimulus or spike event. Calibration bars for unit histograms in response averages: 50 Hz. Movement excursions for active and passive movements were in the range of 50-60°. Upward deflection indicates movement toward flexion for active movement, passive movement, and torque pulse records. PL, palmaris longus; ECR-B, extensor carpi radialis-brevis; ECR-L, extensor carpi radialis-longus; FDP, flexor digitorum profundus; FDS, flexor digitorum superficialis; FCU, flexor carpi ulnaris; FCR, flexor carpi radialis; PT, pronator teres; ICMS, intracortical microstimulation; POS, wrist position; CH 1-4, channels 1-4.

Receptive field testing

Receptive fields of single units or multiunit clusters were classified as cutaneous or proprioceptive. The proprioceptive classification included responses to muscle palpation and/or passive joint rotation. Responses to passive movement about a specific joint in the absence of EMG activity could be from activation of joint capsule receptors or muscle spindles. In some cases an attempt was made to further identify the modality of the response as originating from either joint receptors or muscle receptors by probing the belly of the muscle while being careful that no joint movement occurred. Cutaneous receptive fields consisted of light touch or hair bending in the absence of EMG activity and joint movement. Both proprioceptive and cutaneous responses were further categorized as phasic and/or tonic on the basis of activity during the dynamic and static phases of stimulation. Because each SI area and area 4 have specific sensory properties, we used this information together with the cell's location in relation to the central sulcus and depth in the cortex to initially identify the cortical area of each recording site as area 4, 3a, 3b, 1, or 2. These initial placements were confirmed in later histological reconstruction.

Histological reconstruction

When recording was complete, a sublethal dose of sodium pentobarbital was administered to the monkey, followed by perfusion with 10% buffered formaldehyde in saline. The brain was removed and left in a 30% sucrose/10% formaldehyde solution until it sank. The hand area of pre- and postcentral cerebral cortex was sectioned parasagittally at 50 µm in the plane of the recording tracks, mounted on slides, and stained with cresyl violet.

Boundaries of areas 4, 3a, 3b, 1, 2, and 5 were drawn for each of the sections according to established cytoarchitectonic criteria (Felleman et al. 1983; Ghosh et al. 1987; Hore et al. 1976; Jones and Porter 1980; Jones and Wise 1977; Pons and Kaas 1986; Powell and Mountcastle 1959; Sur et al. 1982; Wolpaw 1980). Specific criteria were as follows: 1) area 4/3a boundary---the appearance of an attenuated layer IV, sharpening of the boundary between gray and white matter, and the loss of large Betz; 2) area 3a to 3b---the appearance of a cell free layer V in 3b, increased density of layers II through IV with a uniform cell population, and maximum narrowing of the gray matter at the corner of the gyrus where it begins to flatten out; 3) area 3b to 1---appearance of laminated cells arranged in a distinct radial organization, a decrease in density of the middle cortical layers II and V, and less densely stained layers IV and VI in area 1; 4) area 1 to 2---an increase in cortical thickness in area 2, the appearance of large pyramidal cells in layers III and V, and the appearance of less densely stained layers IV and VI in area 2; and 5) area 2 to 5---appearance of less dense and thinner layers IV and VI in area 5, an increase in the clarity of lamination in area 5, and a decrease in the thickness as well as the number of pyramidal cells of layer III.

Figure 2 is a representative histological section in which the cytoarchitectonic boundary lines between the five cortical areas are indicated on the basis of the criteria listed above. Individual cells and cell sites were ultimately assigned to specific cytoarchitectonic areas on the basis of the receptive field properties and histological reconstruction. Histological reconstruction was aided by the placement of ink tracks at specific chamber coordinates just before perfusion and by identification of a limited number of microlesions in each monkey (7, 2, and 4 lesions, respectively, in each of three monkeys). Microlesions were made by applying 15-20 µA of current for 10-20 s in some key tracks and locations for each monkey.

Quantifying postspike and poststimulus effects

The magnitude and onset latency of PSpF and postspike suppression (PSpS) were measured as described in previous work (Kasser and Cheney 1985). Peak effects in spike- and stimulus-triggered averages were expressed as a percent of baseline EMG activity with the use of the following expression
% peak PSpF = <FR><NU>peak PSpF point − mean baseline</NU><DE>mean baseline</DE></FR>*100
Statistical comparisons were based on the Kruskal-Wallis one-way analysis of variance by ranks. We chose this nonparametric statistic because some of the comparison groups contained a relatively small number of data points.

    RESULTS
Abstract
Introduction
Methods
Results
Discussion
References

One hundred seventy-one sites in motor cortex and 68 sites in SI of three monkeys were characterized functionally and tested for motor output effects on muscle activity.

Functional properties of neurons at sites in SI and MI tested with ICMS

Our findings on the sensory properties of SI neurons were similar to those reported previously by others (Dykes et al. 1980; Powell and Mountcastle 1959; Prud'homme et al. 1994; Soso and Fetz 1980; Wannier et al. 1991). These properties were used as an aid in identifying the SI area to which a neuron belonged. Each neuron was characterized in terms of its 1) discharge pattern in relation to active wrist movement, 2) response to passive wrist movements, 3) response to extensor and flexor stretching torque perturbations applied during active movement, and 4) receptive field location, size, and modality. Figures 3-7 illustrate examples of these functional properties for individual cells at SI sites where motor output effects were tested.

Comparison of postspike effects from SI and CM cell sites

Spike-triggered averaging of rectified EMG activity was used to test SI cells in an effort to evaluate the possibility of a direct synaptic linkage between these cells and motoneurons. Although such a direct linkage might exist for some cells, it seemed more likely that the linkage between SI cells and motoneurons would be indirect. Effects from indirect linkages should be weaker than those from monosynaptic linkages. In any case, effects from nonmonosynaptic linkages can be detected with spike-triggered averaging. For example, Kasser and Cheney (1985) first showed that inhibitory effects on antagonist muscles from CM cells can be identified with spike-triggered averaging and these effects are undoubtedly mediated by a minimum disynaptic linkage. Postspike suppression from cortical cells has also been reported by Lemon et al. (1986, 1987). Furthermore, Cheney and colleagues (Cheney et al. 1991; Mewes and Cheney 1990) demonstrated clear PSpF from cells in motor thalamus. The minimum linkage to motoneurons from thalamic cells is disynaptic, involving a projection to CM cells.

Of 68 SI cells tested (18 in area 3a, 8 in area 3b, 13 in area 1, and 29 in area 2) for postspike effects in spike-triggered averages of EMG activity, only 1 area 3a cell yielded significant PSpF (Fig. 3). Typical examples of spike-triggered averages from cells in areas 3a, 3b, 1, and 2 are illustrated in Figs. 4-7, respectively. In comparison, 12% (20 of 171) of motor cortex cells tested yielded significant PSpF and were classified as CM cells. Examples of PSpFs from a CM cell are illustrated in Fig. 8. Figure 8, top left, shows clear PSpF in three muscles (ECU, ED4,5, andEDC), with weaker effects in two additional muscles (ECR-Band ECR-L). These postspike effects were confirmed in stimulus-triggered averages with the use of S-ICMS.


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FIG. 4. Functional properties and output effects of a representative cell in area 3a (128J2). This cell had a phasic-tonic discharge pattern in relation to active wrist flexion and showed weak suppression of activity to passive movements in the opposite direction (extension movements). The cell was also inhibited at short latency by extension-directed torque pulses (flexion loading). Flexion-directed torque pulses (extension loading) excited the cell at a latency of 67 ms. This cell was also activated by probing the muscle bellies of ECR-B and ECR-L. No output effects on muscle activity were obtained with spike-triggered averaging (SpTA). However, single-pulse ICMS (S-ICMS) at 40 µA revealed a relatively late, weak poststimulus suppression (PStS) of the extensor muscles and possible weak facilitation in FDP. Records obtained with repetitive ICMS (R-ICMS) at 20 µA show clear inhibition of 5 flexor muscles (PL, FCU, FDP, FCR, and FDS), with weaker, longer-latency inhibitory effects in ECR-L, ECR-B, and ED2,3. Calibrations and Conventions as in Fig. 3. VEL, velocity.


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FIG. 5. Functional properties and output effects elicited from site of a typical area 3b cell (112J2). This cell showed a biphasic response to active wrist flexion and was tonically activated by light touch on the distal pad of the 3rd digit. No postspike effects were observed with spike-triggered averaging. Nor did stimulation at 60 µA with either S-ICMS orR-ICMS produce any effects in either flexor or extensor muscles. Calibrations and conventions as in Fig. 3.


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FIG. 6. Functional properties and output effects elicited from site of a typical area 1 cell (59J1). Cell responded unidirectionally with a phasic-tonic pattern to active wrist flexion. A very similar response pattern was obtained for passive wrist flexion. Flexion-directed torque pulses (extension loading) also elicited a response at short latency, albeit a relatively weak response. During extension-directed torque pulses (flexion loading), cell responded at a latency consistent with the rebound phase (flexion) of the evoked movement. Cell's cutaneous receptive field was located on the glaborous skin of the palm of the hand and covered a relatively large area. Motor output effects from this site were mixed. No effects were observed from this cell with spike-triggered averaging; however, S-ICMS at 60 µA evoked late, weak suppression in EDC and ED4,5 and weak facilitation in 1 flexor, FDS. R-ICMS at 60 µA produced facilitation in ED2,3 but clear suppression in several other extensors (ECR-B, ECR-L, EDC, and ED4,5). Flexors showed weak facilitation followed, in some cases, by suppression. Calibrations and conventions as in Fig. 3.


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FIG. 7. Functional properties and output effects elicited from site of a typical area 2 cell (141J1). This cell shows decrementing tonic activity during hold phase of active wrist extension. Cell's passive movement response was bidirectional. Cell was unresponsive to torque pulse perturbations. Cell's cutaneous receptive field was relatively large and included the hairy skin of digits 3-5 extending proximally from digit 5 along the lateral aspect of the palm. No effects were observed in spike-triggered averages of EMG activity. S-ICMS at 60 µA yielded weak suppression in FCR, FCU, and FDS and weak facilitation followed by suppression in ECR-L, ECR-B, ED4,5, and ECU. R-ICMS produced strong suppression in flexors and mixed effects in extensors. Calibrations and conventions as in Fig. 3.


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FIG. 8. Motor output effects from a CM cell site in motor cortex. This cell increased its discharge during active wrist extension and facilitated multiple extensor muscles in spike-triggered averages of EMG activity. Strongest effects were on ECU, ED4,5, and EDC, with weaker effects on ECR-B and ECR-L. Both S-ICMS and R-ICMS produced effects in the same muscles and with a similar rank order of magnitudes. Effects are shown for S-ICMS at 3, 5, 10, 20, 40, and 60 µA and R-ICMS at 5, 10, 20, 40, and 60 µA. Asterisks: stimulus intensity producing a motor output profile that most closely matched the postspike effects from the CM cell recorded at this site. Note strength of effects from this site compared with effects from typical SI sites in Figs. 4-7. Values in parentheses: number of sweeps on which the average was based.

The properties of the area 3a cell that produced significant PSpF are of particular interest. This 3a cell discharged intensely during active wrist extension (Fig. 3). The pattern of discharge was phasic-tonic, matching the most common pattern for wrist-movement-related CM cells. However, unlike CM cells, the tonic discharge of this cell was not significantly correlated with wrist torque. The onset of discharge was coincident with the onset of target muscle EMG activity. This cell yielded PSpF in four extensor muscles (ED4,5, ED2,3, ECU, and EDC). Two of these PSpFs (ED4,5 and EDC) have a slow, gradually rising component similar to the synchrony facilitation described by Flament et al. (1992). In some cases Flament et al. were able to identify a true PSpF superimposed on synchrony facilitation. The onset of the true PSpF was marked by an increase in the slope of the rising phase of facilitation. We were able to identify such a slope discontinuity in the rising phase of facilitation for ED4,5 and EDC, suggesting the presence of a true PSpF superimposed on synchrony facilitation. Arrowheads mark the points at which onsets were measured in these PSpFs.

Stimulus-triggered averages computed from individual 10-µA stimuli (S-ICMS) applied to this site confirmed facilitation in three of the four muscles with PSpF. Muscles with no significant PSpF (ECR-B, ECR-L) also showed little or no poststimulus facilitation (PStF). The flexor muscles showed no clear changes in average EMG in either spike- or stimulus-triggered averages.

The location of this 3a cell was confirmed histologically (Fig. 3). It was located ~0.5 mm from the white matter border at the bottom of the precentral gyrus. It was also >1 mm from the area 4 border. This reduces the possibility that it could simply be a displaced CM cell. The PSpF from this area 3a cell could have been mediated by direct terminations on motoneurons (Jones and Wise 1977). However, the mean PSpF onset latency for the four extensor muscles facilitated by this cell is 10.2 ms (range: 8.4-12 ms). This compares with a mean PSpF onset latency of 6.8 ms for CM cells in this study, suggesting the possibility of a less direct linkage to motoneurons, perhaps involving connections of this cell to CM cells in motor cortex (Ghosh and Porter 1988; Herman et al. 1985; Zarzecki et al. 1978).

Active movement responses of this 3a cell were determined at six different torque levels. The pattern of discharge in relation to active movement at all load levels was phasic-tonic. CM cell tonic discharge is linearly related to static torque (Cheney and Fetz 1980). In contrast, the tonic discharge of this 3a cell was unrelated to static torque over the ninefold range of torque that was examined (0.018-0.165 Nm). Over this torque range, the average extension-related CM cell would have increased its firing rate threefold.

The magnitude of facilitation from stimulation at the site of this area 3a cell was quantified according to the methods described previously and compared with magnitudes at CM cell sites and other 3a cell sites (Table 1). The magnitudes of PSpF for this 3a cell were not significantly different from the mean PSpFs of CM cells. The average magnitude of PStF evoked from the site of this 3a cell was less than half the mean at CM cell sites, but comparable with other 3a sites.

 
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TABLE 1. Magnitude of PSpF and PStF (S-ICMS) from an area 3a cell and CM cells

Effects on muscle activity elicited with ICMS at SI and MI sites

INCIDENCE OF EFFECTS ON MUSCLE ACTIVITY. One measure of the involvement of a cortical area in motor output is the extent to which effects on muscle activity can be evoked with ICMS. S-ICMS (20 µA) at CM cell sites produced PStF in one or more forelimb muscles at all sites tested. The same stimulation applied to SI yielded effects at only 25, 10, 17, and 8% of area 3a, 3b, 1, and 2 sites respectively. R-ICMS at 20 µA was only slightly more effective, yielding effects at 41, 18, 15, and 9% of sites respectively. Higher intensities of stimulation were more effective but, except for area 3a, the percent of effective sites remained <50% even at 60 µA. Area 3a was clearly the most effective SI area in producing effects on muscle activity, with 57% of sites producing effects at 40 µA and 72% of sites at 60 µA(S-ICMS). Nevertheless, both areas 3a and 2 were relatively ineffective compared with motor cortex, despite containing cells with properties similar to CM cells and relatively dense connections with motor cortex. Typical examples of output effects from areas 3a, 3b, 1, and 2 are illustrated in Figs. 4-7, respectively.

Expressing effects as a percent of the total number of muscles tested yields an even clearer picture of the difference between the motor output capacity of SI and MI (Table 2). Lumping excitatory and inhibitory effects together, area 3a again yielded the largest number of effects on muscle activity of any SI area (16% at 20 µA, S-ICMS), but even this was far less than the frequency of effects observed at CM cell sites (85% at 20 µA, S-ICMS). Area 2 yielded the fewest effects on muscle activity (3% at 20 µA, S-ICMS), raising serious doubts about the motor efficacy of the projection from area 2 to MI.

 
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TABLE 2. Percent of muscles showing facilitation or suppression of EMG activity from stimulation at SI and CM cell sites

The prevalence of suppression versus facilitation represents another sharp distinction between the motor output effects from SI and MI. At CM cell sites, the earliest latency effect in 75% of muscles tested at 20 µA was facilitation. In contrast, at SI sites a much smaller percent of the earliest effects was excitatory (4% for 3a and 1% for areas 3b, 1, and 2 at 20 µA). At SI sites, the earliest effect across all stimulus intensities (S-ICMS, 10-60 µA) and muscles tested was facilitation only 2.8% of the time, compared with suppression 9.3% of the time. No effect was observed in 87.9% of the cases tested. In contrast, at CM cell sites the comparable percentages were 78.4% for facilitation and 6.7% for suppression (Table 2). Suppression was >3 times as common at SI sites than facilitation, whereas at CM cell sites facilitation was almost 12 times more common than suppression. The predominance of suppression from SI sites was true for all sites and virtually all stimulus intensities. Similar differences were found for R-ICMS. In general, the number of muscles with effects from SI areas increased with increasing stimulus intensity, but overall, the absolute number was much lower at all intensities than at CM cell sites.

MAGNITUDE OF EFFECTS ELICITED FROM SI WITH THE USE OF ICMS. The magnitude of effects elicited from SI sites represents still another point of contrast with effects from CM cell sites in area 4. Typical poststimulus effects from an area 4 CM cell site are illustrated in Fig. 8 and can be compared with output effects from SI areas (Figs. 4-7). This CM cell produced clear PSpF in ECU, ED4,5, and EDC, with weaker effects in ECR-B and ECR-L. Both S-ICMS and R-ICMS produced a similar profile of effects. The poststimulus effects with S-ICMS had a threshold between 3 and 5 µA. At 5 µA, PStF was weak but measurable in ECU and ED4,5 and suggestive in EDC, ECR-B, and ECR-L. At 10 µA, these effects became much stronger and the effects in EDC and ECR-B became clearer. At 20 µA, strong effects were present in ECU, ED4,5, and EDC, with weaker effects in ECR-B and ECR-L. This pattern matches very closely the pattern of PSpF obtained from the individual CM cell at this site. At higher intensities of stimulation, all these effects became stronger and a clear PStF also appeared in ED2,3.

Similar effects were obtained at this site with R-ICMS. Note that these effects were based on averages of 40 sweeps rather than the 500-1,000 sweeps used for S-ICMS. The threshold was slightly higher, between 5 and 10 µA, and again the strongest effects were in ECU, ED4,5, and EDC. Facilitation was followed by sharp inhibitory dips when the stimulus was terminated. These dips match the biphasic effects that were obtained with S-ICMS and may reflect an underlying longer-latency inhibition elicited by the stimulus. With R-ICMS, overlapping excitatory and inhibitory effects may have reduced the amplitude of facilitation and increased the threshold. With S-ICMS, overlap and cancellation of effects was minimized because the time between stimuli was longer than the sum of the onset latency and duration of the effect. All effects became stronger with increasing intensity until at 60 µA the effects in all muscles were about equal in magnitude.

In comparison, motor output effects obtained with S-ICMS and R-ICMS from sites in areas 3a, 3b, 1, and 2 were generally very weak (Figs. 4-7). One exception was an area 3a site discussed previously at which an individual 3a cell produced clear PSpF (Fig. 3).

Poststimulus effects were quantified by expressing the peak magnitude of facilitation or suppression as a percent of baseline. The magnitudes of PStF and poststimulus suppression (PStS) from S-ICMS at CM and SI sites are given in Fig. 9. The magnitude of PStF at CM cell sites was 6.5-15.4 times greater (depending on stimulus intensity) than effects at SI sites. S-ICMS at SI sites was not only more frequently unsuccessful in eliciting effects on muscle activity, but the effects obtained were also much weaker than those from CM cell sites. In contrast to PStF, the magnitudes of PStS from SI sites were similar to those from area 4 CM cell sites (Fig. 9). Similar results were obtained with R-ICMS (Fig. 10). The strongest inhibitory effects from SI were from sites in area 3a.


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FIG. 9. Average magnitude of all PStF and PStS effects evoked at SI and CM cell sites with S-ICMS at several different stimulus intensities. Effects are expressed as % increase or decrease in peak facilitation or suppression relative to pretrigger baseline segment of record. Values plotted are means ± SD. Asterisks: no responses were obtained at that stimulus intensity. CM cell sites clearly have much stronger PStF than any of the SI areas. However, PStS is not significantly different at SI and CM cell sites. Responses at 60 µA were obtained at only 2 CM cell sites, which probably explains the fact that the magnitude at 60 µA is less than that at 40 µA. Numbers of cell muscle pairs on which data are based are given in Table 3.


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FIG. 10. Average magnitude of all effects evoked at SI and CM cell sites with R-ICMS at different stimulus intensities. Effects are expressed as % increase or decrease in peak facilitation or suppression compared with baseline segment of record. Values plotted are means ± SD. Asterisks: no responses were obtained at that stimulus intensity. Just as with S-ICMS, CM cell sites clearly produce much stronger facilitation than SI sites. However, suppression is similar in magnitude at both SI and CM cell sites. Numbers of cell muscle pairs on which data are based are given in Table 3.

The magnitude of stimulus-evoked output effects was also evaluated by limiting the analysis to only the muscle at each site with the greatest effect. This analysis avoids biases that could occur if an area consistently yielded weak effects in many muscles in addition to strong effects in a few primary muscles. Again, effects evoked from SI sites were 2-15 times weaker (depending on stimulus intensity) than those from CM cell sites. These findings confirm the results from analysis of all effects from SI sites (Fig. 9) and further emphasize the differences in motor output efficacy between SI and MI.

ONSET LATENCY OF PStF AND PStS FROM SI SITES. The onset latencies of muscle effects elicited with S-ICMS at SI sites are relevant to questions about possible underlying neural pathways that could mediate these effects. Mean onset latencies for PStF and PStS from SI and CM cell sites are given in Table 3. Although the onset latencies between the four SI areas were somewhat different, none of these differences were statistically significant. However, one consistent finding in both the S-ICMS and R-ICMS data was that effects at SI sites had consistently longer latencies than effects from CM cell sites. For example, averaged over all intensities of stimulation, the mean onset latency of S-ICMS-evoked PStF from SI was 10.1 ms, compared with 7.8 ms for effects from CM cell sites. The longer latency of effects from SI sites is consistent with a less direct path to motoneurons from SI, possibly involving connections through motor cortex.

 
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TABLE 3. Mean onset latency of facilitation effects from SI cortical areas and CM cell sites in motor cortex

EFFECTS FROM DIFFERENT CORTICAL LAYERS. Although the site of stimulation could be localized in some cases to a particular layer of cortex on the basis of reconstruction of microlesions, at most sites this was not possible. Effects from SI could differ depending on the cortical layer stimulated. In motor cortex, this could be ruled out because data were collected at the sites of identified CM cells, which are known to be located exclusively in layer V. For SI, we used area 2 to assess the extent to which effects might depend on the cortical layer stimulated. We selected area 2 for this purpose because it is accessible to perpendicular electrode penetrations and it is known to be the origin of both corticospinal projections and a corticocortical projections to motor cortex. The cortex of area 2 was stimulated at 60 µA with the use of R-ICMS at 0.5-mm intervals starting with the first cortical activity and continuing into white matter. Entry into white matter was noted by the absence of cell soma spikes and the presence of axonal spikes (small, short duration ± biphasic spikes).

Stimulus-evoked muscle effects were quantified and the magnitudes were compared. Except for the most superficial stimulus site, effects on muscle activity were obtained at all depths of stimulation. The strongest effects were elicited from the middle layers of area 2 corresponding to stimulation from 0.5 to 1.5 mm below the cortical surface. This is consistent with the depths of layers III and V that are known to be the origin of cells projecting to motor cortex (Ghosh and Porter 1988). At deeper sites of stimulation, effects remained clear but averaged 44% of the magnitude of the effects from the middle cortical layers. Although the magnitude of effects from SI did vary somewhat with the cortical layer stimulated, the magnitude of the differences was not so great that it would have altered the conclusions derived from the SI stimulation studies.

    DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References

The principal finding of this paper is very clear. Although effects on muscle activity can be elicited from SI areas with S-ICMS and R-ICMS, these effects are more limited in number, weaker in magnitude, and much more frequently inhibitory than effects from CM cell sites in motor cortex. The inhibitory character of effects from SI and their weak magnitudes was true even at intensities as high as 60 µA. Moreover, despite extensive testing, only one SI cell yielded a significant PSpF in spike-triggered averages of EMG activity. This was an area 3a cell that resembled a CM cell in many of its functional properties but was located well inside the area 3a/4 border. The characteristics of the muscle effects we obtained from SI indicate that the nature of the linkage between SI areas and motor output is not consistent with a fast, powerful, obligatory type of relay action on muscle activity. Moreover, the coupling between SI areas and MI corticospinal output is more consistent with a some type of modulatory influence. An example of this type of action might be the long-term potentiation reported by Asanuma and colleagues (Iriki et al. 1989) in motor cortex after tetanic stimulation of SI. Of course, we cannot rule out the possibility that operation of the linkage between SI and MI could be task dependent such that under certain circumstances (for example, manipulation of objects where tactile feedback is important), functional output from SI through motor cortex maybe "switched on" or in some way facilitated.

Effects from motor cortex were obtained at identified CM cell sites. Somewhat weaker output effects might have been expected from MI if sites other than CM cell sites had been included. Recording in SI was always at depths below 0.5 mm, but beyond that no effort was made to restrict recording sites to a particular depth. Is it possible that this could have skewed the results strongly in favor of weak effects from SI and strong effects from motor cortex? This seems unlikely. Results from depth stimulation in SI suggested that over the cortical layers corresponding to depths of 0.5-1.5 mm, the magnitude of output effects was relatively constant. At depths below 1.5 mm, the output effects still averaged 44% of the effects obtained from the middle cortical layers. Moreover, even the strongest effects from SI areas were relatively weak compared with those from motor cortex. Therefore it is unlikely that the results would have changed substantially even if stimulation could have been restricted to output layers of SI.

Considerable evidence suggests that activation of neurons by ICMS is largely indirect and occurs by stimulation of intracortical afferents (Jankowska et al. 1975; Porter and Lemon 1993; Lemon et al. 1987). Given that this is true, some of the differences in SI output effects compared with motor cortex might be due to differences in the intracortical organization of afferent inputs to neurons. However, the fact that the output effects remained weak even at intensities as high as 60 µA, where a larger collection of neuronal elements should have been activated directly, suggests that this is probably not a major factor contributing to the results.

Implications for the concept of a sensorimotor cortex

The pioneering work of Schaefer (1900), Penfield and colleagues (Penfield and Boldrey 1937; Penfield and Rasmussen 1952), and Woolsey (1953, 1958) demonstrated that movements can be evoked not only by surface electrical stimulation of the precentral gyrus but also by stimulation of the postcentral gyrus. This early work has been confirmed by a number of more recent studies (Albe-Fessard and Donaldson 1970; Doetsch and Gardner 1972; Wannier et al. 1991). Although somewhat higher stimulus intensities were required, movements evoked by stimulation of SI were described as similar in character to those evoked by stimulation of MI. This finding, coupled with evidence that MI receives substantial sensory input from peripheral receptors, led to the concept of a sensorimotor cortical amalgam lumping together the precentral and postcentral gyrus (Woolsey 1953). Precentral and postcentral cortex were viewed as possessing similar motor and sensory capabilities, although with a different emphasis, as reflected in the designations sensorimotor for postcentral cortex and motor-sensory for precentral cortex (Woolsey 1958).

It is clear that neurons in SI, including pyramidal tract neurons, share many functional properties in common with neurons in motor cortex. These include discharge onsets that precede the onset of movement, similar firing patterns in relation to movement, and firing rates related to the force generated during active movement (Burbaud et al. 1991; Fetz et al. 1980, 1984; Fromm 1983; Fromm and Evarts 1982; Fromm et al. 1984; Gardner and Costanzo 1981; Jennings et al. 1983; Prud'homme and Kalaska 1994; Soso and Fetz 1980). On the other hand, Inase et al. (1989) reported that all the SI neurons they recorded began discharging after the onset of EMG activity in the muscles acting as prime movers for the task. Additional studies have also emphasized the differences in functional properties of movement-related neurons in sensory and motor cortex (Wannier et al. 1986, 1991). Our study focuses primarily on the motor output capabilities of somatosensory and motor cortex. Our findings serve to emphasize some fundamental differences between SI and MI. Of particular significance is the fact that only one SI neuron produced significant PSpF of EMG activity. Moreover, poststimulus effects were weak, infrequent, and predominantly inhibitory. The finding of predominantly inhibitory effects is new and unexpected. We were able to detect inhibitory effects because stimuli were applied in the presence of a significant background level of EMG activity.

The differences between our findings and those reported by several previous studies may be due, in part, to differences in methodology. The early studies on motor output from SI were based on surface stimulation of the cortex with macroelectrodes with the use of relatively high current levels in the anesthetized monkey (Woolsey et al. 1953). More recent work has depended on ICMS to achieve more localized stimulation of cortical tissue, but in all these studies repetitive stimulation (R-ICMS) was used and, in most cases, evoked movement rather than EMG activity was monitored as the output parameter. We used the more sensitive methods of spike- and stimulus-triggered averaging of EMG activity. S-ICMS and R-ICMS were applied in awake monkeys during active movements to increase the sensitivity of the methods and to provide a relatively constant background level of motoneuronal excitability. These methods have revealed clear differences in the motor output capacity of SI compared with motor cortex.

Two previous studies have strongly supported the functional separation of sensory and motor cortex in the primate and are of particular relevance to our findings. The first was a study by Sessle and Wiesendanger (1982). They examined the extent to which motor cortex in the monkey could be clearly distinguished from adjacent cortical areas on the basis of ICMS-evoked motor output effects, sensory responses of neurons, and the location of identified corticospinal neurons. The principal finding was that "microexcitable" cortex, that is, cortex from which movements could be evoked with ICMS at low threshold (currents <30 µA), is sharply delineated at its posterior boundary and did not include area 3a. This result was supported by a parallel finding on the sensory side that although both motor cortex and area 3a neurons could be easily activated at short latency by proprioceptive input in the awake animal, under barbiturate anesthesia responses in motor cortex neurons were largely lost whereas area 3a neurons remained responsive. Sessle and Wiesendanger concluded that the sensory and motor functions of the precentral and postcentral cortices can be clearly distinguished, and argued against the notion of a sensorimotor cortex.

The second study was a more recent report by Hepp-Reymond and colleagues (Wannier et al. 1986, 1991) in which the functional properties of SI neurons were compared with the properties of motor cortex neurons determined under the same conditions. Although SI and motor cortex neurons were similar in several respects, such as firing patterns in relation to movement as noted by previous investigators, a number of important differences was emphasized. First, only 14% of task-related SI neurons changed their discharge in advance of force onset, compared with 56% of neurons in motor cortex. MI also differed clearly from SI in having 1) a much larger fraction of neurons activated by stimulation of deep tissues compared with cutaneous receptors (skin and hair), 2) a larger fraction of neurons with statistically significant linear firing rate---force relations and less scatter in the slopes of these relationships, and 3) a much larger fraction of sites from which motor responses could be evoked with stimuli of <= 15 µA (87% of sites in MI compared with 25% in SI). These authors argue that it is highly unlikely that SI participates in movement initiation, and that the predominant role of SI is processing of sensory information from skin and muscle.

Surprisingly, the threshold currents reported by Wannier et al. (1991) for evoking movements were similar for both MI and SI (10.7 vs. 11.9 µA). Although we did not determine threshold currents, our results (Table 2) would certainly suggest higher thresholds at SI sites than MI sites, as others have reported (Sessle and Wiesendanger 1982). This apparent discrepancy between our results and those of Wannier et al. might be due to differences in methods. For example, our MI sites were sites of identified CM cells, which would be expected to have lower thresholds than unidentified MI sites. Differences in the behavioral task might be another factor. We used a simple alternating wrist movement task, whereas Wannier et al. used a precision grip task that might have been more dependent on sensory feedback, resulting in facilitation of connections from SI to MI. Regardless of the explanation of a possible threshold difference, it is important to emphasize that our findings are similar to those of Wannier et al. in showing that a much smaller percentage of SI sites yields motor output effects with ICMS than MI sites.

Implications for role of SI in trancortical reflex loops

The findings of this study are also relevant to hypotheses about the function of SI in the control of movement. Phillips (1969) first proposed the existence of a long-latency, transcortical stretch reflex loop originating with muscle spindle afferents and including CM cells as the efferent component of the loop. Considerable evidence now exists that CM cells respond with appropriate timing to contribute to the M2 EMG response of muscle to stretch (Cheney and Fetz 1984; Tatton et al. 1975). The pathway by which muscle spindle afferent information reaches motor cortex is less clear. The issue is whether spindle afferent information is transmitted directly to motor cortex from the appropriate thalamic nucleus, or whether it is relayed to motor cortex from an SI area. It is well known that somatosensory cortex receives afferent input from muscle, joint, and cutaneous receptors in the periphery via the medial lemniscus and spinothalamic pathways (Powell and Mountcastle 1959). It is also well established that SI areas 2, 1, and 3a all have significant projections to area 4, with the densest projections coming from area 2 (Aizawa and Tanji 1994; Ghosh et al. 1987; Jones et al. 1978; Jones and Powell 1969; Kaneko et al. 1994; Pons and Kaas 1986; Vogt and Pandya 1977; Zarzecki et al. 1978). Although the presence of a projection from area 3a to motor cortex has been controversial, it is now clear that such a projection exists (Avendano et al. 1992; Ghosh et al. 1987; Phillips et al. 1971; Porter 1991; Zarzecki et al. 1978). Moreover, area 3a is known to receive input from muscle spindle afferents (Hore et al. 1976; Phillips et al. 1971). The remaining issue, which is still not fully resolved, concerns the origin of the proprioceptive responses of neurons in area 4. Is the input to motor cortex for these responses relayed from area 3a (Porter 1990)? Tatton et al. (1975) reported that lesions of the postcentral cortex abolished the long-latency M2 EMG response to muscle stretch, suggesting that muscle spindle afferent information may be relayed from somatosensory cortex to motor cortex. However, a more recent study by Brinkman et al. (1985) failed to show any significant attenuation of responses of motor cortex neurons to passive joint movement during cooling of the postcentral gyrus. Cooling in this case was sufficient to inactivate area 2 and suppress function in area 3a. The results argue strongly against a role of area 2 in mediating the sensory responses of motor cortex neurons. Although a role for area 3a also seems unlikely, it could not be completely ruled out because of insufficient cooling. Nevertheless, these results are consistent with the findings of Asanuma et al. (1979, 1980) showing that somatosensory evoked potentials in motor cortex were not reduced by lesions of the postcentral cortex, and with several studies demonstrating that motor cortex in the monkey receives peripheral somesthetic inputs directly from the thalamus (Asanuma et al. 1980; Horne and Tracy 1979; Lemon and van der Burg 1979). Our result showing the lack of robust, excitatory responses in muscles from stimulation of SI areas provides further evidence against a role of SI as an obligatory link in a transcortical reflex loop mediating long-latency responses of muscles to stretch. This conclusion is strengthened by the fact that the responses of many SI neurons, including area 3a neurons, to torque pulse perturbations were relatively weak and peaked after the M2 EMG response (e.g., Fig. 4).

Mechanism of effects from SI

Effects on muscle activity from SI could be mediated by 1) direct corticospinal projections from SI to motoneurons or to spinal interneurons, 2) SI projections to motor cortex including pyramidal neurons, 3) corticospinal actions on presynaptic terminals of sensory afferents within the spinal cord or neurons in ascending pathways to motor cortex, or 4) activation of collaterals of motor cortex pyramidal neurons projecting to SI. It is well established that SI areas are the source of significant numbers of corticospinal neurons, although the density of these neurons is substantially lower than in MI (Bentivoglio and Rustoni 1986; Coulter and Jones 1977; Coulter et al. 1976; Galea and Darian-Smith 1994; Harting and Noback 1970; Jones and Wise 1977; Murray and Coulter 1981; Nudo and Masterton 1990; Ralston and Ralston 1985; Sessle and Wiesendanger 1982; Toyoshima and Sakai 1982). However, with only one exception, none of the movement-related SI neurons we tested produced PSpF of muscle activity, suggesting that these neurons do not make tight linkages with motoneurons. As others have shown, most of these neurons seem to terminate in the dorsal horn and are probably involved in controlling transmission of sensory afferent information (Fetz 1968). The fact that the latency of SI PStF was longer than the latency of PStF from motor cortex also argues against direct actions on motoneurons from SI. Unfortunately, our experiments do not allow us to exclude in any absolute sense the remaining possibilities by which SI might influence muscle activity. Neither can we distinguish between possible presynaptic and postsynaptic actions of SI at the cortical or spinal level.

Regarding the possible role of motor cortex in mediating effects from SI stimulation, it is important to note that area 3b does not project to motor cortex, yet the effects from area 3b were not substantially different from effects elicited from areas 3a, 1, and 2. This could be a coincidence, but this fact might also suggest that the effects from SI are independent of motor cortex. Early studies in which movements were evoked by stimulation of postcentral cortex after ablation of motor cortex also support a route other than motor cortex for mediating SI effects on muscle activity (Woolsey et al. 1953). However, in these studies the use of relatively large stimulus currents raises the issue of spread to noncortical sites. On the other hand it is interesting to note that Brinkman et al. (1985) found that cooling postcentral cortex in the monkey increased the background discharge of neurons in MI. This suggests the existence of some tonic inhibition of MI neurons by SI, which is consistent with our finding of predominantly inhibitory effects from SI on muscle activity. The exact mechanism by which effects on muscle activity from SI occur will have to await additional experiments. Nevertheless, it is clear from this study that these effects differ quantitatively and qualitatively in fundamental ways from those obtained from motor cortex, and that in the normal brain the function of SI should be viewed as one devoted largely to sensory processing.

    ACKNOWLEDGEMENTS

  This work was supported by National Institutes of Health GrantsNS-25646 and HD-02528 and National Science Foundation Grant BMS8216608.

    FOOTNOTES

   Present address of G. L. Widener: Dept. of Physical Therapy, Samuel Merritt College, Oakland, CA 94609.

  Address for reprint requests: P. D. Cheney, Smith Mental Retardation and Human Development Research Ctr., University of Kansas Medical Center, Kansas City, KS 66160.

  Received 6 September 1996; accepted in final form 15 January 1997.

    REFERENCES
Abstract
Introduction
Methods
Results
Discussion
References

0022-3077/97 $5.00 Copyright ©1997 The American Physiological Society