Tokimura et al. (2000) reported that stimulation o f the median nerve at the wrist and digital nerves of index finger and thumb could suppress MEP responses evoked in hand muscles by TMS. Peripheral nerve stimulation was applied approximately 20 ms before TMS was applied at the motor cortex, which is the approximate conduction time fi*om periphery to cortex. Inhibitory effects of the peripheral nerve stimulation on TMS evoked volleys were then indicated by the suppression o f the MEP response, evoked in IDI activity some 25 ms later. The total time-course of effects (approximately 45 ms following peripheral nerve stimulation) corresponded to the latency o f the inhibitory period (II) o f the reflex response in the ongoing EMG activity, which would have occurred following application of the median nerve stimulation alone. Recordings of descending volleys in the spinal cord, showed that later I-waves evoked by TMS were suppressed by median nerve stimulation (Tokimura et al. 2000). Authors concluded that cortical inhibition observed following peripheral nerve stimulation is likely to be responsible for the early period of inhibition in the long-latency reflex (Tokimura et al. 2000). A similar conclusion was made by Delwaide and Olivier (1990) who showed that H-reflex responses evoked by forearm stimulation were unaffected by peripheral nerve stimulation o f the wrist, suggesting that inhibitory effects observed were of a cortical nature.
Work has been done to see if peripheral inputs can also have excitatory effects on the motor cortex; this would then explain the cortical nature o f the E2 phase (that follows the II phase) o f the long-latency reflex. One study investigated the effects of digital nerve stimulation on MEPs evoked by TMS and TES (Maertens de Noordhout et al. 1992). Activation o f cutaneous inputs by digital nerve stimulation caused suppression of TES evoked MEPs, at latencies equivalent to the inhibitory (II) phase. When longer intervals between digital nerve stimulation and TES were used, excitation was observed, at 55
latencies equivalent to the E2 phase of the reflex. Modulation o f TMS evoked responses by digital nerve stimulation followed a similar pattern o f inhibition and excitation although effects were observed over a different time-course. Suppression of responses occurred at a time equivalent to the early inhibitory phase, however excitatory effects were delayed. These results were confirmed in single motor unit recordings. TMS was set at an intensity to increase the firing probability o f single motor units, as indicated in PSTH analysis. The digital nerve stimulus also increased the firing probability o f the single motor unit at a latency equivalent to the E2 phase. When both stimuli were applied, and TMS was delivered at a latency such that it would have an effect at the onset of the E2 period, the increased firing o f single motor units was less than would be expected by the sum of combined effects. This indicates a prolongation of the earlier inhibitory phase, into the expected E2 phase (Maertens de Noordhout et al. 1992).
Nevertheless, it was concluded that, in addition to inhibitory effects, peripheral input could also have excitatory effects on motor cortex activity (Maertens de Noordhout et al. 1992). This was most clear for effects observed on TES evoked MEPs, although authors admit that this is somewhat difficult to explain, given that TES excites PTN axons directly, at a site far enough away from the cell body to be relatively unaffected by motor cortex excitability. However, note that TES can evoke both D-waves and later I-waves (Edgely et al. 1997), the latter of which can be modulated by peripheral nerve stimulation (Tokimura et al. 2000). That TMS preferentially evokes I-waves, might then explain why inhibitory effects o f the peripheral inputs on TMS evoked responses were prolonged.
In the same study (Maertens de Noordhout et al. 1992), peripheral afferent activation by stretch was shown to have both inhibitory and excitatory effects on TMS evoked MEPs (corresponding to II and E2 phases respectively), although the prolonging of the inhibitory phase (found using digital nerve stimulation) was not observed. This difference 56
in effects o f electrical cutaneous afferent stimulation and natural activation of peripheral inputs, was partly explained by the fact that stretch also activated muscle afferents. In addition, it should also be noted that long-latency reflex responses evoked by electrical stimulation are generally weak and require averaging over trials, before clear effects in EMG are observed. This is in contrast to strong reflex responses evoked by natural activation o f cutaneous inputs that can be observed on a single trial basis (Johansson et al.
1994). Indeed marked facilitation o f TMS evoked MEP responses by natural cutaneous activation (which may have accounted for the lack o f prolonged inhibition observed in the Maertens de Noordhout study), was shown in a study by Johansson et al. (1994). Subjects used a precision grip to restrain an object, which was subjected to pulling loads away from the hand. This loading effect caused an increase in firing o f cutaneous afferents recorded within the median nerve. At a latency o f 40-140 ms following load application, MEPs evoked in hand muscles were greatly facilitated, in a manner separate to the smaller increase in ongoing EMG activity. This suggested a ‘boosting’ effect of task- related cutaneous afferent input on TMS evoked responses. Authors argue that, given the latency o f effects, this facilitation was likely to have occurred in the motor cortex (Johansson et al. 1994).