Modulation of human corticomotor excitability by somatosensory input

Abstract

In humans, somatosensory stimulation results in increased corticomotoneuronal excitability to the stimulated body parts. The purpose of this study was to investigate the underlying mechanisms. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) from abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. MEP amplitudes, recruitment curves (RC), intracortical inhibition (ICI), intracortical facilitation (ICF), resting (rMT) and active motor thresholds (aMT) were recorded before and after a 2-h period of ulnar nerve electrical stimulation at the wrist. Somatosensory input was monitored by recording somatosensory evoked potentials. To differentiate excitability changes at cortical vs. subcortical sites, we recorded supramaximal peripheral M-responses and MEPs to brainstem electrical stimulation (BES). In order to investigate the involvement of GABAergic mechanisms, we studied the influence of lorazepam (LZ) (a GABA(A) receptor agonist) relative to that of dextromethorphan (DM) (an NMDA receptor antagonist) and placebo in a double-blind design. We found that somatosensory stimulation increased MEP amplitudes to TMS only in the ADM, confirming a previous report. This effect was blocked by LZ but not by either DM or placebo and lasted between 8 and 20 min in the absence of (i) changes in MEPs elicited by BES, (ii) amplitudes of early somatosensory-evoked potentials or (iii) M-responses. We conclude that somatosensory stimulation elicited a focal increase in corticomotoneuronal excitability that outlasts the stimulation period and probably occurs at cortical sites. The antagonistic effect of LZ supports the hypothesis of GABAergic involvement as an operating mechanism.

Figure 1. Changes induced by a 2-h period of somatosensory stimulation (A,B,C) or 2 h idle time (D) on the amplitude of motor evoked potentials (MEPs) recorded from the abductor digiti minimi (ADM)

A, representative 3-MEP averages evoked by TMS at intensities 10, 20, 30 and 40 % above motor threshold in one representative experiment, before (thin line) and after (thick line) the 2-h period of somatosensory stimulation. B, grand average of ADM-MEP amplitude (mean ±s.e.m., n = 10) from all subjects recorded at TMS intensities 10, 20, 30 and 40 % above motor threshold (○….○: before intervention; ▪–▪: after 2-h period of somatosensory stimulation). C, recruitment curve (mean of three subjects) recorded at 10 randomly intermixed TMS intensities before (○) and after (▪) the 2-h period of somatosensory stimulation (mean ±s.e.m.). The dotted line represents the Boltzmann sigmoid function estimated by nonlinear regression before the 2-h period of somatosensory stimulation; the thick line represents the Boltzmann function estimated after stimulation. Both curves were significantly different from each other (see Methods for the statistics used). Amplitude is expressed as a percentage of the supramaximal M-response. *P < 0.05. D, a control period consisting of a 2-h idle time (without somatosensory stimulation) did not significantly change the amplitude of MEPs (mean ±s.e.m.) recorded from the ADM at TMS intensities 10, 20, 30 and 40 % above motor threshold (○….○: before the 2-h idle time; ▪–▪: after 2-h period of idle time; n = 6).

Figure 2. Changes induced by a 2-h period of somatosensory stimulation or 2 h idle time on the amplitude of motor-evoked potentials (MEPs) recorded from the median nerve-innervated abductor pollicis brevis (APB)

A, the amplitude of MEPs (mean ±s.e.m.) recorded at TMS intensities 10, 20, 30 and 40 % above motor threshold from APB were not significantly changed by the 2-h period of electrical stimulation of the ulnar nerve (○….○: before intervention; ▪–▪: after 2-h period of somatosensory stimulation; n = 10 subjects). All amplitudes are expressed as a percentage of the supramaximal M-response. B, a control period consisting of a 2-h idle time (without somatosensory stimulation) did not significantly change the amplitude of MEPs (mean ±s.e.m.) recorded from the APB at TMS intensities 10, 20, 30 and 40 % above motor threshold (○….○: before the 2-h idle time; ▪–▪: after 2-h period of idle time; n = 6).

Figure 3. Comparison of the effect of a 2-h period of somatosensory stimulation on motor evoked potential (MEP) amplitudes simultaneously recorded from the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and first dorsal interosseus (FDI)

A, the 2-h period of electrical stimulation of the ulnar nerve typically induced sensation in a region (hatched area) overlapping the ulnar nerve-innervated ADM but not the ulnar nerve-innervated FDI and the median nerve-innervated APB. B, grand average across all subjects (n = 6) of the individually normalized increase in MEP amplitude (MEP peak-to-peak amplitude before intervention set to 100 %) after a 2-h period of somatosensory stimulation. Only MEP amplitude recorded from the ADM was significantly (P < 0.05) larger after the 2-h period of electrical stimulation. C, representative 3-MEP averages from a typical experiment before the intervention (thin line) and after the intervention (thick line) simultaneously recorded from the ADM, FDI (middle trace) and APB (traces on the right-hand side). D, MEP amplitudes (expressed as percentages of the maximal peripheral M-response) recorded from the ADM, FDI and APB, before (dots on the left of each line) and after (dots on the right of each line) a 2-h period of somatosensory stimulation in all six subjects (each line is one experiment).

Figure 4. Time course of the increase in the amplitude of motor-evoked potentials (MEP) recorded from the abductor digiti minimi (ADM) induced by a 2-h period of somatosensory stimulation (mean ±s.e.m., n = 6)

The individually normalized MEP amplitude (as a percentage of pre-intervention values: MEP peak-to-peak amplitude before intervention set to 100 %) was only significantly larger than baseline in the 8- to 20-min period following the intervention. *P < 0.05.

Figure 5. Comparison of the effects of a 2-h period of somatosensory stimulation on motor-evoked potential (MEPs) evoked by transcranial magnetic stimulation (TMS) and brainstem electrical stimulation (BES) recorded from the abductor digiti minimi (ADM)

A and B, each trace represents the mean of five consecutive MEPs recorded before and after the 2-h period of somatosensory stimulation from two subjects. The increase in amplitude of TMS-evoked MEPs induced by a 2-h period of somatosensory stimulation was significant whereas the amplitude of potentials evoked by BES was not significantly changed by the intervention.

Figure 6. Effects of dextromethorphan (DM) and lorazepam (LZ) on the change in amplitude induced by a 2-h period of somatosensory stimulation

MEP amplitude changes relative to pre-intervention values (mean ±s.e.m.) in abductor digiti minimi (ADM; TMS intensity 40 % above rMT; n = 5). Note that LZ blocked the effects of SS stimulation relative to the placebo session. The effect of a 2-h period of somatosensory stimulation was not significantly different under the effects of DM than under the effects of placebo (P, on the left). In contrast, LZ significantly (P < 0.05) blocked the effects of a 2-h period of somatosensory stimulation compared with the placebo session (P, on the right).

Figure 7. Amplitude (in mV) of the early components (N1:N20, P1:P25, N2:N30) of somatosensory-evoked potentials (SEP) recorded during the 2-h period of somatosensory stimulation under the action of dextromethorphan (DM), lorazepam (LZ), and the corresponding placebo (P) sessions

A, each trace is the mean of 300–400 trials recorded in the same representative subject during the 2-h period of somatosensory stimulation (arrows indicate the early components N1, P1, N2 used for the analysis). B, grand average across all subjects (n = 5, mean ±s.e.m.) of the N1-P1 amplitude (▪) and P1-N2 amplitude (□). Neither DM nor LZ significantly modified SEP amplitude compared with placebo.