Modulation of excitability of human motor cortex (M1) by 1 Hz transcranial magnetic stimulation of the contralateral M1

Abstract

Objective: Previous studies demonstrated that single-pulse transcranial magnetic stimulation (TMS) of one motor cortex (M1) exerts a brief inhibitory effect on the contralateral M1. The purpose of this study was to test the hypothesis that 30 min of 1 Hz TMS of M1 will result in a lasting increase in excitability in the contralateral M1.

Methods: Healthy volunteers were tested on 2 separate days, before (baseline) and after one of two interventions: (a) stimulation of M1 with 1 Hz TMS for 30 min at 115% of resting motor threshold, and (b) sham stimulation. Recruitment curves to TMS, pinch force, and simple reaction time were assessed in the hand contralateral to the unstimulated motor cortex.

Results: The main finding of this study was that 30 min of 1 Hz significantly increased recruitment curves in the contralateral motor cortex in the real stimulation condition relative to sham (P<0.005, factorial analysis of variance (ANOVA)). This change outlasted the stimulation period for at least 15 min and occurred in the absence of changes in pinch force or reaction time.

Conclusions: These results raise the potential for inducing lasting modulation of excitability in M1 by 1 Hz TMS of the other M1, a phenomenon possibly reflecting modulation of interhemispheric interactions.

Significance: It is conceivable that 1 Hz TMS applied to M1 may be used to modulate excitability in the opposite motor cortex for therapeutic purposes.

Introduction

Single-pulse transcranial magnetic stimulation (TMS) applied to the primary motor cortex (M1) modulates the amplitude of motor evoked potentials (MEPs) elicited by timed stimulation of the other M1 (Ferbert et al., 1992, Boroojerdi et al., 1996, Gerloff et al., 1998). This phenomenon reflects the predominantly inhibitory interaction between homonymous body part representations in M1 in humans (Ferbert et al., 1992) and may play a role in motor control (Meyer et al., 1998) and motor learning (Andres et al., 1999). Interestingly, TMS of one M1 appears to elicit blood flow changes in the opposite M1 (Fox et al., 1997, Paus et al., 1998, Siebner et al., 2000).

Behavioral and functional studies lend credence to the idea that the corpus callosum plays a major role in interhemispheric inhibition (Ferbert et al., 1992, Gerloff et al., 1998). In children, immature callosal connections correlate with the absence of interhemispheric inhibition and the presence of mirror movements (Heinen et al., 1998). In patients with dysfunction of the corpus callosum due to multiple sclerosis (Boorojerdi et al., 1998), cerebrovascular insult (Boroojerdi et al., 1996), or corpus callosum atrophy (Meyer et al., 1995), interhemispheric inhibition is delayed or absent. Lesions affecting the anterior portions of the corpus callosum preclude interhemispheric inhibition while lesions located elsewhere along the corpus callosum or subcortically leave inhibition intact (Meyer et al., 1995, Boroojerdi et al., 1996). In monkeys, this anterior portion of the corpus callosum interconnects the motor cortices (Pandya and Seltzer, 1986).

Previous studies demonstrated that low frequency TMS for 15–30 min over M1 decreases the excitability of the stimulated motor cortex (Chen et al., 1997, Muellbacher et al., 2000). In this study, we sought to determine whether downregulation of excitability in one M1 by low frequency TMS could elicit an increased excitability in the contralateral, unstimulated M1. A previous study demonstrated that a relatively short period of TMS at an intensity of approximately 105% resting motor threshold (rMT) failed to elicit this effect (Wassermann et al., 1998). Based on this experience, we modified stimulation parameters, prolonging the duration of stimulation and increasing the stimulus intensity. We found that 1 Hz stimulation of M1 led to a lasting enhancement in excitability in the contralateral unstimulated M1.