Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior

Abstract

Objective: To explore effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) on motor excitability and basic motor behavior in humans.

Design and Methods: Seven normal volunteers underwent 1 Hz rTMS of the hand representation of the right M1 for 15 min at an intensity of 115% of the individual resting motor threshold. The effects of rTMS on motor excitability were assessed by monitoring changes in individual resting motor threshold and input-output curves of motor evoked potentials (MEPs) in the flexor pollicis brevis, first dorsal interosseus, abductor digiti minimi and biceps brachii muscles. Changes in basic motor behavior were studied by measuring maximal and mean peak force and peak accelerations of thumb flexions and abductions of the fifth finger before and after rTMS.

Results: rTMS produced a significant increase in resting motor threshold and a significant suppression of MEP input-output curves that persisted for 30 min. The suppressing effect was restricted to the hand motor representation which was the prime target of the stimulation procedure, and there were no significant effects on the biceps representation. Peak force and peak acceleration were not affected while the motor representations of muscles involved in the behavioral measurements were significantly suppressed by rTMS.

Conclusions: Low-frequency rTMS of M1 transiently depresses motor excitability but this does not affect basic motor behavior. This is relevant for the therapeutic use of low-frequency rTMS in disorders with abnormal cortical excitability.

Introduction

Since its introduction, TMS of the human brain has been a useful tool to assess motor cortex excitability non-invasively (Barker et al., 1985). A single magnetic stimulus applied over the cerebral hemisphere evokes responses in contralateral limb muscles and in muscles supplied by cranial nerves. Pairs of stimuli can be used to investigate the excitability of interneuronal circuits in the primary motor cortex (M1) (Kujirai et al., 1993, Ziemann et al., 1996b) Depending on the frequency, duration and stimulus intensity, trains of stimuli have differential effects on motor cortex excitability (Pascual-Leone et al., 1994b). For instance, a short train of 5 Hz stimuli given at suprathreshold intensity evokes progressively larger MEPs with each shock, while stimulation at 10 Hz produces an alternating pattern of facilitated and depressed MEPs (Jennum et al., 1995).

In recent years, repetitive TMS (rTMS) of M1 has been shown to exert effects lasting beyond the time of the stimulus application, making it attractive for use in disorders with abnormal cortical excitability (Wassermann et al., 1996). For instance, lasting effects of high-frequency rTMS (more than 1Hz) on clinical symptoms have been discussed in Parkinson's disease (Pascual-Leone et al., 1994a, Ghabra et al., 1999, Siebner et al., 1999a), and in depressed patients (George et al., 1995, Pascual-Leone et al., 1996). On the other hand, low-frequency rTMS (at or below 1 Hz) can transiently improve symptoms in patients with task-specific focal dystonia (Siebner et al., 1999b). The potential for 1 Hz-rTMS to treat focal epilepsy and cortical myoclonus is currently being studied.

Although these reports demonstrate that rTMS can induce changes in the human motor system that outlast the stimulation period, little is known if the resulting suppression influences basic motor behavior. To address this issue, we studied the effects of low-frequency rTMS over M1 on peak force and peak acceleration. These basic movement parameters were studied because M1 is most closely related to these simple kinetic and kinematic aspects of movement (Georgopoulos et al., 1992, Ashe, 1997), and because previous work indicated some relationship between changes in basic motor behavior and M1 excitability in humans (Muellbacher et al., 1999).