Exp Brain Res (1995) 107:80-86 9 Springer-Verlag 1995 Giampietro Zanette 9 Claudio Bonato 9 Alberto Polo Michele Tinazzi 9 Paolo Manganotti 9 Antonio Fiaschi Long-lasting depression of motor-evoked potentials to transcranial magnetic stimulation following exercise Received: 26 August 1994 / Accepted: 7 June 1995 Abstract We used transcranial magnetic stimulation to study the modulation of motor cortex excitability after rapid repetitive movements. Eleven healthy subjects aged 24-32 years were evaluated. Serial motor-evoked poten- tial (MEP) recordings were performed from the fight the- nar eminence every 5 min for a period of 20 rain at rest and for a period of 35 min after repetitive abduction-ad- duction of the thumb at maximal frequency for 1 min. All subjects presented distinct changes in MEP ampli- tude after exercise with an approximately 55% mean maximal decrease compared with basal conditions and complete recovery 35 min after the end of the exercise. The time course of MEP amplitude changes presented the following trend: (1) a rapid decrease phase within the first 5 rain; (2) a maximal depression phase of 10 min duration (from the 5th to the 15th rain); and (3) a slow recovery phase. No significant modifications in post-exercise MEP amplitude were found in ipsilateral non-exercised muscles. In order to determine the level where these changes take place, we recorded the M and F waves induced by median nerve stimulation at the wrist (all subjects) and MEPs in response to transcranial electrical stimulation (five subjects) at rest and during the decrease and maximal depression phases. None of these tests were significantly affected by exercise, indi- cating that the motor cortex was the site of change. Eval- uation of maps of cortical outputs to the target muscle, performed in four subjects, showed an approximately 40% spatial reduction in stimulation sites evoking a mo- tor response during the maximal depression phase. These data prove that exercise induces a reversible, long-stand- ing depression of cortical excitability, probably related to intracortical presynaptic modulation, which transitorily reduces the motor representation area. G. Zanette ([~) 9 C. Bonato. A. Polo 9 M. Tinazzi 9 R Manganotti A. Fiaschi Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia, Policlinico Borgo Roma, Via delle Menegone, 1-37134 Verona, Italy Key words Transcranial magnetic stimulation - Motor cortex 9 Exercise 9 Plasticity 9 Human Introduction Recent experimental studies have documented the occur- rence of rapid plastic changes in the motor cortex trig- gered by various manipulations of the peripheral nervous system such as nerve transection, ischaemic nerve deaf- ferentation or anaesthetic nerve deafferentation (Donog- hue et al. 1990; Kimberle et al. 1990; Cohen et al. 1991a; Brasil-Neto et al. 1992, 1993a). In a research note, Brasil-Neto et al. (1993b) reported a "myasthenic- like" decrease in the size of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) occurring immediately after the execution of rap- id repetitive movements. The authors suggested that this post-exercise depression of MEPs may be an expression of central nervous system fatigue, probably due to tran- sient depletion of neurotransmitters. In the present study, we investigated the possible long-term effects of exercise on motor system excitabili- ty by evaluating the recovery cycle of MEP amplitude changes in response to TMS. The neural structures and possible mechanisms involved were also studied. Materials and methods We studied 11 healthy volunteers, aged 24-32 years, belonging to the medical staff and the medical students of the University of Ve- rona, who gave their informed consent for the studies. Subjects were comfortably seatedl with their right forearms resting supine on a rigid plane. Several sets of MEPs in response to TMS were recorded by surface electrodes overlying the right thenar eminence at rest and after exercise. The exercise consisted of repetitive movements of abduction-adduction of the thumb against the little finger, per- formed in 1 rain at maximal rate for each subject (the mean rate in the 11 subjects was 103 twitchings/min, range 95-115). The signal was amplified using a band-pass filter of 50-5000 Hz. A Novametrix Magstim 200 magnetic stimulator was used to deliver sets of 12 stimuli with an inter-stimulus interval (ISI) of