Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients

Abstract

Electroconvulsive therapy (ECT) is a widely acknowledged effective treatment for severe major depression. ECT produces considerable anticonvulsant effects that may be related to an increased GABA-ergic neurotransmission. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to investigate these anticonvulsant effects. Therefore, parameters of motor cortical excitability were investigated in 10 patients before and after 10 sessions of right unilateral ECT. After 10 sessions of right unilateral ECT, an enhanced activity of inhibitory circuits in human motor cortex had been observed, as measured by both increased intracortical inhibition and cortical silent period duration, whereas intracortical facilitation and resting motor threshold remained unchanged. The reduction of seizure duration in the course of ECT was associated with clinical improvement and an increase in intracortical inhibition. We interpret this finding as further indirect evidence for changes in inhibitory circuits in the course of ECT in patients with major depression.

Introduction

Electroconvulsive therapy (ECT) continues to have an established and important role in the management of treatment-resistant depression (Eranti and McLoughlin, 2003). A compensatory increase in the function of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) has been suggested as one possible mechanism contributing to both the anticonvulsant and antidepressant actions of ECT (Sackeim, 1999).

Transcranial magnetic stimulation (TMS) has been introduced as a powerful tool to explore the integrity and excitability of the corticospinal system in patients with neurological and psychiatric diseases (Puri and Lewis, 1996, Fitzgerald et al., 2002). A variety of TMS motor cortex excitability measures are available, each with a distinct anatomy and neurophysiological underpinning. Resting motor threshold has been associated with the membrane excitability of cortical motor neurons. The cortical silent period succeeds the contralateral motor evoked potential (MEP) and refers to a silence in the EMG following the MEP. It depends, at least in part, on GABA-ergic neurotransmission (Reis et al., 2002). Intracortical inhibition and facilitation as measured by the paired pulse technique have been associated with the balance of GABA-ergic, dopaminergic, and glutamatergic tone. All these parameters are of special interest in the context of the investigation of ECT effects since they are strongly influenced by the GABA-ergic system (for review, see Daskalakis et al., 2002).

An investigation of a single patient with major depression showed changes of motor cortex excitability in the ECT course (Sommer et al., 2002). In a previous work, enhanced activity of inhibitory circuits in human motor cortex following a single ECT session has been observed (Bajbouj et al., 2003). Finally, a recent study reported an association of the antidepressant effect of bilateral ECT and left hemispheric excitability (Chistyakov et al., 2005).

To our knowledge, changes of all four mentioned TMS measures in the course of a right unilateral ECT treatment have not been studied so far. Therefore, the present study aims to clarify the effect of 10 sessions of electroconvulsive therapy on these TMS parameters associated with central GABA-ergic neurotransmission.