Effects of antipsychotic medication on electromyographic responses to transcranial magnetic stimulation of the motor cortex in schizophrenia

Abstract

Objective-To assess the eVect of antidopaminergic antipsychotic medication on the electromyographic (EMG) responses of thenar muscles to transcranial magnetic stimulation (TMS) of the motor cortex in schizophrenic patients. Methods-A group of nine drug naïve schizophrenic patients was compared with a group of nine schizophrenic patients established on neuroleptic medication. Surface EMG recordings were made from the thenar muscles while patients maintained a weak isometric voluntary contraction. TMS was applied using a 9 cm circular stimulating coil centred over the vertex. The EMG responses to up to 50 magnetic stimuli were rectified and averaged. Results-There was no diVerence in threshold TMS strength for eliciting compound motor evoked potentials (cMEPs), or in their latency, in drug naïve and medicated patients. In some patients the silent period (SP) was clearly made up of two parts and the percentage of control levels of voluntary EMG was measured in each component. During the early component of the SP there was a weaker (P<0.05) suppression of EMG in the medicated patients (mean 73.9 (SEM) 5.5% of control levels) compared with the drug naïve patients (54.7 (SEM) 7.3% of control levels). This resulted in the latency of maximum suppression of voluntary EMG being longer (P<0.05) in the medicated patients (38.3 (2.4) ms) than in the drug naïve patients (28.2 (0.7) ms). During the late component of the SP voluntary EMG was reduced to similar levels (P>0.05) in both medicated (48.2 (7.7)% of control levels) and drug naïve (58 (7.8)% of control levels) patients. Conclusion-The results are discussed with reference to the disrupted inhibition seen in the early part of the SP in Parkinson's disease and drug induced parkinsonism. The future uses of motor responses to TMS as a marker for the status of antipsychotic medication are considered. (J Neurol Neurosurg Psychiatry 1997;63:468-473) Keywords: antipsychotic drugs; schizophrenia; transcranial magnetic stimulation Since the report by Carlsson and Lindquist 1 that the typical antipsychotic drugs chlorpromazine and haloperidol give rise to an accumulation of dopamine metabolites in dopamine rich brain areas in mice, it has been found that all eVective antipsychotic drugs bind to dopamine receptors. The degree of dopamine D2 receptor binding correlates with the clinical eVectiveness of typical antipsychotic drugs.2 3 Furthermore, there are delayed actions of these drugs on presynaptic dopamine activity that closely parallel the time course of their therapeutic action. 4 The mode of action of this class of drugs remains uncertain, and more recent studies (see review 5 ) have implicated several other neurotransmitters and neurohormones.Transcranial magnetic stimulation (TMS) using a coil delivering a rapidly changing magnetic field 6 is a method that can be used safely and painlessly to stimulate the motor cortex through the intact skull. When stimulation is delivered using a circular coil centred over the vertex, compound motor evoked potentials (cMEPs) ar...

Electromagnetic stimulation in psychiatry

“…Although medication may clearly play a role in motor changes in schizophrenia, cMEP latency does not seem to be affected (Davey et al, 1997). However, the silent period after TMS was affected by medication, in that the latency of maximal suppression of the voluntary EMG silent period was increased (Davey et al, 1997). This is in contrast to previous reports in (drug-induced) parkinsonism where the silent period is shortened, so that sampling issues or methodological differences may account for this finding.…”

“…Cortical inhibitory processes may be abnormal in this patient group, and in treatment-naïve patients with schizophrenia there appears to be a shortening of latency in compound MEP (cMEP) triggered by TMS over the motor strip (Puri et al, 1996). Although medication may clearly play a role in motor changes in schizophrenia, cMEP latency does not seem to be affected (Davey et al, 1997). However, the silent period after TMS was affected by medication, in that the latency of maximal suppression of the voluntary EMG silent period was increased (Davey et al, 1997).…”

Evidence for Impaired Cortical Inhibition in Schizophrenia Using Transcranial Magnetic Stimulation

“…Puri et al 20 found no differences in CSP duration in unmedicated patients compared with healthy controls. Davey et al 21 found longer CSP duration among medicated patients compared with unmedicated patients. These studies, however, used TMS intensities that were much lower than those conventionally used in most CSP studies.…”

Cortical excitability in schizophrenia

“…In dieser Arbeit wurden keine signifikanten Differenzen der CSP-Dauer zwischen schizophrenen Patienten und Kontrollen beschrieben. In einer weiteren Untersuchung an einer wiederum kleinen Patientenzahl konnten ebenfalls kein signifikanter Unterschied in der Dauer der CSP, jedoch eine längere initiale Latenz ("onset latency") bei behandelten Patienten gefunden werden [15]. In den letzten Jahren erfolgten dann mehrere Studien, wobei nur Fitzgerald et al [20,21,22] in 3 Untersuchungen konstant eine kürzere CSP bei den Patienten reproduzieren konnten und keinen Einfluss der Medikation (Risperidon und Olanzapin) feststellten.…”