Direct demonstration of the effect of lorazepam on the excitability of thehuman motor cortex

Objectives: The present study explored the effects of lorazepam, a benzodia zepine with agonist action at the GABA(A) receptor, on human motor cortex e xcitability as tested using transcranial magnetic stimulation. Methods: We recorded directly the descending volley evoked by single and pa ired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral d ose of lorazepam. We evaluated the effects of lorazepam on the descending v olleys evoked by a single magnetic stimulation and paired cortical stimulat ion using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprat hreshold conditioning stimulus). Results: Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a d ecrease in the amplitude of the evoked EMG response. Using the intracortica l inhibition paradigm lorazepam increased the amount of corticocortical inh ibition, particularly at 4 and 5 ms interstimulus intervals. There was no e ffect on the amount of facilitation observed in the shea latency intracorti cal facilitation paradigm. Conclusions. The present findings provide direct evidence that lorazepam in creases the excitability of inhibitory circuits in the human motor cortex. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.