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

Objectives: The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABAA receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. Methods: We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold 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 decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. Conclusions: The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.