The impact of GABAergic drugs on TMS-induced brain oscillations in human motor cortex

Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30-200 ms after TMS) synchronization in the alpha- and beta-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200-400 ms) alpha- and beta-desynchronization over the stimulated and contralateral sensorimotor cortex. As GABAergic inhibition plays an important role in shaping oscillatory brain activity, we sought here to understand if GABAergic inhibition contributes to these TMS-induced oscillations. We tested single oral doses of alprazolam, diazepam, Zolpidem (positive modulators of the GABAA receptor), and baclofen (specific GABAB receptor agonist). Diazepam and Zolpidem enhanced, and alprazolam tended to enhance while baclofen decreased the early alpha-synchronization. Alprazolam and baclofen enhanced the early beta-synchronization. Baclofen enhanced the late alpha-desynchronization, and alprazolam, diazepam and baclofen enhanced the late beta-desynchronization. The observed GABAergic drug effects on TMS-induced alpha- and beta-band oscillations were not explained by drug-induced changes on corticospinal excitability, muscle response size, or resting-state EEG power. Our results provide first insights into the pharmacological profile of TMS-induced oscillatory responses of motor cortex.