Abstract
Measuring the brain’s response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15–250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (<80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.
Highlights
Transcranial magnetic stimulation (TMS) is a brain stimulation method capable of non-invasively activating cortical neurons across the scalp in humans via electromagnetic induction[1]
As we were interested in early TMS-evoked EEG potentials (TEPs) peaks, we developed a novel transcranial magnetic stimulation (TMS)-EEG cleaning pipeline including two analysis methods designed to recover early TMS-evoked activity (
We could not detect any differences in TEP amplitudes between baseline recordings for each site indicating that TEPs are reliable within individuals between sessions, so we averaged across baseline conditions to maximise TEP signal strength
Summary
Transcranial magnetic stimulation (TMS) is a brain stimulation method capable of non-invasively activating cortical neurons across the scalp in humans via electromagnetic induction[1]. Several recent studies have shown that residual auditory and somatosensory activity resulting from the TMS pulse contributes to TEPs under certain circumstances despite experimental measures designed to minimise sensory inputs such as auditory masking and foam padding[9,10]. Such findings highlight the need for careful experimental set-up[11] and control conditions[12] in TMS-EEG studies. We measured TEPs following prefrontal (PFC) and parietal (PAR) cortex stimulation before and after a sub-anaesthetic dose of dextromethorphan, an NMDA receptor antagonist, or a placebo in a double-blinded pseudo-randomized crossover design. We compared the effect of dextromethorphan on resting-state oscillations, which are typically reduced in power within low-frequency and increased in high-frequency bands following NMDA receptor antagonists[22]
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