Abstract:
The combination of transcranial magnetic stimulation and electroencephalography (TMS– EEG) is a powerful, non-invasive approach for investigating brain function in both health and disease. Single-pulse TMS–EEG provides a straightforward method: a single TMS pulse stimulates a specific brain region, while concurrent EEG records the resulting cortical responses. However, applying TMS pulses during EEG recordings introduces various artifacts. Among these, sensory-related EEG responses caused by peripheral co-stimulation are particularly problematic, as they closely resemble true TMS–EEG responses and can lead to misinterpretation. Therefore, the first aim of this thesis was to assess whether a sensory control procedure, adapted from previous work, could effectively mitigate sensory confounds.
The effective application of TMS–EEG depends on a deeper understanding of its underlying neurophysiological mechanisms. Combining pharmacological interventions with TMS–EEG offers an avenue for exploring the roles of specific receptor-mediated neurotransmission in shaping TMS–EEG responses. Accordingly, the second aim of this thesis was to investigate the involvement of muscarinic acetylcholine receptor (mAChR)-mediated central cholinergic neurotransmission in TMS–EEG responses.
To achieve these aims, we conducted a randomized, placebo-controlled crossover study involving 24 healthy participants. Each participant received a single oral dose of the non-selective mAChR antagonist scopolamine, the selective mAChR antagonist biperiden, or placebo across three separate sessions. During each session, TMS–EEG responses to stimulation of three brain regions were measured before and after drug administration using the sensory control procedure designed to mitigate sensory confounds. We first demonstrated that ’cleaned’ TMS–EEG responses, with sensory responses removed through the control procedure, strongly represent direct cortical activation. Subsequently, we observed that scopolamine significantly increases the amplitude of a local TEP (TMS-evoked EEG potential) component occurring approximately 40–63 ms following the supplementary motor area stimulation. Previous pharmacological TMS–EEG studies suggest that the TEP component N45 reflects the excitation and inhibition (E/I) balance controlled by glutamatergic and GABAergic transmission. We thus speculate that the increased amplitude of the N45-like TEP component caused by anti-cholinergic drugs might result from the shift in E/I balance, possibly favoring inhibition.
Our results emphasize the importance of sensory control in TMS–EEG studies and provide new insights into the neurophysiology of single-pulse TMS–EEG. Clinically, these findings are informative for interpreting TMS–EEG abnormalities in conditions involving cholinergic deficits and may help guide and monitor therapies targeting the cholinergic system.
TMS-EEG