Tracking causal pathways in TMS-evoked brain responses

Exploring how local perturbations of cortical activity propagate across the brain network not only helps us understanding causal mechanisms of brain networks, but also offers a network insight into neurobiological mechanisms for transcranial magnetic stimulation (TMS) treatment response. The concurrent combination of TMS and electroencephalography (EEG) enables researchers to track the TMS-evoked activity, defined here as scalp-recorded electrical signals reflecting the brain’s response to TMS, with millisecond-level temporal resolution. Based on this technique, we proposed a quantitative framework which combined sparse non-negative matrix factorization and stage-dependent effective connectivity methods to infer the causal pathways in TMS-evoked brain responses. We found that single-pulse TMS firstly induces local activity in the directly stimulated regions (left primary motor cortex, M1), and then propagates to the contralateral hemisphere and other brain regions. Finally, it propagates back from the contralateral region (right M1) to the stimulation region (left M1). This study provides preliminary evidence demonstrating how local perturbations propagate through brain networks to influence various cortical regions, and offers insights into the neural mechanism of TMS-evoked brain responses from a network perspective.Author summary: The concurrent combination of TMS and EEG offers a powerful intervention paradigm for uncovering the causal mechanisms of brain networks. By delivering single-pulse stimulation to a specific brain region and recording the resulting electrical signal using EEG, this technique actively perturbs the system and captures the immediate causal effects of stimulation. TMS-EEG directly tests causal hypotheses, providing evidence of how activity in a stimulated region influences downstream pathways. In this study, we proposed a quantitative framework which combined sparse non-negative matrix factorization and stage-dependent effective connectivity methods to infer the causal pathways in TMS-evoked brain responses. We found that single-pulse TMS firstly induces local activity in the directly stimulated regions (left M1), and then propagates to the contralateral hemisphere and other brain regions. Finally, it propagates back from the contralateral region (right M1) to the stimulation region (left M1). This study provides a preliminary exploration of how local perturbation influence brain network dynamics, and offers insights into the neural mechanism of precise TMS intervention from a network perspective.