Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study

Intermittent theta burst stimulation (iTBS) is a novel treatment approach for post-traumatic stress disorder (PTSD), and recent neuroimaging work indicates that functional connectivity profiles may be able to identify those most likely to respond. However, prior work has relied on functional magnetic resonance imaging, which is expensive and difficult to scale. Alternatively, electroencephalography (EEG) represents a different approach that may be easier to implement in clinical practice. To this end, we acquired an 8-channel resting-state EEG signal on participants before (n = 47) and after (n = 43) randomized controlled trial of iTBS for PTSD (ten sessions, delivered at 80% of motor threshold, 1,800 pulses, to the right dorsolateral prefrontal cortex). We used a cross-validated support vector machine (SVM) to track changes in EEG functional connectivity after verum iTBS stimulation. We found that an SVM classifier was able to successfully separate patients who received active treatment vs. sham treatment, with statistically significant findings in the Delta band (1-4 Hz, p = 0.002). Using Delta coherence, the classifier was 75.0% accurate in detecting sham vs. active iTBS, and observed changes represented an increase in functional connectivity between midline central/occipital and a decrease between frontal and central regions. The primary limitations of this work are the sparse electrode system and a modest sample size. Our findings raise the possibility that EEG and machine learning may be combined to provide a window into mechanisms of action of TMS, with the potential that these approaches can inform the development of individualized treatment methods.