An EEG-fMRI-TMS instrument to investigate BOLD response to EEG guided stimulation

Depression is a serious mental illness that is frequently resistant to a first round of pharmacotherapy. Electroconvulsive therapy (ECT) is effective even for such treatment resistant depression but is associated with significant adverse effects. Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex in comparison causes only mild discomfort but is less effective than ECT. We hypothesize that TMS treatment efficacy could be improved by locking TMS onset to a specific, potentially subject specific phase of the prefrontal alpha rhythm in the electroencephalogram (EEG). Here, we present an instrument that can track and predict phase of the alpha rhythm in the EEG to precisely target TMS while concurrently recording functional magnetic resonance imaging (fMRI) to study local and distributed hemodynamic brain responses to stimulation. Tests of the instrument with three healthy adults indicate that EEG phase-locked TMS can be administered accurately enough to start testing systematically whether specific stimulation protocols can lead to clinically significant improvements in depression. To our knowledge, this is the first system that can deliver TMS phase-locked to the alpha rhythm while concurrently recording fMRI. For patients, such EEG guided TMS treatment could lead to better clinical outcomes and lower incidence of adverse effects.