Cognitive state dependent enhancement of cognitive control with transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), yet variability of therapeutic responses remains high. A key contributor to this variability may be state-dependent effects of brain stimulation, where activity in underlying circuits may shape the propagation of TMS-evoked activity. Thus, constraining the target circuits' state by engaging cognition may make TMS' effects more consistent.

We tested whether TMS' effects on cognitive control, a transdiagnostic construct implicated across psychiatric disorders and a putative mediator of TMS efficacy, are state-dependent.

Participants (N = 23) completed a behavioural assay of cognitive control before and after we delivered intermittent trains of rTMS to the prefrontal cortex (PFC). During rTMS, participants performed either a high PFC-demand cognitive control task (ActiveState_rTMS), or performed a low PFC-demand perceptual discrimination task (ControlState_rTMS). As a function of the behavioural state during stimulation, we assessed changes (relative to baseline) in downstream behavioural metrics of circuit function and neural indices of cognitive control measured from electroencephalography (EEG). We also examined TMS-evoked neural activity as a function of the behavioural state during stimulation via TMS-EEG.

rTMS enhanced downstream readouts of cognitive control only when stimulation was delivered concurrent with the cognitive control task. In addition, after ActiveState_rTMS, but not ControlState_rTMS, the power of task-evoked theta band oscillatory activity was reduced relative to baseline. TMS-EEG data also showed enhanced TMS-evoked theta band oscillatory activity during the cognitive control task, relative to the perceptual one.

These findings demonstrate that TMS' effects on cognitive control are state-dependent, in which endogenous engagement of PFC-anchored networks can shape the magnitude and functional relevance of TMS-evoked activity and the associated modification of circuit function. Constraining cognitive states during TMS may therefore offer a framework to enhance the reliability of TMS' effects.