Inhibitory and excitatory responses in the dorso-medial prefrontal cortex during threat processing

OBJECTIVE: To evaluate cortical excitability during instructed threat processing. METHODS: Single and paired transcranial magnetic stimulation (TMS) pulses were applied to the right dorsomedial prefrontal cortex (dmPFC) during high-density electroencephalography (EEG) recording in young healthy participants (n = 17) performing an instructed threat paradigm in which one of two conditioned stimuli (CS+ but not CS-) was paired with an electric shock (unconditioned stimulus [US]). We assessed TMS-induced EEG responses with spectral power (both at electrode and source level) and information flow (effective connectivity) using Time-resolved Partial Directed Coherence (TPDC). Support vector regression (SVR) was used to predict behavioral fear ratings for CS+ based on TMS impact on excitability. RESULTS: During intracortical facilitation (ICF), frontal lobe theta power was enhanced for CS+ compared to single pulse TMS for the time window 0–0.5 s after TMS pulse onset (t(16) = 3.9, p < 0.05). At source level, ICF led to an increase and short intracortical inhibition (SICI) to a decrease of theta power in the bilateral dmPFC, relative to single pulse TMS during 0–0.5 s. Compared to single pulse TMS, ICF increased information flows, whereas SICI reduced the information flows in theta band between dmPFC, amygdala, and hippocampus (all at p < 0.05). The magnitude of information flows between dmPFC to amygdala and dmPFC to hippocampus during ICF (0–0.5 s), predicted individual behavioral fear ratings (CS+; coefficient above 0.75). CONCLUSION: Distinct excitatory and inhibitory mechanisms take place in the dmPFC. These findings may facilitate future research attempting to investigate inhibitory/facilitatory mechanisms alterations in psychiatric disorders and their behavioral correlates.