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

Venkata C Chirumamilla; Gabriel Gonzalez-Escamilla; Benjamin Meyer; Abdul Rauf Anwar; Hao Ding; Angela Radetz; Tamara Bonertz; Sergiu Groppa; Muthuraman Muthuraman

doi:10.3389/fnins.2022.1065469

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

Front Neurosci. 2023 Jan 9:16:1065469. doi: 10.3389/fnins.2022.1065469. eCollection 2022.

Authors

Venkata C Chirumamilla¹, Gabriel Gonzalez-Escamilla¹, Benjamin Meyer², Abdul Rauf Anwar¹, Hao Ding¹, Angela Radetz¹, Tamara Bonertz¹, Sergiu Groppa¹, Muthuraman Muthuraman¹

Affiliations

¹ Section of Movement Disorders and Neurostimulation, Department of Neurology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
² Neuroimaging Center Mainz, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Abstract

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.

Keywords: cortical excitability; effective connectivity; instructed fear paradigm; paired-pulse TMS; threat processing.