Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

BackgroundThreat detection is essential for protecting individuals from precarious situations. Early studies suggested a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) involved in fear processing. Excitability regulation in the dmPFC might be crucial for physiological fear processing, while an abnormal excitability pattern could lead to mental illness. Non-invasive paradigms to measure excitability regulation during fear processing in humans are missing.\n\nMethodsWe adapted an experimental approach of excitability characterization using electroencephalography (EEG) recordings and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm to dynamically dissect its role in fear processing. Event-related (ERP) and TMS-evoked potentials (TEP) were analyzed to trace dmPFC excitability in healthy young volunteers (n = 40, age = 27.6 {+/-} 5.7 years, 22 females). Moreover, we linked the excitability regulation patterns to individual structural MRI-derived properties of gray matter microstructural integrity of the fear network.\n\nResultsAn increased cortical excitability was demonstrated in the threat (T) condition in comparison to no-threat (NT) as showed by increased amplitude of evoked potentials. Furthermore, TMS over the dmPFC induced markedly increased evoked responses during T condition in relation to NT. Moreover, we found that the structural integrity of the dmPFC and the amygdala predict excitability regulation patterns as measured by ERP and TEP during fear processing.\n\nConclusionsWe describe the dynamic range of excitability regulation in dmPFC during fear processing. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.