Abstract
Threat detection is essential for protecting individuals from adverse situations, in which a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) regions are involved in fear processing. Excitability regulation in the dmPFC might be crucial for fear processing, while abnormal patterns could lead to mental illness. Notwithstanding, non-invasive paradigms to measure excitability regulation during fear processing in humans are missing. To address this challenge we adapted an approach for excitability characterization, combining electroencephalography (EEG) 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. We further linked the excitability regulation patterns to individual MRI-derived gray matter structural integrity of the fear network. Increased cortical excitability was demonstrated to threat (T) processing in comparison to no-threat (NT), reflected by increased amplitude of evoked potentials. Furthermore, TMS at dmPFC enhanced the evoked responses during T processing, while the structural integrity of the dmPFC and amygdala predicted the excitability regulation patterns to fear processing. The dmPFC takes a special role during fear processing by dynamically regulating excitability. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.
Highlights
The dorsomedial prefrontal cortex is involved in working memory, attention, emotion regulation and further distinct mental functions
The first Event-related potential (ERP) component occurred at 152 ms (ERP152), followed by the late positive potential (LPP) with an increased and sustained activity with high amplitude at 500 ms
In the no-transcranial magnetic stimulation (TMS) experiment, the LPP showed a sustained response beyond 1 s, decaying at ~1300 ms, whereas in the artefact-free filtered TMS–EEG data (1–30 Hz; TMS experiment) apart from the same two initial ERPs, additional and differential modulation of the EEG activity after the TMS pulse was observed
Summary
The dorsomedial prefrontal cortex (dmPFC) is involved in working memory, attention, emotion regulation and further distinct mental functions. If excitatory or inhibitory mechanisms are involved or how a regulation of cortical excitability in the dmPFC during fear processing occurs is still unknown These phenomena, play a crucial role for adaptive behavior in threat situations and their dysfunction could lead to the development of neuropsychiatric disorders. Recent technical advances allow the non-invasive assessment of synchronized brain activity by TMS-EEG recordings at the brain surface level[18,19,20,21] and provide the opportunity to track physiological aspects of fear processing at the cortical level while measuring long-range synchronization and excitability properties within the involved network nodes. The development of improved methods to obtain a reliable EEG source estimation should provide spatial information on the evoked neural activity
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