Neural correlates of threat and emotion processing in panic disorder

Early and rapid attention to threat is an adaptive response in healthy individuals; however, in persons with clinical or sub-clinical levels of anxiety, this mechanism appears to be exaggerated and maladaptive. Specifically, anxious individuals seem to be distinctively sensitive to threatening information in the environment, which is called an attentional bias. To better understand the neural mechanisms underlying hypervigilance to threat in clinical and subclinical anxiety, scalp-recorded brain electrical activity (EEG) was recorded while participants performed supraliminal and subliminal versions of an emotional Stroop task where threat and neutral, or positive and neutral words were presented in blocks. Participants responded either to the color of the presented word (supraliminal task), or to the colour of a mask (subliminal task). Study 1 found enhanced early frontal responses (200-320 ms, the EAP) to task-irrelevant threat words relative to neutral words in healthy individuals with high Anxiety Sensitivity (AS) in the supraliminal task, confirming early stage, likely pre-attentive processing of consciously perceived threat information. More interestingly, the high AS group additionally exhibited an enhanced, even earlier frontal effect (starting at 130 ms) in the subliminal Stroop task, indexing pre-conscious processing of threat stimuli below perception threshold. Study 2 extended the analysis of hypervigilance to threat signals to a group of Panic Disorder patients. There was no evidence of early differential frontal ERP modulation to threat words (EAP and P150) in either the supraliminal or subliminal eStroop task. We concluded that in high trait anxiety, early frontal effects may index a hyperactive early threat detection system located in medial PFC or insular cortex. In Panic Disorder patients, on the other hand, threat information triggering a hyperresponsive amygdala would fail to cause sufficient top-down emotion regulating activity from vmPFC, resulting in the absence of a sizeable early EAP. The inverse correlation between symptom severity and prefrontal activation supports the hypothesis that PFC hypoactivation could be a component of the transition of dispositionally high anxiety to disordered anxiety. We propose that presence or absence of the EAP could provide a marker able to quantify such transition.