The relevance of accounting for parasympathetic as well as sympathetic arousal in threat conditioning: methodological and clinical considerations

Abstract Alterations in associative threat learning have been thought to underlie the aetiology and maintenance of anxiety disorders. Recent insights into the facilitatory role of parasympathetic arousal for threat coping have raised the question whether individual differences in parasympathetic versus sympathetic dominance during threat learning may explain the unstable relationship with anxiety vulnerability versus resilience. We applied an established threat-conditioning paradigm in 78 neurotypical individuals and assessed parasympathetic responses (relative bradycardia), as well as sympathetic response patterns (relative tachycardia and increased skin conductance responses -SCR). We observed threat-induced bradycardia as well as tachycardia during associative learning. Additionally, participants not showing conditioned SCR still exhibit significant conditioned threat responses expressed in parasympathetically driven threat bradycardia. Critically, tachycardia, rather than bradycardia, was linked to stronger initial conditioned SCRs and higher trait anxiety. These results suggest individual differences in sympathetic versus parasympathetic dominance may underlie anxiety vulnerability versus resilience. Statement of relevance Our findings underscore the relevance of assessing the whole spectrum of autonomic nervous system responses to threat. By assessing sympathetic and parasympathetic threat responses, we demonstrate associations with anxiety vulnerability, which could not be unveiled by assessing sympathetic arousal alone. Since alterations in associative threat learning are thought to underlie anxiety-related psychopathology, it is of clinical and methodological relevance to assess threat responses with measures that are sensitive to both parasympathetic and sympathetic arousal. Additionally, we show that individuals that lack sympathetically-driven conditioned SCRs -- often classified as non-learners -- in fact do show a parasympathetically-driven HR threat response (bradycardia). Critically, bradycardia was linked to lower trait anxiety. These results imply a paradigm shift in the field of threat learning, shifting the predominant focus on sympathetic arousal towards the balance between sympathetic and parasympathetic arousal. This could advance insights in the role of threat learning in anxiety vulnerability and resilience.