Coping in the Clinic: Effects of Clinically Elevated Anxiety on Dynamic Neurophysiological Mechanisms of Escape/Avoidance Preparation

Christopher T. Sege, Danielle L. Taylor, James W. Lopez, Holly Fleischmann, Evan J. White, Lisa M. McTeague

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Treatments for anxiety and related disorders target exaggerated escape/avoidance as a core feature, but current methods fail to improve escape/avoidance habits for many treatment-seeking individuals. To support developing tools that increase treatment efficacy by targeting mechanisms more directly, the current work examined potential distinctions in the neurophysiologies of escape and avoidance and tested how clinical anxiety affects these neurophysiologies. Methods: Twenty-five treatment-seeking individuals with varied principal diagnoses (e.g., generalized anxiety disorder, posttraumatic stress disorder) and 20 non-treatment-seeking control subjects participated. In the study task, approximately 5.25-second cues predicted aversive images that could be avoided (blocked by a button press before image onset), escaped (ended by a button press after image onset), or not controlled. To examine neural processing and defensive response modulation, anticipatory event-related potentials were derived, and startle reflexes were probed throughout each cue. Results: Multidimensional profiles were observed such that 1) anticipatory event-related potential enhancement was only reliable during avoidance preparation, and event-related potentials potentially reflected perceived/instrumental control; and 2) startle reflexes were inhibited during avoidance preparation, relatively enhanced during escape preparation, and further enhanced during uncontrollable anticipation, thus potentially reflecting fear-related activation. Treatment-seeking status, then, did not affect cortical processing, but it did moderate context-dependent fear (if individuals with severe depression were excluded) such that treatment-seeking individuals without depression showed exaggerated startle during escape, but not avoidance, preparation. Conclusions: Data suggest a specific effect of anxiety on fear system activation during preparation to escape aversion. This effect warrants further investigation as a precision target for interventions that directly modulate the specific underlying neural circuitry.

Original languageEnglish
Pages (from-to)712-719
Number of pages8
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number7
StateAccepted/In press - 2022
Externally publishedYes


  • Anxiety
  • EEG
  • ERP
  • Escape/Avoidance
  • Reflex physiology


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