Neural substrates of overgeneralized conditioned fear in PTSD

Antonia N. Kaczkurkin, Philip C. Burton, Shai M. Chazin, Adrienne B. Manbeck, Tori Espensen-Sturges, Samuel E. Cooper, Scott R. Sponheim, Shmuel Lissek

Research output: Contribution to journalArticle

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Abstract

Objective: Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that "resemble" aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+. Method: Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS-, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS-. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS-, with less steep slopes indicative of stronger generalization. Results: Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus. Conclusions: The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalAmerican Journal of Psychiatry
Volume174
Issue number2
DOIs
StatePublished - Feb 1 2017

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Post-Traumatic Stress Disorders
Fear
Generalization (Psychology)
Cues
Wounds and Injuries
Safety
Brain
Hippocampus
Serving Size
Afghanistan
Iraq
Caudate Nucleus
Veterans
Prefrontal Cortex
Psychopathology
Magnetic Resonance Imaging
Conditioning (Psychology)

ASJC Scopus subject areas

  • Psychiatry and Mental health

MeSH PubMed subject areas

  • Journal Article

Cite this

Kaczkurkin, A. N., Burton, P. C., Chazin, S. M., Manbeck, A. B., Espensen-Sturges, T., Cooper, S. E., ... Lissek, S. (2017). Neural substrates of overgeneralized conditioned fear in PTSD. American Journal of Psychiatry, 174(2), 125-134. DOI: 10.1176/appi.ajp.2016.15121549

Neural substrates of overgeneralized conditioned fear in PTSD. / Kaczkurkin, Antonia N.; Burton, Philip C.; Chazin, Shai M.; Manbeck, Adrienne B.; Espensen-Sturges, Tori; Cooper, Samuel E.; Sponheim, Scott R.; Lissek, Shmuel.

In: American Journal of Psychiatry, Vol. 174, No. 2, 01.02.2017, p. 125-134.

Research output: Contribution to journalArticle

Kaczkurkin, AN, Burton, PC, Chazin, SM, Manbeck, AB, Espensen-Sturges, T, Cooper, SE, Sponheim, SR & Lissek, S 2017, 'Neural substrates of overgeneralized conditioned fear in PTSD' American Journal of Psychiatry, vol 174, no. 2, pp. 125-134. DOI: 10.1176/appi.ajp.2016.15121549
Kaczkurkin AN, Burton PC, Chazin SM, Manbeck AB, Espensen-Sturges T, Cooper SE et al. Neural substrates of overgeneralized conditioned fear in PTSD. American Journal of Psychiatry. 2017 Feb 1;174(2):125-134. Available from, DOI: 10.1176/appi.ajp.2016.15121549

Kaczkurkin, Antonia N.; Burton, Philip C.; Chazin, Shai M.; Manbeck, Adrienne B.; Espensen-Sturges, Tori; Cooper, Samuel E.; Sponheim, Scott R.; Lissek, Shmuel / Neural substrates of overgeneralized conditioned fear in PTSD.

In: American Journal of Psychiatry, Vol. 174, No. 2, 01.02.2017, p. 125-134.

Research output: Contribution to journalArticle

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