Salience and central executive networks track overgeneralization of conditioned-fear in post-traumatic stress disorder

Psychol Med. 2021 Nov;51(15):2610-2619. doi: 10.1017/S0033291720001166. Epub 2020 May 5.

Abstract

Background: Generalization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein.

Methods: fMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans (N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS-), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS-. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS-. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization.

Results: SN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity.

Conclusions: Neural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.

Keywords: Central executive network; conditioned-fear; default network; generalization; post-traumatic stress disorder; salience network.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Afghan Campaign 2001-
  • Armed Conflicts / psychology
  • Cues
  • Fear / physiology
  • Fear / psychology*
  • Generalization, Psychological
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Military Personnel
  • Nerve Net / diagnostic imaging*
  • Nerve Net / physiopathology*
  • Stress Disorders, Post-Traumatic / diagnostic imaging*
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Stress Disorders, Post-Traumatic / psychology*
  • United States
  • Veterans