Hannah Berg1, Yizhou Ma1, Amanda Rueter1, Antonia Kaczkurkin2, Philip C Burton3, Colin G DeYoung1, Angus W MacDonald1, Scott R Sponheim4,5, Shmuel M Lissek1. 1. Department of Psychology, University of Minnesota, Minneapolis, MN, USA. 2. Department of Psychological Sciences, Vanderbilt University, Nashville, TN, USA. 3. Office of the CLA Associate Dean for Research, University of Minnesota, Minneapolis, MN, USA. 4. Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA. 5. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
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.
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.
Authors: Angela R Laird; P Mickle Fox; Simon B Eickhoff; Jessica A Turner; Kimberly L Ray; D Reese McKay; David C Glahn; Christian F Beckmann; Stephen M Smith; Peter T Fox Journal: J Cogn Neurosci Date: 2011-06-14 Impact factor: 3.225
Authors: Andrew A Nicholson; Daniela Rabellino; Maria Densmore; Paul A Frewen; Christian Paret; Rosemarie Kluetsch; Christian Schmahl; Jean Théberge; Tomas Ros; Richard W J Neufeld; Margaret C McKinnon; Jeffrey P Reiss; Rakesh Jetly; Ruth A Lanius Journal: Hum Brain Mapp Date: 2018-07-13 Impact factor: 5.038