Anticipatory prefrontal cortex activity underlies stress-induced changes in Pavlovian fear conditioning

Abstract

Excessive stress exposure often leads to emotional dysfunction, characterized by disruptions in healthy emotional learning, expression, and regulation processes. A prefrontal cortex (PFC)-amygdala circuit appears to underlie these important emotional processes. However, limited human neuroimaging research has investigated whether these brain regions underlie the altered emotional function that develops with stress. Therefore, the present study used functional magnetic resonance imaging (fMRI) to investigate stress-induced changes in PFC-amygdala function during Pavlovian fear conditioning. Participants completed a variant of the Montreal Imaging Stress Task (MIST) followed (25 min later) by a Pavlovian fear conditioning task during fMRI. Self-reported stress to the MIST was used to identify three stress-reactivity groups (Low, Medium, and High). Psychophysiological, behavioral, and fMRI signal responses were compared between the three stress-reactivity groups during fear conditioning. Fear learning, indexed via participant expectation of the unconditioned stimulus during conditioning, increased with stress reactivity. Further, the High stress-reactivity group demonstrated greater autonomic arousal (i.e., skin conductance response, SCR) to both conditioned and unconditioned stimuli compared to the Low and Medium stress-reactivity groups. Finally, the High stress group did not regulate the emotional response to threat. More specifically, the High stress-reactivity group did not show a negative relationship between conditioned and unconditioned SCRs. Stress-induced changes in these emotional processes paralleled changes in dorsolateral, dorsomedial, and ventromedial PFC function. These findings demonstrate that acute stress facilitates fear learning, enhances autonomic arousal, and impairs emotion regulation, and suggests these stress-induced changes in emotional function are mediated by the PFC.

Trauma exposure acutely alters neural function during Pavlovian fear conditioning

“…Thus, our results suggest that there is an acute effect of trauma exposure that modulates the function of the dorsomedial PFC in regards to threat expectancy. Recent research demonstrates acute stress impacts neural activity within the dorsomedial PFC (Wheelock et al, 2016), which has subsequent effects on fear learning-related activity within this region of the brain (Goodman, Harnett, Wheelock, et al, 2018). Thus, acute posttraumatic stress may alter cognitive functions supported by the dorsomedial PFC that lead to changes in fear learning processes.…”

“…For example, prior research has demonstrated that fear acquisition, expression, extinction, and extinction recall are disrupted in chronic PTSD (Blechert, Michael, Vriends, Margraf, & Wilhelm, 2007; Fani et al, 2012; Garfinkel et al, 2014; Grillon & Morgan, 1999; Milad et al, 2009; Norrholm et al, 2011). Further, previous research has demonstrated that acute stress exposure modulates associative fear learning (Goodman, Harnett, Wheelock, et al, 2018; Raio & Phelps, 2015), which is disrupted in chronic PTSD (Blechert et al, 2007; Fani et al, 2012; Garfinkel et al, 2014; Grillon & Morgan, 1999; Milad et al, 2009; Norrholm et al, 2011). For example, physical and psychosocial stress exposure appears to sensitize fear learning processes such that fear-related associations are formed more rapidly, and expressed more strongly and indiscriminately (Dunsmoor, Otto, & Phelps, 2017; Goodman, Harnett, Wheelock, et al, 2018; Rau, DeCola, & Fanselow, 2005; Shors, Weiss, & Thompson, 1992).…”

“…Further, previous research has demonstrated that acute stress exposure modulates associative fear learning (Goodman, Harnett, Wheelock, et al, 2018; Raio & Phelps, 2015), which is disrupted in chronic PTSD (Blechert et al, 2007; Fani et al, 2012; Garfinkel et al, 2014; Grillon & Morgan, 1999; Milad et al, 2009; Norrholm et al, 2011). For example, physical and psychosocial stress exposure appears to sensitize fear learning processes such that fear-related associations are formed more rapidly, and expressed more strongly and indiscriminately (Dunsmoor, Otto, & Phelps, 2017; Goodman, Harnett, Wheelock, et al, 2018; Rau, DeCola, & Fanselow, 2005; Shors, Weiss, & Thompson, 1992). Thus, the prior literature suggests stress exposure can disrupt healthy fear learning and memory processes.…”

Repeatability of Neural and Autonomic Responses to Acute Psychosocial Stress

“…An important goal of the current study was to assess potential stress reactivity during both V1 and V2, independently. As in previous work (Allendorfer et al, 2014(Allendorfer et al, , 2019Goodman et al, 2018Goodman et al, , 2019Orem et al, 2019), a preplanned contrasts of SMT and CMT (SMT -CMT) served as an index of increased BPM during stressful compared to control math conditions. In order to assess whether HR was greater during SMT compared to CMT during both visits, a priori planned contrasts compared HR for Task (CMT, SMT) at each level of Visit (V1, V2).…”

“…In addition to math performance measures, participant autonomic responses to MIST are commonly used to validate and index stress reactivity to the task (Allendorfer et al, 2014(Allendorfer et al, , 2019Wheelock et al, 2016;Elbau et al, 2018;Goodman et al, 2018Goodman et al, , 2019Gossett et al, 2018;Orem et al, 2019). In the present study, we sought to assess whether these measures indicated stress reactivity and whether this reactivity varied across repeated MRI visits.…”