TY - JOUR
T1 - Anticipatory prefrontal cortex activity underlies stress-induced changes in Pavlovian fear conditioning
AU - Goodman, Adam M.
AU - Harnett, Nathaniel G.
AU - Wheelock, Muriah D.
AU - Hurst, Danielle R.
AU - Orem, Tyler R.
AU - Gossett, Ethan W.
AU - Dunaway, Chelsea A.
AU - Mrug, Sylvie
AU - Knight, David C.
N1 - Funding Information:
This research was funded by the National Institute of Mental Health of the National Institutes of Health [grant number MH098348 ].
Funding Information:
We found that stress reactivity during the MIST varied with emotion regulation during the subsequent fear conditioning task. Emotion regulation was indexed via learning-related reductions in the emotional response to threat, a process known as Pavlovian conditioned UCR diminution. Specifically, there is typically a negative relationship between the CR and the UCR during fear conditioning such that as the CR increases, the UCR decreases. Therefore, the negative relationship that is typically observed between the CR and UCR was used to index inhibitory emotion processes that arise from fear learning. Thus, our analysis was designed to determine whether the negative relationship between the CR and UCR was influenced by stress reactivity. Overall, SCRs demonstrated a negative linear relationship between the CR and UCR following stress exposure ( Fig. 3 a). Our neuroimaging results suggest that this inhibitory process was supported by CR activity within the dlPFC and dmPFC that modulated UCR activity within the dlPFC, dmPFC, vlPFC, vmPFC, anterior cingulate cortex, mid cingulate, insula, IPL, and amygdala ( Fig. 5 and Tables S5-8 ). Prior research suggests these brain regions are important for emotion regulation processes ( Knight et al., 2010 ; Lang et al., 2009 ; Marschner et al., 2008 ; Wheelock et al., 2014 ; Wood et al., 2012 , 2013 ). Further, prior work from our laboratory has shown that increased anticipatory PFC activity during the CS+ is associated with decreased threat-elicited (i.e., UCS-evoked) activity in the PFC, IPL, and amygdala ( Wood et al., 2012 ). In the current study, CR activity within the PFC was negatively related to UCR activity within the PFC, cingulate, insula, IPL, and amygdala. Further, the negative relationship between the CR and UCR in these brain regions paralleled the negative relationship between the CR and UCR in the SCRs during fear conditioning. These findings suggest that these brain regions support important inhibitory emotion processes that arise from fear learning.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044168805&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2018.03.030
DO - 10.1016/j.neuroimage.2018.03.030
M3 - Article
C2 - 29555429
AN - SCOPUS:85044168805
SN - 1053-8119
VL - 174
SP - 237
EP - 247
JO - NeuroImage
JF - NeuroImage
ER -