Contemporary theory suggests that prefrontal cortex (PFC) function is associated with individual variability in the psychobiology of the stress response. Advancing our understanding of this complex biobehavioral pathway has potential to provide insight into processes that determine individual differences in stress susceptibility. The present study used functional magnetic resonance imaging to examine brain activity during a variation of the Montreal Imaging Stress Task (MIST) in 53 young adults. Salivary cortisol was assessed as an index of the stress response, trait anxiety was assessed as an index of an individual’s disposition toward negative affectivity, and self-reported stress was assessed as an index of an individual’s subjective psychological experience. Heart rate and skin conductance responses were also assessed as additional measures of physiological reactivity. Dorsomedial PFC, dorsolateral PFC, and inferior parietal lobule demonstrated differential activity during the MIST. Further, differences in salivary cortisol reactivity to the MIST were associated with ventromedial PFC and posterior cingulate activity, while trait anxiety and self-reported stress were associated with dorsomedial and ventromedial PFC activity, respectively. These findings underscore that PFC activity regulates behavioral and psychobiological components of the stress response.

Stress elicits a variety of psychophysiological responses that show large interindividual variability. Determining the neural mechanisms that mediate individual differences in the emotional response to stress would provide new insight that would have important implications for understanding stress-related disorders. Therefore, the present study examined individual differences in the relationship between brain activity and the emotional response to stress. In the largest stress study to date, 239 participants completed the Montreal Imaging Stress Task (MIST) while heart rate, skin conductance response (SCR), cortisol, self-reported stress, and blood oxygen level dependent (BOLD) functional MRI (fMRI) signal responses were measured. The relationship between differential responses (heart rate, SCR, cortisol, and self-reported stress) and differential BOLD fMRI data was analyzed. Dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and amygdala activity varied with the behavioral response (i.e., SCR and self-reported stress). These results suggest the PFC and amygdala support processes that are important for the expression and regulation of the emotional response to stress, and that stress-related PFC and amygdala activity underlie interindividual variability in peripheral physiologic measures of the stress response.

Stress tasks performed during functional magnetic resonance imaging (fMRI) elicit a relatively small cortisol response compared to stress tasks completed in a traditional behavioral laboratory, which may be due to apprehension of fMRI that elicits an anticipatory stress response. The present study investigated whether anticipatory stress is greater prior to research completed in an MRI environment than in a traditional behavioral laboratory. Anticipatory stress (indexed by cortisol) was greater prior to testing in the MRI environment than traditional behavioral laboratory. Furthermore, anticipation of fMRI elicited a cortisol response commensurate with the response to the stress task in the behavioral laboratory. However, in the MRI environment, post-stress cortisol was significantly lower than baseline cortisol. Taken together, these findings suggest the stress elicited by anticipation of fMRI may lead to acute elevations in cortisol prior to scanning, which may in turn disrupt the cortisol response to stress tasks performed during scanning.

Cognitive and emotional functions are supported by the coordinated activity of a distributed network of brain regions. This coordinated activity may be disrupted by psychosocial stress, resulting in the dysfunction of cognitive and emotional processes. Graph theory is a mathematical approach to assess coordinated brain activity that can estimate the efficiency of information flow and determine the centrality of brain regions within a larger distributed neural network. However, limited research has applied graph theory techniques to the study of stress. Advancing our understanding of the impact stress has on global brain networks may provide new insight into factors that influence individual differences in stress susceptibility. Therefore, the present study examined the brain connectivity of participants that completed the Montreal Imaging Stress Task. Salivary cortisol, heart rate, skin conductance response, and self-reported stress served as indices of stress, and trait anxiety served as an index of participant’s disposition towards negative affectivity. Psychosocial stress was associated with a decrease in the efficiency of the flow of information within the brain. Further, the centrality of brain regions that mediate emotion regulation processes (hippocampus, ventral prefrontal cortex, and cingulate cortex) decreased during stress exposure. Interestingly, individual differences in cortisol reactivity were negatively correlated with the efficiency of information flow within this network, whereas cortisol reactivity was positively correlated with the centrality of the amygdala within the network. These findings suggest that stress reduces the efficiency of information transfer and leaves the function of brain regions that regulate the stress response vulnerable to disruption.

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.