Increasing deactivation of limbic structures over psychosocial stress exposure time

ABSTRACT BACKGROUND Understanding the interplay between central nervous system and hypothalamus-pituitary-adrenal axis responses to stress in humans is assumed to be essential to contribute to the central question of stress research, namely how stress can increase disease risk. Therefore, the present study used a neuroimaging stress paradigm to investigate the interplay of three stress response domains. Furthermore, we asked if the brain’s stress response changes over exposure time. METHODS In a functional magnetic resonance imaging study, changes in brain activation, cortisol levels, affect and heart rate in response to an improved ScanSTRESS protocol were assessed in 67 young, healthy participants (31 females). RESULTS Stress exposure led to significant increases in cortisol levels, heart rate and negative affect ratings as well as to activations and deactivations in (pre-)limbic regions. When cortisol increase was used as a covariate, stronger responses in hippocampus, amygdala, medial prefrontal cortex (mPFC) and cingulate gyrus were observed. Responses within the same regions predicted negative affect ratings. Remarkably, an increasing deactivation over the two ScanSTRESS runs was found, again, in the same structures. A reanalysis of an independent sample confirmed this finding. CONCLUSIONS For the first time, reactions in a cluster of (pre-)limbic structures was consistently found to be associated with changes in cortisol and negative affect. The same neural structures showed increasing deactivations over stress exposure time. We speculate that investigating possible associations between exposure time effects in neural stress responses and stress related interindividual differences (e.g. chronic stress), might be a promising new avenue in stress research.