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Intrinsic Spirituality and Acute Stress: Neural Mechanisms Supporting the Relationship Between Spirituality and Reduced Stress Responsivity Clayton Hoi-Yun McClintock Spirituality is a multidimensional construct that refers to the experience of selftranscendence and connection with a higher sacred reality. Previous research has demonstrated that spirituality represents a consistent resilience factor for stress and a range of stress-related mental disorders, but neural mechanisms by which spirituality confers resilience are unknown. This paper focuses on intrinsic spirituality, or the extent to which spirituality functions as a master motive in one’s life regardless of religious affiliation, and reviews the research literature on behaviors and brain structures and functions related to intrinsic spirituality. Additionally, literature is reviewed on adaptive and maladaptive functions of the stress response, its relationship to psychopathology, and its underlying neurobiology. To understand neural responses underlying the link between intrinsic spirituality and stress, the current study utilized a script-guided imagery task to assess brain activity during a stress exposure. Results showed that during a stressful experience higher intrinsic spirituality is associated with greater deactivation in the hippocampus, brain stem, ventral striatum, thalamus, extending to the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (vmPFC), as well as in another cluster comprising of the posterior cingulate cortex (PCC) and right inferior parietal lobule. These regions are implicated in stress responsiveness, emotional and cognitive processing, and self-referential processing. While preliminary, results provide a potential neural substrate for how spirituality may influence stress processing. Moreover, they suggest a role for spirituality in attenuating neural responses to stress responsivity, regulating emotion during exposure to stress, and preventing and treating stress-related