Neuroimaging the temporal dynamics of human avoidance to sustained threat

Many forms of human psychopathology are characterized by sustained negative emotional responses to threat and chronic behavioral avoidance, implicating avoidance as a potential transdiagnostic factor. Evidence from both nonhuman neurophysiological and human neuroimaging studies suggests a distributed frontal-limbic-striatal brain network supports avoidance. However, our understanding of the temporal dynamics of the network to sustained threat that prompts sustained avoidance is limited. To address this issue, 17 adults were given extensive training on a modified free-operant avoidance task in which button pressing avoided money loss during a sustained threat period. Subsequently, subjects underwent functional magnetic resonance imaging while completing the avoidance task. In our regions of interest, we observed phasic, rather than sustained, activation during sustained threat in dorsolateral and inferior frontal regions, anterior and dorsal cingulate, ventral striatum and regions associated with emotion, including the amygdala, insula, substantia nigra and bed nucleus of the stria terminalis complex. Moreover, trait levels of experiential avoidance were negatively correlated with insula, hippocampal and amygdala activation. These findings suggest knowledge that one can consistently avoid aversive outcomes is not associated with decreased threat-related responses and that individuals with greater experiential avoidance exhibit reduced reactivity to initial threat. Implications for understanding brain mechanisms supporting human avoidance and psychological theories of avoidance are discussed.