Don't Stress, It's Under Control: Neural Correlates of Stressor Controllability in Humans

Animal research has repeatedly shown that experience of control over an aversive event can protect against the negative consequences of later uncontrollable stress. Neurobiologically, this effect is assumed to correspond to persistent changes in the pathway linking the ventromedial prefrontal cortex (vmPFC) and the dorsal raphe nucleus. However, it remains unclear to what extent these findings translate to humans. During functional magnetic resonance imaging, we subjected participants to controllable and uncontrollable aversive but non-painful electric stimuli, as well as to a control condition without aversive stimulation. In each trial, a symbol signalled whether participants could terminate the stressor through correct performance in a button-matching task or whether the stressor would be randomly terminated, i.e., uncontrollable. Along with neural responses, we assessed participants accuracy, reaction times, and heart rate. To relate neural activations and subjective experience, we asked participants to rate perceived control, helplessness, and stress. Results were largely in line with our hypotheses. The vmPFC was generally deactivated by stress, but this effect was attenuated when participants could terminate the stressor compared to when their responses had no effect. Furthermore, activation in stress-responsive regions, including the bilateral insula, was reduced during controllable trials. Under uncontrollable stress, greater vmPFC recruitment was linked to reduced feelings of helplessness. An investigation of condition-dependent differences in vmPFC connectivity yielded no significant results. Our findings further corroborate animal research and emphasise the role of the vmPFC in controllability-dependent regulation of stress responses. Based on the results, we discuss future directions in the context of resilience research and mental health promotion.