Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network

Distraction and rumination are distinct response styles that determine how an individual deals with negative thoughts and feelings. Rumination is accompanied by an elevated self-focus, which is associated with increased resting state functional connectivity and decreased reactivity within the default mode network. Interestingly, the NMDA receptor antagonist ketamine reduces functional connectivity in this network, while its effects on blood oxygenation level-dependent (BOLD) responses during stimulus perception are not known. Ketamine might lead to a more variable processing of the external world with an attenuated self-focus by reducing the resting state connectivity. Here, we used an emotional picture-viewing task in combination with functional magnetic resonance imaging to test the hypothesis that a single ketamine administration to healthy subjects increases BOLD reactivity to negative stimuli. We found a region specific increase in BOLD reactivity in the pregenual anterior cingulate cortex and not in a posterior control region after ketamine compared with placebo administration. Moreover, a linear regression revealed that the increase in BOLD reactivity was more pronounced for subjects with a low ability to apply distraction during negative experiences. Our results implicate that ketamine attenuates a potentially pathological increased self-focus during negative experiences.