Deep brain stimulation of the nucleus accumbens releases aversive inhibition of behaviour in obsessive-compulsive disorder

The striatum has long been implicated in motivation, learning, and action. Recent theories have proposed that the striatum is particularly involved in the coupling of these processes, giving rise to motivational biases in the selection and learning of actions. Here we assess the causal role of the ventral striatum in the motivational biasing of action for the first time in humans by directly stimulating the nucleus accumbens with deep brain stimulation (DBS). Treatment-refractory obsessive-compulsive disorder patients (n=8) performed a motivational Go/NoGo task with concurrent EEG recordings. The subjects needed to learn to make Go or NoGo responses in order to win reward or avoid punishment, while DBS was switched ON vs. OFF in a cross-over within-subject design. As previously observed in healthy populations, performance was strongly affected by the cue valence, such that fewer and slower Go responses were made when avoiding punishment than when playing for reward. DBS attenuated the inhibitory influence of punishment cues on reaction times and marginally on the proportion Go responses when Go responses were required. For the Go cues where these Pavlovian response tendencies conflicted with the instrumental requirements, oscillatory theta (4-8Hz) activity increased over the midfrontal cortex. These putative conflict-related midfrontal theta responses were not significantly affected by DBS. Taken together, these results suggest that nucleus accumbens stimulation attenuates the motivational biasing of action, seemingly without affecting frontal control systems. These results causally implicate the human nucleus accumbens in the coupling of motivation and behavioural activation.