GABAA Receptors Predict Aversion-Related Brain Responses: An fMRI-PET Investigation in Healthy Humans

The perception of aversive stimuli is essential for human survival and depends largely on environmental context. Although aversive brain processing has been shown to involve the sensorimotor cortex, the neural and biochemical mechanisms underlying the interaction between two independent aversive cues are unclear. Based on previous work indicating ventromedial prefrontal cortex (vmPFC) involvement in the mediation of context-dependent emotional effects, we hypothesized a central role for the vmPFC in modulating sensorimotor cortex activity using a GABAergic mechanism during an aversive-aversive stimulus interaction. This approach revealed differential activations within the aversion-related network (eg, sensorimotor cortex, midcingulate, and insula) for the aversive-aversive, when compared with the aversive-neutral, interaction. Individual differences in sensorimotor cortex signal changes during the aversive-aversive interaction were predicted by GABA(A) receptors in both vmPFC and sensorimotor cortex. Together, these results demonstrate the central role of GABA in mediating context-dependent effects in aversion-related processing.