Self-awareness is a pivotal component of conscious experience. It is correlated with a paralimbic network of medial prefrontal/anterior cingulate and medial parietal/posterior cingulate cortical "hubs" and associated regions. Electromagnetic and transmitter manipulation have demonstrated that the network is not an epiphenomenon but instrumental in generation of self-awareness. Thus, transcranial magnetic stimulation (TMS) targeting the hubs impedes different aspects of self-awareness with a latency of 160ms. The network is linked by ∼40Hz oscillations and regulated by dopamine. The oscillations are generated by rhythmic GABA-ergic inhibitory activity in interneurons with an extraordinarily high metabolic rate. The hubs are richly endowed with interneurons and therefore highly vulnerable to disturbed energy supply. Consequently, deficient paralimbic activity and self-awareness are characteristic features of many disorders with impaired oxygen homeostasis. Such disorders may therefore be treated unconventionally by targeting interneuron function.

BackgroundWhile it has recently been shown that dopamine release stimulates conscious self‐monitoring through the generation of gamma oscillations in medial prefrontal/anterior cingulate cortex, and that the GABAergic system is effective in producing such oscillations, interaction of the two transmitter systems has not been demonstrated in humans. We here hypothesize that dopamine challenge stimulates the GABA system directly in the medial prefrontal/anterior cingulate region in the human brain.MethodsPositron emission tomography (PET) with the GABA receptor α1/α5 subtype ligand [11C] Ro15‐4513 was used to detect changes in GABA receptor availability after clinical oral doses of levodopa in a double blind controlled study.ResultsWe here provide the first direct evidence for such coupling in the cerebral cortex, in particular in the medial prefrontal anterior cingulate region, by showing that exogenous dopamine decreases [11C] Ro15‐4513 binding widely in the human brain compatible with a fall in α1 subtype availability in GABA complexes due to increased GABA activity.