Dopamine modulates processing speed in the human mesolimbic system

Neural activity in mesolimbic brain regions scales with stimulus novelty but the mechanistic role of neurotransmitters in this process remains unclear. Here, we used magnetoencephalography together with psychopharmacological stimulation in healthy humans to demonstrate that the neuronal dynamics of novelty processing are temporally adaptive and flexible. In particular, enhanced dopaminergic (150mg levodopa) - but not cholinergic (8mg galantamine) - neurotransmission accelerated the onset of novelty signals within the medial temporal lobe (MTL) from ~300 to <100ms. Cholinergic stimulation, on the other hand, led to a shift in underlying neural substrates from medial temporal to prefrontal brain regions. Our findings indicate a causal role of dopamine in regulating the processing speed of novelty sensitive MTL neurons. Moreover, they suggest that the influence of MTL and prefrontal brain regions in novelty processing is mediated by the balance of dopamine and acetylcholine levels.