Differential involvement of brainstem noradrenergic and midbrain dopaminergic nuclei in cognitive control

Several lines of evidence suggest that the lateral prefrontal cortex (PFC), the dorsal anterior cingulate cortex (dACC), the parietal cortex, and the thalamus are central cortical nodes in a network underlying cognitive control. However, the role of catecholamine producing midbrain and brainstem structures has rarely been addressed by functional magnetic resonance imaging (fMRI). We hypothesized differential activation patterns in the ventral tegmental area (VTA)/substantia nigra (SN) and locus coeruleus (LC) with respect to the degree of cognitive control during a Stroop task in healthy subjects. Forty-five healthy subjects were investigated by the manual version of the Stroop task in an event-related fMRI design. We observed significant BOLD activation of both the SN/VTA and LC during the Stroop interference condition (incongruent vs. congruent condition). LC, but not SN/VTA activation significantly correlated with the Stroop interference. Interestingly, a significant linear decrease in BOLD activation during the incongruent condition during the experiment was mainly observed in the fronto-cingulo-striatal network, but not in SN/VTA and LC. Using psychophysiological (PPI) analyses, a significant functional connectivity during cognitive control was observed between SN/VTA and the nigrostriatal/mesolimbic dopaminergic system. For the LC, distinct functional connectivity pattern was observed mainly to the dorsolateral and ventrolateral PFC. Both regions revealed significant functional connectivity to the dACC, parietal and occipital regions. Thus, we demonstrate for the first time that functional activation patterns in the SN/VTA and the LC are modulated by different demands of cognitive control. In addition, these nuclei exhibit distinguishable functional connectivity patterns to cortical brain networks. Hum Brain Mapp 37:2305-2318, 2016. © 2016 Wiley Periodicals, Inc.