Executive control coordinates, prioritizes, and selects task-relevant representations under conditions of conflict. Behavioral evidence has documented that executive resources are separable, finite, and can be temporarily depleted; however, the neural basis for such resource limits are largely unknown. Here, we investigate the neural correlates underlying the fatigue or depletion of interference control, an executive process hypothesized to mediate competition among candidate memory representations. Using a pre/post continuous acquisition fMRI design, we demonstrate that, compared with a nondepletion control group, the depletion group showed a fatigue-induced performance deficit that was specific to interference control and accompanied by a left-to-right shift in the network of active regions. Specifically, we observed decreased BOLD signal in the left inferior frontal gyrus (IFG), striatum, and the cerebellum, along with a corresponding increase in right hemisphere regions including the IFG, insular, and temporal cortex. Depletion-related changes in activation magnitude correlated with behavioral changes, suggesting that decreased recruitment of task-relevant regions, including left IFG, contributes to impaired interference control. These results provide new evidence about the brain dynamics of “process-specific” fatigue and suggest that depletion may pose a significant limitation on the cognitive and neural resources available for executive control.

The catechol O -methyltransferase (COMT) gene—encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)—contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic–phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic–phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic–phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val 158 met polymorphism on different components of working memory.

Previous studies on the neural correlates of perceptual awareness implicate sensory-specific regions and higher cortical regions such as the prefrontal cortex (PFC) in this process. The specific role of PFC regions is, however, unknown. PFC activity could be bottom-up driven, integrating signals from sensory regions. Alternatively, PFC regions could serve more active top-down processes that help to define the content of consciousness. To compare these alternative views of PFC function, we used functional magnetic resonance imaging and measured brain activity specifically related to conscious perception of items that varied in ease of identification (by being presented 0, 12, or 60 times previously). A bottom-up account predicts that PFC activity would be largely insensitive to stimulus difficulty, whereas a top-down account predicts reduced PFC activity as identification becomes easier. The results supported the latter prediction by showing reduced activity for previously presented compared to novel items in the PFC and several other regions. This was further confirmed by a functional connectivity analysis showing that the interaction between frontal and visual sensory regions declined as a function of ease of identification. Given the attribution of top-down processing to PFC regions in combination with the marked decline in PFC activity for easy items, these findings challenge the prevailing notion that the PFC is necessary for consciousness.