Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort. Our results provide evidence that converges with that from association studies relating increased D2 density to deficits in cognitive flexibility in schizophrenia. We suggest that individual differences in striatal D2 signaling in healthy humans modulate goal-directed gating to prefrontal cortex, thus leading to individual differences in switching intentionally to newly relevant behaviors.

These findings provide evidence that cognitive bias modification affects alcohol cue-induced mesolimbic brain activity. Reductions in neural reactivity may be a key underlying mechanism of the therapeutic effectiveness of this training.

Abstract■ An impairment of attentional control in the face of threat-related distracters is well established for high-anxious individuals. Beyond that, it has been hypothesized that high trait anxiety more generally impairs the neural efficiency of cognitive processes requiring attentional control-even in the absence of threat-related stimuli. Here, we use fMRI to show that trait anxiety indeed modulates brain activation and functional connectivities between task-relevant brain regions in an affectively neutral Stroop task. In high-anxious individuals, dorsolateral pFC showed stronger task-related activation and reduced coupling with posterior lateral frontal regions, dorsal ACC, and a word-sensitive area in the left fusiform gyrus. These results support the assumption that a general (i.e., not threat-specific) impairment of attentional control leads to reduced neural processing efficiency in anxious individuals. The increased dorsolateral pFC activation is interpreted as an attempt to compensate for suboptimal connectivity within the cortical network subserving task performance. ■

Behavioral studies have shown an alcohol-approach bias in alcohol-dependent patients: the automatic tendency to faster approach than avoid alcohol compared with neutral cues, which has been associated with craving and relapse. Although this is a well-studied psychological phenomenon, little is known about the brain processes underlying automatic action tendencies in addiction. We examined 20 alcohol-dependent patients and 17 healthy controls with functional magnetic resonance imaging (fMRI), while performing an implicit approach-avoidance task. Participants pushed and pulled pictorial cues of alcohol and soft-drink beverages, according to a contentirrelevant feature of the cue (landscape/portrait). The critical fMRI contrast regarding the alcohol-approach bias was defined as (approach alcohol4avoid alcohol)4(approach soft drink4avoid soft drink). This was reversed for the avoid-alcohol contrast: (avoid alcohol4approach alcohol)4(avoid soft drink4approach soft drink). In comparison with healthy controls, alcohol-dependent patients had stronger behavioral approach tendencies for alcohol cues than for soft-drink cues. In the approach, alcohol fMRI contrast patients showed larger blood-oxygen-level-dependent responses in the nucleus accumbens and medial prefrontal cortex, regions involved in reward and motivational processing. In alcohol-dependent patients, alcohol-craving scores were positively correlated with activity in the amygdala for the approach-alcohol contrast. The dorsolateral prefrontal cortex was not activated in the avoid-alcohol contrast in patients vs controls. Our data suggest that brain regions that have a key role in reward and motivation are associated with the automatic alcoholapproach bias in alcohol-dependent patients.