Identification of neurobiological factors that confer risk for the development of addiction may substantially advance development of new prevention and treatment strategies to combat substance use disorders. This review focuses on the relationship between impulsivity - a behavior that is common to the clinical picture of both substance use disorders (SUD) and childhood disruptive behavior disorders - and neurobiological risk for SUD. It further examines various behaviors within the over-arching domain of impulsivity, ultimately focusing on the more narrowly defined and measurable construct of inhibitory control, and concluding that underlying deficits in inhibitory control may be central to many of the behaviors associated with high risk for SUD. Targeted cross-sectional study of the neural basis of inhibitory dyscontrol in subjects at high risk for SUD, who have not yet begun to abuse drugs, has the potential to generate important hypotheses regarding the neurobiological underpinnings of SUD risk. Hypotheses developed using this approach can be more definitively evaluated in longitudinal studies with these same populations, extending through the period of maximal risk for SUD in adolescence and early adulthood.

The cerebellum is emerging as a key anatomical structure underlying normal attentional and cognitive control mechanisms. Dysregulation within cerebellar circuits may contribute to the core symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). In the present study we aimed to characterize surface morphological features of the cerebellum in ADHD and healthy comparison youths. Further, we studied the association of cerebellar morphology with the severity of ADHD symptoms and the effects of stimulant treatment. We examined 46 youths with ADHD and 59 comparison youths 8–18 years of age in a cross-sectional, case–control study using magnetic resonance imaging. Measures of cerebellar surface morphology were the primary outcome. Relative to comparison participants, youths with ADHD exhibited smaller regional volumes corresponding to the lateral surface of the left anterior and the right posterior cerebellar hemispheres. Stimulant medication was associated with larger regional volumes over the left cerebellar surface, whereas more severe ADHD symptoms were associated with smaller regional volumes in the vermis. We used optimized measures of morphology to detect alterations in cerebellar anatomy specific to ADHD, dimensions of symptomology, and stimulant treatment. Duration of treatment correlated positively with volumes of specific cerebellar subregions, supporting a model whereby compensatory morphological changes support the effects of stimulant treatment.

Existing evidence suggests that reward and attentional networks function in concert and that activation in one system influences the other in a reciprocal fashion; however, the nature of these influences remains poorly understood. We therefore developed a three‐component task to assess the interaction effects of reward anticipation and conflict resolution on the behavioral performance and the activation of brain reward and attentional systems. Sixteen healthy adult volunteers aged 21–45 years were scanned with functional magnetic resonance imaging (fMRI) while performing the task. A two‐way repeated measures analysis of variance (ANOVA) with cue (reward vs. non‐reward) and target (congruent vs. incongruent) as within‐subjects factors was used to test for main and interaction effects. Neural responses to anticipation, conflict, and reward outcomes were tested. Behaviorally there were main effects of both reward cue and target congruency on reaction time. Neuroimaging results showed that reward anticipation and expected reward outcomes activated components of the attentional networks, including the inferior parietal and occipital cortices, whereas surprising non‐rewards activated the frontoinsular cortex bilaterally and deactivated the ventral striatum. In turn, conflict activated a broad network associated with cognitive control and motor functions. Interaction effects showed decreased activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus bilaterally when difficult conflict trials (e.g., incongruent targets) were preceded by reward cues; in contrast, the ventral striatum and orbitofrontal cortex showed greater activation during congruent targets preceded by reward cues. These results suggest that reward anticipation is associated with lower activation in attentional networks, possibly due to increased processing efficiency, whereas more difficult, conflict trials are associated with lower activity in regions of the reward system, possibly because such trials are experienced as less rewarding.