Background Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area may clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. Methods Children were assessed for BI at multiple age points from infancy through age seven. Based on a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (N=44). Participants completed an event-related fMRI attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. Results The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. Conclusions BI during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology.

The detection of threat is a role that the amygdala plays well, evidenced by its increased response to fearful faces in human neuroimaging studies. A critical element of the fearful face is an increase in eye white area (EWA), hypothesized to be a significant cue in activating the amygdala. However, another important social signal that can increase EWA is a lateral shift in gaze direction, which also serves to orient attention to potential threats. It is unknown how the amygdala differentiates between these increases in EWA and those that are specifically associated with fear. Using functional magnetic resonance imaging, we show that the left amygdala distinguished between fearful eyes and gaze shifts despite similar EWA increases whereas the right amygdala was less discriminatory. Additional analyses also revealed selective hemispheric response patterns in the left fusiform gyrus. Our data show clear hemispheric differences in EWA-based fear activation, suggesting the existence of parallel mechanisms that code for emotional face information.

Importance Marijuana use may alter ventral striatal response to reward, which may heighten susceptibility to substance use disorder (SUD). Cross-sectional studies have reported either increased ventral striatal response to reward or no difference in marijuana users compared with controls. Longitudinal research is needed to resolve the inconsistencies and disentangle preexisting susceptibility from the effects of marijuana use on neural function involved in reward responding. Objective To determine whether marijuana use among young adults prospectively impacts nucleus accumbens (NAcc) activation during reward anticipation. Design Longitudinal study of self-report marijuana use and brain function using functional magnetic resonance imaging (fMRI) at three consecutive time points. Setting Data were obtained from young adult participants in the Michigan Longitudinal Study, an ongoing, prospective study of youth at high risk for SUD and a contrast sample of control families. Participants The sample consisted of 108 young adults (36% female; 78% family history of SUD) who underwent three fMRI scans at approximately age 20 (time 1), 22 (time 2), and 24 (time 3). Main Outcome and Measures We investigated the impact of marijuana use on neural response in the NAcc to reward anticipation during a monetary incentive delay task (MIDT) using a cross-lagged model. Covariates for analyses included sex, age at first scan, family history of SUD, prior marijuana use, and binge drinking (prior and concurrent). This model was also tested separately with the inclusion of cigarette smoking. Results Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β=−0.26, P=0.04; time 2 to time 3: β=−0.25, P=0.01). When we tested the cross-lagged model with the inclusion of prior and concurrent cigarette use, the impact of marijuana use from time 2 to time 3 remained significant and the effect of cigarette use was non-significant. Conclusions and Relevance Our findings indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of non-drug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase risk for continued drug use and later addiction.