We propose that structural and functional connectivity of the anterior cingulate cortex (ACC) represents a critical component of adolescent developmental psychopathology. We hypothesize that connectivity of the ACC, a hub for integrating cognitive, affective, and social information to guide self-regulation across domains, supports adaptive development of self-regulation during adolescence and that, conversely, disrupted maturation of ACC connectivity contributes to the development of depression. To integrate findings on typical development, we report results of a meta-analysis of diffusion imaging findings of typical adolescent development of the cingulum and anterior thalamic radiation, the tracts most relevant to ACC connectivity, and provide a critical review of the literature on ACC functional connectivity. Finally, we review the evidence for altered structural and functional connectivity in adolescents with depression. Although the evidence for our claim is persuasive, a more comprehensive understanding of the ACC’s role depends upon future investigations with sophisticated modeling of networks, prospective and longitudinal designs, and examination of structure-function associations.

Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n=53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)—a recently developed, whole-brain approach—was used to identify pre-treatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Post-treatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared to healthy subjects (n=38). CPM identified an opioid abstinence network ( p =.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at post-treatment related to abstinence at 6-month follow-up (p<.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and non-responders. These data indicate dissociable anatomical substrates of opioid versus cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

The current opioid epidemic is an urgent public health problem, with enormous individual, societal, and healthcare costs. Despite effective, evidence-based treatments, there is significant individual variability in treatment responses and relapse rates are high. In addition, the neurobiology of opioid-use disorder (OUD) and its treatment is not well understood. This review synthesizes published fMRI literature relevant to OUD, with an emphasis on findings related to opioid medications and treatment, and proposes areas for further research. We conducted a systematic literature review of Medline and Psychinfo to identify (i) fMRI studies comparing OUD and control participants; (ii) studies related to medication, treatment, abstinence or withdrawal effects in OUD; and (iii) studies involving manipulation of the opioid system in healthy individuals. Following application of exclusionary criteria (e.g., insufficient sample size), 45 studies were retained comprising data from~1400 individuals. We found convergent evidence that individuals with OUD display widespread heightened neural activation to heroin cues. This pattern is potentiated by heroin, attenuated by medication-assisted treatments for opioids, predicts treatment response, and is reduced following extended abstinence. Nonetheless, there is a paucity of literature examining neural characteristics of OUD and its treatment. We discuss limitations of extant research and identify critical areas for future neuroimaging studies, including the urgent need for studies examining prescription opioid users, assessing sex differences and utilizing a wider range of clinically relevant task-based fMRI paradigms across different stages of addiction.Neuropsychopharmacology (2019) 44:259-273; https://doi.

Background There is emerging evidence that the increased susceptibility to developing alcohol and substance use disorders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results High-risk subjects showed poorer Working Memory functioning. Cau-date volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.