One of the most exciting advances in our understanding of brain functioning over the past two decades is the mapping of the human brain “connectome,” or the brain’s integrated neural circuitry, through which we have learned about the brain’s connectivity. Brain connectivity can be evaluated in terms of integrity of white matter fiber tracts (structural) or temporal correlation of neural signals across brain regions (functional). In addiction research, atypical brain connectivity has been observed in various substance abusing groups (e.g., alcohol, cocaine, marijuana) across the lifespan (i.e., adolescents, adults) as well as in those considered sub-clinical or at-risk. This special issue highlights advancements in our knowledge of the “addiction connectome” (i.e., the neural structural and functional wiring in the addicted brain) and its role in the development and maintenance of addiction. These invited papers demonstrate the multiple dimensions by which addiction research has informed current knowledge through various approaches in brain connectivity (e.g., independent component analysis [ICA]; psychophysiological interaction [PPI]; diffusion tensor imaging [DTI]).
This introduction offers a brief overview of the wide range of studies presented in this special issue. Specifically, this body of work sheds light on the vulnerability to addiction (e.g., potential neural risk markers that predate the onset of the clinical presentations of addiction), the biologic underpinnings of addiction (e.g., provides an improved understanding of the fundamental neurobiological circuitry that underlies the complex symptoms of addiction, such as impulsivity, reward/motivation), and treatment approaches to addiction (e.g., how might our knowledge of the addiction connectome facilitate the improvement of treatment strategies?). The specific contributions of the individual articles are described.
1. Vulnerability to addiction
Potential markers in neural connectivity that reflect vulnerability to addiction are described by Luciana et al. (pages 345 to 355). In a two-year prospective study, the authors teased apart structural connectivity patterns that distinguish adolescents who transitioned into regular alcohol use from those who did not. Neural distinctions revolved around the blunted development of white matter in several areas coupled with decreased white matter integrity, as measured by diffusion tensor imaging (DTI) and fractional anisotropy (FA), despite the lack of difference in premorbid characteristics. This deviation from typical neurodevelopment suggests a possible neurodevelopmental lag in those who are at-risk for alcohol use disorders (AUD).
Spadoni et al. (pages 356 to 364) tested this “neuromaturational lag” hypothesis directly by comparing adolescents with a family history of alcohol use disorders from those without a family history and also in older adolescents. They report that during a spatial working memory task, functional connectivity differed in those with familial risk compared to both young adolescents without a family history of AUD and in older adolescents. These findings propose that less mature connectivity can identify adolescents at risk for drinking problems.
2. The biologic underpinnings of addiction
Thayer et al.’s (pages 365 to 371) study provides evidence that decreased white matter integrity via lower DTI FA is also evident following the onset of problematic drinking. The authors compared juvenile justice–involved adolescents with high scores on the Alcohol Use Disorders Identification Test (AUDIT) with juvenile justice–involved adolescents with low AUDIT scores and found lower FA values in projection fibers of the basal ganglia. Exploratory analyses further showed an inverse relationship between FA and impulsivity scores. This demonstrates potential neurotoxic effects of heavy alcohol use on white matter microstructure that is associated with risk-taking in adolescents.
Orr et al. (pages 372 to 381) evaluated how intrinsic connectivity networks differed between marijuana dependent and non-dependent adolescents. The authors report increased spontaneous signal fluctuations (amplitude of the low frequency fluctuations [ALFF]) underlying resting-state functional connectivity (rsFC) in right hemispheric regions in dependent adolescents. They further noted stronger intra-hemispheric functional connectivity in the marijuana dependent adolescents versus controls.
These differential connectivity patterns based on severity of use are consistent with those observed in marijuana-using adults. Filbey and Yezhuvath (pages 382 to 391) explored inhibitory control networks in dependent versus non-dependent adult users. While network activation did not differ between the two severity groups, greater network connectivity was found in dependent compared to non-dependent users.
The report by Mitchell et al. (pages 392 to 402) further supports the possibility of either a compensatory mechanism or a failure of inhibitory networks to regulate in addiction. Specifically, the authors examined task-dependent connectivity using the Stroop Task, a classic task of response inhibition, in cocaine users. Compared to non-users, cocaine users showed greater connectivity in inhibitory and reward networks, suggesting greater motivational processes in cocaine users.
Focusing on the role of the insular connectivity during impulsivity, Wisner et al. (pages 403 to 413) report on weaker inter-network connectivity between intrinsic connectivity networks (ICNs) in frontal areas as well as an ICN in the striatum in cocaine users relative to controls. This pattern was inversely related to impulsivity in cocaine users, elaborating on the interaction between frontal control and reward areas as they relate to impulsivity.
3. Treatment approaches to addiction
In high-risk adolescents from the juvenile justice system, Houck et al. (pages 414 to 423) investigated how intrinsic resting state connectivity networks may be related to marijuana use. They found that during rest, an area within the frontal control network positively correlated with marijuana use. This investigation of high-risk adolescents that are intermediary between community and treatment samples provides a unique opportunity for directly linking risk with implications for treatment.
Trait impulsivity (versus state) is also thought to be due to dysregulation in frontal cortical function coupled with striatal function. McHugh et al. (pages 424 to 432) investigated this notion in cocaine-addicted individuals during resting state. Reductions in cortico-striatal circuit connectivity was found to be mediated by impulsivity scores and, importantly, primarily driven by cocaine-addicted individuals who subsequently relapsed. This work discusses the role of connectivity in determining risk for relapse and poses a potential target for more effective treatment strategies.
Orban et al. (pages 433 to 440) examined how resting state networks related to state anxiety may also be related to symptoms of alcohol use. They found reductions in connectivity in anxiety-related networks in alcohol-dependent patients. This provides evidence for varying neural correlates of state anxiety between alcohol dependent patients who do not have anxiety disorders and patients with clinical anxiety disorders. These findings have implications for those with comorbid addictions and affective disorders.
In conclusion, our rapidly growing understanding of the addiction connectome has given us new avenues to probe the integrated brain systems that underlie addiction. Future work can expand on this knowledge by determining individual differences, such as genetic and environmental factors, that influence the addiction connectome.
Thank you to all of the authors who contributed their important work to this special issue.
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