Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Contributions of cerebral white matter hyperintensities, age, and pedal perception to postural sway in people with HIV.

OBJECTIVE: With aging, people with HIV (PWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables. DESIGN: Mixed cross-sectional/longitudinal data were acquired over 15 years in 141 PWH and 102 age-range matched controls, 25-80 years old. METHODS: Multimodal structural MRI data were quantified for seven total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and nonpath data on sway path-WMH relations. RESULTS: In simple correlations, longer sway paths were associated with larger WMH volumes in PWH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and two-point pedal discrimination. Although the sway-WMH relations in PWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for five of the seven regions in the eyes-open condition. CONCLUSION: The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.

Contributions of Cerebral White Matter Hyperintensities to Postural Instability in Aging With and Without Alcohol Use Disorder.

BACKGROUND: Both postural instability and brain white matter hyperintensities (WMHs) are noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to the sway path-WMH relationship in individuals with AUD and healthy control participants. METHODS: The data comprised 404 balance platform sessions, yielding sway path length and magnetic resonance imaging data acquired cross-sectionally or longitudinally in 102 control participants and 158 participants with AUD ages 25 to 80 years. Balance sessions were typically conducted on the same day as magnetic resonance imaging fluid-attenuated inversion recovery acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to the relationship between WMH volumes and postural instability were age, sex, socioeconomic status, education, pedal 2-point discrimination, systolic and diastolic blood pressure, body mass index, depressive symptoms, total alcohol consumed in the past year, and race. RESULTS: Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path-WMH relationships. Inclusion of these factors as predictors in multiple regression analyses substantially attenuated the sway path-WMH relationships in both AUD and healthy control groups. Women, irrespective of diagnosis or race, had shorter sway paths than men. Black participants, irrespective of diagnosis or sex, had shorter sway paths than non-Black participants despite having modestly larger WMH volumes than non-Black participants, which is possibly a reflection of the younger age of the Black sample. CONCLUSIONS: Longer sway paths were related to larger WMH volumes in healthy men and women with and without AUD. Critically, however, age almost fully accounted for these associations.

Frontal cortical volume deficits as enduring evidence of childhood abuse in community adults with AUD and HIV infection comorbidity.

Background: Childhood abuse is an underappreciated source of stress, associated with adverse mental and physical health consequences. Childhood abuse has been directly associated with risky behavior thereby increasing the likelihood of alcohol misuse and risk of HIV infection, conditions associated with brain structural and functional deficits. Here, we examined the neural and behavioral correlates of childhood trauma history in alcohol use disorder (AUD), HIV infection (HIV), and their comorbidity (AUD+HIV). Methods: Occurrence of childhood trauma was evaluated by retrospective interview. Cortical (frontal, temporal, parietal, and occipital), subcortical (hippocampus, amygdala), and regional frontal volumes were derived from structural MRI, adjusted for intracranial volume and age. Test scores of executive functioning, attention/working memory, verbal/visual learning, verbal/visual memory, and motor speed functional domains were standardized on age and education of a laboratory control group. Results: History of childhood abuse was associated with smaller frontal lobe volumes regardless of diagnosis. For frontal subregional volumes, history of childhood abuse was selectively associated with smaller orbitofrontal and supplementary motor volumes. In participants with a child abuse history, poorer verbal/visual memory performance was associated with smaller orbitofrontal and frontal middle volumes, whereas in those without childhood abuse, poorer verbal/visual memory performance was associated with smaller orbitofrontal, frontal superior, and supplemental motor volumes. Conclusions: Taken together, these results comport with and extend the findings that childhood abuse is associated with brain and behavioral sequelae in AUD, HIV, and AUD+HIV comorbidity. Further, these findings suggest that sequelae of abuse in childhood may be best conceptualized as a spectrum disorder as significant deficits may be present in those who may not meet criteria for a formal trauma-related diagnosis yet may be suffering enduring stress effects on brain structural and functional health.

Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI.

Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.

Identifying high school risk factors that forecast heavy drinking onset in understudied young adults.

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.

Multi-dimensional predictors of first drinking initiation and regular drinking onset in adolescence: A prospective longitudinal study.

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (ßs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

Craving dynamics and related cerebral substrates predict timing of use in alcohol, tobacco, and cannabis use disorders.

Background: Patients treated for Substance Use Disorders exhibit highly fluctuating patterns of craving that could reveal novel prognostic markers of use. Accordingly, we 1) measured fluctuations within intensively repeated measures of craving and 2) linked fluctuations of craving to connectivity indices within resting-state (rs) brain regions to assess their relation to use among patients undergoing treatment for Alcohol, Tobacco and Cannabis Use Disorders. Method: Participants -64 individuals with SUD for tobacco, alcohol, or cannabis and 35 healthy controls-completed a week of Ecological Momentary Assessment (EMA) during which they reported craving intensity and substance use five times daily. Before EMA, a subsample of 50 patients, and 34 healthy controls also completed resting-state (rs)-MRI acquisitions. Craving temporal dynamics within each day were characterized using Standard Deviation (SD), Auto-Correlation Factor (ACF), and Mean Successive Square Difference (MSSD). Absolute Difference (AD) in craving between assessments was a prospective prediction measure. Results: Within-day, higher MSSD predicted greater substance use while controlling for mean craving. Prospectively higher AD predicted later increased substance use independently of previous use or craving level. Moreover, MSSD was linked to strength in five functional neural connections, most involving frontotemporal systems. Cerebello-thalamic and thalamo-frontal connectivity were also linked to substance use and distinguished the SUD from the controls. Conclusion: To the best of our knowledge, this is the first study to indicate that instability in craving may be a trigger for use in several SUD types, beyond the known effect of craving intensity.

Effects of Childhood Trauma and Alcoholism History on Neuropsychological Performance in Adults with HIV Infection: An Initial Study.

Background: Childhood trauma carries heightened risk for neuropsychological impairment and is a frequent concomitant of HIV infection (H) and alcoholism (Alc). Little is known about compounded effects of childhood trauma and these diseases on cognitive and motor functioning. We queried the relation between childhood trauma history (experiencing at least 1 of 13 specified traumas before age 18) and cognitive and motor performance in HIV infection with and without lifetime alcoholism. Methods: Relations between childhood trauma history (Tr) and four performance domains (episodic memory, information processing speed, executive function, and fine motor function) were examined via ANCOVAs covarying for age and education in four HIV groups: 21 H+Alc+Tr, 19 H+Alc, 19 H+Tr, and 25 HComp (H comparison group without Tr or Alc). Results: H+Tr, irrespective of Alc, performed poorly on the episodic memory domain. Specifically, immediate and delayed verbal recall, and immediate visual recall were affected in those with HIV and history of childhood trauma with or without alcoholism history. By contrast, H+Alc+Tr performed faster than H+Alc or H+Tr in information processing speed. Conclusion: The findings of poorer episodic memory in HIV infection with childhood trauma history corroborates previous reports and now extends findings to H+Alc+Tr trimorbidity. The novel interaction of alcoholism and trauma in HIV infection suggests that information processing speed is slowed with trauma history or alcoholism history alone in HIV but not with HIV+Alc+Tr trimorbidity, possibly reflecting greater impulsivity and hyperarousal in multiply-affected individuals.