2025

Edith Vioni Sullivan

• Mutual age-varying influences of binge drinking and cannabis use during emerging adulthood in the NCANDA cohort.

  Waddell, J. T., Brumback, T., Baker, F. C., Cheek, S., Clark, D. B., Goldston, D. B., Grove, J. L., Nagel, B. J., Nooner, K. B., Pfefferbaum, A., Pohl, K. M., Sullivan, E. V., Tapert, S. F., Thompson, W. K., Brown, S. A.

  Alcohol, clinical & experimental research

  ABSTRACT
  Binge drinking peaks during emerging adulthood and is associated with negative developmental outcomes. Within-person changes in cannabis use have been shown to coincide with binge drinking; however, whether within-person changes in binge drinking and cannabis use prospectively predict one another and whether these relations vary by age remain unknown. The current study sought to fill these gaps.Data come from National Consortium on Alcohol and Neurodevelopment (NCANDA) participants aged 18-25 years reporting alcohol and cannabis use (N = 526). Parallel-process state-trait mixed effect growth models tested whether: (1) binge drinking across emerging adulthood was correlated with cannabis use (random intercepts); (2) steeper growth in binge drinking across emerging adulthood correlated with growth in cannabis use (random slopes); and (3) age-specific, within-person changes in binge drinking/cannabis use reciprocally predicted one another.Across individuals, more frequent binge drinking was correlated with more frequent concurrent cannabis use, and steeper increases in binge drinking were correlated with steeper increases in cannabis use during emerging adulthood. Within-person changes in binge drinking and cannabis use covaried. Within-person increases in cannabis use predicted subsequent increases in binge drinking between ages 18 and 21 years but decreases in binge drinking between ages 24 and 25 years. Within-person changes in binge drinking did not predict subsequent changes in cannabis use during emerging adulthood.Changes in cannabis use coincided with changes in binge drinking, concurrently and subsequently, particularly between ages 18 and 21 years when changes in cannabis use predicted subsequent increases in binge drinking and ages 24 and 25 years when changes in cannabis use predicted decreases in subsequent binge drinking. Incorporating motivational approaches to reduce cannabis use in alcohol interventions may be efficacious in early emerging adulthood.

  https://www.ncbi.nlm.nih.gov/pubmed/41020924 https://doi.org/10.1111/acer.70139

  More

• Risks and effects of alcohol use during dual-system brain and cognitive development in adolescence and young adulthood

  Zhao, Q., Milecki, L., Pfefferbaum, A., Sullivan, E., Pohl, K.

• Thalamic Nuclear Volumes in Fetal Alcohol Spectrum Disorders: from Adolescence to Middle-Age 20 Years Later.

  Pfefferbaum, A., Sullivan, E. V., Saranathan, M., Pohl, K. M., Bischoff-Grethe, A., Stoner, S. A., Riley, E. P.

  Biological psychiatry. Cognitive neuroscience and neuroimaging

  ABSTRACT
  Midline orofacial and brain structures, including the multinucleated thalamus, may be differentially sensitive to prenatal alcohol exposure and vulnerable to accelerated aging.Two sets of MRI data separated by 20 years are reported for controls, individuals with fetal alcohol syndrome (FAS), and nondysmorphic individuals with heavy fetal alcohol exposure (FAE). MRI1 included 179 participants with 69 reassessed at MRI2. Segmentation produced estimates of bilateral thalamic volume and 10 bilateral nuclei, which were aggregated into Anterior, Ventral, Posterior, and Medial Volumes. Differences were assessed without and with correction for intracranial volume (ICV).MRI1 revealed stepwise group differences in ICV, total thalamic volume, and Anterior and Ventral regions uncorrected for ICV, where Controls>FAE>FAS. Corrected for ICV, the smaller volumes endured in the Anterior and Ventral regions, although differences between FAE and FAS groups were attenuated. Nuclei volumes were selectively smaller in the alcohol-exposed groups than controls even after controlling for ICV. Longitudinally, thalamic volumes typically declined over time maintaining the stepwise effects and with little evidence for accelerated decline in the FAE or FAS groups.These novel data revealed stable deficits in thalamic nuclei of the groups with heavy fetal alcohol exposure. After 20 years, the deficits endured but without accelerated age-related decline and following the same aging pattern as controls. Despite parallel aging functions in all groups, ICV adjustment yielded volume deficits localized to the anterior and ventral thalamic nuclei, differing from patterns in the remaining thalamic nuclei and cortical brain structures.

  https://www.ncbi.nlm.nih.gov/pubmed/40254272 https://doi.org/10.1016/j.bpsc.2025.04.002

  More

• Socioemotional and Executive Control Mismatch in Adolescence and Risks for Initiating Drinking.

  Zhao, Q., Milecki, L., Kuceyeski, A., Grosenick, L., Brumback, T., Pfefferbaum, A., Sullivan, E. V., Pohl, K. M.

  JAMA network open

  ABSTRACT
  Maturational imbalance between the expression of heightened socioemotional drivers and immature executive control creates a period of vulnerability to risk-taking behaviors during adolescence. Developmental imbalance of the brain functional activity coupled with these behaviors may explain the propensity to develop heavy drinking.To compare the longitudinal trajectories of socioemotion and executive control in non-heavy drinkers with those of heavy drinkers before and after drinking onset.This cohort study was conducted from January 13, 2013, to January 15, 2022, among participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort with resting-state functional magnetic resonance imaging and neuropsychological assessment data. All participants were individuals who abstained from drinking or drank very little at the baseline visit. The statistical analysis was conducted between October 11, 2024, and July 3, 2025.Categorical drinking levels that summarized self-reported alcohol consumption in the past year.Brain-behavioral system z scores that reflected the association of selective brain connectivity patterns with selected behaviors were calculated. Higher scores indicated higher reactivity strength of socioemotion or executive control.A total of 3076 visits among 633 participants (mean [SD] age at baseline, 15.7 [2.6] years; 318 female [50.2%]) were analyzed. A total of 238 participants (37.6%) who initiated heavy drinking during the study showed significantly elevated brain-behavior scores (score increase, 0.18; 95% CI, 0.08-0.28) in the socioemotional system prior to drinking onset, in contrast to their developmental trajectories of the executive control deviation occurring in both systems (score increase, 0.44; 95% CI, 0.33-0.54), with the effect size in the socioemotional system significantly greater (z = 3.51; P < .001) compared with before initiating drinking.These findings suggest that asynchronized maturation of socioemotion- and executive function-coupled brain connectivity in adolescence may be a risk factor for heavy drinking onset in emerging adulthood. In turn, drinking was associated with deficits in the executive control system and exacerbated alteration in the socioemotional system. Recognition of these early-age developmental discrepancies could aid in averting alcohol use disorder in adulthood.

  https://www.ncbi.nlm.nih.gov/pubmed/40938600 https://doi.org/10.1001/jamanetworkopen.2025.31378

  More

• Physiological and brain mechanisms contributing to postural tremor in aging with and without alcohol use disorder.

  Sullivan, E. V., Sassoon, S. A., Pohl, K. M., Saranathan, M., Zahr, N. M., Pfefferbaum, A.

  Translational psychiatry

  ABSTRACT
  Postural instability, a concomitant of falls, can persist in people with alcohol use disorder (AUD) even with sustained sobriety. Balance testing using a force plate, which detects micromovements while standing still, can be quantified with spectral analysis and expressed as temporal frequency, an index of truncal (i.e., postural) tremor. Here, we investigated physiological and brain structural factors that may contribute to a mechanistic understanding of postural instability during quiet standing in AUD. This mixed cross-sectional/longitudinal design included 462 observations in 292 participants (age 25-75 years): 120 men and 44 women with DSM-5-determined AUD and 75 control men and 53 control women. All participants completed balance testing on a force plate under two conditions: eyes open and eyes closed, both with feet together. Most participants also underwent two-point discrimination testing on the soles of the feet and structural MRI, typically within the week of balance testing. Linear mixed-effects models revealed greater tremor in all conditions in the AUD than control group with the diagnostic differences attributed to AUD men. Age effects did not differ significantly between AUD and control groups. By contrast, stronger correlations were detected between greater tremor, measured as a 2-5 Hz/0-2 Hz frequency quotient, and smaller regional brain volumes selective to motor centers (frontal supplemental motor cortex, thalamus, pallidum, cerebellar white matter) of the AUD men. The salient signs of postural instability were attributable to AUD men who consumed alcohol exceeding NIAAA guideline limits in the year prior to testing.

  https://www.ncbi.nlm.nih.gov/pubmed/40890118 https://doi.org/10.1038/s41398-025-03552-8

  More

• Postural instability in alcohol use disorder: Relations to thalamic regional and nuclear volumes

  Sassoon, S., Fama, R., Saranathan, M., Pohl, K., Sullivan, E., Pfefferbaum, A.

• Identifying unique pathways towards heavy alcohol drinking during adolescence

  Gonzalez, C., Nguyen-Louie, T., Sullivan, E., Pfefferbaum, A., Zhao, Q., Adeli, E., Tapert, S., Pohl, K.

2024

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

  Sassoon, S. A., Fama, R., Pohl, K. M., Pfefferbaum, A., Sullivan, E. V.

  Neurobiology of stress

  ABSTRACT
  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.

  https://www.ncbi.nlm.nih.gov/pubmed/38323165 https://doi.org/10.1016/j.ynstr.2024.100608

  More

• Contributions of Cerebral White Matter Hyperintensities to Postural Instability in Aging with and without Alcohol Use Disorder.

  Sullivan, E. V., Zahr, N. M., Zhao, Q., Pohl, K. M., Sassoon, S. A., Pfefferbaum, A.

  Biological psychiatry. Cognitive neuroscience and neuroimaging

  ABSTRACT
  Postural instability and brain white matter hyperintensities (WMH) are both noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to sway path/WMH relations in individuals with AUD and healthy control participants.The data comprised 404 balance platform sessions, yielding sway path length and MRI acquired cross-sectionally or longitudinally, in 102 control and 158 AUD participants, ages 25-80 years. Balance sessions were typically conducted on the same day as MRI FLAIR acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to relations 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.Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path/WMH relations. Inclusion of these factors as predictors in multiple regression analysis substantially attenuated the sway/WMH relations 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, possibly a reflection of the younger age of the Black sample.Longer sway paths were related to larger WMH volumes in healthy men and women, with and without AUD. Critically, however, age nearly fully accounted for these relations.

  https://www.ncbi.nlm.nih.gov/pubmed/38569932 https://doi.org/10.1016/j.bpsc.2024.03.005

  More

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

  Sullivan, E. V., Zahr, N. M., Zhao, Q., Pohl, K. M., Sassoon, S. A., Pfefferbaum, A.

  AIDS (London, England)

  ABSTRACT
  With aging, people living with HIV (PLWH) 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 PLWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.Mixed cross-sectional/longitudinal data acquired over 15 years in 141 PLWH and 102 age-range matched controls, 25-80 years old.Multimodal structural MRI data were quantified for 7 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 non-path data on sway path-WMH relations.In simple correlations, longer sway paths were associated with larger WMH volumes in PWLH 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 2-point pedal discrimination. Although the sway-WMH relations in PLWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for 5 of the 7 regions in the eyes-open condition.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.

  https://www.ncbi.nlm.nih.gov/pubmed/38537080 https://doi.org/10.1097/QAD.0000000000003894

  More

• Anterior and Posterior Thalamic Volumes Differentially Correlate with Memory, Attention, and Motor Processes in HIV Infection and Alcohol Use Disorder Comorbidity.

  Fama, R., Sassoon, S. A., Müller-Oehring, E. M., Saranathan, M., Pohl, K. M., Zahr, N. M., Pfefferbaum, A., Sullivan, E. V.

  Brain research bulletin

  ABSTRACT
  The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills). Volumes of thalamic subregions were derived from automatic segmentations of standard T1 weighted MRIs of 65 individuals with HIV, 189 with AUD, 80 with HIV+AUD comorbidity, and 141 healthy controls (CTRL). Total thalamic volume was smaller and cognitive and motor composite scores were lower in the three diagnostic groups relative to the CTRL group. The AUD and HIV+AUD groups had significantly smaller thalamic subregional volumes than the CTRL group. The HIV+AUD group had smaller anterior thalamic volume than the HIV-only group and smaller ventral thalamic volume than the AUD-only group. In the HIV+AUD group, memory scores correlated with anterior thalamic volumes, attention/working memory scores correlated with posterior and medial thalamic volumes, and motor skill scores correlated with posterior thalamic volumes. Exploratory analyses focused on the HIV+AUD group indicated that within the posterior thalamic region, the pulvinar and medial geniculate nuclei were related to attention/working memory scores, and the pulvinar was related to motor skills scores. This study is novel in locating volume deficits in specific thalamic subregions, in addition to the thalamus as a whole, in HIV, AUD, and their comorbidity and in identifying functional ramifications of these deficits. Taken together, this study highlights the relevance of thalamic subregional volume deficits to dissociable cognitive and motor processes.

  https://www.ncbi.nlm.nih.gov/pubmed/39343322 https://doi.org/10.1016/j.brainresbull.2024.111085

  More

• Data-Driven Discovery of Movement-Linked Heterogeneity in Neurodegenerative Diseases.

  Endo, M., Nerrise, F., Zhao, Q., Sullivan, E. V., Fei-Fei, L., Henderson, V. W., Pohl, K. M., Poston, K. L., Adeli, E.

  Nature machine intelligence

  ABSTRACT
  Neurodegenerative diseases manifest different motor and cognitive signs and symptoms that are highly heterogeneous. Parsing these heterogeneities may lead to an improved understanding of underlying disease mechanisms; however current methods are dependent on clinical assessments and somewhat arbitrary choice of behavioral tests. Herein, we present a data-driven subtyping approach using video-captured human motion and brain functional connectivity (FC) from resting-state (rs)-fMRI. We applied our framework to a cohort of individuals at different stages of Parkinson's disease (PD). The process mapped the data to low-dimensional measures by projecting them onto a canonical correlation space that identified three PD subtypes: Subtype I was characterized by motor difficulties and poor visuospatial abilities; Subtype II exhibited difficulties in non-motor components of activities of daily living and motor complications (dyskinesias and motor fluctuations); and Subtype III was characterized by predominant tremor symptoms. We conducted a convergent validity analysis by comparing our approach to existing and widely used approaches. The compared approaches yielded subtypes that were adequately well-clustered in the motion-brain representation space we created to delineate subtypes. Our data-driven approach, contrary to other forms of subtyping, derived biomarkers predictive of motion impairment and subtype memberships that were captured objectively by digital videos.

  https://www.ncbi.nlm.nih.gov/pubmed/40357335 https://doi.org/10.1038/s42256-024-00882-y

  More

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

  Chirokoff, V., Berthoz, S., Fatseas, M., Misdrahi, D., Dupuy, M., Abdallah, M., Serre, F., Auriacombe, M., Pfefferbaum, A., Sullivan, E. V., Chanraud, S.

  Translational psychiatry

  ABSTRACT
  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.

  https://www.ncbi.nlm.nih.gov/pubmed/38897999 https://doi.org/10.1038/s41398-024-02949-1

  More

• Aging, HIV infection, and alcohol exert synergist effects on regional thalamic volumes resulting in functional impairment.

  Pfefferbaum, A., Zahr, N. M., Sassoon, S. A., Fama, R., Saranathan, M., Pohl, K. M., Sullivan, E. V.

  NeuroImage. Clinical

  ABSTRACT
  OBJECTIVE: Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50% living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown is whether aging with HIV affects thalamic nuclei and associated functions differentially and whether the common comorbidity of alcohol use disorder (AUD)+HIV accelerates aging.METHODS: This mixed cross-sectional/longitudinal design examined 216 control, 69 HIV, and 74 HIV+AUD participants, age 25-75years old at initial visit, examined 1-8 times. MRI thalamic volumetry, parcellated using THalamus Optimized Multi-Atlas Segmentation (THOMAS), identified 10 nuclei grouped into 4 functional regions for correlation with age and measures of neuropsychological, clinical, and hematological status.RESULTS: Aging in the control group was best modeled with quadratic functions in the Anterior and Ventral regions and with linear functions in the Medial and Posterior regions. Relative to controls, age-related decline was even steeper in the Anterior and Ventral regions of the HIV group and in the Anterior region of the comorbid group. Anterior volumes of each HIV group declined significantly faster after age 50 (HIV=-2.4%/year; HIV+AUD=-2.8%/year) than that of controls (-1.8%/year). Anterior and Ventral volumes were significantly smaller in the HIV+AUD than HIV-only group when controlling for infection factors. Although compared with controls HIV+AUD declined faster than HIV alone, the two HIV groups did not differ significantly from each other in aging rates. Declining Attention/Working Memory and Motor Skills performance correlated with Anterior and Posterior volume declines in the HIV+AUD group.CONCLUSIONS: Regional thalamic volumetry detected normal aging declines, differential and accelerated volume losses in HIV, relations between age-related nuclear and performance declines, and exacerbation of volume declines in comorbid AUD contributing to functional deficits.

  https://www.ncbi.nlm.nih.gov/pubmed/39423567 https://doi.org/10.1016/j.nicl.2024.103684

  More

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

  Chirokoff, V., Pohl, K. M., Berthoz, S., Fatseas, M., Misdrahi, D., Serre, F., Auriacombe, M., Pfefferbaum, A., Sullivan, E. V., Chanraud, S.

  Addiction biology

  ABSTRACT
  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.

  https://www.ncbi.nlm.nih.gov/pubmed/38706091 https://doi.org/10.1111/adb.13400

  More

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

  Nguyen-Louie, T. T., Thompson, W. K., Sullivan, E. V., Pfefferbaum, A., Gonzalez, C., Eberson-Shumate, S. C., Wade, N. E., Clark, D. B., Nagel, B. J., Baker, F. C., Luna, B., Nooner, K. B., de Zambotti, M., Goldston, D. B., Knutson, B., Pohl, K. M., Tapert, S. F.

  Developmental cognitive neuroscience

  ABSTRACT
  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 (βs=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.

  https://www.ncbi.nlm.nih.gov/pubmed/39089172 https://doi.org/10.1016/j.dcn.2024.101424

  More

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

  Zhao, Q., Paschali, M., Dehoney, J., Baker, F. C., de Zambotti, M., De Bellis, M. D., Goldston, D. B., Nooner, K. B., Clark, D. B., Luna, B., Nagel, B. J., Brown, S. A., Tapert, S. F., Eberson, S., Thompson, W. K., Pfefferbaum, A., Sullivan, E. V., Pohl, K. M.

  Developmental cognitive neuroscience

  ABSTRACT
  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.

  https://www.ncbi.nlm.nih.gov/pubmed/38943839 https://doi.org/10.1016/j.dcn.2024.101413

  More

• Memorial of Kenneth R. Warren, 1943-2024.

  Riley, E. P., Pfefferbaum, A., Sullivan, E. V., Charness, M. E.

  Alcohol, clinical & experimental research

  https://www.ncbi.nlm.nih.gov/pubmed/39322616 https://doi.org/10.1111/acer.15452

  More

• Metadata-conditioned generative models to synthesize anatomically-plausible 3D brain MRIs.

  Peng, W., Bosschieter, T., Ouyang, J., Paul, R., Sullivan, E. V., Pfefferbaum, A., Adeli, E., Zhao, Q., Pohl, K. M.

  Medical image analysis

  ABSTRACT
  Recent advances in generative models have paved the way for enhanced generation of natural and medical images, including synthetic brain MRIs. However, the mainstay of current AI research focuses on optimizing synthetic MRIs with respect to visual quality (such as signal-to-noise ratio) while lacking insights into their relevance to neuroscience. To generate high-quality T1-weighted MRIs relevant for neuroscience discovery, we present a two-stage Diffusion Probabilistic Model (called BrainSynth) to synthesize high-resolution MRIs conditionally-dependent on metadata (such as age and sex). We then propose a novel procedure to assess the quality of BrainSynth according to how well its synthetic MRIs capture macrostructural properties of brain regions and how accurately they encode the effects of age and sex. Results indicate that more than half of the brain regions in our synthetic MRIs are anatomically plausible, i.e., the effect size between real and synthetic MRIs is small relative to biological factors such as age and sex. Moreover, the anatomical plausibility varies across cortical regions according to their geometric complexity. As is, the MRIs generated by BrainSynth significantly improve the training of a predictive model to identify accelerated aging effects in an independent study. These results indicate that our model accurately capture the brain's anatomical information and thus could enrich the data of underrepresented samples in a study. The code of BrainSynth will be released as part of the MONAI project at https://github.com/Project-MONAI/GenerativeModels.

  https://www.ncbi.nlm.nih.gov/pubmed/39208560 https://doi.org/10.1016/j.media.2024.103325

  More

• Multi-domain predictors of grip strength differentiate individuals with and without alcohol use disorder.

  Paschali, M., Zhao, Q., Sassoon, S. A., Pfefferbaum, A., Sullivan, E. V., Pohl, K. M.

  Addiction biology

  ABSTRACT
  Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data-driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5-fold stratified cross-validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (R2 = 0.255, p = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (R2 = 0.162, p = 0.002). These cohort-specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort-specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.

  https://www.ncbi.nlm.nih.gov/pubmed/39532141 https://doi.org/10.1111/adb.70007

  More