BRAIN RESPONSES TO ALCOHOL CUES IN YOUTH AT RISK FOR SUBSTANCE USE DISORDERS (SUDS): A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY
Bibliographic record
Abstract
Abstract Background Adolescent alcohol use is the norm, but only some develop a substance use disorder (SUD). The most common vulnerability traits are characterized by diverse externalizing (EXT) behaviors (e.g., poor impulse-control and emotion regulation). Preliminary studies suggest that this increased risk may be influenced by altered mesocorticolimbic processing of drug and non-drug reward-related cues. The effects are complex. Whereas functional magnetic resonance imaging (fMRI) measured responses to alcohol cues are elevated in young adults with an alcohol use disorder compared to healthy drinkers (1), high-risk youth who have not developed an SUD are reported to poorly differentiate cues associated with high vs low reward; e.g., monetary reward (2). Aims & Objectives Measure brain activation responses to alcohol and non-alcohol cues in high- vs low- EXT youth who have been followed since birth. Method Seventy-one longitudinally followed young social drinkers (age 18.5±0.6) underwent fMRI scans and completed the Alcohol Use Disorders Identification Test (AUDIT), Barratt Impulsiveness Scale (BIS- 11), Substance Use Risk Profile Scale (SURPS), and Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). fMRI blood-oxygen-level-dependent (BOLD) activations were measured while participants received 1ml beverage tastants consisting of their preferred alcohol beverage, their preferred fruit juice, and water. Fourteen participants were excluded due to image quality issues, resulting in a final sample of 57, 27 high EXT (15F/12M) and 30 low EXT (20F/10M). As previously reported, most of these participants also had [18F]fallypride (47/57) and [11C]ABP688 (47/57) positron emission tomography scans and the high EXT group exhibited widespread increases in dopamine DRD2/3 receptors (3) and decreases in type 5 metabotropic glutamate receptors (4). Results As anticipated, high vs low EXT participants had higher AUDIT scores, alcohol binge occasions, lifetime uses of cannabis, impulsivity scores (SURPS and BIS-11), and prevalence of psychiatric disorders (mostly mood, anxiety, ADHD, and mild SUDs). For the alcohol (vs water) fMRI contrast, both groups exhibited activations in the thalamus, but only the high EXT group had significant activations in the anterior and posterior cingulate cortex, right calcarine, and post central gyrus. Significant group differences, in comparison, were only seen when contrasting the two flavored reward cues, alcohol vs juice. Whereas the low EXT group exhibited larger mesocorticolimbic BOLD responses to alcohol (vs water) than juice (vs water), these responses were undifferentiated in the high EXT group. Discussion & Conclusion The results add to the evidence that, in high-risk youth, mesocorticolimbic activations poorly distinguish reward-related cues, extending this observation to alcohol vs juice. The neurotransmitters mediating these responses remain unknown, but disrupted differentiations of reward- related cues might erode the ability to make optimal choices, increasing the risk for SUDs and their commonly comorbid conditions. References 1. Tapert, S. F., Cheung, E. H., Brown, G. G., Frank, L. R., Paulus, M. P., Schweinsburg, A. D., Meloy, M. J., &Brown, S. A. (2003). Neural response to alcohol stimuli in adolescents with alcohol use disorder. Archives of General Psychiatry, 60(7), 727–735. 2.Bü chel, C., Peters, J., Banaschewski, T., Bokde, A. L. W., Bromberg, U., Conrod, P. J., Flor, H., Papadopoulos, D., Garavan, H., Gowland, P., Heinz, A., Walter, H., Ittermann, B., Mann, K., Martinot, J.-L., Paillè re-Martinot, M.-L., Nees, F., Paus, T., Pausova, Z., … IMAGEN consortium. (2017). Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents. Nature Communications, 8, 14140. 3.Jaworska N, Cox SML, Tippler M, Castellanos-Ryan N, Benkelfat C, Parent S, Dagher A, Vitaro F, Boivin M, Pihl RO, Cô té S, Tremblay RE, Sé guin JR, Leyton M. (2020) Extra-striatal dopamine2/3 receptor availability in youth at-risk for addictions. Neuropsychopharmacology, 45(9), 1498-1505. 4.Cox SML, Tippler M, Jaworska N, Smart K, Castellanos-Ryan N, Durand F, Allard D, Benkelfat C, Parent S, Dagher A, Vitaro F, Boivin M, Pihl RO, Cô té S, Tremblay RE, Sé guin JR, Leyton M. (2020) mGlu5 receptor availability in youth at risk for addictions: effects of vulnerability traits and cannabis use. Neuropsychopharmacology, 45(11), 817-1825.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".