Abstract
Cortical thickness changes dramatically during development and is associated with adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying spatially heterogeneous effects of alcohol. In this study, adolescents (n = 657; 12–22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study who endorsed little to no alcohol use at baseline were assessed with structural magnetic resonance imaging and followed longitudinally at four yearly intervals. Seven unique spatial patterns of covarying cortical thickness were obtained from the baseline scans by applying an unsupervised machine learning method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants’ longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. We found in six NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts. Among moderate drinkers the decline was faster in the younger adolescent cohort and slower in the older cohort. Among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort. The findings suggested that unsupervised machine learning successfully delineated spatially coordinated patterns of vertex-level cortical thickness variation that are unconstrained by neuroanatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers, an effect that is strongest among heavy drinkers.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Data availability
Data used here are from the data release NCANDA_PUBLIC_3Y_REDCAP_V03 (https://doi.org/10.7303/syn23702728) and NCANDA_PUBLIC_3Y_STRUCTURAL_V01 (https://doi.org/10.7303/syn22213272) distributed to the public according to the NCANDA Data Distribution agreement (www.niaaa.nih.gov/research/major-initiatives/nationalconsortium-alcohol-and-neurodevelopment-adolescence/ncandadata).
References
Tamnes CK, Herting MM, Goddings AL, Meuwese R, Blakemore SJ, Dahl RE, et al. Development of the cerebral cortex across adolescence: a multisample study of inter-related longitudinal changes in cortical volume, surface area, and thickness. J Neurosci. 2017;37:3402–12.
Pfefferbaum A, Rohlfing T, Pohl KM, Lane B, Chu WW, Kwon D, et al. Adolescent development of cortical and white matter structure in the NCANDA sample: role of sex, ethnicity, puberty, and alcohol drinking. Cereb Cortex. 2016;26:4101–21.
Amlien IK, Fjell AM, Tamnes CK, Grydeland H, Krogsrud SK, Chaplin TA, et al. Organizing principles of human cortical development-thickness and area from 4 to 30 years: insights from comparative primate neuroanatomy. Cereb Cortex. 2016;26:257–67.
Lees B, Meredith LR, Kirkland AE, Bryant BE, Squeglia LM. Effect of alcohol use on the adolescent brain and behavior. Pharmacol Biochem Behav. 2020;192:172906.
Cservenka A, Brumback T. The burden of Binge and heavy drinking on the brain: effects on adolescent and young adult neural structure and function. Front Psychol. 2017;8:1111.
Squeglia LM, Tapert SF, Sullivan EV, Jacobus J, Meloy MJ, Rohlfing T, et al. Brain development in heavy-drinking adolescents. Am J Psychiat. 2015;172:531–42.
Johnston LD, Miech RA, O'Malley PM, Bachman JG, Schulenberg JE, Patrick ME. "Monitoring the Future National Survey Results on Drug Use, 1975-2018: Overview, Key Findings on Adolescent Drug Use." Institute for Social Research (2019).
Chung T, Creswell KG, Bachrach R, Clark DB, Martin CS. Adolescent Binge drinking developmental context and opportunities for prevention. Alcohol Res-Curr Rev. 2018;39:5–15.
SAMHSA. U.S. Department of Health and Human Services (HHS), Substance Abuse and Mental Health Services Administration (SAMHSA), 2018.
Wilson S, Malone SM, Thomas KM, Iacono WG. Adolescent drinking and brain morphometry: a co-twin control analysis. Dev Cogn Neuros-Neth. 2015;16:130–38.
Mashhoon Y, Czerkawski C, Crowley DJ, Cohen-Gilbert JE, Sneider JT, Silveri MM. Binge alcohol consumption in emerging adults: anterior cingulate cortical “thinness” is associated with alcohol use patterns. Alcohol Clin Exp Res. 2014;38:1955–64.
Luciana M, Collins PF, Muetzel RL, Lim KO. Effects of alcohol use initiation on brain structure in typically developing adolescents. Am J Drug Alcohol Abus. 2013;39:345–55.
Squeglia LM, Sorg SF, Schweinsburg AD, Wetherill RR, Pulido C, Tapert SF. Binge drinking differentially affects adolescent male and female brain morphometry. Psychopharmacol (Berl). 2012;220:529–39.
Infante MA, Eberson SC, Zhang Y, Brumback T, Brown SA, Colrain IM, et al. Adolescent Binge drinking is associated with accelerated decline of Gray Matter Volume. Cereb Cortex. 2022;32:2611–20.
Jacobus J, Castro N, Squeglia LM, Meloy MJ, Brumback T, Huestis MA, et al. Adolescent cortical thickness pre- and post marijuana and alcohol initiation. Neurotoxicol Teratol. 2016;57:20–9.
Lee DD, Seung HS. Learning the parts of objects by non-negative matrix factorization. Nature. 1999;401:788–91.
Mirzal A. NMF versus ICA for blind source separation. Adv Data Anal Cl. 2017;11:25–48.
Sotiras A, Toledo JB, Gur RE, Gur RC, Satterthwaite TD, Davatzikos C. Patterns of coordinated cortical remodeling during adolescence and their associations with functional specialization and evolutionary expansion. P Natl Acad Sci USA. 2017;114:3527–32.
Brown SA, Brumback TY, Tomlinson K, Cummins K, Thompson WK, Nagel BJ, et al. The national consortium on alcohol and neuro-development in adolescence (NCANDA): a multisite study of adolescent development and substance use. J Stud Alcohol Drugs. 2015;76:895–908.
Galbraith S, Bowden J, Mander A. Accelerated longitudinal designs: an overview of modelling, power, costs and handling missing data. Stat Methods Med Res. 2017;26:374–98.
Wilson S. Commentary: substance use and the brain: it is not straightforward to differentiate cause from consequence - a commentary on Kim-Spoon et al. (2020). J Child Psychol Psychiatry. 2021;62:437–40.
Phillips RD, De Bellis MD, Brumback T, Clausen AN, Clarke-Rubright EK, Haswell CC, et al. Volumetric trajectories of hippocampal subfields and amygdala nuclei influenced by adolescent alcohol use and lifetime trauma. Transl Psychiatry. 2021;11:1–13.
Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger JI Jr., et al. A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J Stud Alcohol. 1994;55:149–58.
Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012;61:1402–18.
Fortin JP, Cullen N, Sheline YI, Taylor WD, Aselcioglu I, Cook PA, et al. Harmonization of cortical thickness measurements across scanners and sites. Neuroimage. 2018;167:104–20.
Kuhn HW. The Hungarian Method for the assignment problem. Nav Res Log. 2005;52:7–21.
Benjamini Y, Hochberg Y. Controlling the false discovery rate - a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57:289–300.
Friederici AD, Gierhan SM. The language network. Curr Opin Neurobiol. 2013;23:250–4.
Fede SJ, Grodin EN, Dean SF, Diazgranados N, Momenan R. Resting state connectivity best predicts alcohol use severity in moderate to heavy alcohol users. Neuroimage Clin. 2019;22:101782.
Spear LP. Effects of adolescent alcohol consumption on the brain and behaviour. Nat Rev Neurosci. 2018;19:197–214.
Squeglia LM, Rinker DA, Bartsch H, Castro N, Chung Y, Dale AM, et al. Brain volume reductions in adolescent heavy drinkers. Dev Cogn Neurosci. 2014;9:117–25.
Crews F, He J, Hodge C. Adolescent cortical development: a critical period of vulnerability for addiction. Pharm Biochem Behav. 2007;86:189–99.
Ewing SW, Sakhardande A, Blakemore SJ. The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth. Neuroimage Clin. 2014;5:420–37.
Sanefuji M, Craig M, Parlatini V, Mehta MA, Murphy DG, Catani M, et al. Double-dissociation between the mechanism leading to impulsivity and inattention in attention deficit hyperactivity disorder: a resting-state functional connectivity study. Cortex. 2017;86:290–302.
Farre-Colomes A, Gerhardt S, Luderer M, Sobanski E, Kiefer F, Vollstadt-Klein S. Common and distinct neural connectivity in attention-deficit/hyperactivity disorder and alcohol use disorder studied using resting-state functional magnetic resonance imaging. Alcohol Clin Exp Res. 2021;45:948–60.
Weiland BJ, Sabbineni A, Calhoun VD, Welsh RC, Bryan AD, Jung RE, et al. Reduced left executive control network functional connectivity is associated with alcohol use disorders. Alcohol Clin Exp Res. 2014;38:2445–53.
Squeglia LM, Schweinsburg AD, Pulido C, Tapert SF. Adolescent Binge drinking linked to abnormal spatial working memory brain activation: differential gender effects. Alcohol Clin Exp Res. 2011;35:1831–41.
Crego A, Rodriguez-Holguin S, Parada M, Mota N, Corral M, Cadaveira F. Reduced anterior prefrontal cortex activation in young binge drinkers during a visual working memory task. Drug Alcohol Depen. 2010;109:45–56.
Parada M, Corral M, Mota N, Crego A, Rodriguez Holguin S, Cadaveira F. Executive functioning and alcohol binge drinking in university students. Addict Behav. 2012;37:167–72.
Seeley WW. The Salience network: a neural system for perceiving and responding to homeostatic demands. J Neurosci. 2019;39:9878–82.
Whelan R, Watts R, Orr CA, Althoff RR, Artiges E, Banaschewski T, et al. Neuropsychosocial profiles of current and future adolescent alcohol misusers. Nature. 2014;512:185.
Ames SL, Wong SW, Bechara A, Cappelli C, Dust M, Grenard JL, et al. Neural correlates of a Go/NoGo task with alcohol stimuli in light and heavy young drinkers. Behav Brain Res. 2014;274:382–89.
Raichle ME. The Brain’s default mode network. Annu Rev Neurosci. 2015;38:433–47.
Wetherill RR, Bava S, Thompson WK, Boucquey V, Pulido C, Yang TT, et al. Frontoparietal connectivity in substance-naive youth with and without a family history of alcoholism. Brain Res. 2012;1432:66–73.
Muller-Oehring EM, Kwon D, Nagel BJ, Sullivan EV, Chu WW, Rohlfing T, et al. Influences of age, sex, and moderate alcohol drinking on the intrinsic functional architecture of adolescent brains. Cereb Cortex. 2018;28:1049–63.
Zeigler DW, Wang CC, Yoast RA, Dickinson BD, McCaffree MA, Robinowitz CB, et al. The neurocognitive effects of alcohol on adolescents and college students. Prev Med. 2005;40:23–32.
Baum GL, Cui ZX, Roalf DR, Ciric R, Betzel RF, Larsen B, et al. Development of structure-function coupling in human brain networks during youth. P Natl Acad Sci USA. 2020;117:771–78.
Zhao Q, Sullivan EV, Műller‐Oehring EM, Honnorat N, Adeli E, Podhajsky S, et al. Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls. Addict Biol. 2021;26:e12914.
Jones SA, Lueras JM, Nagel BJ. Effects of Binge drinking on the developing brain. Alcohol Res. 2018;39:87–96.
Guerri C, Pascual M. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol. 2010;44:15–26.
Koppen WP, Christmas WJ, Crouch DJM, Bodmer WF, Kittler JV. Extending non-negative matrix factorisation to 3D registered data. In 2016 International Conference on Biometrics (ICB), IEEE; 2016. pp. 1–8.
De Bellis MD, Nooner KB, Brumback T, Clark DB, Tapert SF, Brown SA. Posttraumatic stress symptoms predict transition to future adolescent and young adult moderate to heavy drinking in the NCANDA sample. Curr Addict Rep. 2020;7:99–107.
Henderson KE, Vaidya JG, Kramer JR, Kuperman S, Langbehn DR, O’Leary DS. Cortical thickness in adolescents with a family History of alcohol use disorder. Alcohol Clin Exp Res. 2018;42:89–99.
Esposito F. A review on initialization methods for nonnegative matrix factorization: towards omics data experiments. Mathematics. 2021;9:1006.
Albaugh MD, Ottino-Gonzalez J, Sidwell A, Lepage C, Juliano A, Owens MM, et al. Association of cannabis use during adolescence with neurodevelopment. JAMA Psychiatry. 2021;78:1031–40.
Sullivan EV, Brumback T, Tapert SF, Fama R, Prouty D, Brown SA, et al. Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction. Neuropsychology. 2016;30:449–73.
Sun D, Rakesh G, Haswell CC, Logue M, Baird CL, O'Leary EN, et al. A comparison of methods to harmonize cortical thickness measurements across scanners and sites. NeuroImage. 2022;261:119509.
Acknowledgements
We would like to recognize Mary Nicole Buckley and Molly Monsour for their help with the visual inspection of segmentations. We also thank the anonymous reviewers for their thoughtful comments and suggestions.
Funding
RAM was supported by the Department of Veterans Affairs Mid-Atlantic MIRECC. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. This work was made possible with support by NIH Grants AA021697, AA021695, AA021692, AA021696, AA021681, AA021690, AA021691, and R01AG067103.
Author information
Authors and Affiliations
Contributions
DS analyzed data and drafted the manuscript. VA analyzed data and drafted the manuscript, RP analyzed data. HB drafted the manuscript. AS developed the analysis methods. AM coordinated the research. FB coordinated the research. ST coordinated the research. SB coordinated the research. DC coordinated the research. DG coordinated the research. KN coordinated the research. BN coordinated the research. WT coordinated the research. MDB coordinated and designed the research. RM designed and coordinated the research and drafted the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Sun, D., Adduru, V.R., Phillips, R.D. et al. Adolescent alcohol use is linked to disruptions in age-appropriate cortical thinning: an unsupervised machine learning approach. Neuropsychopharmacol. 48, 317–326 (2023). https://doi.org/10.1038/s41386-022-01457-4
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41386-022-01457-4
This article is cited by
-
Adolescent substance use initiation and long-term neurobiological outcomes: insights, challenges and opportunities
Molecular Psychiatry (2024)
-
The Influence of Different Dimensions of the Parent–Child Relationship in Childhood as Longitudinal Predictors of Substance Use in Late Adolescence. The Mediating Role of Self-Control
International Journal of Mental Health and Addiction (2024)
-
Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods
Neuropsychopharmacology (2024)
-
Consequences of adolescent drug use
Translational Psychiatry (2023)
