Distinct Multimodal Brain Profiles Bridging Age of First Alcohol Use and Subsequent Substance Use in Young Adults
- 1McLean Hospital
Abstract
Age of first alcohol use is associated with alterations in brain development and an increased risk of problematic substance use later in life. However, it remains unclear if neurobiological alterations associated with first-use age are present in young adulthood and how these alterations may be associated with different patterns of adult substance use. In this study, we employed SuperBigFLICA, a semi-supervised multimodal imaging data fusion approach, to identify joint structural morphometric and functional MRI (fMRI) brain profiles present in adulthood that are most predictive of age of alcohol first-use in the Human Connectome Project-Young Adult cohort (n=622). Our model achieved moderate performance (r=0.22 in external validation), identifying multimodal structure-function profiles predictive of first-use largely involving frontal regions. We then utilized Canonical Correlation Analysis to determine whether these multimodal brain profiles were differentially linked to patterns of adult substance use behaviors. We identified three significant brain modes (Mode 1: r = 0.2750, p = 0.014; Mode 2: r = 0.2249, p = 0.005; Mode 3: r = 0.1568, p = 0.029) associated with distinct profiles of alcohol and cannabis use. Together, we identified multimodal brain patterns in young adults that predict age of first use of alcohol and demonstrated that resulting multimodal structure-function brain profiles capture distinct multivariate patterns of adult substance use, providing a more integrated view of substance use neurobiology.
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BibTeX
@misc{hannon2026distinct,
title = {{Distinct Multimodal Brain Profiles Bridging Age of First Alcohol Use and Subsequent Substance Use in Young Adults}},
author = {K. Hannon and N. G. Harnett and Y. Cheng and J. E. Cohen-Gilbert and C. G. Korponay and P. Kumar and M. M. Silveri and L. D. Nickerson},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.26364406},
url = {https://www.medrxiv.org/content/10.64898/2026.09.30.26364406v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Distinct Multimodal Brain Profiles Bridging Age of First Alcohol Use and Subsequent Substance Use in Young Adults
AU - K. Hannon
AU - N. G. Harnett
AU - Y. Cheng
AU - J. E. Cohen-Gilbert
AU - C. G. Korponay
AU - P. Kumar
AU - M. M. Silveri
AU - L. D. Nickerson
PY - 2026
DA - 2026/09/30
PB - medRxiv
DO - 10.64898/2026.09.30.26364406
UR - https://www.medrxiv.org/content/10.64898/2026.09.30.26364406v1
AB - Age of first alcohol use is associated with alterations in brain development and an increased risk of problematic substance use later in life. However, it remains unclear if neurobiological alterations associated with first-use age are present in young adulthood and how these alterations may be associated with different patterns of adult substance use. In this study, we employed SuperBigFLICA, a semi-supervised multimodal imaging data fusion approach, to identify joint structural morphometric and functional MRI (fMRI) brain profiles present in adulthood that are most predictive of age of alcohol first-use in the Human Connectome Project-Young Adult cohort (n=622). Our model achieved moderate performance (r=0.22 in external validation), identifying multimodal structure-function profiles predictive of first-use largely involving frontal regions. We then utilized Canonical Correlation Analysis to determine whether these multimodal brain profiles were differentially linked to patterns of adult substance use behaviors. We identified three significant brain modes (Mode 1: r = 0.2750, p = 0.014; Mode 2: r = 0.2249, p = 0.005; Mode 3: r = 0.1568, p = 0.029) associated with distinct profiles of alcohol and cannabis use. Together, we identified multimodal brain patterns in young adults that predict age of first use of alcohol and demonstrated that resulting multimodal structure-function brain profiles capture distinct multivariate patterns of adult substance use, providing a more integrated view of substance use neurobiology.
ER -