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. 2025 Feb;49(2):332-344.
doi: 10.1111/acer.15511. Epub 2024 Dec 26.

A multimodal neuroimaging study of youth at risk for substance use disorders: Functional magnetic resonance imaging and [18F]fallypride positron emission tomography

Maja Nikolic  1 , Sylvia M L Cox  2 , Natalia Jaworska  3   4 , Natalie Castellanos-Ryan  5 , Alain Dagher  6 , Frank Vitaro  5   7 , Mara Brendgen  7   8 , Sophie Parent  5 , Michel Boivin  9   10 , Sylvana Côté  7   11 , Richard E Tremblay  5   12   13   14   15 , Jean R Séguin  7   16 , Marco Leyton  1   2   6   17
Affiliations

A multimodal neuroimaging study of youth at risk for substance use disorders: Functional magnetic resonance imaging and [18F]fallypride positron emission tomography

Maja Nikolic et al. Alcohol Clin Exp Res (Hoboken). 2025 Feb.

Abstract

Background: Adolescent alcohol use is the norm, but only some develop a substance use disorder. The increased risk might reflect heightened mesocorticolimbic responses to reward-related cues but results published to date have been inconsistent.

Methods: Young social drinkers (age 18.5 ± 0.6 y.o.) who have been followed since birth were recruited from high- versus low-risk trajectories based on externalizing (EXT) behavioral traits. All had functional magnetic resonance imaging (fMRI) scans to measure mesocorticolimbic responses to alcohol, juice, and water cues (High EXT: 20F/10M; Low EXT: 15F/12M). Most had positron emission tomography (PET) [18F]fallypride scans to measure brain regional dopamine D2 receptor availabilities (n = 47).

Results: Compared with the low EXT group, high EXT participants reported larger subjective responses to the alcohol and juice cues (vs. water). Despite this, a main effect of group was not seen for brain activation responses to the alcohol and juice cues. Instead, low EXT participants exhibited higher mesocorticolimbic activations to alcohol than juice, whereas these activations did not differ in the high EXT group. Across all participants, alcohol (vs. water) blood oxygen level-dependent (BOLD) responses in the striatum and amygdala were associated with midbrain [18F]fallypride BPND values.

Conclusion: Young social drinkers at high versus low risk for substance use disorders did not exhibit larger mesocorticolimbic BOLD activations to alcohol-related cues and their responses poorly differentiated alcohol from juice. These observations raise the possibility that (i) diminished mesocorticolimbic BOLD differentiations between reward-related cues might be a marker of increased risk for substance use disorders, and (ii) previously reported large BOLD responses to drug-related cues in people with substance use disorders might better identify the disease than pre-existing vulnerability.

Keywords: addiction; biomarker; endophenotype; reward processing.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Alcohol visual‐gustatory fMRI task.
FIGURE 2
FIGURE 2
Mean beta weights for alcohol versus water cues and juice versus water cues in those ROI with significant Group × Beverage interactions. (A) associative striatum, (B) sensorimotor striatum, (C) amygdala, (D) anterior cingulate cortex, (E) insula, and (F) Across all ROIs (p = 0.03). *p < 0.05 response to alcohol (minus water) versus juice (minus water). ACC, anterior cingulate cortex; AS, associative striatum; SS, sensorimotor striatum.
FIGURE 3
FIGURE 3
Mean beta weights for the alcohol versus juice cue in all 10 ROIs. The low EXT group showed greater mesocorticolimbic activation in the alcohol versus juice contrast compared to the high EXT group (p = 0.031). ACC, anterior cingulate cortex; AS, associative striatum; dlPFC, dorsolateral prefrontal cortex; PCC, posterior cingulate cortex; SS, sensorimotor striatum; vmPFC, ventromedial prefrontal cortex; VS, ventral striatum. *p < 0.05, High versus Low EXT groups.
FIGURE 4
FIGURE 4
Association between alcohol intensity scores and alcohol versus juice cue‐induced responses in the midbrain.
FIGURE 5
FIGURE 5
Associations between midbrain [18F]fallypride BPND values and cue‐induced brain responses during the alcohol versus water condition in the sensorimotor striatum (top) and amygdala (bottom).
See this image and copyright information in PMC

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