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Peer-reviewedCC BY-NC-NDBiological psychiatry. Cognitive neuroscience and neuroimaging

Mechanistically Distinct Subtypes of Individuals with Cocaine Use Disorder Identified by Neural Cue-Reactivity and Prediction of Clinical Outcomes

  • Tarik S. Bel-Bahar1
  • Riaz B. Shaik1
  • Nelly Alia-Klein1,2
  • Rita Z. Goldstein1,2
  • Muhammad A. Parvaz1,2,3
  1. 1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  2. 2Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  3. 3Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Abstract

BACKGROUND: Drug cue reactivity is a known predictor of relapse in individuals with substance use disorders. However, its robust detection is impeded by interindividual heterogeneity, which remains insufficiently characterized and may reflect divergent neurobiological phenotypes that differentially influence clinical outcomes. Here we investigated neurophysiological heterogeneity during cue-reactivity in individuals with cocaine use disorder (CUD). METHODS: Eighty-eight individuals with CUD completed an electroencephalography cue-reactivity task; the final analytic sample included 70 participants (14 female, 55 male, and 1 participant with missing sex information). The late positive potential (LPP) amplitude, a robust neurophysiological marker of drug cue reactivity, was extracted in the 400- to 1000-ms window after cocaine cue onset. Sensor-level LPP topographical heterogeneity was used to identify subtypes, and source-amplitude and beta oscillation analyses were subsequently used to mechanistically characterize subtype differences. RESULTS: Posterior cue reactors (PCR) (n = 29) and frontal cue reactors (FCR) (n = 41) were determined based on spatially distinct sensor patterns of cue-reactivity LPP maxima. PCR (vs. FCR) showed hypoactivations in lingual, pericalcarine, isthmus cingulate, temporal, frontal, and precentral regions and hyperactivations in postcentral and cuneus regions. PCR (vs. FCR) also showed beta hypoactivations in orbitofrontal and rostral anterior cingulate cortex, with hyperactivations in paracentral and pericalcarine regions. Cue-induced regional activations were associated with clinical outcomes, including craving and withdrawal severity, years of regular use, prospective abstinence, and percent use days. CONCLUSIONS: Results showed that cocaine cue reactivity is heterogeneous and may involve distinct neurobiological subtypes in individuals with CUD. Future research should validate these neurophysiological patterns in independent samples and examine their stability and clinical relevance longitudinally to inform targeted interventions addressing subtype-specific neural circuit disruptions.

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Cite

BibTeXRIS
BibTeX
@article{belbahar2026mechanistically,
  title = {{Mechanistically Distinct Subtypes of Individuals with Cocaine Use Disorder Identified by Neural Cue-Reactivity and Prediction of Clinical Outcomes}},
  author = {Tarik S. Bel-Bahar and Riaz B. Shaik and Nelly Alia-Klein and Rita Z. Goldstein and Muhammad A. Parvaz},
  journal = {Biological psychiatry. Cognitive neuroscience and neuroimaging},
  year = {2026},
  month = jul,
  doi = {10.1016/j.bpsc.2026.07.008},
  url = {https://doi.org/10.1016/j.bpsc.2026.07.008},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Mechanistically Distinct Subtypes of Individuals with Cocaine Use Disorder Identified by Neural Cue-Reactivity and Prediction of Clinical Outcomes
AU  - Tarik S. Bel-Bahar
AU  - Riaz B. Shaik
AU  - Nelly Alia-Klein
AU  - Rita Z. Goldstein
AU  - Muhammad A. Parvaz
PY  - 2026
DA  - 2026/07/29
JO  - Biological psychiatry. Cognitive neuroscience and neuroimaging
DO  - 10.1016/j.bpsc.2026.07.008
UR  - https://doi.org/10.1016/j.bpsc.2026.07.008
AB  - BACKGROUND: Drug cue reactivity is a known predictor of relapse in individuals with substance use disorders. However, its robust detection is impeded by interindividual heterogeneity, which remains insufficiently characterized and may reflect divergent neurobiological phenotypes that differentially influence clinical outcomes. Here we investigated neurophysiological heterogeneity during cue-reactivity in individuals with cocaine use disorder (CUD). METHODS: Eighty-eight individuals with CUD completed an electroencephalography cue-reactivity task; the final analytic sample included 70 participants (14 female, 55 male, and 1 participant with missing sex information). The late positive potential (LPP) amplitude, a robust neurophysiological marker of drug cue reactivity, was extracted in the 400- to 1000-ms window after cocaine cue onset. Sensor-level LPP topographical heterogeneity was used to identify subtypes, and source-amplitude and beta oscillation analyses were subsequently used to mechanistically characterize subtype differences. RESULTS: Posterior cue reactors (PCR) (n = 29) and frontal cue reactors (FCR) (n = 41) were determined based on spatially distinct sensor patterns of cue-reactivity LPP maxima. PCR (vs. FCR) showed hypoactivations in lingual, pericalcarine, isthmus cingulate, temporal, frontal, and precentral regions and hyperactivations in postcentral and cuneus regions. PCR (vs. FCR) also showed beta hypoactivations in orbitofrontal and rostral anterior cingulate cortex, with hyperactivations in paracentral and pericalcarine regions. Cue-induced regional activations were associated with clinical outcomes, including craving and withdrawal severity, years of regular use, prospective abstinence, and percent use days. CONCLUSIONS: Results showed that cocaine cue reactivity is heterogeneous and may involve distinct neurobiological subtypes in individuals with CUD. Future research should validate these neurophysiological patterns in independent samples and examine their stability and clinical relevance longitudinally to inform targeted interventions addressing subtype-specific neural circuit disruptions.
SN  - 2451-9022
SN  - 2451-9030
ER  -