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PreprintCC BY-NC-NDbioRxiv

Multimodal Connectome Markers of Disruptive Behavior Problems in Youth: Distinct Patterns of Concurrent Severity and Prospective Symptom Change

  • Eleni Christofilea1
  • Kaiting Mai1
  • Qinghao Liang2
  • Raimundo X. Rodriguez3
  • Caroline Lloyd1
  • Yize Zhao4,5,6,7
  • Dustin Scheinost1,2,6,7,8,9
  • Denis G. Sukhodolsky1
  • Karim Ibrahim1,6,7,10,11
11 affiliations
  1. 1Child Study Center, Yale School of Medicine, New Haven, Connecticut, USA
  2. 2Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA
  3. 3Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, USA
  4. 4Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
  5. 5Department of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, Connecticut, USA
  6. 6Wu Tsai Institute, Yale University, New Haven, Connecticut, USA
  7. 7Yale Biomedical Imaging Institute, Yale School of Medicine, New Haven, Connecticut, USA
  8. 8Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
  9. 9Department of Statistics and Data Science, Yale University, New Haven, Connecticut, USA
  10. 10Department of Psychology, Yale University, New Haven, Connecticut, USA
  11. 11Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, Connecticut, USA
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Abstract

Disruptive behaviors problems, such as irritability/anger and maladaptive aggression, are associated with altered connectivity across networks supporting emotion regulation. However, multimodal connectome markers of concurrent severity and prospective symptom change, including sex-specific patterns, remain unclear. Using a large, sex-balanced sample from the Adolescent Brain Cognitive Development (ABCD) Study, we applied multimodal connectome-based predictive modelling (CPM) to test whether resting-state functional (n = 7,556; 49.3% female) and structural (N = 8,978; 48.4%) connectivity predicted baseline disruptive behavior severity (at ages 9-10) and 2-year symptom change (from ages 9-10 to 11-12). Models were adjusted for covariates, permutation-tested, and FDR corrected. Secondary analyses tested sex-stratified models separately in males and females. In models emerging as significant, follow-up analyses tested for distinct vs shared predictive edges. Functional and structural connectomes predicted baseline severity ({rho} = 0.087 and {rho} = 0.071, respectively). Functional connectivity also predicted prospective symptom change ({rho} = 0.038), whereas prospective structural prediction was predominately with negative edges ({rho} = 0.026). Functional connectivity models were significant in both sexes, while prospective structural connectivity models were significant in males, but not females. Frontoparietal, medial frontal, sensorimotor, salience, cerebellar, and visual networks contributed across models. Cross-sectional models showed a more distributed pattern while prospective models showed a more focal pattern. These findings identify complementary, largely distinct functional and structural connectome patterns associated with current disruptive behavior risk and subsequent symptom change, supporting the importance of developmental timing, sex, and imaging modality in developing brain-based biomarkers of disruptive behavior risk in youth.

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Cite

BibTeXRIS
BibTeX
@misc{christofilea2026multimodal,
  title = {{Multimodal Connectome Markers of Disruptive Behavior Problems in Youth: Distinct Patterns of Concurrent Severity and Prospective Symptom Change}},
  author = {Eleni Christofilea and Kaiting Mai and Qinghao Liang and Raimundo X. Rodriguez and Caroline Lloyd and Yize Zhao and Dustin Scheinost and Denis G. Sukhodolsky and Karim Ibrahim},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.26.761676},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761676v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Multimodal Connectome Markers of Disruptive Behavior Problems in Youth: Distinct Patterns of Concurrent Severity and Prospective Symptom Change
AU  - Eleni Christofilea
AU  - Kaiting Mai
AU  - Qinghao Liang
AU  - Raimundo X. Rodriguez
AU  - Caroline Lloyd
AU  - Yize Zhao
AU  - Dustin Scheinost
AU  - Denis G. Sukhodolsky
AU  - Karim Ibrahim
PY  - 2026
DA  - 2026/10/26
PB  - bioRxiv
DO  - 10.64898/2026.10.26.761676
UR  - https://www.biorxiv.org/content/10.64898/2026.10.26.761676v1
AB  - Disruptive behaviors problems, such as irritability/anger and maladaptive aggression, are associated with altered connectivity across networks supporting emotion regulation. However, multimodal connectome markers of concurrent severity and prospective symptom change, including sex-specific patterns, remain unclear. Using a large, sex-balanced sample from the Adolescent Brain Cognitive Development (ABCD) Study, we applied multimodal connectome-based predictive modelling (CPM) to test whether resting-state functional (n = 7,556; 49.3% female) and structural (N = 8,978; 48.4%) connectivity predicted baseline disruptive behavior severity (at ages 9-10) and 2-year symptom change (from ages 9-10 to 11-12). Models were adjusted for covariates, permutation-tested, and FDR corrected. Secondary analyses tested sex-stratified models separately in males and females. In models emerging as significant, follow-up analyses tested for distinct vs shared predictive edges. Functional and structural connectomes predicted baseline severity ({rho} = 0.087 and {rho} = 0.071, respectively). Functional connectivity also predicted prospective symptom change ({rho} = 0.038), whereas prospective structural prediction was predominately with negative edges ({rho} = 0.026). Functional connectivity models were significant in both sexes, while prospective structural connectivity models were significant in males, but not females. Frontoparietal, medial frontal, sensorimotor, salience, cerebellar, and visual networks contributed across models. Cross-sectional models showed a more distributed pattern while prospective models showed a more focal pattern. These findings identify complementary, largely distinct functional and structural connectome patterns associated with current disruptive behavior risk and subsequent symptom change, supporting the importance of developmental timing, sex, and imaging modality in developing brain-based biomarkers of disruptive behavior risk in youth.
SN  - 2692-8205
ER  -