Presented During:
Wednesday, June 26, 2024: 11:30 AM - 12:45 PM
COEX
Room:
Grand Ballroom 101-102
Poster No:
540
Submission Type:
Abstract Submission
Authors:
Sofie Valk1, Foivos Georgiadis2, Meike Hettwer3, Sophia Thomopoulos4, Paul Thompson5, Scott Mackey6, Patricia Conrod7, Hugh Garavan8, Clara Moreau9, Boris Bernhardt10, Matthias Kirschner11, ENIGMA Addiction Working Group12
Institutions:
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2University of Zurich, Zurich, Switzerland, 3Forschungszentrum Jülich, Jülich, North Rhine-Westphalia, 4USC, Marina del Rey, CA, 5USC, Marina Del Rey, CA, 6The University of Vermont, Burlington, VT, 7University of Montreal, Montreal, Quebec, 8University of Vermont, Burlington, VT, 9University of Southern California, Los Angeles, CA, 10Montreal Neurological Institute and Hospital, Montreal, Quebec, 11Geneva University Hospitals (HUG), Thonex, Geneva, 12UCLA, Burlington, Vermont
First Author:
Sofie Valk
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig, Germany
Co-Author(s):
Meike Hettwer
Forschungszentrum Jülich
Jülich, North Rhine-Westphalia
Boris Bernhardt
Montreal Neurological Institute and Hospital
Montreal, Quebec
Introduction:
Substance use disorders are highly comorbid with other neuropsychiatric disorders and share with them widespread structural brain alterations (Eaton, Rodriguez-Seijas, Carragher, & Krueger, 2015; Mackey et al., 2019; Reich-Erkelenz, Schmitt, & Falkai, 2015). Previous work has shown that structural alterations across neuropsychiatric conditions are organized in a systematic fashion, linked to the intrinsic organization of the human connectome (Hettwer et al., 2022). However, to what extent similar coordinated co-alteration effects extend to substance use disorders remains to be established. Here, we investigated substance use co-alteration networks (pathological structural covariance) to elucidate concordant macroscale principles of illness and substance-use effects across the cortex.
Methods:
We derived maps of case-control differences in cortical thickness from 2,847 patients with six substance use disorders (SUDs: alcohol, amphetamines, cocaine, opioids, cannabis, and nicotine; Fig. 1A) and 1,951 non-affected individuals from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Addiction Working Group (Thompson et al., 2020; Mackey, 2020). We investigated substance use co-alteration networks via inter-regional SUD association with cortical thickness (Fig. 1B). Hub regions are regions that show high co-alteration profiles across disorders and were computed as the sum of top 20% covariance strengths in each region. Next, we identified potential substance use co-alteration epicenters, i.e., regions whose normative connectivity profiles (based on data from the Human Connectome Project, (Van Essen et al., 2013)) are correlated with substance use co-alteration hubs. Last, we compared the effects of substance use disorder-related co-alterations and neuropsychiatric disease-related co-alterations based on prior work (Hettwer et al., 2022). To do so, we probed regional embedding and inter-relational organizational axes (Vos de Wael et al., 2020).
Results:
We identified organizational principles of shared cortical thickness alterations across SUDs (SUDcov). Co-alteration network hubs followed normative functional (r=0.527, pspin<0.05) and structural (r=0.314, pspin<0.05) connectivity patterns (Fig. 1C). Functional epicenters included temporal regions, precuneus, right frontal cortex and hippocampus and amygdala, and structural epicenters were found in posterior/mid cingulate, preSMA, right sensory-motor regions, and the thalamus (Fig. 1C). We observed a high overlap between SUDcov and structural covariance patterns of cortical thickness, except in inferior temporal areas and mOFC (Fig. 2A and B). Similar associations were observed when comparing SUDcov with neuropsychiatric cross-disorder impact (Fig. 2C). Studying low-dimensional organizations of SUDcov, the primary gradient of substance use disorder differentiated OFC, inferior temporal regions, and anterior cingulate from the rest of the cortex and mirrored the second covariance and neuropsychiatric co-alteration gradients (pspin<0.05). The second SUDcov gradient differentiated parietal and OFC areas from the rest of the cortex (Fig 2DE). Overall, SUD co-alterations varied stronger along G2cov (median r=0.25) relative to G1cov (median r=0.15), and the reverse was observed in neuropsychiatric co-alteration gradients (G1 median r=0.33, G2 median r=0.15). Hierarchical clustering of SUD and neuropsychiatric co-alteration patterns further underlined this differentiation (Fig. 2F).
![Supporting Image: addiction1.png](https://files.aievolution.com/prd/hbm2401/abstracts/abs_2208/addiction1.png)
·Cross-substance use disorder covariance
![Supporting Image: addiction2.png](https://files.aievolution.com/prd/hbm2401/abstracts/abs_2208/addiction2.png)
·Substance use covariance network embedding.
Conclusions:
The shared association of SUDs with cortical thickness covaries in a network-like fashion. These patterns partly mirror those of normative structural covariance, underscoring the differentiation between inferior/paralimbic and superior regions of the cerebral cortex by SUDs as probed by a gradient framework (Valk et al., 2020). We observed differentiation between SUDs versus neuropsychiatric co-alteration networks, possibly related to a differentiation between co-morbidity and neurodevelopment (Hettwer et al., 2022).
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 2
Keywords:
Addictions
Computational Neuroscience
Psychiatric Disorders
Other - Disease co-alterations
1|2Indicates the priority used for review
Provide references using author date format
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Hettwer, M. D., Lariviere, S., Park, B. Y., van den Heuvel, O. A., Schmaal, L., Andreassen, O. A., . . . Valk, S. L. (2022). Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders. Nat Commun, vol. 13, no. 1, pp. 6851
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