Common spatial patterns link network correlates of cocaine use disorder and D2/3 receptor densities
Poster No:
465
Submission Type:
Abstract Submission
Authors:
Jocelyn Ricard1, Loic Labache2, Ashlea Segal2, Elvisha Dhamala3, Carrisa Cocuzza2, Grant Jones4, Sarah Yip2, Sidhant Chopra2, Avram Holmes5
Institutions:
1Stanford University, Stanford, CA, 2Yale University, New Haven, CT, 3Feinstein Institutes for Medical Research, Glen Oaks, NY, 4Harvard University, Cambridge, MA, 5Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ
First Author:
Co-Author(s):
Introduction:
Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits and associated aspects of the dopamine system, with relatively less attention on corresponding alterations within and across large-scale functional brain networks (Koob et al., 2010). Critically, the functional connectome correlates of substance use and their specificity to dopamine receptor densities relative to other metabotropic receptors classes remains to be established.
Methods:
In an open-access dataset of participants with cocaine use disorder (n=69) and healthy matched controls (n=62) (Angeles-Valdez et al., 2022), we characterized brain-wide functional connectivity (FC) for each subject by computing pairwise Pearson correlations between timeseries extracted from 432 regions. To comprehensively delineate brain-wide alterations in FC, we examine group differences at each edge, using the Network Based Statistic (Zalesky et al., 2010) to correct for multiple comparisons. We present the results at three different scales: (a) the level of individual connections (i.e., where edges are either under- or over-connected, or hypo- versus hyperconnectivity, respectively); (b) the level of individual brain regions, to identify specific brain areas which had a high number of significant connections, and (c) the level of large-scale functional brain networks, analyzed both within- and between- networks. Further, we studied the relationship between the observed FC signatures of cocaine use and the spatial distribution of a broad range of normative neurotransmitter receptor and transporter bindings as assessed through positron emission tomography (PET) using an open-access toolbox, neuromaps (Markello et al., 2022).
Results:
Our analyses identified a widespread profile of FC differences between individuals with cocaine use disorder and matched healthy comparison participants (8.8% of total edges; 8,185 edges; pFWE=0.025). Broadly, we observed reduced between-network connectivity linking default network and subcortical regions in participants with cocaine use disorder. Higher within-network connectivity in the default network was also evident in participants with cocaine use disorder (Figure 1). Furthermore, our observations revealed consistent replicable associations between signatures of cocaine use and normative spatial density of dopamine D2/3 receptors (Figure 2).
Conclusions:
Our analyses revealed a widespread profile of altered connectivity in individuals with cocaine use disorder that extends across the functional connectome and implicates multiple circuits. This profile is robustly coupled with normative dopamine D2/3 receptors densities. Thus, this work has broad implications on the neurobiological mechanisms of cocaine use disorder and potential development of personalized interventions.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
PET Modeling and Analysis
Novel Imaging Acquisition Methods:
Multi-Modal Imaging
Keywords:
Addictions
FUNCTIONAL MRI
Neurotransmitter
Positron Emission Tomography (PET)
Psychiatric Disorders
1|2Indicates the priority used for review
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