Dysfunctional network organization in opioid use disorder revealed by inhibitory control: Preliminary results from graph theoretic analyses of task-based fMRI among methadone-maintained patients

Background

Inhibitory control deficits are central to the pathophysiology of opioid use disorder (OUD). Relative to non-substance-using comparators, case-control studies show that OUD patients exhibit deficits in motor response inhibition proficiency and diminished functional activation in prefrontal, cingulate, and motor cortices. However, little is known about the presumably dysfunctional network interactions that underlie response inhibition deficits in OUD which motivated this study.

Methods

Functional magnetic resonance imaging data (TR=2.0 s, TE=35.29 ms, 2.6 mm isotropic; Siemens Verio 3T) were acquired in methadone-maintained OUD patients (n=15; 42.9±12.2yrs old; 66.7% male; 97.8±54.9mg/day methadone; 100% smokers) and well-matched non-OUD comparators (n=18; 39.5±9.0yrs old; 77.8% male; 88.9% smokers) during a motor control paradigm with conditions for response excitation (‘All-Go’) and response inhibition (‘Go/No-Go’) (four 48 s blocks of each). From each participant’s imaging data, undirected weighted graphs were generated in 246 brain nodes with 30,135 unique edges (weighted by undirected functional connectivity) to estimate each node’s Betweenness Centrality (BC) for inter-group comparison (p_FDR<.05).

Results

Response proficiency did not differ between groups (ps>0.10). During Go/No-Go, OUD patients evoked aberrantly reduced BC across 15 brain nodes (with no increases), indicative of diminished network integration across frontal, temporal, and parietal cortices, and nucleus accumbens. Higher BC in BA44 and BA9 were correlated with more attempts to discontinue opioid use among OUD patients (ps<0.05).

Discussion

This is the first application of graph theoretical analyses to investigate the network connectomic bases of inhibitory control deficits in OUD. Disordered functional network integration during inhibitory control in OUD may impact patients’ ability to inhibit opioid use behavior.