# Resting-state fMRI analysis of functional connectivity and temporal dynamics differences between cocaine users and healthy controls

## TL;DR

This study uses brain imaging to compare how cocaine users and healthy people connect different brain regions, finding key differences in connectivity patterns and brain states.

## Contribution

The study introduces a novel application of Energy Landscape Analysis to identify whole-brain connectivity differences in cocaine users.

## Key findings

- Cocaine users showed stronger connectivity between the cerebellum and inferior temporal gyrus compared to healthy controls.
- Healthy controls exhibited more frequent visits to low-energy brain states, driven by higher transition rates.
- Cocaine users displayed reduced connectivity between the cerebellum and visual regions.

## Abstract

Understanding alterations in functional connectivity among individuals with substance use disorder (SUD) is critical for elucidating the neural mechanisms underlying addiction. In this study, we applied Energy Landscape Analysis (ELA), an energy-based machine learning method, to examine whole-brain functional connectivity differences between SUD patients and healthy controls (HCs). A key methodological challenge in ELA lies in the selection of appropriate Regions of Interest (ROIs) from comprehensive brain atlases. To address this, we employed seed-based connectivity analysis to identify task-relevant ROIs, thereby overcoming the limitation of focusing on a restricted subset of regions. The dataset comprised 53 cocaine users (CUs) and 52 age- and sex-matched HCs, with functional MRI data preprocessed using the CONN toolbox. ROI-to-ROI seed-based connectivity was computed through first- and second-level analyses. ELA revealed that HCs exhibited stronger positive connectivity between cerebellar and visual regions, whereas CUs showed stronger positive connectivity between the cerebellum and the inferior temporal gyrus (temporooccipital part; toITG). Seven low-energy connectivity states were identified that differentiated the two groups. In these states, the cerebellum and toITG demonstrated antagonistic activation patterns, while the cerebellum and visual cortex co-activated in HCs. Temporal dynamics analyses further indicated that HCs visited these low-energy states more frequently, driven by shorter dwell times but higher transition rates. These findings suggest that cocaine addiction may reflect a weakening of adaptive, protective (“guardian”) connectivity patterns, rather than an increased propensity to remain in maladaptive connectivity states. Collectively, these results highlight key network-level distinctions between HCs and CUs and offer new insights into the neurobiological mechanisms of cocaine addiction.

•Energy Landscape Analysis (ELA) explored whole-brain ROI functional connectivity differences between Cocaine users and healthy controls using CONN toolbox for ROI selection.•Cocaine users showed reduced connectivity between the superior temporal gyrus, basal ganglia network, and visual network and cerebellum.•Cocaine users showed stronger connectivity between the inferior temporal gyrus (toITG) and the cerebellum.•Distinctive states showed antagonistic connectivity between the cerebellum and toITG, and cooperative connectivity between the cerebellum and primary visual network.•HCs visited low-energy states more often, suggesting functional brain state differences are based on occurence frewuency and not dwell times.

Energy Landscape Analysis (ELA) explored whole-brain ROI functional connectivity differences between Cocaine users and healthy controls using CONN toolbox for ROI selection.

Cocaine users showed reduced connectivity between the superior temporal gyrus, basal ganglia network, and visual network and cerebellum.

Cocaine users showed stronger connectivity between the inferior temporal gyrus (toITG) and the cerebellum.

Distinctive states showed antagonistic connectivity between the cerebellum and toITG, and cooperative connectivity between the cerebellum and primary visual network.

HCs visited low-energy states more often, suggesting functional brain state differences are based on occurence frewuency and not dwell times.