Functional connectivity of orbitofrontal cortex predicts cocaine relapse: Protective and risk circuits, individual...

Area of Science:

• Neuroscience
• Psychiatry
• Addiction Medicine

Background:

• Substance use disorder (SUD) presents a major public health challenge due to high relapse rates and limited treatment efficacy.
• The orbitofrontal cortex (OFC) is implicated in decision-making and reward processing, making it a potential target for SUD neuromodulation therapies.
• The precise OFC regions for effective neuromodulation remain unidentified due to the OFC's large and complex structure.

Purpose of the Study:

• To identify specific regions within the OFC and their associated functional circuits that predict cocaine relapse.
• To validate these predictive circuits in independent patient cohorts.

Main Methods:

• Utilized Cox regression-based prediction modeling on resting-state functional connectivity data from 20 OFC regions of interest (ROIs).
• Analyzed data from treated cocaine use disorder patients.
• Employed cross-validation and external validation using area under the receiver operating characteristic curve (AUC) to assess predictive accuracy.

Main Results:

• Identified two left lateral OFC ROIs with high accuracy in predicting cocaine relapse (cross-validated AUC=0.896, external AUC=0.780).
• Each identified ROI demonstrated distinct protective and risk circuits influencing relapse.
• The findings provide system-level insights into the neural mechanisms underlying drug relapse.

Conclusions:

• The identified OFC ROIs and their functional circuits offer potential targets for novel neuromodulation strategies in SUD treatment.
• These findings may aid in distinguishing SUD subtypes and personalizing treatment approaches.
• Further clinical trials can test the efficacy of targeting these specific OFC regions.