Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse: implications for neuromodulation treatment

Featured Paper of the Month – November 2021

Published in Brain Communications by Tianye Zhai and Yihong Yang et al. in the NIDA IRP Magnetic Resonance Imaging and Spectroscopy Section.

Summary

Cocaine use disorder is a highly relapsing chronic brain disease with current treatments relatively ineffective. Finding brain areas and brain functional circuits that are relevant to cocaine relapse is crucial in understanding the brain mechanisms of addiction as well as in developing effective treatment protocols. By combining the resting-state fMRI and the Cox regression based predictive modeling, Zhai et al. identified three sets of dorsolateral prefrontal cortex (dlPFC)-centric functional circuits that predict cocaine relapse with high accuracy, provide insights into the multiple roles ofthe dlPFC in brain functioning that affect treatment outcome, and suggest these dlPFC loci as potential neuromodulation targets for addiction treatment.

Publication Information

Zhai, Tianye; Salmeron, Betty Jo; Gu, Hong; Adinoff, Bryon; Stein, Elliot A; Yang, Yihong

Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse: implications for neuromodulation treatment Journal Article

In: Brain Commun, vol. 3, no. 2, pp. fcab120, 2021, ISSN: 2632-1297.

Abstract | Links

@article{pmid34189458,

title = {Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse: implications for neuromodulation treatment},

author = {Tianye Zhai and Betty Jo Salmeron and Hong Gu and Bryon Adinoff and Elliot A Stein and Yihong Yang},

url = {https://pubmed.ncbi.nlm.nih.gov/34189458/},

doi = {10.1093/braincomms/fcab120},

issn = {2632-1297},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Brain Commun},

volume = {3},

number = {2},

pages = {fcab120},

abstract = {Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that are implicated in the phenotypes of both substance use disorders and other neuropsychiatric diseases and has become the principal site to deliver transcranial magnetic stimulation for their treatment. However, the dorsolateral prefrontal cortex is an anatomically large and functionally heterogeneous region, and the specific dorsolateral prefrontal cortex locus and dorsolateral prefrontal cortex-based functional circuits that contribute to drug relapse and/or treatment outcome remain unknown. We systematically investigated the relationship of cocaine relapse with functional circuits from 98 dorsolateral prefrontal cortex regions-of-interest defined by evenly sampling the entire surface of bilateral dorsolateral prefrontal cortex in a cohort of cocaine dependent patients ( = 43, 5 Fr) following a psychosocial treatment intervention. Cox regression models were utilized to predict relapse likelihood based on dorsolateral prefrontal cortex functional connectivity strength. Functional connectivity from only 3 of the 98 dorsolateral prefrontal cortex loci, one in the left and two in the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.6% and 85.4%, respectively. Combining all three loci significantly improved prediction validity to 87.5%. Protective and risk circuits related to these dorsolateral prefrontal cortex loci were identified that have previously been implicated to support 'bottom up' drive to use drug and 'top down' control over behaviour together with social emotional, learning and memory processing. Three dorsolateral prefrontal cortex-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct dorsolateral prefrontal cortex-based circuits provide insights into the multiple roles played by the dorsolateral prefrontal cortex in cognitive and affective functioning that affects treatment outcome. The identified dorsolateral prefrontal cortex loci may serve as potential neuromodulation targets to be tested in subsequent clinical studies for addiction treatment and as clinically relevant biomarkers of its efficacy. Zhai et al. identify three dorsolateral prefrontal cortex (dlPFC)-centric circuits that predict cocaine relapse with high accuracy, providing insights into the multiple roles of the dlPFC in brain functioning that affects treatment outcome and suggesting the dlPFC loci as potential neuromodulation targets for addiction treatment.},

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pubstate = {published},

tppubtype = {article}

}

Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that are implicated in the phenotypes of both substance use disorders and other neuropsychiatric diseases and has become the principal site to deliver transcranial magnetic stimulation for their treatment. However, the dorsolateral prefrontal cortex is an anatomically large and functionally heterogeneous region, and the specific dorsolateral prefrontal cortex locus and dorsolateral prefrontal cortex-based functional circuits that contribute to drug relapse and/or treatment outcome remain unknown. We systematically investigated the relationship of cocaine relapse with functional circuits from 98 dorsolateral prefrontal cortex regions-of-interest defined by evenly sampling the entire surface of bilateral dorsolateral prefrontal cortex in a cohort of cocaine dependent patients ( = 43, 5 Fr) following a psychosocial treatment intervention. Cox regression models were utilized to predict relapse likelihood based on dorsolateral prefrontal cortex functional connectivity strength. Functional connectivity from only 3 of the 98 dorsolateral prefrontal cortex loci, one in the left and two in the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.6% and 85.4%, respectively. Combining all three loci significantly improved prediction validity to 87.5%. Protective and risk circuits related to these dorsolateral prefrontal cortex loci were identified that have previously been implicated to support 'bottom up' drive to use drug and 'top down' control over behaviour together with social emotional, learning and memory processing. Three dorsolateral prefrontal cortex-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct dorsolateral prefrontal cortex-based circuits provide insights into the multiple roles played by the dorsolateral prefrontal cortex in cognitive and affective functioning that affects treatment outcome. The identified dorsolateral prefrontal cortex loci may serve as potential neuromodulation targets to be tested in subsequent clinical studies for addiction treatment and as clinically relevant biomarkers of its efficacy. Zhai et al. identify three dorsolateral prefrontal cortex (dlPFC)-centric circuits that predict cocaine relapse with high accuracy, providing insights into the multiple roles of the dlPFC in brain functioning that affects treatment outcome and suggesting the dlPFC loci as potential neuromodulation targets for addiction treatment.