AUGMENTING DORSOLATERAL PREFRONTAL CORTEX-TARGETED TDCS WITH COGNITIVE REAPPRAISAL IN COCAINE USE DISORDER

Background

Cocaine use disorder (CUD) remains a major public health challenge in the United States. In 2022, approximately 5.3 million individuals reported past-year crack or cocaine use, 1.4 million met criteria for CUD, and cocaine-related overdose deaths continued to rise, highlighting the absence of FDA-approved pharmacological treatments and the urgent need for additional evidence-based treatment options. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), a key node in inhibitory control and salience regulation, has demonstrated efficacy in reducing craving in CUD. Cognitive reappraisal (CR) is a dlPFC-dependent learning strategy that we have shown to reduce drug cue-reactivity in CUD. Whether combining dlPFC-targeted tDCS with CR produces superior regulatory effects remains unknown.

Methods

Thirty-six individuals with CUD were randomized to sham (n=13), real (n=13), or real+CR (n=13) conditions to receive 15 sessions of dlPFC-targeted tDCS over 5 weeks. Following Phase 1 procedures, in this Phase 2 study, cocaine craving was measured using the Obsessive-Compulsive Cocaine Scale subscale and item 5 of the five-item Cocaine Craving Questionnaire before and after treatment; at the same times, drug cue-reactivity was measured using late positive potentials (LPP) during an EEG cue-reactivity task. Rest-activity rhythms were continuously monitored over the 5 weeks using 24/7 ActiGraph and processed with GGIR package to derive daily activity and circadian rhythm metrics. Hidden Markov models will be applied to characterize latent rest-activity states and circadian transitions, and multivariate models will be used to integrate craving, LPP, and rest-activity rhythm features to identify markers of treatment response.

Results

There was a significant group by time interaction on combined cravings, F(2,18)=3.77, p=.043, partial eta squared (pes)=.295, driven by greater craving reductions in the real+CR group, t(8.98)=2.79, p=.021, d=1.49, and the real group, t(9.55)=2.13, p=.059, d=1.14, relative to sham. We hypothesize that craving reductions will be accompanied by decreased drug-biased LPPs and by normalization of rest-activity rhythms, with the strongest effects in the real+CR group.

Conclusions

These findings suggest that dlPFC-targeted tDCS, particularly when combined with CR, significantly reduces cocaine craving. Ongoing analyses of LPP and rest-activity rhythms will clarify whether treatment-related changes in brain reactivity and circadian organization track craving reduction. Together, this work supports cognitively enhanced neuromodulation approaches that combine cognitive strategies with brain stimulation to improve therapeutic outcomes in cocaine use disorder. Supported By NIDA 5N95020C00024

Learning Objective 1: Describe how dlPFC-targeted tDCS, alone and combined with cognitive reappraisal, modulates craving, rest-activity rhythms, and drug cue-reactivity in cocaine use disorder.

Learning Objective 2: Explain how multimodal measures, including EEG-derived LPP and rest-activity rhythm modeling, can be used to identify neural and behavioral markers of treatment response in interventional psychiatry.

References

: Gaudreault P-O, Sharma A, Datta A, et al. A double-blind shamcontrolled phase 1 clinical trial of tDCS of the dorsolateral prefrontal cortex in cocaine inpatients: Craving, sleepiness, and contemplation to change. Eur J Neurosci. 2021; 53: 3212–3230. M.A. Parvaz,P. Malaker,A. Zilverstand,S.J. Moeller,N. Alia-Klein, and R.Z. Goldstein, Attention bias modification in drug addiction: Enhancing control of subsequent habits, Proc. Natl. Acad. Sci. U.S.A. 118 (23) e2012941118