(105) Transcranial Electrical Stimulation in Meth Craving: A Mechanistic Dose-Response RCT

Background: Transcranial direct current stimulation [1] has shown several potentials to modulate cortical excitability, activity, and connectivity associated with chronic substance use disorders. However, the neural mechanism(s) underlying tDCS is still an open question [2, 3].

Aim: Here, we aimed to evaluate the efficacy of tDCS at the level of brain functions across a population with drug addiction in a randomized triple-blind sham-controlled clinical trial.

Method: Sixty participants with methamphetamine use disorder were randomly assigned to two groups (n=30 in each group) to receive 20 minutes of active or sham tDCS over right DLPFC (anode/cathode over F4/Fp1 in EEG standard system with 2 mA current intensity). Neuroimaging data of a methamphetamine cue reactivity (MCR) task were collected immediately before and after stimulation with subjective craving assessed before, during, and after fMRI scans.
Result: Self-report craving scores showed a significant reduction across time in both groups and did not show a time by group interaction. Self-reported craving obtained during the scan after blocks of cues showed effect size Hedges’ g = -0.50 with 95% CI -1.03-0.03 (differences between meth and neutral blocks in post-stimulation compared to the pre-stimulation). Whole-brain analysis of fMRI data during the MCR task revealed that brain activation decreased in all parts of the brain in the second (post-stimulation) scan after sham stimulation that can be considered as an indicator of habituation but this uniform decrease did not occur throughout the brain in the active group. Time (after vs. before stimulation) by group (active vs. sham) interaction analysis using linear mixed effect models (voxel-level threshold: p uncorrected <0.005, cluster size>40) showed significantly higher activations in the active group in five main regions; medial frontal gyrus (F-value in peak: 18.61), anterior insula (F-value in peak: 21.31), inferior parietal lobule (F-value in peak: 17.58), precuneus (F-value in peak: 15.92), and inferior frontal gyrus (F-value in peak: 21.88). To simulate electric field distribution patterns, individualized computational head models were generated for all participants using high-resolution T1-weighted images. There was a significant group effect in the relationship between the level of current in the above-mentioned significant clusters and changes in task-modulated activation. We also found that brain regions with the highest electric fields in the prefrontal cortex showed a significant time by group interaction in task-modulated connectivity (psychophysiological interaction during MCR) in the frontoparietal network. Significant correlations between task-based connectivity alterations and electric field patterns were also found in the active group (frontoparietal connectivity: r=0.44, P=0.021, frontolimbic connectivity: r=0.53, P=0.005).

Conclusion: Drug craving decreased after the application of both active and sham tDCS with no significant time by group interaction. However, alterations in functional activity/connectivity and the association between tDCS-induced electric fields and neural responses suggest potentials to facilitate clinical translation of tDCS applications in addiction medicine.

References: 1. Nitsche, M.A. and W. Paulus, Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of physiology, 2000. 527(3): p. 633-639.
2. Ekhtiari, H., et al., Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Neuroscience & Biobehavioral Reviews, 2019.
3. Trojak, B., et al., Outcome of non-invasive brain stimulation in substance use disorders: a review of randomized sham-controlled clinical trials. The Journal of neuropsychiatry and clinical neurosciences, 2017. 29(2): p. 105-118.

Diversity, Equity, and Inclusion: We recruited a sample that is representative of all ethnicities and minorities in Oklahoma. The research group and authors are also representing a diverse set of gender and ethnical backgrounds.