Transcranial Direct Current Stimulation to Modulate fMRI Drug Cue Reactivity in Methamphetamine Users: A Randomized Clinical Trial

Abstract

Transcranial direct current stimulation (tDCS) has been studied as an adjunctive therapeutic option to alter maladaptive cortical excitability, activity, and connectivity associated with chronic substance use via the application of a weak direct current through the brain. The underlying mechanism of action remains ambiguous, however. We present a randomized, triple-blind, sham-controlled, clinical trial with two parallel arms conducted to determine the neural substrates of tDCS effects on drug craving using an fMRI drug cue reactivity paradigm. Sixty participants with methamphetamine use disorder were randomly assigned to two groups: 30 participants to active tDCS (5x7 cm2, 2 mA, for 20 minutes, anode/cathode over the F4/Fp1 in EEG 10-20 standard system) and 30 participants to the sham group. Neuroimaging data of a methamphetamine cue reactivity (MCR) task were collected immediately before and after stimulation with subjective craving assessed before, after, and during fMRI scans. There was a significant reduction in self-reported craving after stimulation (main effect of time) without any significant effect of group, time, or by group-time interaction. Our whole-brain analysis demonstrated that brain activation decreased in all parts of the brain in the second (post-stimulation) MCR imaging session after sham stimulation (habituation) but this uniform decrease did not occur throughout the brain in the active group. There were significant interactions between the group (active vs. sham) and time (after vs. before stimulation) in five main regions; medial frontal gyrus, anterior insula, inferior parietal lobule, precuneus, and inferior frontal gyrus with higher activations after active stimulation. We simulated computational head models for each individual. There was a significant effect of group in the relationship between 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. In this two-parallel-arms triple-blind randomized control trial, we did not find any significant effect of the one session of active F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues among people with methamphetamine use disorder.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity

“…This systematic review aims to provide a comprehensive overview of the entire FDCR field and the broad inclusion criteria for study participants included studies of individuals who met SUD diagnostic criteria and those who used substances without meeting such criteria and did not exclude studies of participants with various comorbidities. These and the methodological heterogeneities reported in this systematic review prevent us from performing a meta-analysis across studies, but future meta-analyses and mega-analyses of clusters of studies in the database are possible and facilitated by our ongoing effort to catalog and share FDCR studies …”

“…Detailed methods and results of the systematic review sections are presented in the eMethods and eResults in the Supplement, and the search terms and syntax can be found in eTables 1 and 2 in the Supplement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, and the protocol for this systematic review was preregistered . The annual update of this live systematic review can be found online .…”

Closing the loop between brain and electrical stimulation: Towards precision neuromodulation treatments

“…Task design should activate brain regions related to the desired brain state one wishes to target. Fatigue or learning effects, including adaptation or habituation that can cause a significant decrease of the BOLD response, should be minimized during task performance [94][95][96][97].…”

Dose-Response in Modulating Brain Function with Transcranial Direct Current Stimulation: From Local to Network Levels

“…This study was conducted in accordance with the Declaration of Helsinki and all methods were carried out following relevant guidelines and regulations. More details on inclusion and exclusion criteria can be found here [27].…”

“…T1 and T2-weighted MRI data were used to generate head models for each individual to simulate electric fields (Figure 3). More details on neuroimaging and tDCS parameters can be found here [27]. fMRI data preprocessing fMRI preprocessing was performed in AFNI.…”