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 a therapeutic option to alter maladaptive brain functions associated with chronic substance use.We present a randomized, triple-blind, sham-controlled, clinical trial to determine the neural substrates of tDCS effects on drug craving. Sixty participants with methamphetamine use disorder were assigned to two groups: active tDCS (5 x 7 cm 2 , 2 mA, 20 min, anode/cathode over the F4/Fp1) and sham stimulation. Neuroimaging data of a methamphetamine cue reactivity task were collected immediately before and after stimulation. There was a significant reduction in self-reported craving after stimulation without any significant effect of time-by-group interaction. Our wholebrain analysis demonstrated that there was a global decrease in brain reactivity to cues following sham but not active tDCS. There were significant time-by-group interactions in five main clusters in middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and precuneus with higher activations after active stimulation. There was a significant effect of stimulation type in the relationship between electrical current at the individual level and changes in task-modulated activation. Brain regions with the highest electric current in the prefrontal cortex showed a significant timeby-group interaction in task-modulated connectivity in the frontoparietal network. In this trial, there was no significant effect of the one session of active-F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, activation and connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders

“…We included 110 studies, encompassing a total of 4820 participants . The majority of participants were male (2959 [61.4%] compared with 1861 females [38.6%]), and the mean (SD) age was 43 (8.8) years.…”

Are we really targeting and stimulating DLPFC by placing transcranial electrical stimulation (tES) electrodes over F3/F4?

“…A pre-post tDCS-fMRI study on MUD participants showed a significant correlation between changes in brain functions in response to drug cues and the averaged EF strength solely in the frontopolar area, not other prefrontal regions (Esmaeilpour et al, 2019). A larger cohort of individuals with MUDs also showed similar results; a significant correlation was observed between the normal component of the EF and changes in functional activity in the frontopolar area during a standard drug cue reactivity task (Ekhtiari et al, 2022).…”

“…However, similar to healthy participants, in both DLPFC montages, frontopolar received the highest EFs in the MUD group. This suggests the frontopolar area may play a role in tES over DLPFC for SUDs while much of the initial attention is focused on the DLPFC with more promising results with symmetric compared to asymmetric montages (Ekhtiari et al, 2022) Maybe the reason behind the significant rise in functional activity within VMPFC upon DLPFC stimulation is linked to the highest EF intensity in this particular brain area, which remains unexplored. Dose-response relationship analysis, which integrated head models with fMRI (refer to Supplementary materials section S7), found further support for the importance of EF strength in frontopolar area involvement in DLPFC stimulation for SUDs (Ekhtiari et al, 2022;Esmaeilpour et al, 2019).…”

“…This suggests the frontopolar area may play a role in tES over DLPFC for SUDs while much of the initial attention is focused on the DLPFC with more promising results with symmetric compared to asymmetric montages (Ekhtiari et al, 2022) Maybe the reason behind the significant rise in functional activity within VMPFC upon DLPFC stimulation is linked to the highest EF intensity in this particular brain area, which remains unexplored. Dose-response relationship analysis, which integrated head models with fMRI (refer to Supplementary materials section S7), found further support for the importance of EF strength in frontopolar area involvement in DLPFC stimulation for SUDs (Ekhtiari et al, 2022;Esmaeilpour et al, 2019). A pre-post tDCS-fMRI study on MUD participants showed a significant correlation between changes in brain functions in response to drug cues and the averaged EF strength solely in the frontopolar area, not other prefrontal regions (Esmaeilpour et al, 2019).…”

Optimizing Individual Targeting of Fronto-Amygdala Network with Transcranial Magnetic Stimulation (TMS): Biophysical, Physiological and Behavioral Variations in People with Methamphetamine Use Disorder

“…This study was conducted in accordance with the Declaration of Helsinki and all methods were carried out in accordance with relevant guidelines and regulations. More details on inclusion/exclusion criteria are in supplementary materials (Section S1) [42].…”