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Methamphetamine use disorder (MUD) is among the costliest and deadliest substance use disorders (SUDs) world-wide and is frequently comorbid with other mental health conditions. There is no empirically validated medical treatment for MUD. Drug craving is the signature aspect of MUD and other substance use disorders and has been associated with continued drug use and relapse. The investigators and others have shown that transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC) can modulate drug craving in different SUDs. tDCS is a method of non-invasive brain stimulation and is a low-cost scalable technology without any serious side effects that delivers low levels of direct current (0.1-2 mAmp) transcranially. However, there are significant inter-individual differences in response to tDCS, which is not well understood but can have profound impact on efficacy. Meanwhile, there are no studies with neuroimaging to show how tDCS affects drug craving. Investigators propose the first combined tDCS/functional Magnetic Resonance Imaging (fMRI) study to examine the acute effects of tDCS on neural substrates underlying drug induced craving.
Methamphetamine use disorder (MUD) is among the costliest and deadliest substance use disorders (SUDs) world-wide and is frequently comorbid with other mental health conditions. There is no empirically validated medical treatment for MUD. Drug craving is the signature aspect of MUD and other substance use disorders and has been associated with continued drug use and relapse. The investigators and others have shown that transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC) can modulate drug craving in different SUDs. tDCS is a method of non-invasive brain stimulation and is a low-cost scalable technology without any serious side effects that delivers low levels of direct current (0.1-2 mAmp) transcranially. However, there are significant inter-individual differences in response to tDCS, which is not well understood but can have profound impact on efficacy. Meanwhile, there are no studies with neuroimaging to show how tDCS affects drug craving. The investigators propose the first combined tDCS/functional Magnetic Resonance Imaging (fMRI) study to examine the acute effects of tDCS on neural substrates underlying drug induced craving. The investigators hypothesize that tDCS amplifies DLPFC's top-down modulatory role via its connectivity to other cortical-subcortical areas. In this double blind randomized experimental design, the investigators will recruit 60 people with MUD during their early abstinence phases into parallel arms with active and sham DLPFC tDCS. Each subject will undergo resting state and task based (drug cue exposure paradigm) functional MRI pre and post tDCS. The investigators will conduct individual difference analyses to explore the potential predictors for tDCS response, including pre-tDCS top-down connectivity measures of DLPFC and other subjective, clinical, behavioral, structural, and functional variables. The results of this study will provide neuroscience-based evidence for the efficacy of tDCS and will advance the field towards precision addiction medicine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active | Experimental | Participants in the active arm will receive 2 milliamp anodal transcranial Direct Current Stimulation (tDCS) over the Dorso-Lateral Pre-Frontal Cortex (DLPFC). |
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| Sham | Placebo Comparator | Participants in the Sham arm will receive sham transcranial Direct Current Stimulation (tDCS) over the Dorso-Lateral Pre-Frontal Cortex (DLPFC). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active transcranial Direct Current Stimulation (tDCS) | Device | Transcranial Direct Current Stimulation (tDCS) as a device-based technology is employed by applying a very weak (2 mAmp) direct current over the skull for 1200 seconds with 30 seconds ramp up to 2 mAmp, and 30 seconds ramp down at the end. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Drug Cue Reactivity BOLD Signal in fMRI from before to after Intervention | Drug Cue Reactivity BOLD Signal is measured as average blood oxygen level dependent (BOLD) signal difference with voxel-wise analysis in the regions of interests (ROIs) (prefrontal cortex parcels, insula segments, striatum nuclei, thalamus nuclei and extended amygdala nuclei) in craving > neutral contrast in drug cue exposure fMRI task with blocks of neutral and drug related images | Immediate before and immediate after intervention |
| Change in Drug Cue Reactivity Self-Report from before to after Intervention | Drug cue reactivity self-report is measured as the difference in subjective response to "On a scale of 0-100, How much drug craving are you experiencing RIGHT NOW" measured on a visual analog scale (0-100) before and after drug cue exposure fMRI task | Immediate before and immediate after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cortical-Subcortical Connectivity in Resting State fMRI from before to after Intervention | Cortical-Subcortical Connectivity is measured as correlation between resting-state average blood oxygen level dependent (BOLD) signal time series in subcortical ROIs and voxels within prefrontal cortex and Insula | Immediate before and immediate after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Drug Cue Control Response from before to after Intervention | Drug cue control response is measured as the difference in subjective response to "On a scale of 0-100, How much CONTROL over your drug craving are you experiencing RIGHT NOW" measured on a visual analog scale (0-100) before and after drug cue exposure fMRI task | Immediate before and immediate after intervention |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hamed Ekhtiari, MD, PhD | Laureate Institute for Brain Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laureate Institute for Brain Research | Tulsa | Oklahoma | 74136 | United States |
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| Sham transcranial Direct Current Stimulation (tDCS) | Device | Sham Transcranial Direct Current Stimulation (tDCS) as a device-based technology is employed by applying a very weak direct current over the skull. Sham mode will have just 30 seconds ramp up to 2 mAmp, 40 seconds on 2 mAmp stimulation and, 30 seconds ramp down with 1160 seconds no stimulation (just impedance control). |
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| Change in Cortical-Subcortical Task-based Connectivity in Cue Exposure fMRI from before to after Intervention | Cortical-subcortical task-based connectivity in cue exposure fMRI is measured as psychophysiological interaction (PPI) between average blood oxygen level dependent (BOLD) signal time series in subcortical ROIs and voxels within prefrontal cortex and insula, using craving > neutral contrast regressor | Immediate before and immediate after intervention |
| Change in RAI in Resting State fMRI from before to after Intervention | Resource Allocation Index (RAI) is measured with the correlation among default mode network (DMN), saliency network (SN) and Executive Control Network (ECN) in resting state fMRI based on Lerman, et al., 2014. | Immediate before and immediate after intervention |
| Change in Area Under Electrode Connectivity in Resting State fMRI from before to after Intervention | Area under electrode connectivity is measured with voxel-wise correlation between average blood oxygen level dependent (BOLD) signal in the cortical area under the Anode and Cathode electrodes and whole brain | Immediate before and immediate after intervention |
| Change in Area Under Electrode Task-based Connectivity in Cue Exposure fMRI from before to after Intervention | Area under electrode task-based connectivity is measured with voxel-wise Psychophysiological Interaction (PPI) between average blood oxygen level dependent (BOLD) signal in the cortical area under the Anode and Cathode electrodes and whole brain using craving > neutral contrast regressor in block-design drug cue exposure fMRI task | Immediate before and immediate after intervention |
| Change in Momentary Craving Self-Report from before to after Intervention | Momentary craving self-report is assessed with subjective response to "On a scale of 0-100, How much drug craving are you experiencing RIGHT NOW" measured on a visual analog scale (0-100) | Immediate before and immediate after intervention |
| Change in DI DDQ Score from before to after Intervention | DI DDQ score is measured as response to the "desire and intention" (DI) subscore of the Desire for Drug Questionnaire (DDQ) for Methamphetamine (Franken, et al., 2002). | Immediate before and immediate after intervention |
| Change in NR DDQ Score from before to after Intervention | NR DDQ score is measured as response to the "negative reinforcement" (NR) subscore of the Desire for Drug Questionnaire (DDQ) for Methamphetamine (Franken, et al., 2002). | Immediate before and immediate after intervention |
| Change in DDT Score from before to after Intervention | DDT score is measured with responses to the Delayed Discounting Task (DDT) (Green & Myerson, 2004) | Immediate before and immediate after intervention |