Deep TMS of Neural Circuits Associated With Stimulant Use Disorder

This study aims to evaluate the efficacy of deep transcranial magnetic stimulation (dTMS) as a treatment for Veterans with a methamphetamine use disorder (MUD).

To date, TMS has emerged as a promising treatment avenue for addiction and is being tested in clinical trials with some encouraging results. A recent systematic review and meta-analysis highlights that 7/8 (87.5%) studies using TMS for MUD or 38/50 (88%) in addiction more broadly have targeted the left DLPFC alone. While this strategy has been useful in reducing craving, treated individuals resume use shortly after treatment at similar rates to those receiving sham. Here, utilizing a data-driven and innovative approach, the investigators aim to modulate target brain function that has been shown to predict treatment outcomes for individuals with MUD. The literature describes how TMS treatment is associated with physiological changes in the brain at the target area and in remote structurally or functionally connected brain areas. TMS has been associated with changes in long-term potentiation (LTP) or depression (LTD) to increase neuroplasticity through increases in brain-derived neurotrophic factor (BDNF) and implicated in influencing the excitatory/inhibitory balance of GABAergic synapses. H-coil designs have the potential to target deeper regions of the brain as well as multiple downstream, interacting brain networks in a novel manner. For example, insula stimulation has the potential to strengthen the salience network broadly and subsequently ameliorate relapse risk.

An emerging advancement is the use of coils that target deeper regions of the brain and have the potential of targeting multiple, interacting brain networks. The H-coil configuration in this technique stimulates a broader area (e.g., up to 17 cubic centimeters) as well as a deeper area (e.g., up to 4 cm), relative to standard figure-of-eight coils, further enhancing innovation and generalizability. With this coil, the investigators hypothesize modifying the salience network nodes that are otherwise not reached by figure-of-eight coils. Notably, published studies to date that utilize these H-coils for addiction yield promising results. However, whether the proposed stimulation strategies will have objectively measurable impact on their respective brain targets or similar impact in individuals with MUD remains unclear.

The proposed study fills a critical, scientific gap of the need to evaluate a novel, non-invasive brain stimulation technique for MUD.

The investigators believe this proposed work will provide preliminary data for a larger grant submission that could allow for a more complex study design to fully answer gaps in current knowledge about deep TMS H4 coil as a possible treatment approach for MUD.

Eligibility Criteria:
Inclusion:

* Must be within the age range of 25-75.
* Participants must meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate to severe MUD (≥4 diagnostic symptoms).
* Participants must be able to obtain a Motor Threshold (MT), which will be determined during the screening process.
* Participants must have an adequately stable condition and environment to enable attendance at scheduled clinic visits.
* Participants must be able to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participation in study procedures in English.
* If participants are on a medication regimen for comorbid symptoms, that regimen will be stable for the duration of the study and patient will be willing to remain on this regimen during the treatment phase.
* Participants must be fluent in English

Exclusion criteria:

* Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) contraindications: such as a cardiac pacemaker, cochlear implant, or an implanted device (deep brain stimulation, ferromagnetic metal in the head and body, claustrophobia, pregnant or breastfeeding or other ferromagnetic device/object in the head and body within 30 cm of the treatment coil.
* General medical condition, disease, or neurological disorder that interferes with the assessments or participation.
* Unable to safely withdraw, at least two weeks prior to treatment, from medications that increase seizure risk.
* Current substance abuse as determined by positive toxicology screen
* Have a mass lesion, cerebral infarct, or other active CNS disease, including a seizure disorder.
* A recent suicide attempt (defined as within the last 30 days) or presence of current suicidal plan or intent. Patients at risk for suicide will be required to establish a written safety plan involving their primary therapist before entering the study.
* Severe impediment to vision, hearing and/or hand movement, as this is likely to interfere with the ability to follow study protocols.
* Greater than mild traumatic brain injury (defined as greater than 10 minutes loss of consciousness).
* Taking benzodiazepines or neuroleptic medications, or any medication known to alter seizure threshold.
* Acute or unstable chronic illness.
* Current or lifetime history of bipolar disorder or psychosis.
* Participation in another concurrent intervention-based clinical trial.