Deep TMS Neuromodulation of Neural Circuits Associated With Stimulant Use Disorder

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.