Mini Theta Burst TMS in MDD Patients (NARSAD)

This is not a treatment study. In this study, the researchers are primarily interested in examining whether functional MRI (fMRI)-guided transcranial magnetic stimulation (TMS) may be more effective than traditional TMS methods at temporarily influencing neural circuit communication. The investigators test this by combining TMS and fMRI technologies to probe and modulate brain activity. If the novel fMRI-guided TMS stimulation used in this study is more effective than traditional methods, future studies may utilize similar personalized TMS targeting methods to yield even better clinical outcomes.

Non-invasive transcranial magnetic stimulation (TMS) is now FDA-approved for the treatment of major depressive disorder (MDD). However, there is growing evidence that the targeting strategy for delivering TMS treatment may yield superior clinical outcomes if it is tailored to individual neuroanatomy. In this observational study, the investigators plan to examine this theory by using individualized TMS targets created from participants' own fMRI scans. This is not a treatment study, and stimulation is not designed to provide treatment in this study. Instead, the TMS delivery is meant to temporarily modify brain circuit communication between the lateral prefrontal cortex and subcortical structures. The research team administers TMS inside of the MRI scanner to prove that this pathway can be influenced non-invasively with TMS. These subcortical structures are important to affective disorder, and may contribute to the symptoms that patients suffering from depression are experiencing. The researchers hope that this innovative TMS research will confirm neural networks important to affective disorders, and guide future treatment options.

All subjects receive active TMS to the novel fMRI-guided targeting site. Participants will first receive TMS in the MRI scanner, then over the course of three consecutive "mini TMS" days, and lastly in a final MRI scan.

The study uses a modified repetitive TMS stimulation protocol. Participants receive active TMS on five separate days: a baseline TMS/ fMRI scan, three "mini TMS" sessions, and a final TMS/ fMRI scan. Again, this level of stimulation is considered to be sub-threshold for that of a TMS treatment protocol.

Evoked response (change in functional brain activity) to TMS performed at an fMRI-guided brain target, measured using fMRI

Evoked functional brain activity to TMS, compared from the baseline fMRI scan to the final fMRI scan following the three day mini-TMS stimulation

Correlation of change in MDD symptoms from baseline to final fMRI visit, and change in evoked brain response to TMS from baseline to final fMRI scan

Inclusion Criteria: 18 to 60 years old, inclusive Right-handed Currently experiencing a major depressive episode (MDD) Capacity to give informed consent and follow study procedures Command of English language to understand/ respond to written and verbal instructions Exclusion Criteria: MRI contraindications (i.e., metal in body, claustrophobia, etc.) TMS contraindications (i.e., seizure disorder) Diagnosis of exclusionary psychiatric disorder (i.e., schizophrenia, bipolar) Current use of psychiatric medication and unable/ willing to safely withdraw Refusal to abstain from alcohol or drugs for duration of study Medication use that reduces seizure threshold Medication that interferes with blood flow (i.e., opioids, antihypertensive) Known neurological disorder or significant disability that interferes with study procedures Woman who is pregnant or breastfeeding