Overview

This study originally included 100 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data was utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. This was the only study group until August 30, 2022, and the primary outcome was analyzed for the 10Hz-TMS group.

Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed intermittent theta burst (iTBS), in September 2022 a second group was added to include patients receiving this new form of TMS. This second group included another 100 patients with medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data will be utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement.

Eligibility

Inclusion Criteria:

1. Male or female
2. Aged 18-70.
3. Have previously received or will receive TMS to the left dorsal-lateral prefrontal cortex as part of the clinical treatment program at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for treatment of medication resistant depression

Exclusion Criteria:

1. History of bipolar disorder (lifetime), schizophrenia or psychosis (lifetime), obsessive-compulsive disorder (unstable in past six months), posttraumatic stress disorder (unstable in past six months), eating disorders (unstable in past six months), or moderate to severe substance use disorders (currently active, with the exception of nicotine and cannabis)
2. Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke, Alzheimer's Disease, tumor, multiple sclerosis, epilepsy). Of note, many of these are also contraindications to receiving TMS and these patients would not be enrolled in the clinical treatment program.
3. Patients who are pregnant or lactating (by menstrual history)
4. Current abuse of an illicit substance (e.g. marijuana, cocaine, heroin, hallucinogens, psychostimulants)
5. Positive MRI screen that would preclude the subject from undergoing magnetic resonance imaging. These include, but are not limited to any of the following:
   1. Known metal in the head (such as a surgical aneurysm clip), or a history of prior neurosurgical procedures
   2. Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means such as: cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts
   3. Subjects who have or might have bullet fragments or other metal fragments (veterans or workers exposed to metal in their work environment)
   4. Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)
   5. Subjects expressing significant anxiety or claustrophobia about being in the magnet.
6. Subjects that cannot adhere to the experimental protocol for any reason.