Brain Imaging of rTMS Treatment for Depression

Not Applicable

Completed

Brief Summary: The overarching goal of this research program is to elucidate causal and directional neural network- level abnormalities in depression, and how they are modulated by an individually-tailored, circuit-directed intervention. By using concurrent TMS and fMRI, the investigators can overcome a major limitation of neuroimaging - the inability to demonstrate causality. The investigators' findings will serve as a platform for future studies wherein TMS treatment can be directly guided by the investigators' ability to image and causally manipulate specific neural networks.

Aim 1: To examine causal interactions between two major brain networks in depression.

Aim 2: To examine the impact of antidepressant TMS on causal network abnormalities in depression.

Hypothesis 1: Depressed subjects will show blunted responses, compared to healthy controls, in two targeted and interacting networks, using concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI).

Hypothesis 2: Treatment of patients with high-frequency repetitive TMS (rTMS) will result in normalization of baseline network-level deficits, and be predicted by degree of baseline network abnormalities.

Detailed Description: This study has a single primary outcome measure and other measures are exploratory. Previous versions of this study record incorrectly listed some exploratory outcome measures as secondary.

Recruitment & Eligibility

Inclusion Criteria

Men and women, ages 18 to 50
Depression assessed through phone screen
Must comprehend English well to ensure adequate comprehension of the fMRI and TMS instructions, and of clinical scales
Has failed >1 previous adequate antidepressant medication trials
Right-handed
No current or history of neurological disorders
No seizure disorder or risk of seizures

Exclusion Criteria

Any contraindication to being scanned in the 3T scanners at the Lucas Center or CNI such as having a pacemaker or implanted device that has not been cleared for scanning at the Lucas Center or CNI
Any unstable medical condition, any significant CNS neurological condition such as stroke, seizure, tumor, hemorrhage, multiple sclerosis, etc
Current rTMS treatment or prior treatment failure with rTMS
Current electroconvulsive therapy (ECT) or prior treatment failure with ECT
Currently pregnant or breastfeeding

Arm && Interventions

Group	Intervention	Description
rTMS Treatment	rTMS Treatment	rTMS will be delivered for 20 sessions over 4 weeks. Active 10 Hz rTMS will be delivered using neuro-navigation based on participants' own fMRI images. Daily treatment regiments will last 36.5 minutes and rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sessions for adverse events and/or side effects.
Sham Treatment	Sham rTMS Treatment	rTMS will be delivered for 20 sessions over 4 weeks. Placebo 10Hz rTMS will be delivered through sham stimulation electrodes. The rTMS coil will be positioned using neuro-navigation based on participants' own fMRI images, mimicking active rTMS treatment. Daily treatment regiments will last 36.5minutes and sham rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sham sessions for adverse events and/or side effects. Upon completing the sham 20 sessions participants are unblinded and offered 20 further treatments of guaranteed open-label treatment. The open-label treatment would follow the active rTMS treatment protocol.

Primary Outcome Measures

Name	Time	Method
Clinician Administered HAM-D	Baseline; Day 10; Day 20	The Hamilton Depression Rating Scale (HAM-D) is a 24-item clinician-administered assessment utilized as a way of determining a patient's level of depression before, during, and after treatment. It takes approximately 15-20 minutes to complete the interview and score the results. Subscale scores are 0-2 (10 questions), 0-3 (2 questions), and 0-4 (12 questions). Subscales are totaled for an overall score (range 0 -76). For the overall score and all subscales, lower scores correspond to fewer symptoms, and higher scores correspond more symptoms.

Secondary Outcome Measures

Name	Time	Method