An observational study in Depression, Depressive Disorder, Treatment-Resistant and COVID Stress, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years to 89 Years. Per ClinicalTrials.gov, last updated 2026-08-03.
Sponsored by VA Office of Research and Development · Observational
There are two protocols, one involving rTMS therapy in people with treatment resistant depression and one involving tDCS in people with stress from the COVID 19 pandemic.
Clinic-Based rTMS Therapy: Repetitive pulse transcranial magnetic stimulation (rTMS) is a noninvasive treatment that involves stimulating the brain; however, treatment benefit depends on placing a TMS coil in the correct place on the head to reach critical brain regions below. Clinicians typically use scalp-based targeting, a process in which rather than using MRI guidance to target brain regions for stimulation, they use landmarks on the scalp. Several researchers, including the investigators' lab, showed that the current scalp-based targeting techniques do not position stimulation above the correct brain region, and patients fail to respond. The investigators propose to improve clinical scalp-based targeting by comparing it to MRI guided targeting. The most common clinical population receiving rTMS therapy is depressed patients. The investigators' plan is to study the accuracy of certain scalp-based rules in patients with depression. Accurate brain stimulation targeting is critical for effective rTMS therapy.
Home-Based Neuromodulation: For participants who are not undergoing rTMS therapy who have COVID-19 distress, we are offering a combined home-based neuromodulation (transcranial electrical stimulation) and focused psychotherapy program dedicated to improving the same outcome measure, quality of life. Transcranial electrical stimulation (tES) stimulates the brain over a large region; however, we are able to model with brain imaging which brain regions receive the strongest stimulation. Our goal is still to examine stimulation precision, but we will test whether strength of tES in the same brain regions that rTMS is targeting will also lead to improved quality of life. We will also carefully assess whether it is possible to measure healthy functioning, an outcome in the rTMS study, because sheltering in place may reduce activities and thus distort our measure. We will also test whether our psychotherapy intervention will mitigate this effect and, if so, we may make it available to all those depressed Veterans in whom we're studying the effect of neuromodulation on functioning.
Potential participants are first identified and contact is made. Potential participants are then screened for inclusionary and exclusionary information (see tab 9. Eligibility) that relate to whether they can safely and comfortably perform the procedures and whether they are considered healthy or have the disorder for which brain stimulation therapy will be delivered. They will undergo informed consent that will disclose all the different risks and benefits for the procedures they will undergo. The list of procedures in which participants consent to participate is below. Participants may do either or both of the activities detailed below.
PROCEDURES:
For participants in the MRI and TMS targeting activity:
Psychological / functional assessments:
Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
TMS-transcranial magnetic stimulation which will be collected at the Palo Alto VA. Part of this procedure may include electromyography (EMG) which involves placing electrodes on the skin, typically the hand, and measuring indicators of muscle contraction. Sometimes this information is used to decide stimulation intensity during TMS and sometimes the TMS induced response will be a source of data in itself. Typically, this is only a measure conducted in parallel with other procedures and thus will not be given its own consent. MRI Guided TMS. An MRI will be used to target a selective brain region. To accomplish this, the MRI will be displayed on a computer screen and an infrared camera enables identification of the correspondence between the image and the participant's head. To study errors in scalp-based targeting, the investigators will perform scalp targeting while under MRI guidance but without the typical visual feedback provided by the MRI. Then this will be compared to scalp targeting with MRI guidance. The difference will identify typical errors in scalp targeting. Typically, a session will last approximately 1.5 hours.
For participants in the home-based neuromodulation and focused psychotherapy program:
Psychological / functional assessments:
Interview, computerized, and paper and pencil measures of psychological functioning. These measures are used to characterize patients' diagnosis and psychological status. For example, depressed patients will answer questions about depressive symptoms and potentially comorbid symptoms such as post-traumatic stress disorder. This testing typically lasts 2 hours.
8,059 studies on the registry are indexed under Depression; 1,643 are open to participants now.
This study's enrollment of 54 is below the median of 160 across 1,084 observational studies indexed under Depression.
Browse Depression studies →VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.
Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
Veteran patients with depression or COVID-19-related distress
Inclusion Criteria:
Cohort 1:
Capacity and willingness to participant in TMS, and fMRI as well as satisfying criteria for diagnosis.
Cohort 2:
Exclusion Criteria:
If their language is not primarily English they may be excluded depending on how dependent the imaging and cognitive tasks are on language
For TMS the investigators will follow safety guidelines set by Rossi et. al.,2009
Lifetime history of moderate or severe traumatic brain injury, current unstable medical conditions, current (or past if appropriate) significant neurological disorder, or lifetime history of:
Exclusion Criteria for Cohort 2:
Have a lifetime diagnosis of:
Patients with treatment resistant major depression
Behavioral: Psychological / Functional Assessment · Other: Structural and Functional MRI · Device: Transcranial Magnetic Brain Stimulation and MR Image Guidance
Veterans with COVID-19-related distress
Behavioral: Psychological / Functional Assessment · Other: Structural and Functional MRI · Device: Transcranial Electrical Stimulation (tES)
Psychological and functional assessment battery to characterize participants.
Structural and functional magnetic resonance imaging session.
MRI guided transcranial magnetic stimulation and measurement of targeting accuracy.
Home-based Transcranial Direct Current Stimulation
Acceptable distance between TMS treatment location and brain target: Anticorrelation with Subgenual Cingulate
Targeting accuracy was defined as being within 1.36 cm which is within the resolution of the TMS coil and which should be achievable based on work by Mir-Moghtadaei et al 2015 comparing to a fixed coordinate. The anticorrelation with the subgenual cingulate is a resting-state functional connectivity-based target that has evidence of being effective in reducing depression (Cash et al, 2020)
Time frame: [Within a week of clinical measures]
Acceptable distance between TMS treatment location and brain target: fMRI Emotional Working Memory
Targeting accuracy was defined as being within 1.36 cm which is within the resolution of the TMS coil and which should be achievable based on work by Mir-Moghtadaei et al 2015 comparing to a fixed coordinate. The peak fMRI coordinate will be identified within an a priori left dorsolateral prefrontal brain region. The fMRI Emotion Working Memory task involves holding in mind emotional and nonemotional images has been demonstrated to have strong cross-site reliability (Brown et al, 2011).
Time frame: [Within a week of clinical measures]
Correlation between change in World Health Organization Disability Assessment Schedule 2.0 (WHODAS) and distance from optimal TMS brain targets
The WHODAS is an assessment of global functioning (range from 0 to 100 \[0 = no disability, 100 = full disability\]). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Time frame: Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.
Correlation between change in Veterans RAND 36-Item (VR-36) and distance from optimal TMS brain targets
The VR-36 is an assessment of self-reported health-related quality of life. Physical and Mental Component Scores (PCS and MCS) are normed (x = 50, sd = 10) and range from 0 to 100 (0 = worst health, 100 = best health). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Time frame: Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.
Correlation between change in the Hamilton Depression Rating Scale-17 Items (HAMD-17) and distance from optimal TMS brain targets
The HAMD-17 is a clinician-administered depression symptom assessment scale. Total score ranges from 0 (no depressive symptoms) to 52 (severe depressive symptoms). The distance derived from the primary outcome analyses to look at precision will be applied as a continuous variable to correlate with change in the outcome measure from pre to post rTMS therapy targeted clinically with the Beam F3.
Time frame: Within one week before beginning clinical rTMS therapy and within one week after rTMS therapy termination.
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