Targeting Specific Brain Networks to Treat Specific Symptoms in Depression
Purpose
Repetitive transcranial magnetic stimulation (rTMS) is a way of non-invasively stimulating specific brain networks and is an established treatment for Major Depressive Disorder (MDD). This proposal will reveal network mechanisms of the therapeutic effects of rTMS by investigating how stimulating each network specifically changes network connectivity and behavior. This will be done in a highly individualized manner in depressed and healthy patients, leading to more effective and more individualized treatments for depression.
Condition
- Major Depressive Disorder
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
for healthy participants: - 18-65 years of age - Capacity to provide informed consent form to participate in the study Inclusion Criteria for participants with Major Depressive Disorder (MDD): - 18-65 years of age - Capacity to provide informed consent form to participate in the study - Currently in a major depressive episode. Comorbid anxiety disorders and personality disorders will be allowed provided that MDD is the primary diagnosis.
Exclusion Criteria
for all participants: - Meeting criteria, in the past or currently, for bipolar affective disorder, hypomania or mania. - Meeting criteria, in the past or currently, for a primary psychotic disorder (e.g., schizophrenia). - Neurological conditions with known structural brain lesions, e.g., intracranial masses, multiple sclerosis. - Any personal history of seizures or a family history of epilepsy in a first-degree relative. - Metal in the body that is ferromagnetic or metallic injury to the eyes. - Implanted pacemakers, medication pumps, vagal stimulators, deep brain stimulators, or ventriculoperitoneal shunts, etc. - Substance abuse or dependence that is current and active within the last six months, as indicated by self-report (e.g., heroin, cocaine, methamphetamines). - Inability to meet the safety criteria for MRI scanning for any other reason. - Severe or unstable medical illness. - Currently pregnant, as assessed with urine pregnancy test in women of childbearing age.
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Crossover Assignment
- Intervention Model Description
- Within-subject crossover study
- Primary Purpose
- Other
- Masking
- Double (Participant, Outcomes Assessor)
- Masking Description
- Participants will receive active or sham stimulation and will be blinded as to the stimulation type.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
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Experimental DLPFC Salience network target |
iTBS delivered four times daily to an individually defined salience network representation in left dorsolateral prefrontal cortex (DLPFC). |
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Experimental DLPFC Control network target |
iTBS delivered four times daily to an individually defined control network representation in left dorsolateral prefrontal cortex (DLPFC). |
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Experimental DLPFC Default network A target |
iTBS delivered four times daily to an individually defined default network A representation in left dorsolateral prefrontal cortex (DLPFC). |
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Experimental dmPFC Default network B target |
iTBS delivered four times daily to an individually defined default network B representation in left dorsomedial prefrontal cortex (DMPFC). |
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Experimental vmPFC limbic-reward network target |
iTBS delivered four times daily to an individually defined reward network representation in left ventromedial prefrontal cortex (vMPFC). |
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Sham Comparator SHAM stimulation |
SHAM iTBS delivered four times daily to an individually defined SHAM region in left dorsolateral prefrontal cortex (DLPFC). |
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Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- Massachusetts General Hospital
Study Contact
Detailed Description
Network models are increasingly invoked to characterize the neurobiological underpinnings of mental illnesses. Dysfunction within specific circuits promotes the formation of specific symptoms. This suggests an opportunity to treat specific symptoms by modulating specific circuits. Repetitive transcranial magnetic stimulation (rTMS) is capable of circuit-specific neuromodulation. It is also an established treatment for Major Depressive Disorder (MDD). Clinical experience suggests that rTMS treats different symptom constructs by stimulating different circuits. However, there remains a critical lack of mechanistic evidence to support putative network mechanisms of rTMS, limiting its ability to treat patients with more personalized and optimized approaches. This mechanistic proposal will first use resting-state functional connectivity (FC) MRI and customized analytic pipelines to characterize functional network topography in healthy and depressed individuals at high resolution.This data will be used to derive rTMS targets functionally situated in discrete prefrontal networks (e.g., control, default, salience, limbic/reward). Next, patients will take part in a within-subject design in which they undergo rTMS to each target on separate days. Each target will be stimulated four times on a given day, and after each stimulation changes will be measured with: (1) REST-BOLD MRI (to assess FC changes), (2) TASK-BOLD MRI (to assess changes in BOLD activation on paradigms validated to test RDoC constructs), (3) state-based questionnaires or (4) neuropsychological tests. This work will facilitate individualized neuromodulation approaches based on network topography. This will pollinate large-scale clinical trials assessing the effects of differential circuit modulation. It will also illuminate circuit-construct relationships across neuropsychiatric disorders.
