Probing the Functional and Behavioral Impact of Precision Circuit Modulation in Neuropsychiatric Diseases
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Major Depressive Disorder
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Blood oxygenation level dependent (BOLD) activation
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
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.
Investigators
Mark C. Eldaief, MD
Assistant Professor of Neurology
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Blood oxygenation level dependent (BOLD) activation
Time Frame: 1 hour
Changes in activation resulting from performing a specific functional MRI (fMRI) task
Delayed Match to Sample Task
Time Frame: 5 minutes
Subjects match patterns to a recently viewed sample pattern. Score ranges from 0-30, with higher scores indicating better performance.
Applied Cognition-General Concerns scale
Time Frame: 10 minutes
Subjects rate how statements about cognition and attention apply to them, e.g., "Thinking is foggy." Score range is 8-40, with higher scores indicating lesser cognitive concerns.
Fawcett-Clark Pleasure Capacity Scale
Time Frame: 5-10 minutes
Subjects anticipate how much they would enjoy a certain scenario, e.g., "you sit watching a beautiful sunset in an isolated part of the world." Score range is 36 to 180, higher scores indicate higher pleasure capacity.
Face-name Associative Paradigm
Time Frame: 30 minutes
Subjects must remember names paired with certain faces (DN-A). Scores range from 0-32, with higher scores indicating better performance.
Reading the Mind Through the Eyes Test
Time Frame: 10 minutes
Subjects judge another person's mental state by looking at pictures of only their eyes. Score ranges from 0-41, higher scores indicate better performance.
Profile of Mood States Vigor subscale
Time Frame: 5 minutes
Subjects rate how much mood adjectives apply to them at that moment, e.g., "full of pep," "energetic," "vigorous." Score range 0-28, higher scores indicating more vigor.
Digit-Span Test
Time Frame: 5 minutes
Subjects repeat number lists in forward or reverse order (maximum score is 8 forwards and 8 backwards, higher scores indicate better performance).
The Simon Test
Time Frame: 5 minutes
Subjects press different buttons based on incongruent spatial and/or color cues. Scores range from 0-30, with higher scores indicating better performance.
Resting-state functional connectivity (FC)
Time Frame: 1 hour
Changes in connectivity within and between brain networks
Profile of Mood States Dejection subscale
Time Frame: 5 minutes
Subjects rate how much mood adjectives apply to them at that moment, e.g., "unworthy." Score range 0-28, higher scores indicating higher dejection.
State Shame and Guilt Scale
Time Frame: 5-10 minutes
Subjects rate how much certain statements apply to them, e.g., "I feel regret." Score range is 10-50, higher scores indicate more shame/guilt.
Tower of London Task
Time Frame: 5-10 minutes
Subjects plan a series of moves to match a start set to a goal set.
Profile of Mood States Tension subscale
Time Frame: 5 minutes
Subjects are asked to rate how much certain adjectives about their mood apply to them at that moment, e.g., "tense", "nervous", "shaky." Score range: 0-28, higher scores indicating more tension.