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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
80
iTBS is a form of non-invasive brain stimulation used to treat depression. It works on the principles of electromagnetic induction.
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGResting-state functional connectivity (FC)
Changes in connectivity within and between brain networks
Time frame: 1 hour
Blood oxygenation level dependent (BOLD) activation
Changes in activation resulting from performing a specific functional MRI (fMRI) task
Time frame: 1 hour
Applied Cognition-General Concerns scale
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.
Time frame: 10 minutes
Profile of Mood States Tension subscale
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.
Time frame: 5 minutes
Profile of Mood States Vigor subscale
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.
Time frame: 5 minutes
Profile of Mood States Dejection subscale
Subjects rate how much mood adjectives apply to them at that moment, e.g., "unworthy." Score range 0-28, higher scores indicating higher dejection.
Time frame: 5 minutes
State Shame and Guilt Scale
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.
Time frame: 5-10 minutes
Fawcett-Clark Pleasure Capacity Scale
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.
Time frame: 5-10 minutes
Digit-Span Test
Subjects repeat number lists in forward or reverse order (maximum score is 8 forwards and 8 backwards, higher scores indicate better performance).
Time frame: 5 minutes
Tower of London Task
Subjects plan a series of moves to match a start set to a goal set.
Time frame: 5-10 minutes
Delayed Match to Sample Task
Subjects match patterns to a recently viewed sample pattern. Score ranges from 0-30, with higher scores indicating better performance.
Time frame: 5 minutes
The Simon Test
Subjects press different buttons based on incongruent spatial and/or color cues. Scores range from 0-30, with higher scores indicating better performance.
Time frame: 5 minutes
Face-name Associative Paradigm
Subjects must remember names paired with certain faces (DN-A). Scores range from 0-32, with higher scores indicating better performance.
Time frame: 30 minutes
Reading the Mind Through the Eyes Test
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.
Time frame: 10 minutes
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