Targeting Specific Brain Networks to Treat Specific Symptoms in Depression

Официальное название

Probing the Functional and Behavioral Impact of Precision Circuit Modulation in Neuropsychiatric Diseases

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Intermittent Theta Burst Stimulation (iTBS)
  iTBS is a form of non-invasive brain stimulation used to treat depression. It works on the principles of electromagnetic induction.

Первичные конечные точки

• Resting-state functional connectivity (FC) [Срок оценки: 1 hour]
• Blood oxygenation level dependent (BOLD) activation [Срок оценки: 1 hour]
• Applied Cognition-General Concerns scale [Срок оценки: 10 minutes]
• Profile of Mood States Tension subscale [Срок оценки: 5 minutes]
• Profile of Mood States Vigor subscale [Срок оценки: 5 minutes]
• Profile of Mood States Dejection subscale [Срок оценки: 5 minutes]
• State Shame and Guilt Scale [Срок оценки: 5-10 minutes]
• Fawcett-Clark Pleasure Capacity Scale [Срок оценки: 5-10 minutes]
• Digit-Span Test [Срок оценки: 5 minutes]
• Tower of London Task [Срок оценки: 5-10 minutes]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Massachusetts General Hospital — Boston

Публикации

• Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12. PMID 22160708
• Fox MD, Halko MA, Eldaief MC, Pascual-Leone A. Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage. 2012 Oct 1;62(4):2232-43. doi: 10.1016/j.neuroimage.2012.03.035. Epub 2012 Mar 19. PMID 22465297

Идентификаторы

NCT: NCT05523817 · 2022P002110 · 1R01MH129367-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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