Mapsd Dual-target cTBS (Auditory Cortex and M1) for Generalized Anxiety Disorder

Официальное название

Efficacy and Neural Mechanisms of Neuroimage-guided Dual-target Continuous Theta Burst Stimulation (Auditory Cortex and M1) for Generalized Anxiety Disorder

Обзор

The purpose of this study is to investigate the effectiveness of a dual-target non-invasive brain stimulation technique called continuous Theta Burst Stimulation (cTBS) for treating Generalized Anxiety Disorder (GAD). The researchers will use a neuronavigation system, which acts like a GPS for the brain, to guide the stimulation to two specific targets: the left auditory association cortex and the primary motor cortex (M1). Participants will be randomly assigned to one of two groups. One group will receive active dual-target cTBS treatment, while the other will receive a sham (placebo) stimulation that feels similar but has no therapeutic effect. The treatment will be given three times a day for seven consecutive days. Before and after the treatment period, all participants will complete clinical questionnaires to measure their anxiety and undergo Magnetic Resonance Imaging (MRI) scans to help researchers understand how cTBS affects brain activity.

Подробное описание

This study is a randomized, triple-blind, sham-controlled trial designed to evaluate the efficacy and neural mechanisms of neuronavigation-guided dual-target continuous Theta Burst Stimulation (cTBS) in patients with Generalized Anxiety Disorder (GAD).

A total of participants diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) will be recruited. After providing informed consent, participants will be randomized in a 1:1 ratio to receive either active dual-target cTBS or sham cTBS.

The active intervention involves stimulating two sequential targets using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil:

Target 1 (Auditory Cortex): The first target is the left auditory association cortex (posterior superior temporal sulcus), located using a Brainsight neuronavigation system based on individual MRI scans transformed from MNI coordinates (-62, -40, 10).

Target 2 (M1): The second target is the primary motor cortex (M1), located at the site where the resting motor threshold (RMT) is determined.

Stimulation of the auditory cortex target will be immediately followed by stimulation of the M1 target. The cTBS protocol for each target consists of 3-pulse bursts at 50 Hz, repeated at a 5 Hz frequency, for a total of 600 pulses (40 seconds duration) per target. The stimulation intensity will be set at 100% of the individual's RMT. To achieve cumulative aftereffects, this dual-target protocol will be repeated three times per day with 15-minute intervals between sessions, for seven consecutive days.

The sham intervention will utilize an identical-looking sham coil that produces similar sounds and scalp sensations without inducing a significant magnetic field. The procedure, including neuronavigation, coil placement, and duration, is identical to the active group to maintain the triple-blind design (masking for participants, investigators, and outcomes assessors).

All participants will undergo comprehensive assessments at baseline, post-intervention, and follow-up. Assessments include clinical scales such as the Hamilton Anxiety Rating Scale (HAMA) and multimodal MRI (structural, rs-fMRI, and DTI) to examine neural network dynamics.

Вмешательства

• Устройство Active Dual-target cTBS
  A non-invasive brain stimulation technique using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil. Targets: 1. Left auditory association cortex (MNI: -62, -40, 10), located using Brainsight neuronavigation. 2. Primary Motor Cortex (M1), determined by the resting motor threshold (RMT) hotspot. Protocol: Stimulation of the auditory cortex is immediately followed by M1 stimulation. Each target receives a standard cTBS protocol (3-pulse 50 Hz bursts repeated at 5 Hz, total 60
• Устройство Sham Dual-target cTBS
  A placebo procedure using an inert sham coil that is identical in appearance and sound to the active coil but does not deliver a significant magnetic field to the cortex. Blinding: The procedure includes identical neuronavigation setup, dual-target coil positioning (Auditory Cortex then M1), duration, and treatment schedule (3 times/day for 7 days) to maintain the blind.

Первичные конечные точки

• Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Score [Срок оценки: Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up]
• Change from Baseline in Resting-State Neural Activity [Срок оценки: Baseline (Day 1) and Post-intervention (Day 9)]

Вторичные конечные точки (4)

• Change from Baseline in Hamilton Depression Rating Scale (HAMD-17) Score [Срок оценки: Baseline (Day 1) and Post-intervention (Day 9)]
• Change from Baseline in Self-Rating Anxiety Scale (SAS) Score [Срок оценки: Baseline (Day 1), Post-intervention (Day 9), and 2-week Follow-up]
• Change from Baseline in Patient Health Questionnaire-15 (PHQ-15) Score [Срок оценки: Baseline (Day 1) and Post-intervention (Day 9)]
• Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score [Срок оценки: Baseline (Day 1) and Post-intervention (Day 9)]

Критерии участия

Критерии включения

• Diagnosis of Generalized Anxiety Disorder (GAD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), confirmed by at least two psychiatrists.
• Hamilton Anxiety Rating Scale (HAMA) score > 14.
• Age between 18 and 60 years.
• Right-handed.
• More than 5 years of education.
• Patients are either medication-free or maintain a consistent medication regimen during cTBS treatment.
• Willing and able to provide written informed consent.
• Normal or corrected-to-normal visual acuity and hearing.

Критерии исключения

• Presence of other psychiatric disorders, such as substance abuse, schizophrenia, schizoaffective disorder, hysteria, autism, or bipolar disorder.
• History of epilepsy, seizures, or severe neurological diseases (e.g., stroke, organic brain lesions).
• Presence of severe somatic diseases, such as severe heart, liver, or renal insufficiency.
• Pregnant or lactating women.
• Contraindications to Transcranial Magnetic Stimulation (TMS) or Magnetic Resonance Imaging (MRI), such as the presence of a cardiac pacemaker, cochlear implant, cerebrovascular metal stent, or metal dentures.
• Inability to cooperate with experimental procedures due to conditions such as severe claustrophobia.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Anhui Medical University — Хэфэй

Публикации

• Neri F, Cappello C, Viberti F, Donniacuo A, Burzi L, Cinti A, Benelli A, Luca Smeralda C, Romanella S, Santarnecchi E, Mandala M, Rossi S. rTMS of the auditory association cortex improves speech intelligibility in patients with sensorineural hearing loss. Clin Neurophysiol. 2024 Apr;160:38-46. doi: 10.1016/j.clinph.2024.02.007. Epub 2024 Feb 9. PMID 38395005

Идентификаторы

NCT: NCT07403591 · AHMU-GAD-Dual-ACM1-2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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