Bryan R. Barksdale, Lauren Enten, Annamarie DeMarco, Rachel Kline, Manoj K. Doss, Charles B. Nemeroff, Gregory A. Fonzo
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In a target engagement study, magnetic resonance imaging (MRI)-guided tFUS to the left amygdala was administered during functional MRI (tFUS/fMRI) to test for acute modulation of blood oxygenation level dependent (BOLD) signal in a double-blind, within-subject, sham-controlled design in patients with MATRDs (N = 29) and healthy comparison subjects (N = 23). In an unblinded treatment trial, the same patients then underwent 3-week daily (15 sessions) MRI-guided repetitive tFUS (rtFUS) to the left amygdala to examine safety, feasibility, symptom change, and change in amygdala reactivity to emotional faces. Active vs. sham tFUS/fMRI reduced, on average, left amygdala BOLD signal and produced patient-related differences in hippocampal and insular responses. rtFUS was well-tolerated with no serious adverse events. 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引用次数: 0
摘要
情绪、焦虑和创伤相关障碍(matrd)是非常普遍和合并症。相当数量的患者对一线治疗没有反应。非侵入性神经调节是一种二线治疗方法,但目前的方法依赖于皮质靶点来间接调节皮质下结构,例如与matds有关的杏仁核。低强度经颅聚焦超声(tFUS)是一种直接皮质下神经调节的无创技术,但其安全性、可行性和作为潜在治疗方法的前景在很大程度上是未知的。在一项目标参与研究中,在功能MRI (tFUS/fMRI)期间,在磁共振成像(MRI)引导下,将tFUS植入左杏仁核,在双盲、受试者内、假对照设计中,对患有MATRDs的患者(N = 29)和健康对照受试者(N = 23)进行血氧水平依赖(BOLD)信号的急性调节测试。在一项非盲治疗试验中,同样的患者接受了为期3周的每日(15个疗程)mri引导下的左侧杏仁核重复tFUS (rtFUS),以检查安全性、可行性、症状变化以及杏仁核对情绪化面孔的反应性变化。主动与假tFUS/fMRI平均减少左杏仁核BOLD信号,并产生海马和岛岛反应的患者相关差异。rtFUS耐受性良好,无严重不良事件。主要转归(情绪与焦虑症状问卷一般困扰量表;p = 0.001, Cohen’s d = 0.77)、次要结果(Cohen’s d = 0.43-1.50)和杏仁核对情绪刺激的激活。研究结果提供了tFUS调节杏仁核功能的初步证据,rtFUS在matrd中的安全性和可行性,并激励双盲随机对照试验来检验其有效性
Low-intensity transcranial focused ultrasound amygdala neuromodulation: a double-blind sham-controlled target engagement study and unblinded single-arm clinical trial
Mood, anxiety, and trauma-related disorders (MATRDs) are highly prevalent and comorbid. A sizable number of patients do not respond to first-line treatments. Non-invasive neuromodulation is a second-line treatment approach, but current methods rely on cortical targets to indirectly modulate subcortical structures, e.g., the amygdala, implicated in MATRDs. Low-intensity transcranial focused ultrasound (tFUS) is a non-invasive technique for direct subcortical neuromodulation, but its safety, feasibility, and promise as a potential treatment is largely unknown. In a target engagement study, magnetic resonance imaging (MRI)-guided tFUS to the left amygdala was administered during functional MRI (tFUS/fMRI) to test for acute modulation of blood oxygenation level dependent (BOLD) signal in a double-blind, within-subject, sham-controlled design in patients with MATRDs (N = 29) and healthy comparison subjects (N = 23). In an unblinded treatment trial, the same patients then underwent 3-week daily (15 sessions) MRI-guided repetitive tFUS (rtFUS) to the left amygdala to examine safety, feasibility, symptom change, and change in amygdala reactivity to emotional faces. Active vs. sham tFUS/fMRI reduced, on average, left amygdala BOLD signal and produced patient-related differences in hippocampal and insular responses. rtFUS was well-tolerated with no serious adverse events. There were significant reductions on the primary outcome (Mood and Anxiety Symptom Questionnaire General Distress subscale; p = 0.001, Cohen’s d = 0.77), secondary outcomes (Cohen’s d of 0.43–1.50), and amygdala activation to emotional stimuli. Findings provide initial evidence of tFUS capability to modulate amygdala function, rtFUS safety and feasibility in MATRDs, and motivate double-blind randomized controlled trials to examine efficacy.
期刊介绍:
Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.