Neuromodulation of Social Cognitive Circuitry in People with Schizophrenia Spectrum Disorders

精神分裂症谱系障碍患者社会认知回路的神经调节

• 批准号: 10580135
• 负责人: ROBERT W BUCHANAN
• 金额: $ 36.85万
• 依托单位: CENTRE FOR ADDICTION AND MENTAL HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10580135
• 关键词: Anatomy; Authorization documentation; Behavioral; Brain; Brain imaging; Brain region; Clinical Trials; Cognitive; Cognitive deficits; Exhibits; Goals; Impaired cognition; Impairment; Individual; Intervention; Knowledge; Lead; Location; Mental Health; Modality; Modeling; Multicenter Studies; National Institute of Mental Health; Neurobiology; Outcome Measure; Persons; Phase; Prefrontal Cortex; Randomized; Schizoaffective Disorders; Schizophrenia; Schizophreniform Disorder; Site; Social Functioning; Techniques; Testing; Work; brain circuitry; cognitive performance; improved; member; neural circuit; neuroregulation; novel strategies; novel therapeutic intervention; primary outcome; repetitive transcranial magnetic stimulation; schizophrenia-spectrum disorder; secondary outcome; social; trial comparing; uptake

PROJECT SUMMARY People with schizophrenia spectrum disorders (SSDs) (i.e., schizophrenia, schizoaffective disorder, schizophreniform disorder) exhibit considerable impairment in social functioning. Current treatments are minimally effective, and impairments tend to persist. Our recent collaborative multi-center study increased knowledge regarding the neurobiology of social cognitive (SCog) impairment in people with SSDs, identifying the neural circuitry of SCog impairments and their behavioral and functional correlates. The present study aims to use repetitive transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural circuitry of SCog impairments in people with SSDs. In the 2-year R61 phase of this application, we will randomize 60 people with SSDs to three groups: 20 to a conventional form of rTMS (i.e., 10Hz rTMS); 20 to a newer, more rapid form known as intermittent theta burst stimulation (iTBS); and 20 to either sham 10 Hz rTMS stimulation or sham iTBS. We will determine whether these treatments can change the functional connectivity of key SCog brain circuits by targeting a brain region known as the dorsomedial prefrontal cortex (DMPFC). Since each person’s anatomical and functional brain profile is slightly different, we will optimize the orientation and location of the placement of the brain stimulation coils in each individual, using novel approaches pioneered by members of our team and others, to maximize the impact on brain function. If we find that either form of active brain stimulation (compared to sham) we can changes functional connectivity in the hypothesized SCog brain circuit at a predetermined effect size, we will have achieved our ‘Go/No-Go criterion’ and will then request permission to proceed to the 3-year R33 phase. In the R33 phase, we will apply brain stimulation for 4 -weeks (5 days/week), carrying forward the brain stimulation modality which best engaged the target, and compare to sham. Wewill randomize 120 people with an SSD across our three sites. Our primary outcome measure will be SCog performance at the end of the four week period, and our secondary outcome measure will be FC change in SCog circuitry. We will determine if this treatment can lead to improvements in SCog performance in people with SSDs, and accompanying changes in FC of SCog circuitry. We will also evaluate SCog performance at 8 weeks to determine the sustained effect of brain stimulation. Overall, our proposal is modeled directly on the NIMH clinical trials target engagement framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs. iTBS) and individualizing coil placement for optimal targeting. We anticipate that brain stimulation will demonstrate target engagement, and potentially ameliorate SCog deficits in people with SSDs. The main goal of the current study is to demonstrate and optimize a novel therapeutic approach for SCog impairment, which we hope will ultimately lead to confirmatory efficacy work, and ideally broader uptake by mental health practitioners helping people with SSDs.

项目概要 患有精神分裂症谱系障碍 (SSD) 的人（即精神分裂症、分裂情感性 精神分裂症）表现出相当大的社会功能障碍。 目前的治疗效果甚微，而且我们最近的损伤往往会持续存在。 协作多中心研究增加了有关社会神经生物学的知识 SSD 患者的认知 (SCog) 障碍，识别 SCog 的神经回路 本研究旨在使用损伤及其行为和功能相关性。 重复经颅磁刺激 (rTMS) 是一种神经调节形式，可针对 SSD 患者 SCog 神经回路损伤的 2 年 R61 阶段。 应用程序中，我们将 60 名拥有 SSD 的人随机分为三组： 20 人为传统形式 rTMS（即 10Hz rTMS）；20 到一种更新、更快速的形式，称为间歇性 theta 爆发 刺激（iTBS）；以及 20 假 10 Hz rTMS 刺激或假 iTBS。 确定这些治疗是否可以改变关键 SCog 大脑的功能连接 通过针对称为背内侧前额叶皮层（DMPFC）的大脑区域的电路。 每个人的大脑解剖结构和功能都略有不同，我们会优化 每个人脑刺激线圈的放置方向和位置，使用 我们团队成员和其他人开创的新颖方法，以最大限度地提高对 如果我们发现任何一种形式的主动大脑刺激（与假手术相比），我们就可以 以预定效果改变 SCog 大脑回路中的功能连接 大小，我们将达到“通过/不通过标准”，然后请求许可继续进行 到 3 年 R33 阶段 在 R33 阶段，我们将应用脑刺激 4 周（5 周）。 天/周），推进最能吸引目标的大脑刺激方式，以及 与假的相比，我们将在我们的三个主要站点中随机抽取 120 名拥有 SSD 的人。 结果衡量标准将是四个星期结束时 SCog 的表现，我们的 次要结果指标是 SCog 电路中的 FC 变化，我们将确定这是否发生。 治疗可以改善 SSD 患者的 SCog 表现，并且 伴随 SCog 电路 FC 的变化，我们还将评估 SCog 在 8 时的性能。 几周来确定大脑刺激的持续效果总体而言，我们的建议是建模的。 直接关注 NIMH 临床试验目标参与框架，包括有关细节 测试大脑刺激参数（即 rTMS 与 iTBS）并个性化线圈放置 我们预计大脑刺激将展示目标参与度，以及 可能改善 SSD 患者的 SCOG 缺陷 当前研究的主要目标是 展示和优化 SCOG 损伤的新治疗方法，我们希望 最终将导致验证性功效工作，并理想地被心理健康领域更广泛地采用 治疗师帮助 SSD 患者。