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.

项目总结 患有精神分裂症谱系障碍(SSD)的人(即精神分裂症、分裂情感 精神障碍、分裂样障碍)表现出相当大的社会功能障碍。 目前的治疗效果微乎其微，而且损伤往往会持续下去。我们最近 协作的多中心研究增加了关于社会的神经生物学的知识 SSD患者的认知(SCOG)损害，确定SCOG的神经回路 损伤及其行为和功能的相关性。本研究旨在使用 重复经颅磁刺激(RTMS)，一种神经调节形式，靶向于 固态硬化症患者SCOG损害的神经回路。在此的2年R61阶段 应用程序，我们将60名SSD患者随机分为三组：20名为常规形式 RTMS(即10赫兹rTMS)；20到一种更新、更快速的形式，称为间歇性theta爆发 刺激(ITBS)；20至假10 HzrTMS刺激或假ITBS。我们会 确定这些治疗是否可以改变关键的SCOG脑的功能连接 通过瞄准被称为背内侧前额叶皮质(DmPFC)的大脑区域进行环路。自.以来 每个人的解剖和功能大脑轮廓略有不同，我们将优化 在每个个体中放置脑刺激线圈的方向和位置，使用 由我们的团队成员和其他人开创的新方法，以最大限度地提高 大脑功能。如果我们发现任何一种活跃的大脑刺激形式(与假刺激相比)，我们都可以 以预定的效果改变假想的SCOG脑回路中的功能连接 大小，我们将达到我们的‘去/不去标准’，然后将请求许可继续进行 到3年的R33阶段。在R33阶段，我们将实施为期4周的脑刺激(5 天/周)，推广最适合目标的脑刺激方式，以及 与Sham相比。我们将在我们的三个网站上随机选择120名使用SSD的人。我们的初选 结果衡量标准是四周结束时的SCOG表现，我们的 次要结果测量将是SCOG电路中的FC变化。我们将确定这是否 治疗可以改善SSD患者的SCOG表现，以及 随之而来的是SCOG电路FC的变化。我们还将在8点评估SCOG的表现 以确定脑刺激的持续效果。总体而言，我们的提案是以 直接在NIMH临床试验目标参与框架上，包括关于 测试脑刺激参数(即rTMS与ITBS)和个性化线圈放置 最佳目标。我们预计，脑刺激将展示目标参与，以及 潜在地改善SSD患者的SCOG缺陷。当前研究的主要目标是 展示和优化一种治疗SCOG损伤的新方法，我们希望 最终将导致验证性疗效工作，理想情况下将被心理健康人员更广泛地接受 帮助人们使用固态硬盘的从业者。