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.

项目摘要 精神分裂症患者（SSD）（即精神分裂症，精神分裂症） 障碍，精神分裂症）在社会功能方面表现出很大的损害。 当前的治疗方法最少有效，损害往往会持续存在。我们的最新消息 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）损害，识别SCOG的神经回路 障碍及其行为和功能相关。本研究旨在使用 重复的经颅磁刺激（RTMS），一种神经调节形式，以靶向 SSD患者的SCOG障碍的神经回路。在这两年的R61阶段 应用程序，我们将将60名SSD的人随机为三个组：20个传统表格 RTMS（即10Hz RTMS）; 20到新的，更迅速的形式，称为间歇性theta爆发 刺激（ITB）；和20个假手术10 Hz RTMS刺激或假ITB。我们将 确定这些处理是否可以改变关键SCOG大脑的功能连接性 通过靶向被称为背部前额叶皮层（DMPFC）的大脑区域的电路。自从 每个人的解剖学和功能性的大脑曲线都略有不同，我们将优化 大脑刺激线圈在每个个体中放置的方向和位置，使用 我们团队成员和其他人开创的新颖方法，以最大程度地影响 大脑功能。如果我们发现两种形式的主动脑刺激（与假手术相比），我们可以 在预定的效果下改变了假设的SCOG脑电路的功能连通性 大小，我们将实现“ GO/No-Go Criterion”，然后请求允许继续进行 到3年R33阶段。在R33阶段，我们将对4周应用大脑刺激（5个 天/周），继续进行大脑刺激方式，最能参与目标，并且 比较假。我们将在我们的三个站点中随机将120人随机使用SSD。我们的主要 结果措施将是在四个星期结束时的SCOG表现，而我们的 次要结果度量将是SCOG电路的FC变化。我们将确定这是否 治疗可以改善SSD患者的SCOG性能，以及 参与SCOG电路FC的变化。我们还将在8点评估SCOG性能 几周来确定大脑刺激的持续作用。总体而言，我们的建议是建模的 直接在NIMH临床试验中目标参与框架，包括有关 测试大脑刺激参数（即RTMS vs. ITB）和个性化线圈的位置 最佳目标。我们预计大脑刺激将证明目标参与，并且 潜在的改善SCOG在患有SSD的人中定义。当前研究的主要目标是 演示和优化一种新型的SCOG损伤热方法，我们希望这 最终将导致确认有效性工作，并因心理健康而更广泛地吸收 从业者帮助患有SSD的人。