Repetitive Transcranial Magnetic Stimulation as a Probe of Episodic Memory Neurocircuitry in Schizophrenia

重复经颅磁刺激作为精神分裂症情景记忆神经回路的探针

• 批准号: 9894111
• 负责人: Michael M Francis
• 金额: $ 19.81万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-17 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894111
• 关键词: Affect; Anterior; Brain; Brain region; Chronic; Clinical; Clinical Trials; Cognitive; Data; Development; Employment; Episodic memory; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impaired cognition; Impairment; Independent Living; Individual; Intervention; Light; Memory impairment; Mental disorders; Neurobiology; Occupational; Outcome; Performance; Phase; Physiological; Play; Prefrontal Cortex; Psychotic Disorders; Research Personnel; Rest; Role; Schizophrenia; Structure; Task Performances; Therapeutic; Translating; Wages; cingulate cortex; cognitive performance; compliance behavior; episodic memory impairment; improved; innovation; insight; neural network; relating to nervous system; repetitive transcranial magnetic stimulation; response; social

Project Abstract Schizophrenia is a disabling illness associated with impairments in independent living and functioning. Episodic memory (EM) is an important cognitive domain commonly impaired in schizophrenia. The precuneus is a key node in EM circuitry that has reciprocal connections with other EM relevant structures, including the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). Alterations in precuneus connectivity are associated with EM deficits in schizophrenia. However, the exact mechanisms by which precuneus dysfunction is related to EM impairment is unclear. There is a critical need to better define the neural underpinnings subserving this clinical phenomenon. Repetitive transcranial magnetic stimulation (rTMS) enables direct manipulation of local brain activation and indirect manipulation of activation in the target's associated neural networks. This creates an opportunity to effect disparate physiologic changes in brain circuits, clarifying the role of disrupted neural structures and networks in psychiatric illness. Our objectives are to demonstrate that rTMS engages the precuneus and to clarify the mechanisms underlying EM dysfunction in schizophrenia. Our central hypotheses are that rTMS will modulate functional activation of the precuneus and connectivity with associated EM circuitry. We will also examine the effect of rTMS on EM performance. Our long-term goal is to provide a path for investigators considering the precuneus as a potential target for the treatment of EM dysfunction in schizophrenia. In Aim 1, we will demonstrate the impact of rTMS targeting the precuneus on functional activation during performance of an in-scanner EM task. We hypothesize that rTMS will modulate precuneus activity, serving as evidence of rTMS target engagement. We expect that, compared to sham stimulation, 1 Hz rTMS will decrease activation and 20 Hz rTMS will increase activation of the precuneus. In Aim 2, we will demonstrate the effects of rTMS on precuneus functional connectivity in individuals with schizophrenia. We hypothesize that rTMS will alter resting state functional connectivity between the precuneus and associated EM circuitry, specifically the DLPFC and the ACC. We expect that, compared to sham stimulation, functional connectivity at rest between the precuneus, the DLPFC, and the ACC will decrease in response to 1 Hz rTMS and increase in response to 20 Hz rTMS. In Aim 3, we will demonstrate the effect of rTMS on EM performance in schizophrenia. We hypothesize that precuneus rTMS will be associated with changes in EM performance. We expect that compared to sham stimulation, 1 Hz rTMS will impair performance and that 20 Hz rTMS will improve performance during an in-scanner EM task. This study will provide evidence that rTMS modulates activity within the precuneus and associated EM circuitry in individuals with schizophrenia. This will inform subsequent clinical trials targeting the precuneus for the treatment of EM dysfunction in schizophrenia.

项目摘要 精神分裂症是一种与独立生活和功能障碍有关的致残性疾病。 情节记忆（Episodic memory，EM）是精神分裂症患者常见的重要认知功能障碍。楔前叶 是EM电路中的关键节点，其与其他EM相关结构（包括 背外侧前额叶皮层（DLPFC）和前扣带皮层（ACC）。楔前叶改变 连接与精神分裂症中的EM缺陷相关。然而，确切的机制， 楔前叶功能障碍与EM损伤的关系尚不清楚。迫切需要更好地界定 神经基础支持这种临床现象。 重复经颅磁刺激（rTMS）可以直接操纵局部大脑激活 以及间接操纵目标相关神经网络的激活。这就创造了一个机会 在大脑回路中产生不同的生理变化，澄清破坏神经结构的作用， 精神疾病的网络我们的目标是证明rTMS参与楔前叶， 阐明精神分裂症EM功能障碍的潜在机制。我们的中心假设是，rTMS将 调节楔前叶的功能激活和与相关EM电路的连接。我们还将 检查rTMS对EM性能的影响。我们的长期目标是为调查人员提供一条道路， 认为楔前叶是治疗精神分裂症EM功能障碍的潜在靶点。 在目标1中，我们将证明靶向楔前叶的rTMS对功能激活的影响 在执行扫描仪内EM任务期间。我们假设rTMS会调节楔前叶的活动， 作为rTMS目标参与的证据。我们预计，与假刺激相比，1 Hz rTMS 将减少激活，20 Hz rTMS将增加楔前叶激活。在目标2中，我们将 证明了rTMS对精神分裂症患者楔前叶功能连接的影响。我们 假设rTMS将改变楔前叶和相关的神经元之间的静息状态功能连接， EM电路，特别是DLPFC和ACC。我们预计，与假刺激相比， 静息状态下，楔前叶、DLPFC和ACC之间的连通性将随着1 Hz rTMS的出现而降低 20 Hz rTMS时增加。在目标3中，我们将展示rTMS对EM性能的影响 精神分裂症我们假设楔前叶rTMS将与EM性能的变化相关。 我们预计，与假刺激相比，1 Hz rTMS将损害性能，20 Hz rTMS将 提高了扫描仪内EM任务性能。这项研究将提供证据表明，rTMS调节 活动在楔前叶和相关的EM电路在个人与精神分裂症。这将通知 随后针对楔前叶治疗精神分裂症EM功能障碍的临床试验。