Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia

通过无创脑刺激治疗早期精神分裂症，增强前额叶振荡活动和工作记忆表现

• 批准号: 10668480
• 负责人: Fabio Ferrarelli
• 金额: $ 64.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-07 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668480
• 关键词: Acute; Affect; Assessment tool; Attention; Biological Markers; Brain; Chronic; Chronic Schizophrenia; Conscious; Disease; Dose; Economic Burden; Economics; Electroencephalography; Electrophysiology (science); Frequencies; Functional disorder; Future; Goals; Impaired cognition; Impairment; Individual; Intervention; Measures; Memory; Memory impairment; Motivation; Neurons; Patients; Pattern; Performance; Physiologic pulse; Prefrontal Cortex; Quality of life; Reporting; Role; Schizophrenia; Short-Term Memory; Transcranial magnetic stimulation; Work; cognitive benefits; cognitive function; design; follow-up; improved; neural; neural circuit; neural network; neuroimaging; neuronal circuitry; neuroregulation; noninvasive brain stimulation; novel; severe mental illness; verbal

Project Summary. Schizophrenia is a severe mental illness with an estimated economic burden of more than $160 billion per year in the US alone. To mitigate this burden, a promising approach involves the discovery of novel treatment interventions targeting specific neuronal circuit dysfunction, especially early in the illness, thus ameliorating the course of the disorder. In recent work, we found that the oscillatory activity of the dorsolateral prefrontal cortex (DLPFC), assessed with Transcranial Magnetic Stimulation (TMS) and EEG, was markedly reduced in chronic schizophrenia (Ch-SCZ) patients. DLPFC oscillatory deficits are also present in early course (EC-SCZ) patients and are associated to their reduced working memory (WM) performance. But findings to date are limited by a correlational/cross-sectional design, leaving the potential causal role of DLPFC oscillatory deficits in SCZ cognitive dysfunction unclear. The overarching goal of this proposal is to establish whether, by acutely enhancing DLPFC oscillatory activity, we see a corresponding improvement in WM function in EC-SCZ patients. In addition to being used to assess cortical function, as in combination with EEG, TMS can be delivered in repetitive, high-frequency patterns (rTMS), to modulate brain activity, including prefrontal cortical oscillations. Theta Burst Stimulation (TBS) is a type of rTMS that induces more rapid effects on neural activity than conventional rTMS; continuous TBS (cTBS) and intermittent TBS (iTBS) can decrease and enhance cortical excitability, respectively. Recent studies have shown that iTBS of DLPFC can acutely enhance prefrontal excitability in healthy individuals. Yet, the immediate impact of TBS on DLPFC oscillatory activity in patients with SCZ remains unknown. The first broad Aim of this proposal is to use iTBS to acutely ameliorate deficits in DLPFC oscillatory activity in EC-SCZ patients. WM relies on a neural network in which DLPFC serves as a central hub. EEG studies have reported that SCZ patients have DLPFC oscillatory abnormalities during WM tasks, and we recently found that reduced DLPFC oscillatory activity predicts poorer WM performance in EC-SCZ patients. It therefore stands to reason that enhancing DLPFC oscillatory activity with TBS may benefit cognitive functioning. The second broad Aim of this proposal is to use iTBS to acutely ameliorate WM impairments in EC-SCZ patients. To achieve these goals, we will perform TMS/EEG assessments of DLPFC oscillatory parameters and evaluate WM ability before and after two TBS sessions (iTBS and sham TBS of DLPFC) in seventy-five EC-SCZ patients. The proposed study aims to provide initial evidence that TBS can acutely enhance DLPFC oscillatory activity, which in turn predicts better WM performance, in EC-SCZ patients. Building on these findings, future neuromodulation-based treatment interventions applying chronic doses of TBS may more persistently ameliorate/restore DLPFC oscillatory parameters and related WM impairments in SCZ patients early during the illness, thus significantly improving their cognitive functioning and overall quality of life.

项目摘要。精神分裂症是一种严重的精神疾病，估计经济负担超过 仅在美国，每年1600亿美元。为了减轻这种负担，一种有希望的方法涉及发现 针对特定神经元功能障碍的新型治疗干预措施，尤其是在疾病早期，因此 改善疾病的过程。在最近的工作中，我们发现背外侧的振荡活性 用经颅磁刺激（TMS）和EEG评估的前额叶皮层（DLPFC）显着 慢性精神分裂症（CH-SCZ）患者的降低。 DLPFC振荡缺陷也存在于早期课程中 （EC-SCZ）患者的工作记忆（WM）表现降低。但是迄今为止的发现 受相关/横截面设计的限制，留下了DLPFC振荡缺陷的潜在因果关系 在SCZ认知功能障碍中不清楚。该提议的总体目标是确定是否敏锐地确定 增强了DLPFC振荡活性，我们看到EC-SCZ患者WM功能的相应改善。 除了与脑电图结合使用外，还可以将TMS交付 重复，高频模式（RTMS），以调节大脑活动，包括前额叶皮质振荡。 theta爆发刺激（TBS）是一种RTM，它对神经活动的影响比 常规RTM；连续的TBS（CTB）和间歇性TBS（ITB）可以减少并增强皮质 兴奋性分别。最近的研究表明，DLPFC的ITB可以急性增强前额叶 健康个体的兴奋性。然而，TBS对DLPFC振荡活动的直接影响对患者 SCZ仍然未知。该提案的第一个广泛目的是使用ITB急性缓解DLPFC中的缺陷 EC-SCZ患者的振荡活性。 WM依赖于DLPFC充当中央枢纽的神经网络。脑电图研究报告了SCZ 患者在WM任务期间患有DLPFC振荡异常，我们最近发现DLPFC降低了 振荡活性预测EC-SCZ患者的WM性能较差。因此，认为 用TBS增强DLPFC振荡活性可能会使认知功能受益。第二个范围的目标 提案是使用ITB急性改善EC-SCZ患者的WM损伤。 为了实现这些目标，我们将对DLPFC振荡参数进行TMS/EEG评估并评估 在75例EC-SCZ患者中，两个TBS会话前后的WM能力（DLPFC的ITB和假TBS）。 拟议的研究旨在提供最初的证据，表明TBS可以急性增强DLPFC振荡活性，即 反过来，在EC-SCZ患者中，这会预测更好的WM性能。以这些发现为基础 基于神经调节的治疗干预措施应用了慢性剂量的TBS可能会更持久 早期SCZ患者的改善/还原DLPFC振荡参数和相关的WM损伤 疾病，因此可以显着改善其认知功能和整体生活质量。