Neurometabolic mechanisms of aberrant resting brain activity in schizophrenia

精神分裂症异常静息脑活动的神经代谢机制

• 批准号: 10116956
• 负责人: Michael Jacob
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116956
• 关键词: Address; Affect; Anatomy; Animals; Antipsychotic Agents; Arousal; Autonomic nervous system; Biological Assay; Biological Markers; Blood; Blood Vessels; Body mass index; Brain; Brain region; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinical; Clinical Research; Cognitive; Collaborations; Coupling; Data; Diabetes Mellitus; Educational workshop; Electroencephalography; Frequencies; Functional Magnetic Resonance Imaging; Funding; Genetic study; Glucose; Goals; Grant; Heart; Human; Impairment; Lead; Link; Measures; Medical; Mental Health; Mental disorders; Mentors; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolic syndrome; Metabolism; Methodology; Methods; Mitochondria; Modality; Modeling; Modification; Neuroanatomy; Neuronal Dysfunction; Neurosciences; Output; Oxygen; Participant; Pathology; Patients; Periodicity; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Physiology; Principal Investigator; Psychopathology; Research; Research Personnel; Rest; Risk; Role; Schizophrenia; Severities; Signal Transduction; Smoking; Stress; Testing; Tissues; Training; Variant; Vascular Diseases; Veterans; blood oxygen level dependent; cardiovascular disorder risk; career; clinical biomarkers; comorbidity; dosage; functional magnetic resonance imaging/electroencephalography; hemodynamics; indexing; mindfulness; multimodality; neuroimaging; neuropsychiatric disorder; neurotransmission; novel; premature; psychiatric symptom; psychotic symptoms; recruit; relating to nervous system; respiratory; response; sedentary lifestyle; tool

Schizophrenia is a debilitating psychiatric illness that increases the risk for medical comorbidities, such as metabolic syndrome, diabetes, and cardiovascular disease. Metabolic comorbidities are the leading causes of premature death for veterans with schizophrenia. Although cellular and genetic studies have suggested that metabolic impairments may underlie neural dysfunction, studies in clinical neuroscience are limited. Resting state, functional magnetic resonance imaging (fMRI), is widely used as a clinical research tool and has identified a “default mode network” that is hypermetabolic in schizophrenia and may underlie psychiatric symptoms. fMRI does not assay neural activity directly, and instead, reflects slow changes in the regional level of blood oxygen commonly interpreted as a surrogate for neural activity. Moreover, these metabolic signals are influenced by systemic physiology, including cardiorespiratory activity under the control of the autonomic nervous system. Metabolic signals from fMRI are typically modeled to reflect neurometabolic coupling, the recruitment of blood and oxygen to support active neural tissue. However, autonomic dysregulation and metabolic dysfunction can impair neurometabolic coupling. In schizophrenia, autonomic signals are dysregulated and are associated with aberrant default mode network activity, but links to neural activity and neurometabolic coupling remain unknown. Electroencephalography (EEG), can measure neural activity directly, but with limited temporal precision. The use of concurrent, simultaneous EEG-fMRI is a promising research tool utilized in animal and human studies to examine neurometabolic coupling. This CDA-1 proposal hypothesizes that neurometabolic coupling is dysregulated in schizophrenia and can be measured using simultaneous EEG-fMRI The experimental context for this CDA-1 is Dr. Judith Ford’s Merit grant, which examines simultaneously acquired EEG-fMRI data of cognitive processing during rumination and mindfulness. This CDA- 1 proposes a path to scientific independence by examining the role of neurometabolic coupling and autonomic activity in aberrant, resting brain activity in schizophrenia. Treatments targeting underlying pathology in schizophrenia are lacking and current pharmacotherapies exacerbate metabolic disease. Measures of neurometabolic coupling may serve as a biomarker to guide novel treatments, leading to new perspectives on the intersection between metabolic disease and mental health. This two-year CDA-1 provides training in the acquisition and analysis of simultaneous EEG-fMRI to examine neurometabolic coupling. In addition, this CDA -1 generates pilot data examining the role of autonomic activity in neurometabolic coupling to support a CDA-2 application. The career and training plan will develop the Principal Investigator’s expertise in multimodal, psychiatric neuroimaging through coursework, methodological workshops, and collaboration with established investigators. This study combines modalities (Autonomic signals, EEG and fMRI) to achieve two specific aims: 1) Examine the neuroanatomy and temporal dynamics of neurometabolic coupling in schizophrenia and, 2) Assess the role of autonomic activity on neurometabolic coupling in SZ, by measuring cardiorespiratory activity concurrently with simultaneous EEG-fMRI. All aims support the primary goal of mentored training in simultaneous EEG-fMRI to develop scientific independence and expertise in the role of neurometabolism and autonomic activity in schizophrenia. This goal will be accomplished through this proposed CDA-1, the primary findings generated by Aim #1 and the pilot data generated by Aim #2 to support a CDA-2 application.

精神分裂症是一种使人衰弱的精神疾病，会增加合并症的风险，例如 代谢综合征、糖尿病和心血管疾病是主要原因。 尽管细胞和遗传学研究表明，患有精神分裂症的退伍军人过早死亡。 代谢障碍可能是神经功能障碍的基础，临床神经科学的研究有限。 状态，功能磁共振成像（fMRI），被广泛用作临床研究工具，并具有 确定了精神分裂症中代谢亢进的“默认模式网络”，可能是精神病的基础 功能磁共振成像不直接测定神经活动，而是缓慢反映区域水平的变化。 血氧含量通常被解释为神经活动的替代信号。 受全身生理学的影响，包括自主神经控制下的心肺活动 来自功能磁共振成像的代谢信号通常被建模以反映神经代谢耦合，即 补充血液和氧气来支持活跃的神经组织，但是，自主神经失调和 代谢功能障碍会损害精神分裂症中的神经代谢耦合。 失调并与异常的默认模式网络活动相关，但与神经活动和 神经代谢耦合仍然未知，脑电图（EEG）可以测量神经活动。 直接进行，但时间精度有限，同时使用 EEG-fMRI 是一种很有前途的方法。 该 CDA-1 提案用于动物和人类研究中检查神经代谢耦合的研究工具。 发现精神分裂症中神经代谢耦合失调，可以使用 同时脑电图-功能磁共振成像 CDA-1 的实验背景是 Judith Ford 博士的优异奖，该奖检查了 同时获取了沉思和正念期间认知处理的 EEG-fMRI 数据。 1 通过研究神经代谢耦合和自主神经的作用，提出了一条通往科学独立的道路 针对精神分裂症的异常、静息大脑活动的治疗。 精神分裂症缺乏治疗措施，目前的药物治疗加剧了代谢性疾病。 神经代谢耦合可以作为指导新治疗的生物标志物，从而带来新的视角 这个为期两年的 CDA-1 提供了代谢疾病和心理健康之间的交叉点的培训。 同步 EEG-fMRI 的采集和分析以检查神经代谢耦合此外，该 CDA。 -1 生成试验数据，检查自主活动在神经代谢耦合中的作用，以支持 CDA-2 职业和培训计划将培养首席研究员在多式联运、 通过课程作业、方法研讨会以及与既定机构的合作进行精神科神经影像学研究 这项研究结合了多种模式（自主信号、脑电图和功能磁共振成像）来实现两个具体目标： 1) 检查精神分裂症神经代谢耦合的神经解剖学和时间动态，2) 通过测量心肺活动来评估自主活动对 SZ 神经代谢耦合的作用 与同步脑电图-功能磁共振成像同时进行，所有目标都支持指导培训的主要目标。 同步脑电图-功能磁共振成像 (EEG-fMRI) 旨在培养神经代谢和神经代谢作用方面的科学独立性和专业知识 这一目标将通过提议的主要 CDA-1 来实现。 目标 #1 生成的结果和目标 #2 生成的试点数据支持 CDA-2 应用。