Stressed heart-brain communication in Veterans with schizophrenia: neurovascular and autonomic mechanisms

患有精神分裂症的退伍军人心脑通讯压力：神经血管和自主神经机制

• 批准号: 10589714
• 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: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589714
• 关键词: Acceleration; Anatomy; Antipsychotic Agents; Arithmetic; Autonomic nervous system; Behavioral; Biological Assay; Biological Markers; Blood; Blood Pressure; Blood Pressure Monitors; Blood Vessels; Blood flow; Brain; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cessation of life; Clinical; Clinical Research; Cognition; Cognitive; Cognitive deficits; Collaborations; Communication; Coupled; Coupling; Development; Diagnosis; Disease; Doctor of Philosophy; Educational workshop; Electrocardiogram; Electroencephalography; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Genetic study; Goals; Heart; Heart Diseases; Heart Rate; Hyperactivity; Impairment; Intervention; Investigation; Lead; Life Style; Link; Measures; Mediating; Mediation; Medical; Mental Health; Mental disorders; Mentors; Metabolic; Metabolic Diseases; Methodology; Methods; Modality; Modeling; Monitor; Myocardial dysfunction; Nervous System Physiology; Neuronal Dysfunction; Neurosciences; Oxygen; Participant; Pathology; Pharmaceutical Preparations; Pharmacotherapy; Physiology; Population; Principal Investigator; Psyche structure; Psychiatrist; Psychopathology; Psychoses; Regulation; Research; Research Personnel; Resources; Rest; Risk; Role; Schizophrenia; Signal Transduction; Stimulus; Stress; Structure; Surveys; Symptoms; Tissues; Training; Training Support; Veterans; Work; aging brain; biomarker development; brain health; brain research; cardiovascular disorder risk; cardiovascular risk factor; career; cognitive task; comorbidity; diagnostic biomarker; executive function; experience; functional disability; heart function; hemodynamics; moderate obesity; multimodal neuroimaging; neural; neuroimaging; neurovascular; neurovascular coupling; novel; novel strategies; patient stratification; premature; psychiatric symptom; psychotic symptoms; recruit; response; tool

Schizophrenia is a debilitating psychiatric illness that also increases the risk of cardiovascular disease. Cardiovascular and metabolic disease is the leading cause of premature death for veterans with schizophrenia. Although cellular and genetic studies have suggested that metabolic impairments may underlie neural and cardiac dysfunction, studies in clinical neuroscience are limited. Functional magnetic resonance imaging (fMRI) is widely used as a clinical research tool and has identified aberrant activity across brain networks that may underlie psychiatric symptoms. Aberrant brain activity in schizophrenia is inefficient: excessive hemodynamic recruitment at rest and deficient hemodynamic recruitment during cognitively demanding tasks. However, fMRI does not assay neural activity directly, and instead, reflects slow changes in the regional level of blood oxygen (hemodynamics) commonly interpreted as a surrogate for neural activity. Moreover, these vascular brain signals are influenced by systemic physiology, including cardiac activity under the control of the autonomic nervous system (ANS). Therefore, brain inefficiency in schizophrenia (as measured using fMRI) might reflect cardiovascular dysfunction or inefficiency in the coupling of neural activity to vascular blood flow. In turn, brain inefficiency may underlie cognitive deficits, the leading cause of functional impairment in schizophrenia. Vascular signals from fMRI are typically modeled to reflect neurovascular coupling, the recruitment of blood and oxygen to support active neural tissue. Stress signals within the ANS delay neurovascular coupling in the brain and increase heart rate, blood pressure and cardiac output to meet behavioral demands. In schizophrenia, ANS signals are dysregulated, and neurovascular coupling is delayed, while at rest. The relationships between neural, hemodynamic, and ANS activity are unknown in schizophrenia; new approaches are needed to understand neurovascular coupling and the relationship to ANS stress physiology. Electroencephalography (EEG) can measure neural activity directly, and when used concurrently with fMRI (EEG-fMRI), is a promising research tool for examining neurovascular coupling. Continuous blood pressure monitoring (CBP) can be used to examine the ANS function, but links between CBP derived measure of ANS function and neurovascular coupling in the brain are unknown. This CDA-2 proposal hypothesizes that neurovascular coupling is inefficient in schizophrenia, can be measured using simultaneous CBP-EEG-fMRI and is mediated by dysregulated ANS activity as assayed by CBP. This CDA-2 enables a path to scientific independence by examining the role of neurovascular and autonomic function in relation to cognitive and clinical symptoms in schizophrenia. Treatments targeting underlying pathology in schizophrenia are lacking and current pharmacotherapies exacerbate metabolic disease. Measures of neurovascular coupling may serve as a biomarker to guide novel treatments, leading to new perspectives on the intersection between cardiovascular disease and mental health. This five-year CDA-2 provides training in the acquisition and analysis of ANS physiology with ongoing training in simultaneous EEG- fMRI. The career and training plan will develop the Principal Investigator’s experience in ANS physiology and multimodal neuroimaging through coursework, methodological workshops, and collaboration with established investigators. This study combines modalities (CBP, EEG and fMRI) to achieve three specific aims: 1) Examine neurovascular coupling in schizophrenia and healthy veterans at rest and during cognitive stress, 2) Assess the role of ANS function in schizophrenia and healthy veterans during cognitive stress and 3) Determine associations between autonomic dysregulation, neurovascular coupling, and psychiatric symptoms. All aims support the primary goal of mentored training in heart-brain health to develop scientific independence and expertise in the role of stress on neurovascular and cardiovascular function in psychiatric illness.

精神分裂症是一种使人衰弱的精神疾病，也会增加患心血管疾病的风险。 心血管和代谢疾病是精神分裂症退伍军人过早死亡的主要原因。 虽然细胞和遗传研究表明，代谢障碍可能是神经和 心功能不全，临床神经科学研究有限。功能磁共振成像 被广泛用作临床研究工具，并已识别出大脑网络中的异常活动， 是精神症状的基础精神分裂症患者异常的大脑活动是低效的：过度的血液动力学 静息时复张和认知要求高的任务期间血流动力学复张不足。然而，功能磁共振成像 不直接测定神经活动，而是反映局部血氧水平的缓慢变化 （血液动力学）通常被解释为神经活动的替代物。此外，这些血管脑 信号受到全身生理学的影响，包括在自主神经控制下的心脏活动。 神经系统（ANS）。因此，精神分裂症患者的脑功能低下（使用功能磁共振成像测量）可能反映了 心血管功能障碍或神经活动与血管血流耦合效率低下。反过来，大脑 低效率可能是认知缺陷的基础，认知缺陷是精神分裂症功能障碍的主要原因。 来自fMRI的血管信号通常被建模以反映神经血管耦合， 血液和氧气来支持活跃的神经组织ANS内的应激信号延迟神经血管耦联 增加心率、血压和心输出量以满足行为需求。在 精神分裂症，ANS信号失调，神经血管耦合延迟，而在休息。的 精神分裂症中神经、血液动力学和ANS活动之间的关系尚不清楚;新的方法 需要了解神经血管耦合和ANS应激生理学的关系。 脑电图（EEG）可以直接测量神经活动，当与fMRI同时使用时， 脑电功能磁共振成像（EEG-fMRI）是一种很有前途的研究工具，检查神经血管耦合。连续血压 监测（CBP）可用于检查ANS功能，但CBP导出的ANS测量之间的联系 脑中的神经血管功能和耦合是未知的。该CDA-2提案假设， 神经血管耦合在精神分裂症中是无效的，可以使用同步CBP-EEG-fMRI来测量 并且由CBP测定的失调的ANS活性介导。 该CDA-2通过检查神经血管的作用， 精神分裂症患者自主神经功能与认知和临床症状的关系治疗靶向 缺乏精神分裂症的潜在病理学，目前的药物治疗加剧了代谢紊乱， 疾病神经血管耦合的测量可以作为生物标志物来指导新的治疗， 心血管疾病和心理健康之间的交叉点的新观点。为期五年的CDA-2 提供ANS生理学采集和分析方面的培训，同时提供EEG方面的持续培训- 功能磁共振成像。职业和培训计划将发展主要研究者在ANS生理学方面的经验， 多模式神经成像通过课程，方法研讨会，并与建立 investigators.本研究结合了多种方式（CBP、EEG和fMRI）来实现三个特定目标：1）检查 精神分裂症和健康退伍军人在休息和认知应激期间的神经血管耦合，2）评估 ANS功能在精神分裂症和健康退伍军人认知应激中的作用; 3）确定 自主神经失调、神经血管耦合和精神症状之间的关系。区域所有 支持心脑健康指导培训的主要目标，以发展科学独立性， 在精神疾病中压力对神经血管和心血管功能的作用方面的专业知识。