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

精神分裂症是一种衰弱的精神疾病，也会增加心血管疾病的风险。 心血管和代谢疾病是患有精神分裂症的退伍军人过早死亡的主要原因。 尽管细胞和遗传学研究表明，新陈代谢损伤可能是神经和 心脏功能障碍，临床神经科学方面的研究有限。功能磁共振成像(FMRI) 被广泛用作临床研究工具，并已发现大脑网络中的异常活动可能 这是精神症状的基础。精神分裂症患者异常的脑活动是无效的：血流动力学过度 安静时的招募和认知要求高的任务中血流动力学不足的招募。然而，功能磁共振成像 并不直接分析神经活动，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品。此外，这些血管脑 信号受系统生理的影响，包括自主神经控制下的心脏活动。 神经系统(ANS)。因此，精神分裂症患者的大脑效率低下(使用功能磁共振成像测量)可能反映了 心血管功能障碍或在神经活动与血管血流的耦合方面效率低下。反过来，大脑 低效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。 来自功能磁共振成像的血管信号通常被建模以反映神经血管耦合，招募 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偶联 并提高心率、血压和心输出量，以满足行为需求。在……里面 精神分裂症，ANS信号失调，休息时神经血管耦合延迟。这个 精神分裂症患者的神经、血流动力学和ANS活动之间的关系未知；新方法 是了解神经血管耦合及其与ANS应激生理学的关系所必需的。 脑电(EEG)可以直接测量神经活动，当与功能磁共振同时使用时 (EEG-fMRI)，是一种很有前途的检测神经血管耦合的研究工具。持续血压 监测(CBP)可用于检查ANS功能，但CBP派生的ANS测量之间的链接 大脑中的功能和神经血管耦合尚不清楚。这份CDA-2提案假设 精神分裂症患者的神经血管偶联效率低下，可以同时使用CBP-EEG-fMRI进行测量 并由CBP检测的ANS活性失调所介导。 这种CDA-2通过检测神经血管和血管的作用而使科学独立成为可能。 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 精神分裂症的潜在病理缺乏，目前的药物治疗加剧了代谢 疾病。神经血管偶联的测量可以作为生物标记物来指导新的治疗方法，导致 关于心血管疾病和心理健康之间的交集的新视角。这份为期5年的CDA-2 提供获取和分析ANS生理学方面的培训，同时提供同步EEG方面的培训 功能磁共振成像。职业生涯和培训计划将发展首席调查员在ANS生理学和 通过课程作业、方法研讨会和与已建立的 调查人员。本研究结合模式(CBP、EEG和fMRI)来实现三个具体目的：1)检查 精神分裂症患者和健康退伍军人在休息和认知应激时的神经血管偶联，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 自主神经失调、神经血管偶联和精神症状之间的联系。所有目标 支持心脑健康导师培训的主要目标，以发展科学独立性和 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。

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.