Cerebellar timing dysfunction in schizophrenia

精神分裂症的小脑计时功能障碍

• 批准号: 7612135
• 负责人: WILLIAM P HETRICK
• 金额: $ 32.78万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7612135
• 关键词: 6-Cyano-7-nitroquinoxaline-2,3-dione; AMPA Receptors; Accounting; Address; Affect; Affective; Antipsychotic Agents; Area; Behavior; Behavior Disorders; Behavioral; Blinking; Brain; Cell Nucleus; Cells; Cerebellar Diseases; Cerebellar cortex structure; Cerebellum; Clinical; Cognitive; Communication impairment; Conditioned Stimulus; Conscious; Data; Discrimination; Disease; Dysmetria; Exhibits; Fingers; Functional Magnetic Resonance Imaging; Functional disorder; Gait; Glutamates; Human; Impaired cognition; Infusion procedures; Investigation; Knowledge; Laboratories; Lead; Learning; Liquid substance; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Methods; Modality; Modeling; Motor; Motor output; Movement; Nature; Neurobiology; Neurosciences; Nuclear; Oryctolagus cuniculus; Outcome; Output; Pathway interactions; Patients; Pharmaceutical Preparations; Picrotoxin; Play; Posture; Procedures; Process; Property; Purkinje Cells; Reaction Time; Research; Research Personnel; Role; Schizophrenia; Sensory Process; Source; Stimulus; Structure; Symptoms; Synapses; System; Testing; Thalamic structure; Time; Translational Research; Translations; base; conditioning; human subject; improved; indexing; information processing; neural model; neuromechanism; neuropsychological; programs; psychologic; relating to nervous system; research study; response; stellate cell; stimulus processing; theories

DESCRIPTION (provided by applicant): A translational research program will investigate the integrity of cerebellar-mediated timing functions in schizophrenia and identify mechanisms that may modulate synaptic properties of cerebellar timing networks. Mounting theoretical and empirical evidence indicates that schizophrenia is associated with a fundamental disturbance in the timing of neural processes and behavior. This deficit in the temporal coordination of information processing, sometimes referred to as cognitive dysmetria, may lead to poor temporal coordination of perceptual, cognitive, affective, and motor processes. Abnormalities in a cortico-cerebellar-thalamic-cortical (CCTC) brain circuit, which is responsible for fluid, temporal coordination of sequences of behavior, are a likely source of the timing anomalies in schizophrenia. The proposed research will examine the functional integrity of the cerebellar mode of this circuit. Parallel and complementary human and non-human studies will be conducted primarily using cerebellar-dependent eye-blink conditioning tasks. The overarching aims are to: (1) comprehensively characterize the nature of the eyeblink conditioning (EEC) acquisition and timing abnormalities in schizophrenia and use a rabbit model to identify cerebellar mechanisms that may be responsible for the observed deficits; (2) examine the contribution of primary sensory processes associated with stimulus modality and intensity to the observed EBC acquisition and timing abnormalities in schizophrenia and a rabbit model; (3) systematically explore the effect of stable, antipsychotic medication treatment on EBC and other cerebellar-dependent measures of timing; and (4) determine the clinical, behavioral, and structural neuroanatomical correlates of EBC deficits in schizophrenia. Taken together, the studies will determine the functional integrity of the cerebellar node of the cortico-cerebellar-thalamic-cortical circuit in schizophrenia and test models of impaired cerebellar functioning that may give rise to timing deficits in the disorder. This research will result in knowledge about neural mechanisms associated with an extraordinarily debilitating psychological disorder, schizophrenia. A better understanding of these mechanisms will advance knowledge about the pathophysiology of schizophrenia, and may lead to the identification of neurobiological targets of treatment.

描述（由申请人提供）：一项翻译研究计划将研究小脑介导的时间定时功能在精神分裂症中的完整性，并确定可能调节小脑时序网络突触特性的机制。安装理论和经验证据表明，精神分裂症与神经过程和行为时机的根本干扰有关。信息处理时间协调的这种赤字有时称为认知障碍，可能导致感知，认知，情感和运动过程的时间协调不佳。负责流体，行为序列的时间协调的皮质 - 脑脑丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑（CCTC）的异常，这可能是精神分裂症的时机异常的来源。拟议的研究将检查该电路小脑模式的功能完整性。平行和互补的人类和非人类研究将主要使用小脑依赖性的眼睛调节任务进行。总体目的是：（1）全面表征精神分裂症的8lekblink条件（EEC）采集和时序异常，并使用兔模型来识别可能导致观察到的缺陷的小脑机制； （2）检查与刺激形式和强度相关的主要感觉过程对精神分裂症和兔模型中观察到的EBC获取和时间异常的贡献； （3）系统地探索稳定的抗精神病药物治疗对EBC和其他小脑依赖性计量的影响； （4）确定精神分裂症EBC缺陷的临床，行为和结构神经解剖学相关性。综上所述，研究将确定精神分裂症中皮质甲状腺丘脑丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑 - 丘脑功能的功能完整性以及小脑功能受损的测试模型，这可能会导致该疾病中的时间缺陷。这项研究将导致有关与异常使人衰弱的心理障碍，精神分裂症相关的神经机制的知识。对这些机制的更好理解将提高人们对精神分裂症的病理生理学知识，并可能导致鉴定治疗的神经生物学靶标。