Neurobehavioral correlates of bipolar disorder

描述（由申请人提供）：双相情感障碍（BD）以情绪、认知和运动水平的周期性不稳定为特征。心理生理学数据表明，这种不稳定性可能与时间同步和毫秒级分析时间同步的干扰并行。这些缺陷包括较差的神经同步，延迟的处理，减少的反应幅度，以及更大的受试者心理生理反应的变异性。本研究的目的是：(1)区分双相情感障碍的时间加工和协调的状态和特征相关的神经行为测量；(2)确定这些措施与临床症状和认知表现的关系；(3)检验这些神经行为测量是否能预测后续结果。在一项横断面研究中，I型双相情感障碍的颞加工功能完整性将使用三种神经行为协议进行评估。高频脑电伴动将用于测试听觉神经回路的频率响应。眨眼经典条件反射将测试脑干和小脑计时回路。听觉P300潜伏期将用于评估认知加工速度和变异性。从这些任务中得出的测量结果产生了时间处理的动态功能测量（频率响应、相位同步、处理速度、反应变异性），并且对涉及跨时间调节认知和情感过程的大脑结构（小脑、颞叶皮层）和神经递质系统（多巴胺、GABA）敏感。一年的测试-再测试将确定观察到的异常在时间上的持久性。纵向多变量方法将测试入组时神经行为缺陷与随后的功能和症状结果之间的关系。这些结果将表征双相情感障碍的时间加工障碍，识别与该疾病相关的潜在神经行为内表型，并确定这些神经行为异常是否可预测该疾病的预后。

DESCRIPTION (provided by applicant): Bipolar disorder (BD) is characterized by cyclic instability in mood, cognition, and motor activity levels. Psychophysiological data suggests that this instability may be paralleled by disturbances of temporal synchronization and timing at the millisecond scale of analysis. These deficits include poorer neural synchronization, delayed processing, reduced response amplitude, and greater within-subject variability in psychophysiological responses. The aims of this study are to: (1) differentiate state and trait related neurobehavioral measures of temporal processing and coordination in bipolar disorder; (2) determine the relationship of these measures to clinical symptoms and cognitive performance; and (3) test whether these neurobehavioral measures predict subsequent outcomes. In a cross-sectional study, the functional integrity of temporal processing in Type I bipolar disorder will be evaluated using three neurobehavioral protocols. High frequency EEG entrainment will be used to test auditory neural circuit frequency response. Eye-blink classical conditioning will test brainstem and cerebellar timing circuits. Auditory P300 latency will be used to evaluate cognitive processing speed and variability. Measures derived from these tasks yield dynamic functional measures of temporal processing (frequency response, phase synchronization, processing speed, response variability) and are sensitive to brain structures (cerebellum, temporal cortex) and neurotransmitter systems (dopamine, GABA) implicated in the regulation of cognitive and affective processes across time. One year test-retests will determine the persistence of observed abnormalities across time. Longitudinal multivariate methods will test the association between neurobehavioral deficits at entry and subsequent functional and symptomatic outcomes. These results will characterize disturbances of temporal processing in bipolar disorder, identify potential neurobehavioral endophenotypes associated with the illness, and determine whether these neurobehavioral abnormalities are predictive of outcomes in the disorder.