Neurobehavioral correlates of bipolar disorder

描述(由申请人提供)：双相情感障碍(BD)的特征是情绪、认知和运动活动水平的周期性不稳定。心理生理学数据表明，这种不稳定性可能与毫秒级分析中的时间同步和计时干扰平行。这些缺陷包括较差的神经同步性，延迟的处理，反应幅度降低，以及受试者内部心理生理反应的更大变异性。本研究的目的是：(1)区分双相情感障碍患者与状态和特质相关的时间加工和协调的神经行为测量；(2)确定这些测量与临床症状和认知表现的关系；以及(3)检验这些神经行为测量是否可以预测后续结果。在一项横断面研究中，将使用三种神经行为方案评估I型双相情感障碍患者时间处理的功能完整性。高频脑电夹带将被用来测试听神经回路频率响应。眨眼的经典条件反射将测试脑干和小脑的计时电路。听觉P300潜伏期将被用来评估认知加工速度和变异性。从这些任务中衍生出来的测量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、响应变异性)，并且对大脑结构(小脑、颞叶皮质)和神经递质系统(多巴胺、GABA)敏感，这些神经递质系统涉及到随时间调节认知和情感过程。一年的测试重新测试将确定观察到的异常随时间的持久性。纵向多变量方法将测试进入时神经行为缺陷与随后的功能和症状结果之间的关联。这些结果将表征双相情感障碍的时间处理障碍，识别与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以预测疾病的结果。

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.