Neurobehavioral correlates of bipolar disorder

Indiana University Bloomington, Bloomington IN

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Abstract

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.