Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction

Abstract

Despite the extraordinary personal and societal burden of bipolar disorder (BD), relatively little is known about neural mechanisms associated with the unusual swings and shifts in affective and cognitive function that characterize the disorder. Accumulating evidence suggests that structures (e.g., the cerebellum and basal ganglia) and neurotransmitter systems (e.g., dopamine and glutamate) associated with neural timing processes are abnormal in mood disorders (1-5). The overarching theoretical model under investigation in the present study posits that classic symptoms of BD may arise from poor cerebellar-mediated temporal coordination of networks distributing and integrating cognitive and affective information. Although conventional conceptualizations of the cerebellum have been confined to motor coordination, a growing body of empirical and theoretical evidence indicates that the cerebellum plays a significant role in psychological functions as well, including modulation of perceptual, cognitive, and affective functions (6-12). This evidence is broadening the traditional notion of the cerebellum and illuminating new avenues of research into the mechanisms of psychiatric illness (13, 14). Objectives: Accumulating research implicates the cerebellum in nonmotor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD.Methods: Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls.Results: Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses.Conclusions: These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness.

Increased Timing Variability in Schizophrenia and Bipolar Disorder

“…Moreover, lesions to the cerebellum can cause disturbances in mood including mania, depression, and mood lability [65]. Finally, our group has documented abnormalities in bipolar disorder on several tasks for which the cerebellum is critical including classical delay eyeblink conditioning [66], paced finger tapping [28], and postural sway [67]. This evidence supports a possible role for the cerebellum in bipolar disorder and suggests that dysfunctional cerebellar circuitry may contribute to timing deficits observed in the present study.…”

Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study

“…The cerebellum is a brain area that has long been considered to be mainly important for the control of movement [32,33] . However, the cerebellum has also been associated with attention [34] , working memory [35] , language [36] , executive functions [37] , emotion and affection [38][39][40] . The cerebellum can be divided into three parts: the anterior lobe (lobuli I-V), the posterior lobe (lobuli VI-IX) and the medial flocculonodular lobe (lobule X) [41] .…”

Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans

“…Previous research using a single-cue delay EBC paradigm found deficits in clinical groups with conditions including schizophrenia Brown et al, 2005), bipolar disorder (Bolbecker, Mehta, Johannesen, et al, 2009), and drug abuse (Skosnik et al, 2007). However, few studies involving the CS-US ISI have been completed, and none involving clinical groups.…”