Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Abstract

BackgroundExploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Methodology and Principal FindingsTwelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Conclusions/SignificanceManic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease.

Resting state EEG power and coherence abnormalities in bipolar disorder and schizophrenia

“…Interestingly, novel stimuli induce significantly more activation in the parietal region (Arbabshirani et al 2012), and this region also shows greater synchronous activity with the DMN found in BP relative to SZ and NC (Ongür et al 2010). Given this pair of results, the robust increase in beta power at rest observed in our study may indicate that BP are more responsive to novel stimuli in the environment, an effect that corresponds to recent findings (Minassian et al 2011). Importantly, that mania symptoms predicted beta power in BP in our study suggests that perhaps these symptoms are driven by erratic oscillations between internal trains of thought and distraction by novel stimuli.…”

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features

“…Previously, we observed a consistent pattern of increased activity, increased exploration, and more linear patterns of movement in mice administered GBR12909 or DAT KD mice in the mouse BPM (Perry et al 2009; Young et al 2010a; b), mimicking the behavior of manic (Minassian et al 2011) and euthymic BD patients (Henry et al 2013). In the current studies, GBR12909 at 13 mg/kg again produced this mania-like behavior in mice.…”

“…Previously, we demonstrated that mice with reduced dopamine transporter (DAT) functioning model exploratory profiles of BD mania (Perry et al 2009). Both DAT knockdown (KD) mice and mice receiving the selective DAT inhibitor GBR12909 exhibit hyperactivity, increased exploration, and straight paths of movement as quantified by the mouse behavioral pattern monitor (BPM) (Young et al 2010a; b) similar to patients with BD mania (Minassian et al 2011; Perry et al 2010) and euthymia (Henry et al 2013) in a human BPM. Although some of the abnormal behavior observed in these GBR12909-treated mice, such as impaired decision-making (van Enkhuizen et al 2013b), is also present in depressed patients with BD performing similar human tasks (Adida et al 2011), their hyperactivity, increased motivation (Young and Geyer 2010), and reduced immobility times in the tail suspension test (TST) (Sarkisyan et al 2010) and FST (Esumi et al 2013) more closely model the manic phase of BD.…”

Heteroplasmy of Mouse mtDNA Is Genetically Unstable and Results in Altered Behavior and Cognition

“…Under normal housing conditions, the heteroplasmic mice had reduced food intake, spontaneous activity levels, and metabolic rates during the dark cycle (Etain et al, 2011). However, under stressful conditions, the heteroplasmic mice were more excitable and resistant to despair (Flaisher-Grinberg et al, 2010; Gindre and Swendsen, 2010; Minassian et al, 2011). The heteroplasmic mice also showed impaired spatial learning and retention.…”