A Novel Unsupervised Machine Learning Approach to Assess Postural Dynamics in Euthymic Bipolar Disorder.

Bipolar disorder (BD) is a mood disorder with different phases alternating between euthymia, manic or hypomanic episodes, and depressive episodes. While motor abnormalities are commonly seen during depressive or manic episodes, not much attention has been paid to postural abnormalities during periods of euthymia and their association with illness burden. We collected 24-hour posture data in 32 euthymic participants diagnosed with BD using a shirt-based wearable. We extracted a set of nine time-domain features, and performed unsupervised participant clustering. We investigated the association between posture variables and 12 clinical characteristics of illness burden. Based on their postural dynamics during the daytime, evening, or nighttime, participants clustered in three clusters. Higher illness burden was associated with lower postural variability, in particular during daytime. Participants who exhibited a mostly upright sitting/standing posture during the night with frequent nighttime postural transitions had the highest number of lifetime depressive episodes. Euthymic participants with BD exhibit postural abnormalities that are associated with illness burden, especially with the number of depressive episodes. Our results contribute to understanding the role of illness burden on posture changes and sleep consolidation in periods of euthymia.

A History of Suicide Attempt Is Associated with Increased Sympathetic Activation in Bipolar Disorder.

OBJECTIVE: Suicide risk in bipolar disorder (BD) is estimated to be up to 20 times higher than in the general population. While there is a large body of evidence suggesting that increased sympathetic activation is associated with disease and death, there is a paucity of research on the role of autonomic nervous system (ANS) dysfunction in patients with BD who have attempted suicide. METHODS: Fifty-three participants with BD used a wearable device to assess the association between history of suicide attempt, current suicidal ideation, and ANS dysfunction, including measures of heart rate variability (HRV) and respiratory rate. Data were analyzed in a series of unadjusted and adjusted bivariate models of association controlling for relevant variables. RESULTS: A history of suicide attempts was significantly associated with an increase in respiratory rate (p < 0.01). These results remained significant after adjusting for age, BMI, and current mood state. There was no association between current suicidal ideation and heart rate or respiratory rate. In the frequency domain, HRV parameters suggest reduced parasympathetic (i.e., vagal) activity in participants with a history of suicide attempts and in those with current suicidality, suggesting changes in sympathicovagal balance in BD. CONCLUSIONS: Our results suggest that changes in the ANS in patients with BD and a history of suicide attempt are not restricted to pure vagally mediated HRV parameters, but rather signal a general ANS dysregulation. This ANS imbalance may be contributing to illness burden and cardiovascular disease. Further research on the relationship between ANS and suicidality in BD is needed.

Increased sympathetic tone is associated with illness burden in bipolar disorder.

BACKGROUND: We recently described an association between reduced heart rate variability (HRV) and illness burden in bipolar disorder (BD) using a novel Illness Burden Index (IBI). We aimed to further characterize this association by using spectral analyses to assess whether the IBI is also associated with autonomic imbalance in BD patients. METHODS: In this cross-sectional study, 53 participants with BD wore a device for 24 h to assess association between HRV spectral measures and the IBI or each of its components (age of onset, number and type of previous episode(s), duration of the most severe episode, history of suicide attempts or psychotic symptoms during episodes, co-morbid psychiatric disorders, and family history). We ran both unadjusted models and models controlling for age, sex, years of education, marital status, BMI, pharmacotherapy, and baseline functional cardiovascular capacity. RESULTS: HRV low-frequency (LF) normalized values were almost twice as high as published in healthy controls. Higher IBI was associated with higher LF and lower High Frequency (HF) values, resulting in a higher LF/HF ratio, indicating an increased sympathetic tone. Four individual components of the IBI were similarly associated with measures of increased sympathetic tone: earlier age of onset, number of depressive episodes, co-morbid anxiety disorders, and family history of suicide. Adjusted and unadjusted models had similar results. LIMITATIONS: Our models used mean LF and HF and do not consider their dynamic variations over 24 h or phase of the illness. CONCLUSIONS: Burden of illness is associated with increased sympathetic tone in patients with BD, putting them at risk for arrythmias and sudden death.

The futility of long-term predictions in bipolar disorder: mood fluctuations are the result of deterministic chaotic processes.

BACKGROUND: Understanding the underlying architecture of mood regulation in bipolar disorder (BD) is important, as we are starting to conceptualize BD as a more complex disorder than one of recurring manic or depressive episodes. Nonlinear techniques are employed to understand and model the behavior of complex systems. Our aim was to assess the underlying nonlinear properties that account for mood and energy fluctuations in patients with BD; and to compare whether these processes were different in healthy controls (HC) and unaffected first-degree relatives (FDR). We used three different nonlinear techniques: Lyapunov exponent, detrended fluctuation analysis and fractal dimension to assess the underlying behavior of mood and energy fluctuations in all groups; and subsequently to assess whether these arise from different processes in each of these groups. RESULTS: There was a positive, short-term autocorrelation for both mood and energy series in all three groups. In the mood series, the largest Lyapunov exponent was found in HC (1.84), compared to BD (1.63) and FDR (1.71) groups [F (2, 87) = 8.42, p < 0.005]. A post-hoc Tukey test showed that Lyapunov exponent in HC was significantly higher than both the BD (p = 0.003) and FDR groups (p = 0.03). Similarly, in the energy series, the largest Lyapunov exponent was found in HC (1.85), compared to BD (1.76) and FDR (1.67) [F (2, 87) = 11.02; p < 0.005]. There were no significant differences between groups for the detrended fluctuation analysis or fractal dimension. CONCLUSIONS: The underlying nature of mood variability is in keeping with that of a chaotic system, which means that fluctuations are generated by deterministic nonlinear process(es) in HC, BD, and FDR. The value of this complex modeling lies in analyzing the nature of the processes involved in mood regulation. It also suggests that the window for episode prediction in BD will be inevitably short.

Reduced heart rate variability is associated with higher illness burden in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with premature death and ischemic heart disease is the main cause of excess mortality. Heart rate variability (HRV) predicts mortality in patients with or without cardiovascular disease. While several studies have analyzed the association between HRV and BD, none has analyzed the association of HRV with illness burden in BD. METHODS: 53 participants with BD I and II used a wearable device to assess the association between HRV and factors characterizing illness burden, including illness duration, number and type of previous episode(s), duration of the most severe episode, history of suicide attempts or psychotic symptoms during episodes, and co-morbid psychiatric disorders. We ran unadjusted models and models controlling statistically for age, sex, pharmacotherapy, baseline functional cardiovascular capacity, BMI, years of education, and marital status. We also explored the association between HRV and an overall illness burden index (IBI) integrating all these factors using a weighted geometric mean. RESULTS: Adjusted and unadjusted models had similar results. Longer illness duration, higher number of depressive episodes, longer duration of most severe manic/hypomanic episode, co-morbid anxiety disorders, and family history of suicide were associated with reduced HRV, as was bipolar depression severity in the participants experiencing a depressive episode. Finally, a higher IBI score was associated with lower HRV. CONCLUSIONS: High illness burden is associated with reduced HRV in BD. While the IBI needs to be validated in a larger sample, it may provide an overall measure that captures illness burden in BD.

Visual Feedback Modulates Aftereffects and Electrophysiological Markers of Prism Adaptation.

Prism adaptation (PA) is both a model for visuomotor learning and a promising treatment for visuospatial neglect after stroke. The task involves reaching for targets while prism glasses horizontally displace the visual field. Adaptation is hypothesized to occur through two processes: strategic recalibration, a rapid self-correction of pointing errors; and spatial realignment, a more gradual adjustment of visuomotor reference frames that produce prism aftereffects (i.e., reaching errors upon glasses removal in the direction opposite to the visual shift). While aftereffects can ameliorate neglect, not all patients respond to PA, and the neural mechanisms underlying successful adaptation are unclear. We investigated the feedback-related negativity (FRN) and the P300 event-related potential (ERP) components as candidate markers of strategic recalibration and spatial realignment, respectively. Healthy young adults wore prism glasses and performed memory-guided reaching toward vertical-line targets. ERPs were recorded in response to three different between-subject error feedback conditions at screen-touch: view of hand and target (Experiment 1), view of hand only (Experiment 2), or view of lines to mark target and hand position (view of hand occluded; Experiment 3). Conditions involving a direct view of the hand-produced stronger aftereffects than indirect hand feedback, and also evoked a P300 that decreased in amplitude as adaptation proceeded. Conversely, the FRN was only seen in conditions involving target feedback, even when aftereffects were smaller. Since conditions producing stronger aftereffects were associated with a phase-sensitive P300, this component may index a "context-updating" realignment process critical for strong aftereffects, whereas the FRN may reflect an error monitoring process related to strategic recalibration.

Using brain potentials to understand prism adaptation: the error-related negativity and the P300.

Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN)-a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuomotor responding is shifted to the opposite direction of that initially induced by the prisms. This visuomotor aftereffect has been used to study visuomotor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA's use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN.

Hierarchical error evaluation: the role of medial-frontal cortex in postural control.

Motor error evaluation appears to be a hierarchically organized process subserved by 2 distinct systems: a higher level system within medial-frontal cortex responsible for movement outcome evaluation (high-level error evaluation) and a lower level posterior system(s) responsible for the mediation of within-movement errors (low-level error evaluation). While a growing body of evidence suggests that a reinforcement learning system within medial-frontal cortex plays a crucial role in the evaluation of high-level errors made during discrete reaching movements and continuous motor tracking, the role of this system in postural control is currently unclear. Participants learned a postural control task via a feedback-driven trial-and-error shaping process. In line with previous findings, electroencephalographic recordings revealed that feedback about movement outcomes elicited a feedback error-related negativity: a component of the human event-related brain potential associated with high-level outcome evaluation within medial-frontal cortex. Thus, the data provide evidence that a high-level error-evaluation system within medial-frontal cortex plays a key role in learning to control our body posture.