Time-Frequency Characterization of Resting Brain in Bipolar Disorder during Euthymia-A Preliminary Study.

The goal of this paper is to investigate the baseline brain activity in euthymic bipolar disorder (BD) patients by comparing it to healthy controls (HC) with the use of a variety of resting state functional magnetic resonance imaging (rs-fMRI) analyses, such as amplitude of low frequency fluctuations (ALFF), fractional ALFF (f/ALFF), ALFF-based functional connectivity (FC), and r egional homogeneity (ReHo). We hypothesize that above-mentioned techniques will differentiate BD from HC indicating dissimilarities between the groups within different brain structures. Forty-two participants divided into two groups of euthymic BD patients (n = 21) and HC (n = 21) underwent rs-fMRI evaluation. Typical band ALFF, slow-4, slow-5, f/ALFF, as well as ReHo indexes were analyzed. Regions with altered ALFF were chosen as ROI for seed-to-voxel analysis of FC. As opposed to HC, BD patients revealed: increased ALFF in left insula; increased slow-5 in left middle temporal pole; increased f/ALFF in left superior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right putamen, and bilateral thalamus. There were no significant differences between BD and HC groups in slow-4 band. Compared to HC, the BD group presented higher ReHo values in the left superior medial frontal gyrus and lower ReHo values in the right supplementary motor area. FC analysis revealed significant hyper-connectivity within the BD group between left insula and bilateral middle frontal gyrus, right superior parietal gyrus, right supramarginal gyrus, left inferior parietal gyrus, left cerebellum, and left supplementary motor area. To our best knowledge, this is the first rs-fMRI study combining ReHo, ALFF, f/ALFF, and subdivided frequency bands (slow-4 and slow-5) in euthymic BD patients. ALFF, f/ALFF, slow-5, as well as REHO analysis revealed significant differences between two studied groups. Although results obtained with the above methods enable to identify group-specific brain structures, no overlap between the brain regions was detected. This indicates that combination of foregoing rs-fMRI methods may complement each other, revealing the bigger picture of the complex resting state abnormalities in BD.

Relationship between neurological and cerebellar soft signs, and implicit motor learning in schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) patients share deficits in motor functions in the form of neurological (NSS) and cerebellar soft signs (CSS), and implicit motor learning disturbances. Here, we use cluster analysis method to assess (1) the relationship between those abnormalities in SZ and BD and (2) the differences between those groups. METHODS: 33 SZ patients, 33 BD patients as well as 31 healthy controls (HC) took part in the study. We assessed CSS with the International Cooperative Ataxia Rating Scale (ICARS) and NSS with the Neurological Evaluation Scale (NES). Implicit motor learning was evaluated with the Serial Reaction Time Task (SRTT). Participants were divided into clusters (Ward's method) based on the mean response time and mean error rate in SRTT. The difference in ICARS and NES scores, and SRTT variables between clusters were evaluated. We have measured associations between SRTT parameters and both ICARS and NES total scores and subscores. RESULTS: Cluster analysis based on the SRTT parameters allowed to extract three clusters. Those were characterized by the increasing disruption of motor functioning (psychomotor retardation, the severity of NSS and CSS) regardless of the diagnosis. Cluster 1 covered almost all of HC and was characterized by faster reaction times and small number of errors. BD and SZ patients represented in cluster 1, although fully functional in performing the SRTT, showed higher rates of NSS and CSS. Patients with BD and SZ were set apart in clusters 2 and 3 in a similar proportion. Cluster 2 presented significantly slower reaction times but with the comparable number of errors to cluster 1. Cluster 3 consisted of participants with normal or decreased reaction time and significantly increased number of errors. None of the clusters were predominantly composed of the patients representing one psychiatric diagnosis. CONCLUSIONS: To our best knowledge, we are presenting the first data indicating the relationship between implicit motor learning and NSS and CSS in SZ and BD patients' groups. Lack of clusters predominantly represented by patients with the diagnosis of SZ or BD may refer to the model of schizophrenia-bipolar disorder boundary, pointing out the similarities between those two disorders.

Altered Functional Connectivity Differences in Salience Network as a Neuromarker of Suicide Risk in Euthymic Bipolar Disorder Patients.

OBJECTIVE: The occurrence of death by suicide in patients diagnosed with bipolar disorder is as much as 60 times greater than in the general population. Even during the state of euthymia patients are characterized by suicide risk. The aim of the study is to investigate the baseline brain activity in euthymic bipolar disorder patients in regard to suicide risk. We hypothesized that patients compared to healthy control group will demonstrate altered functional connectivity among resting state networks which will be directly related to current suicide risk. METHOD: 41 subjects were enrolled in the study consisting control group (n = 21) and euthymic bipolar disorder patients group (n = 20). Functional magnetic resonance imaging was used to evaluate resting state brain activity and ROI-ROI functional connectivity analysis was performed. Suicidal risk was estimated using The Suicide Behaviors Questionnaire-Revised. RESULTS: A two sample t-test revealed decreased functional connectivity between regions involved in the salience network in patients compared to the control group. This decrease was negatively correlated with current suicide risk. CONCLUSION: Obtained results suggest the association between risk of suicide and activity of regions responsible for functions such as learning from mistakes, prospective thinking, and sensory integration.

Vergence eye movements in bipolar disorder. / Ruchy wergencyjne w chorobie afektywnej dwubiegunowej.

OBJECTIVES: With respect to bipolar disorder (BD), previous research have demonstrated saccadic eye movements abnormalities, manifested mainly as an increase in reaction time (latency) in both prosaccadic and antisaccadic task. So far, there were no studies related to vergence eye movements in subjects with BD. Our primary aim was to evaluate vergence tracking performance in this clinical group. METHODS: 30 patients with BD in remission and 23 healthy controls were enrolled. Subjects underwent optometric examination where near point of convergence was measured by the use of Wolff Wand. Instrumented convergence measurements were performed using infrared eye tracker and dedicated vergence stimuli generator. RESULTS: BD patients presented significantly higher average error between eyes' convergence and convergence required to fixate the target and higher number of saccadic intrusions compared with healthy controls group. Principal component analysis performed on oculometric parameters revealed differences between BD patients and healthy controls. Significant correlations between the vergence disturbances and saccadic intrusions were found. CONCLUSIONS: BD patients showed the alterations of the vergence eye movements similar to the disturbances of eye movements in the fronto-parallel plane. While the abnormalities of vergence eye movements in some mental disorders have been reported, we have for the first time objectively measured this phenomenon in BD.

Altered functional connectivity among frontal eye fields, thalamus and cerebellum in bipolar disorder. / Zaburzenia polaczen funkcjonalnych miedzy czolowymi polami okoruchowymi, wzgórzem a mózdzkiem w chorobie afektywnej dwubiegunowej.

OBJECTIVES: The aim of our study is to evaluate functional connectivity of cerebellothalamo-cortical networks linking frontal eye fields (FEF) and cerebellar regions associated with oculomotor control: nodulus (X), uvula (IX), flocculus (H X) and ventral paraflocculus (H IX) in bipolar disorder (BD) with the use of resting state functional magnetic resonance imaging (rsfMRI). METHODS: 19 euthymic BD patients and 14 healthy controls underwent rsfMRI examination. Functional connectivity between bilateral FEF, thalamus and cerebellar regions associated with oculomotor control was evaluated. RESULTS: BD patients revealed decreased functional connectivity between following structures: right FEF and bilateral thalamus, flocculus (H X), uvula (IX); right thalamus and right FEF; between right flocculus (H X) and right FEF, left thalamus; between left thalamus and bilateral FEF and right flocculus (H X). CONCLUSIONS: BD patients presented decreased functional connectivity among FEF, thalamus and cerebellar structures associated with eye movements control. Oculomotor evaluation of BD patients assessed with rsfMRI may help to determine whether altered functional connectivity observed in our study is associated with eye movements deficits in BD.

Mental rotation task in bipolar disorder. / Test rotacji mentalnych w chorobie afektywnej dwubiegunowej.

OBJECTIVES: Bipolar disorder (BD) significantly affects level of cognitive and motor functioning. Studies on cognitive function in BD shows i.a. deficits in visuospatial processing and visuospatial memory. However, studies have not used Mental Rotation Task to evaluate these functions so far. Our aim is to introduce this method to assess abovementioned deficits in euthymic BD patients. METHODS: 31 euthymic BD patients and 27 healthy volunteers matched for age and years of education were recruited. All participants performed digital version of Mental Rotation Task. In this task, participants were asked to compare two figures rotated against each other and declare its similarity or difference indicating whether the figures are identical or whether they constitute their own mirror image. RESULTS: The test revealed significantly longer reaction times in the group of BD patients when images were rotated by - 90, - 45, 45, 90 degrees, or not rotated at all. There was no significant difference in condition of - 135, 135 or 180 degrees. The accuracy rate was significantly lower in the patient group than in the control group for the entire test and in each condition. The correlation between the average response time and the accuracy rate turned out to be insignificant. CONCLUSIONS: Our results are consistent with studies presenting visuospatial deficits in bipolar disorder. In this study we show for the first time that mental rotation deficits are present in euthymic state of BD patients.

The role of affective temperaments assessed by the Temperament Evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A) in the relationship between morningness-eveningness and bipolarity.

BACKGROUND: Growing number of studies indicates a link between eveningness chronotype, affective temperaments and bipolarity, both in patients with mood disorders and in general population. Given these tripartite associations, we hypothesized that the effect of circadian preferences on the bipolarity may be mediated by the temperamental traits. METHODS: The study included 1449 subjects (402 men and 1047 women). They all fulfilled a web-based questionnaire, consisting of the Composite Scale of Morningness (CSM), Mood Disorder Questionnaire (MDQ), Hypomania Checklist-32 (HCL-32) and the Temperament Evaluation of the Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The role of temperamental traits in the relationship between morningness-eveningness and bipolarity was assessed using mediation analysis. RESULTS: Morningness is correlated with lower bipolarity measured by the MDQ and HCL-32, and to lower scores of depressive, cyclothymic, irritable and anxious temperaments of the TEMPS-A. There is no significant association between morningness and hyperthymic traits. Cyclothymic and irritable traits are full mediators of the association between chronotype and bipolarity, influencing bipolarity independently from circadian preferences. Depressive and anxious traits are partial mediators of this association, increasing the effect of eveningness on bipolarity. LIMITATIONS: The indirectness of the findings in the web-based study and disproportion of participants' gender. CONCLUSIONS: Our study confirmed that eveningness is associated with bipolarity. In case of depressive and anxious temperaments, bipolarity is associated stronger with eveningness than with the TEMPS-A scores. On the other hand, cyclothymic and irritable temperaments were associated with bipolarity independently from circadian preferences.

Disrupted implicit motor sequence learning in schizophrenia and bipolar disorder revealed with ambidextrous Serial Reaction Time Task.

BACKGROUND: Impairment of implicit motor sequence learning was shown in schizophrenia (SZ) and, most recently, in bipolar disorder (BD), and was connected to cerebellar abnormalities. The goal of this study was to compare implicit motor sequence learning in BD and SZ. METHODS: We examined 33 patients with BD, 33 patients with SZ and 31 healthy controls with a use of ambidextrous Serial Reaction Time Task (SRTT), which allows exploring asymmetries in performance depending on the hand used. RESULTS: BD and SZ patients presented impaired implicit motor sequence learning, although the pattern of their impairments was different. While BD patients showed no signs of implicit motor sequence learning for both hands, the SZ group presented some features of motor learning when performing with the right, but not with the left hand. CONCLUSIONS: To our best knowledge this is the first study comparing implicit motor sequence learning in BD and SZ. We show that both diseases share impairments in this domain, however in the case of SZ this impairment differs dependently on the hand performing SRTT. We propose that implicit motor sequence learning impairments constitute an overlapping symptom in BD and SZ and suggest further neuroimaging studies to verify cerebellar underpinnings as its cause.

Morningness-eveningness and affective temperaments assessed by the Temperament Evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A).

Chronotype is a stable trait presenting one's circardian preference. Since chronotype disturbances are common in patients with affective disorders, our aim is to evaluate chronotypes related to affective temperaments, measured with the temperament evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The study included 618 subjects (151 men and 467 women) within the framework of web-based design. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Sleep Wake Pattern Assessment Questionnaire (SWPAQ), and the TEMPS-A scale. Multiple regression models revealed that after controlling for age and gender: irritable and cyclothymic temperaments were negatively associated with total CSM score, CSM morning affect and circadian preference components, Sleepability (S), Vigilance (V), Wakeability (W) and positively with Morningness (M) and Eveningness (E) subscales of SWPAQ; anxious temperament was negatively associated with total CSM scores, CSM morning affect and with S, V, W subscales of SWPAQ; depressive temperament was negatively associated with Falling asleep, S, V, W subscales of SWPAQ; hyperthymic temperament was positively associated with CSM morning affect and V, W and negatively with M subscales of SWPAQ. The results show distinctiveness of the associations between hyperthymic temperament and circadian preferences, compared to all other TEMPS-A temperaments (depressive, cyclothymic, irritable and anxious). In the CMS scale, only hyperthymic temperament was related to morning affect. In the SWPAQ scale, hyperthymic temperament was the only one associated with earlier morningness (earlier wake up time preference), increased parameters of vigor - wakeability, vigilance, and also the only one not associated with decreased plasticity of circadian rhythm (sleepability and falling asleep). Results also point to some similarities between cyclothymic and irritable temperaments in some aspects of the chronotype.

The Biological Rhythms Interview of Assessment in Neuropsychiatry in patients with bipolar disorder: correlation with affective temperaments and schizotypy

Objective: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. Methods: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. Results: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. Conclusion: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

The Biological Rhythms Interview of Assessment in Neuropsychiatry in patients with bipolar disorder: correlation with affective temperaments and schizotypy.

OBJECTIVE:: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. METHODS:: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. RESULTS:: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. CONCLUSION:: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

A Study of Biological Rhythm Disturbances in Polish Remitted Bipolar Patients using the BRIAN, CSM, and SWPAQ Scales.

BACKGROUND/AIMS: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) is a novel tool allowing for a complex assessment of biological rhythms. We compared patients with bipolar disorder (BD) and healthy control subjects (HC) using the Polish version of the BRIAN scale. METHOD: Fifty-four remitted BD patients (17 males and 37 females aged 52 ± 13 years) and 54 healthy control subjects (25 males and 29 females aged 42 ± 14 years) were studied. In addition to the BRIAN scale, the Composite Scale of Morningness (CSM) and the Sleep-Wake Pattern Assessment Questionnaire (SWPAQ) were employed. RESULTS: The Polish version of the BRIAN scale displayed high feasibility and consistency, showing that the patients had greater biological rhythm disturbances than the controls. After regression analysis, significant differences were obtained for the BRIAN subscales activity and predominant chronotype, and for the SWPAQ items quality of night-time sleep and ability to stay awake. We obtained positive correlations between higher BRIAN scores and morningness and eveningness, but the correlations with vigilance and the ability to stay awake (on the SWPAQ) were negative. CONCLUSIONS: Using the BRIAN scale, we confirmed the greater disturbances of biological rhythm in Polish remitted bipolar patients, compared with healthy controls. The differences between these 2 groups in sleep-awake patterns were also demonstrated by the SWPAQ scores. In contrast to other studies, we were unable to confirm an evening chronotype as a discriminating factor between remitted bipolar patients and healthy subjects. This can be explained by the older age and the use of lithium by a significant proportion of the patients.

[Emotional disorders in patients with cerebellar damage--case studies]. / Zaburzenia emocjonalne u pacjentów z uszkodzeniem mózdzku--studium przypadków.

AIM: Growing number of research shows the role of the cerebellum in the regulation of affect. Lesions of the cerebellum can lead to emotional disregulation, a significant part of the Cerebellar Cognitive Affective Syndrome. The aim of this article is to analyze the most recent studies concerning the cerebellar participation in emotional reactions and to present three cases: two female and one male who suffered from cerebellar damage and presented post-traumatic affective and personality change. METHOD: The patients' neuropsychological examination was performed with Raven's Progressive Matrices Test--standard version, Trial Making Test, Wisconsin Card Sorting Test, Auditory Verbal Learning Test by Luria, Benton Visual Retention Test, Verbal Fluency Test, Stroop Interference Test, Attention and Perceptivity Test (Test Uwagi i Spostrzegawczosci TUS), Frontal Behavioral Inventory (FBI). RESULTS: The review of the literature suggest cerebellar participation, especially teh vermis and paravermial regions, in the detection, integration and filtration of emotional information and in regulation of autonomic emotional responses. In the described patients we observed: oversensitivity, irritability, impulsivity and self-neglect. The man and the woman with right-sided lesions presented similar symptoms: rigidity ofthought, stubbornness, lack of criticism,jocular and inappropriate behavior. The woman with left-sided cerebellar lesion was adynamic, apathic and passive, she presented emotional blunting, social isolation, lack of interests and motivation, general cognitive slowdown. CONCLUSIONS: Both the analyzed research and the described cases indicate the connection between the cerebellum and emotion regulation. The symptoms presented by the described patients were most probably a consequence of damaged cerebellar projections to subcortical structures (the limbic system) and frontal areas. The diversification of symptoms depending on the localization of lesions had not been described yet and seems to indicate an interesting direction for future research.