Brain Under Fatigue - Can Perceived Fatigability in Multiple Sclerosis Be Seen on the Level of Functional Brain Network Architecture?

Background: Fatigue is one of the most common symptoms of multiple sclerosis (MS), significantly affecting the functioning of the patients. However, the neural underpinnings of physical and mental fatigue in MS are still vague. The aim of our study was to investigate the functional architecture of resting-state networks associated with fatigue in patients with MS. Methods: The sum of 107 high-functioning patients underwent a resting-state scanning session and filled out the 9-item Fatigue Severity Scale (FSS). Based on the FSS score, we identified patients with different levels of fatigue using the cluster analysis. The low-fatigue group consisted of n = 53 subjects, while the high-fatigue group n = 48. The neuroimaging data were analyzed in terms of functional connectivity (FC) between various resting-state networks as well as amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuations (fALFF). Results: Two-sample t-test revealed between-group differences in FC of posterior salience network (SN). No differences occurred in default mode network (DMN) and sensorimotor network (SMN). Moreover, differences in fALFF were shown in the right middle frontal gyrus and right superior frontal gyrus, however, no ALFF differences took place. Conclusion: Current study revealed significant functional network (FN) architecture between-group differences associated with fatigue. Present results suggest the higher level of fatigue is related to deficits in awareness as well as higher interoceptive awareness and nociception.

Diurnal variations of resting-state fMRI data: A graph-based analysis.

Circadian rhythms (lasting approximately 24 h) control and entrain various physiological processes, ranging from neural activity and hormone secretion to sleep cycles and eating habits. Several studies have shown that time of day (TOD) is associated with human cognition and brain functions. In this study, utilizing a chronotype-based paradigm, we applied a graph theory approach on resting-state functional MRI (rs-fMRI) data to compare whole-brain functional network topology between morning and evening sessions and between morning-type (MT) and evening-type (ET) participants. Sixty-two individuals (31 MT and 31 ET) underwent two fMRI sessions, approximately 1 hour (morning) and 10 h (evening) after their wake-up time, according to their declared habitual sleep-wake pattern on a regular working day. In the global analysis, the findings revealed the effect of TOD on functional connectivity (FC) patterns, including increased small-worldness, assortativity, and synchronization across the day. However, we identified no significant differences based on chronotype categories. The study of the modular structure of the brain at mesoscale showed that functional networks tended to be more integrated with one another in the evening session than in the morning session. Local/regional changes were affected by both factors (i.e., TOD and chronotype), mostly in areas associated with somatomotor, attention, frontoparietal, and default networks. Furthermore, connectivity and hub analyses revealed that the somatomotor, ventral attention, and visual networks covered the most highly connected areas in the morning and evening sessions: the latter two were more active in the morning sessions, and the first was identified as being more active in the evening. Finally, we performed a correlation analysis to determine whether global and nodal measures were associated with subjective assessments across participants. Collectively, these findings contribute to an increased understanding of diurnal fluctuations in resting brain activity and highlight the role of TOD in future studies on brain function and the design of fMRI experiments.

The Influence of Intraocular Lens Implantation and Alterations in Blue Light Transmittance Level on the Brain Functional Network Architecture Reorganization in Cataract Patients.

BACKGROUND: Cataract is one of the most common age-related vision deteriorations, leading to opacification of the lens and therefore visual impairment as well as blindness. Both cataract extraction and the implantation of blue light filtering lens are believed to improve not only vision but also overall functioning. METHODS: Thirty-four cataract patients were subject to resting-state functional magnetic resonance imaging before and after cataract extraction and intraocular lens implantation (IOL). Global and local graph metrics were calculated in order to investigate the reorganization of functional network architecture associated with alterations in blue light transmittance. Psychomotor vigilance task (PVT) was conducted. RESULTS: Graph theory-based analysis revealed decreased eigenvector centrality after the cataract extraction and IOL replacement in inferior occipital gyrus, superior parietal gyrus and many cerebellum regions as well as increased clustering coefficient in superior and inferior parietal gyrus, middle temporal gyrus and various cerebellum regions. PVT results revealed significant change between experimental sessions as patients responded faster after IOL replacement. Moreover, a few regions were correlated with the difference in blue light transmittance and the time reaction in PVT. CONCLUSION: Current study revealed substantial functional network architecture reorganization associated with cataract extraction and alteration in blue light transmittance.

Brain Functional Network Architecture Reorganization and Alterations of Positive and Negative Affect, Experiencing Pleasure and Daytime Sleepiness in Cataract Patients after Intraocular Lenses Implantation.

Background: Cataracts are associated with progressive blindness, and despite the decline in prevalence in recent years, it remains a major global health problem. Cataract extraction is reported to influence not only perception, attention and memory but also daytime sleepiness, ability to experience pleasure and positive and negative affect. However, when it comes to the latter, the magnitude and prevalence of this effect still remains uncertain. The current study aims to evaluate the hemodynamic basis of daytime sleepiness, ability to experience pleasure and positive and negative affect in cataract patients after the intraocular lens (IOL) implantation. Methods: Thirty-four cataract patients underwent resting-state functional magnetic resonance imaging evaluation before and after cataract extraction and intraocular lens implantation. Both global and local graph metrics were calculated in order to investigate the hemodynamic basis of excessive sleepiness (ESS), experiencing pleasure (SHAPS) as well as positive and negative affect (PANAS) in cataract patients. Results: Eigenvector centrality and clustering coefficient alterations associated with cataract extraction are significantly correlated with excessive sleepiness, experiencing pleasure as well as positive and negative affect. Conclusions: The current study reveals the hemodynamic basis of sleepiness, pleasure and affect in patients after cataract extraction and intraocular lens implantation. The aforementioned mechanism constitutes a proof for changes in functional network activity associated with postoperative vision improvement.

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.

Identifying Diurnal Variability of Brain Connectivity Patterns Using Graph Theory.

Significant differences exist in human brain functions affected by time of day and by people's diurnal preferences (chronotypes) that are rarely considered in brain studies. In the current study, using network neuroscience and resting-state functional MRI (rs-fMRI) data, we examined the effect of both time of day and the individual's chronotype on whole-brain network organization. In this regard, 62 participants (39 women; mean age: 23.97 ± 3.26 years; half morning- versus half evening-type) were scanned about 1 and 10 h after wake-up time for morning and evening sessions, respectively. We found evidence for a time-of-day effect on connectivity profiles but not for the effect of chronotype. Compared with the morning session, we found relatively higher small-worldness (an index that represents more efficient network organization) in the evening session, which suggests the dominance of sleep inertia over the circadian and homeostatic processes in the first hours after waking. Furthermore, local graph measures were changed, predominantly across the left hemisphere, in areas such as the precentral gyrus, putamen, inferior frontal gyrus (orbital part), inferior temporal gyrus, as well as the bilateral cerebellum. These findings show the variability of the functional neural network architecture during the day and improve our understanding of the role of time of day in resting-state functional networks.

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.

Prevalence of Misophonia and Correlates of Its Symptoms among Inpatients with Depression.

Misophonia is an underexplored condition that significantly decreases the quality of life of those who suffer from it. It has neurological and physiological correlates and is associated with a variety of psychiatric symptoms; however, a growing body of data suggests that it is a discrete disorder. While comorbid diagnoses among people with misophonia have been a matter of research interest for many years there is no data on the frequency of misophonia among people with psychiatric disorders. This could be the next step to reveal additional mechanisms underlying misophonia. Until recently, the use of a variety of non-validated questionnaires and the dominance of internet-based studies have been also a major obstacles to a proper definition of misophonia. A total of 94 inpatients diagnosed with depression were assessed for misophonia with face-to-face interviews as well as with MisoQuest-a validated misophonia questionnaire. The prevalence of misophonia among these patients and the congruence of MisoQuest with face-to-face interviews were evaluated. Additionally, the patients filled in a series of questionnaires that measured a variety of psychiatric symptoms and psychological traits. Anxiety, depression, impulsivity, somatic pain, vegetative symptoms, post-traumatic stress disorder (PTSD) symptoms, gender, and age were analyzed in relation to the severity of symptoms of misophonia. Between 8.5 to 12.76% of inpatients with depression were diagnosed with misophonia (depending on measurement and inclusion criteria). MisoQuest accuracy was equal to 92.55%, sensitivity-66.67% and specificity-96.34%. Severity of misophonia symptoms was positively correlated to the greatest extent with anxiety. Moderate positive correlation was also found between severity of misophonia symptoms and depressive symptoms, intrusions, and somatic pain; a weak positive correlation was found between severity of misophonia and non-planning impulsivity, motor impulsivity, avoidance, and vegetative symptoms. There was no relationship between the severity of misophonia symptoms and attentional impulsivity or the age of participants.