Brain network topological changes in inflammatory bowel disease: an exploratory study.

Although the aetio-pathogenesis of inflammatory bowel diseases (IBD) is not entirely clear, the interaction between genetic and adverse environmental factors may induce an intestinal dysbiosis, resulting in chronic inflammation having effects on the large-scale brain network. Here, we hypothesized inflammation-related changes in brain topology of IBD patients, regardless of the clinical form [ulcerative colitis (UC) or Crohn's disease (CD)]. To test this hypothesis, we analysed source-reconstructed magnetoencephalography (MEG) signals in 25 IBD patients (15 males, 10 females; mean age ± SD, 42.28 ± 13.15; mean education ± SD, 14.36 ± 3.58) and 28 healthy controls (HC) (16 males, 12 females; mean age ± SD, 45.18 ± 12.26; mean education ± SD, 16.25 ± 2.59), evaluating the brain topology. The betweenness centrality (BC) of the left hippocampus was higher in patients as compared with controls, in the gamma frequency band. It indicates how much a brain region is involved in the flow of information through the brain network. Furthermore, the comparison among UC, CD and HC showed statistically significant differences between UC and HC and between CD and HC, but not between the two clinical forms. Our results demonstrated that these topological changes were not dependent on the specific clinical form, but due to the inflammatory process itself. Broader future studies involving panels of inflammatory factors and metabolomic analyses on biological samples could help to monitor the brain involvement in IBD and to clarify the clinical impact.

Neuronal avalanches in temporal lobe epilepsy as a noninvasive diagnostic tool investigating large scale brain dynamics.

The epilepsy diagnosis still represents a complex process, with misdiagnosis reaching 40%. We aimed at building an automatable workflow, helping the clinicians in the diagnosis of temporal lobe epilepsy (TLE). We hypothesized that neuronal avalanches (NA) represent a feature better encapsulating the rich brain dynamics compared to classically used functional connectivity measures (Imaginary Coherence; ImCoh). We analyzed large-scale activation bursts (NA) from source estimation of resting-state electroencephalography. Using a support vector machine, we reached a classification accuracy of TLE versus controls of 0.86 ± 0.08 (SD) and an area under the curve of 0.93 ± 0.07. The use of NA features increase by around 16% the accuracy of diagnosis prediction compared to ImCoh. Classification accuracy increased with larger signal duration, reaching a plateau at 5 min of recording. To summarize, NA represents an interpretable feature for an automated epilepsy identification, being related with intrinsic neuronal timescales of pathology-relevant regions.

Flexibility of brain dynamics is increased and predicts clinical impairment in relapsing-remitting but not in secondary progressive multiple sclerosis.

Large-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting-state functional connectivity is characterized by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease. Brain flexibility has been recently found increased in multiple sclerosis, but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the multiple sclerosis clinical phenotypes remain unexplored so far. We performed a brain dynamics study quantifying brain flexibility utilizing the 'functional repertoire' (i.e. the number of configurations of active brain areas) through source reconstruction of magnetoencephalography signals in a cohort of 25 multiple sclerosis patients (10 relapsing-remitting multiple sclerosis and 15 secondary progressive multiple sclerosis) and 25 healthy controls. Multiple sclerosis patients showed a greater number of unique reconfigurations at fast time scales as compared with healthy controls. This difference was mainly driven by the relapsing-remitting multiple sclerosis phenotype, whereas no significant differences in brain dynamics were found between secondary progressive multiple sclerosis and healthy controls. Brain flexibility also showed a different predictive power on clinical disability according to the multiple sclerosis type. For the first time, we investigated brain dynamics in multiple sclerosis patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the multiple sclerosis phenotype and its relationship with clinical disability.

Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture. METHODS: We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches. RESULTS: ALS patients presented higher values of the nodal strength in both cortical and sub-cortical brain areas. This parameter correlated directly with disease duration. CONCLUSIONS: In this work, we provide a deeper characterization of neuronal avalanches propagation in ALS, describing their spatio-temporal trajectories and identifying the brain regions most likely to be involved in the process. This makes it possible to recognize the brain areas that take part in the pathogenic mechanisms of ALS. Furthermore, the nodal strength of the involved regions correlates directly with disease duration. SIGNIFICANCE: Our results corroborate the clinical relevance of aperiodic, fast large-scale brain activity as a biomarker of microscopic changes induced by neurophysiological processes.

The Effect of Sleep Deprivation on Brain Fingerprint Stability: A Magnetoencephalography Validation Study.

This study examined the stability of the functional connectome (FC) over time using fingerprint analysis in healthy subjects. Additionally, it investigated how a specific stressor, namely sleep deprivation, affects individuals' differentiation. To this aim, 23 healthy young adults underwent magnetoencephalography (MEG) recording at three equally spaced time points within 24 h: 9 a.m., 9 p.m., and 9 a.m. of the following day after a night of sleep deprivation. The findings indicate that the differentiation was stable from morning to evening in all frequency bands, except in the delta band. However, after a night of sleep deprivation, the stability of the FCs was reduced. Consistent with this observation, the reduced differentiation following sleep deprivation was found to be negatively correlated with the effort perceived by participants in completing the cognitive task during sleep deprivation. This correlation suggests that individuals with less stable connectomes following sleep deprivation experienced greater difficulty in performing cognitive tasks, reflecting increased effort.

The effect of dopaminergic treatment on whole body kinematics explored through network theory.

Three-dimensional motion analysis represents a quantitative approach to assess spatio-temporal and kinematic changes in health and disease. However, these parameters provide only segmental information, discarding minor changes of complex whole body kinematics characterizing physiological and/or pathological conditions. We aimed to assess how levodopa intake affects the whole body, analyzing the kinematic interactions during gait in Parkinson's disease (PD) through network theory which assess the relationships between elements of a system. To this end, we analysed gait data of 23 people with PD applying network theory to the acceleration kinematic data of 21 markers placed on participants' body landmarks. We obtained a matrix of kinematic interactions (i.e., the kinectome) for each participant, before and after the levodopa intake, we performed a topological analysis to evaluate the large-scale interactions among body elements, and a multilinear regression analysis to verify whether the kinectome's topology could predict the clinical variations induced by levodopa. We found that, following levodopa intake, patients with PD showed less trunk and head synchronization (p-head = 0.048; p-7th cervical vertebrae = 0.032; p-10th thoracic vertebrae = 0.006) and an improved upper-lower limbs synchronization (elbows right, p = 0.002; left, p = 0.005), (wrists right, p = 0.003; left, p = 0.002; knees right, p = 0.003; left, p = 0.039) proportional to the UPDRS-III scores. These results may be attributable to the reduction of rigidity, following pharmacological treatment.

Brain flexibility increases during the peri-ovulatory phase as compared to early follicular phase of the menstrual cycle.

The brain operates in a flexible dynamic regime, generating complex patterns of activity (i.e. neuronal avalanches). This study aimed at describing how brain dynamics change according to menstrual cycle (MC) phases. Brain activation patterns were estimated from resting-state magnetoencephalography (MEG) scans, acquired from women at early follicular (T1), peri-ovulatory (T2) and mid-luteal (T3) phases of the MC. We investigated the functional repertoire (number of brain configurations based on fast high-amplitude bursts of the brain signals) and the region-specific influence on large-scale dynamics across the MC. Finally, we assessed the relationship between sex hormones and changes in brain dynamics. A significantly larger number of visited configurations in T2 as compared to T1 was specifically observed in the beta frequency band. No relationship between changes in brain dynamics and sex hormones was evident. Finally, we showed that the left posterior cingulate gyrus and the right insula were recruited more often in the functional repertoire during T2 as compared to T1, while the right pallidum was more often part of the functional repertoires during T1 as compared to T2. In summary, we showed hormone-independent increased flexibility of the brain dynamics during the ovulatory phase. Moreover, we demonstrated that several specific brain regions play a key role in determining this change.

Multimodal Physical Exercise Affects Visuo-Spatial Working Memory: Preliminary Evidence from a Descriptive Study on Tai-Chi Practitioners and Runners.

Recent evidence has shown a relationship between physical exercise (PE) and cognitive functioning. However, it is unknown if unimodal and multimodal modalities of PE affect cognitive abilities in different ways. To fill this gap, we analyzed the effects of unimodal PE (running) and multimodal PE (Tai Chi) on specific cognitive abilities. A sample of 33 participants (mean age = 52.6 ± 7.2) divided into eleven runners, eleven Tai Chi practitioners, and eleven age-matched sedentary individuals were subjected to a neuropsychological tests battery to assess shifting and problem solving abilities (Rule Shift Cards, BADS-RS, and Key Search tasks), verbal fluency (semantic and phonemic verbal fluency tasks), verbal memory (Rey's 15 words test), visuo-spatial working memory (Corsi test), and global cognitive functioning (clock-drawing test). The results showed significantly higher BADS-RS scores in runners and Tai Chi practitioners in comparison to the sedentary participants, thus evidencing improved shifting abilities for active individuals. Interestingly, post hoc analysis showed significantly higher span scores of Corsi test only in Tai Chi practitioners as compared to sedentary participants, suggesting how multimodal PE facilitates the visuo-spatial working memory processes. Although preliminary, our descriptive study indicates that the type of PE could modulate specific cognitive domains, even if the practice of motor activity favors a global cognitive improvement.

Topological changes of fast large-scale brain dynamics in mild cognitive impairment predict early memory impairment: a resting-state, source reconstructed, magnetoencephalography study.

Functional connectivity has been used as a framework to investigate widespread brain interactions underlying cognitive deficits in mild cognitive impairment (MCI). However, many functional connectivity metrics focus on the average of the periodic activities, disregarding the aperiodic bursts of activity (i.e., the neuronal avalanches) characterizing the large-scale dynamic activities of the brain. Here, we apply the recently described avalanche transition matrix framework to source-reconstructed magnetoencephalography signals in a cohort of 32 MCI patients and 32 healthy controls to describe the spatio-temporal features of neuronal avalanches and explore their topological properties. Our results showed that MCI patients showed a more centralized network (as assessed by higher values of the degree divergence and leaf fraction) as compared to healthy controls. Furthermore, we found that the degree divergence (in the theta band) was predictive of hippocampal memory impairment. These findings highlight the role of the changes of aperiodic bursts in clinical conditions and may contribute to a more thorough phenotypical assessment of patients.

Brain fingerprint is based on the aperiodic, scale-free, neuronal activity.

Subject differentiation bears the possibility to individualize brain analyses. However, the nature of the processes generating subject-specific features remains unknown. Most of the current literature uses techniques that assume stationarity (e.g., Pearson's correlation), which might fail to capture the non-linear nature of brain activity. We hypothesize that non-linear perturbations (defined as neuronal avalanches in the context of critical dynamics) spread across the brain and carry subject-specific information, contributing the most to differentiability. To test this hypothesis, we compute the avalanche transition matrix (ATM) from source-reconstructed magnetoencephalographic data, as to characterize subject-specific fast dynamics. We perform differentiability analysis based on the ATMs, and compare the performance to that obtained using Pearson's correlation (which assumes stationarity). We demonstrate that selecting the moments and places where neuronal avalanches spread improves differentiation (P < 0.0001, permutation testing), despite the fact that most of the data (i.e., the linear part) are discarded. Our results show that the non-linear part of the brain signals carries most of the subject-specific information, thereby clarifying the nature of the processes that underlie individual differentiation. Borrowing from statistical mechanics, we provide a principled way to link emergent large-scale personalized activations to non-observable, microscopic processes.

Reduced clinical connectome fingerprinting in multiple sclerosis predicts fatigue severity.

BACKGROUND: Brain connectome fingerprinting is progressively gaining ground in the field of brain network analysis. It represents a valid approach in assessing the subject-specific connectivity and, according to recent studies, in predicting clinical impairment in some neurodegenerative diseases. Nevertheless, its performance, and clinical utility, in the Multiple Sclerosis (MS) field has not yet been investigated. METHODS: We conducted the Clinical Connectome Fingerprint (CCF) analysis on source-reconstructed magnetoencephalography signals in a cohort of 50 subjects: twenty-five MS patients and twenty-five healthy controls. RESULTS: All the parameters of identifiability, in the alpha band, were reduced in patients as compared to controls. These results implied a lower similarity between functional connectomes (FCs) of the same patient and a reduced homogeneity among FCs in the MS group. We also demonstrated that in MS patients, reduced identifiability was able to predict, fatigue level (assessed by the Fatigue Severity Scale). CONCLUSION: These results confirm the clinical usefulness of the CCF in both identifying MS patients and predicting clinical impairment. We hope that the present study provides future prospects for treatment personalization on the basis of individual brain connectome.

The Effects of Vibratory and Acoustic Stimulations on Postural Control in Healthy People: A Systematic Review.

Research on human posture and balance control has grown in recent years, leading to continued advances in their understanding. The ability to maintain balance is attributed to the interplay of the visual, vestibular, and somatosensory systems, although an important role is also played by the auditory system. The lack or deficit in any of these systems leads to a reduced stability that may be counterbalanced by the integration of all the remaining sensory information. Auditory and vibratory stimulation have been found to be useful to enhance balance alongside daily activities either in healthy or pathological subjects; nevertheless, while widely investigated, the literature relating to these approaches is still fragmented. This review aims at addressing this by collecting, organising, and discussing all the literature to date on the effects of the various acoustic and vibratory stimulation techniques available on static upright posture in healthy subjects. In addition, this review intends to provide a solid and comprehensive starting point for all the researchers interested in these research areas. A systematic search of the literature was performed and a total of 33 articles (24 on vibratory stimulation and 9 on acoustic stimulation) were included in our analysis. For all articles, several elements were highlighted including: the study sample, the characteristics of the stimulations, the recording instruments, the experimental protocols, and outcomes. Overall, both stimulations analysed were found to have a positive effect on balance but more research is needed to align those alternative approaches to the traditional ones.

Fading of brain network fingerprint in Parkinson's disease predicts motor clinical impairment.

The clinical connectome fingerprint (CCF) was recently introduced as a way to assess brain dynamics. It is an approach able to recognize individuals, based on the brain network. It showed its applicability providing network features used to predict the cognitive decline in preclinical Alzheimer's disease. In this article, we explore the performance of CCF in 47 Parkinson's disease (PD) patients and 47 healthy controls, under the hypothesis that patients would show reduced identifiability as compared to controls, and that such reduction could be used to predict motor impairment. We used source-reconstructed magnetoencephalography signals to build two functional connectomes for 47 patients with PD and 47 healthy controls. Then, exploiting the two connectomes per individual, we investigated the identifiability characteristics of each subject in each group. We observed reduced identifiability in patients compared to healthy individuals in the beta band. Furthermore, we found that the reduction in identifiability was proportional to the motor impairment, assessed through the Unified Parkinson's Disease Rating Scale, and, interestingly, able to predict it (at the subject level), through a cross-validated regression model. Along with previous evidence, this article shows that CCF captures disrupted dynamics in neurodegenerative diseases and is particularly effective in predicting motor clinical impairment in PD.

Boosting effect of regular sport practice in young adults: Preliminary results on cognitive and emotional abilities.

Several studies have shown that physical exercise (PE) improves behavior and cognitive functioning, reducing the risk of various neurological diseases, protecting the brain from the detrimental effects of aging, facilitating body recovery after injuries, and enhancing self-efficacy and self-esteem. Emotion processing and regulation abilities are also widely acknowledged to be key to success in sports. In this study, we aim to prove that regular participation in sports enhances cognitive and emotional functioning in healthy individuals. A sample of 60 students (mean age = 22.12; SD = 2.40; M = 30), divided into sportive and sedentary, were subjected to a neuropsychological tests battery to assess their overall cognitive abilities (Raven's Advanced Progressive Matrices, APM), verbal and graphic fluency (Word Fluency Task and modified Five Point Test, m-FPT), as well as their emotional awareness skills (Toronto Alexithymia Scale, TAS-20). Our results showed that sportive students performed better than sedentary ones in all cognitive tasks. Regarding emotional processing abilities, significant differences were found in the TAS-20 total score as well as in the Difficulty Describing Feelings (DDF) subscale and the Difficulty Identifying Feeling (DIF) subscale. Lastly, gender differences were found in the External-Oriented Thinking (EOT) subscale. Overall, our findings evidence that PE has positive effects on cognitive functioning and emotion regulation, suggesting how sports practice can promote mental health and wellbeing.

Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular, and neuroimaging evidence. As a consequence, predicting clinical features requires a description of large-scale neuronal dynamics. Normally, brain activity dynamically reconfigures over time, recruiting different brain areas. Brain pathologies induce stereotyped dynamics which, in turn, are linked to clinical impairment. Hence, based on recent evidence showing that brain functional networks become hyperconnected as ALS progresses, we hypothesized that the loss of flexible dynamics in ALS would predict the symptoms severity. METHODS: To test this hypothesis, we quantified flexibility using the "functional repertoire" (i.e., the number of configurations of active brain areas) as measured from source-reconstructed magnetoencephalography (MEG) in patients with ALS and healthy controls. The activity of brain areas was reconstructed in the classic frequency bands, and the functional repertoire was estimated to quantify spatiotemporal fluctuations of brain activity. Finally, we built a k-fold cross-validated multilinear model to predict the individual clinical impairment from the size of the functional repertoire. RESULTS: Comparing 42 patients with ALS and 42 healthy controls, we found a more stereotyped brain dynamics in patients with ALS (p < 0.05), as conveyed by the smaller functional repertoire. The relationship between the size of the functional repertoire and the clinical scores in the ALS group showed significant correlations in both the delta and the theta frequency bands. Furthermore, through a k-fold cross-validated multilinear regression model, we found that the functional repertoire predicted both clinical staging (p < 0.001 and p < 0.01, in the delta and theta bands, respectively) and symptoms severity (p < 0.001, in both the delta and theta bands). DISCUSSION: Our work shows that (1) ALS pathology reduces the flexibility of large-scale brain dynamics, (2) subcortical regions play a key role in determining brain dynamics, and (3) reduced brain flexibility predicts disease stage and symptoms severity. Our approach provides a noninvasive tool to quantify alterations in brain dynamics in ALS (and, possibly, other neurodegenerative diseases), thus opening new opportunities in disease management and a framework to test, in the near future, the effects of disease-modifying interventions at the whole-brain level.

The kinectome: A comprehensive kinematic map of human motion in health and disease.

Human voluntary movement stems from the coordinated activations in space and time of many musculoskeletal segments. However, the current methodological approaches to study human movement are still limited to the evaluation of the synergies among a few body elements. Network science can be a useful approach to describe movement as a whole and to extract features that are relevant to understanding both its complex physiology and the pathophysiology of movement disorders. Here, we propose to represent human movement as a network (that we named the kinectome), where nodes represent body points, and edges are defined as the correlations of the accelerations between each pair of them. We applied this framework to healthy individuals and patients with Parkinson's disease, observing that the patients' kinectomes display less symmetrical patterns as compared to healthy controls. Furthermore, we used the kinectomes to successfully identify both healthy and diseased subjects using short gait recordings. Finally, we highlighted topological features that predict the individual clinical impairment in patients. Our results define a novel approach to study human movement. While deceptively simple, this approach is well-grounded, and represents a powerful tool that may be applied to a wide spectrum of frameworks.

Brain network topology and personality traits: A source level magnetoencephalographic study.

Personality neuroscience is focusing on the correlation between individual differences and the efficiency of large-scale networks from the perspective of the brain as an interconnected network. A suitable technique to explore this relationship is the magnetoencephalography (MEG), but not many MEG studies are aimed at investigating topological properties correlated to personality traits. By using MEG, the present study aims to evaluate how individual differences described in Cloninger's psychobiological model are correlated with specific cerebral structures. Fifty healthy individuals (20 males, 30 females, mean age: 27.4 ± 4.8 years) underwent Temperament and Character Inventory examination and MEG recording during a resting state condition. High harm avoidance scores were associated with a reduced centrality of the left caudate nucleus and this negative correlation was maintained in females when we analyzed gender differences. Our data suggest that the caudate nucleus plays a key role in adaptive behavior and could be a critical node in insular salience network. The clear difference between males and females allows us to suggest that topological organization correlated to personality is highly dependent on gender. Our findings provide new insights to evaluate the mutual influences of topological and functional connectivity in neural communication efficiency and disruption as biomarkers of psychopathological traits.

Sensitivity to gait improvement after levodopa intake in Parkinson's disease: A comparison study among synthetic kinematic indices.

The synthetic indices are widely used to describe balance and stability during gait. Some of these are employed to describe the gait features in Parkinson's disease (PD). However, the results are sometimes inconsistent, and the same indices are rarely used to compare the individuals affected by PD before and after levodopa intake (OFF and ON condition, respectively). Our aim was to investigate which synthetic measure among Harmonic Ratio, Jerk Ratio, Golden Ratio and Trunk Displacement Index is representative of gait stability and harmony, and which of these are more sensitive to the variations between OFF and ON condition. We found that all indices, except the Jerk Ratio, significantly improve after levodopa. Only the improvement of the Trunk Displacement Index showed a direct correlation with the motor improvement measured through the clinical scale UPDRS-III (Unified Parkinson's Disease Rating Scale-part III). In conclusion, we suggest that the synthetic indices can be useful to detect motor changes induced by, but not all of them clearly correlate with the clinical changes achieved with the levodopa administration. In our analysis, only the Trunk Displacement Index was able to show a clear relationship with the PD clinical motor improvement.

A night of sleep deprivation alters brain connectivity and affects specific executive functions.

Sleep is a fundamental physiological process necessary for efficient cognitive functioning especially in relation to memory consolidation and executive functions, such as attentional and switching abilities. The lack of sleep strongly alters the connectivity of some resting-state networks, such as default mode network and attentional network. In this study, by means of magnetoencephalography (MEG) and specific cognitive tasks, we investigated how brain topology and cognitive functioning are affected by 24 h of sleep deprivation (SD). Thirty-two young men underwent resting-state MEG recording and evaluated in letter cancellation task (LCT) and task switching (TS) before and after SD. Results showed a worsening in the accuracy and speed of execution in the LCT and a reduction of reaction times in the TS, evidencing thus a worsening of attentional but not of switching abilities. Moreover, we observed that 24 h of SD induced large-scale rearrangements in the functional network. These findings evidence that 24 h of SD is able to alter brain connectivity and selectively affects cognitive domains which are under the control of different brain networks.

The effects of different frequencies of rhythmic acoustic stimulation on gait stability in healthy elderly individuals: a pilot study.

The efficacy of rhythmic acoustic stimulation (RAS) to improve gait and balance in healthy elderly individuals is controversial. Our aim was to investigate, through 3D gait analysis, the effect of different types of RAS (fixed frequency and based on subject-specific cadence), using conventional gait parameters and the trunk displacement as readouts. Walking at a fixed frequency of 80 bpm, the subjects showed extended duration of gait cycle and increased gait variability while the same individuals, walking at a fixed frequency of 120 bpm, showed reduced trunk sway and gait cycle duration. With regard to the RAS at subject-specific frequencies, walking at 90% of the subject-specific average cadence did not significantly modify the gait parameters, except for the speed, which was reduced. In contrast, walking at 100% and 110% of the mean cadence caused increased stride length and a slight reduction of temporal parameters and trunk sway. In conclusion, this pilot study shows that using RAS at fixed frequencies might be an inappropriate strategy, as it is not adjusted to individual gait characteristics. On the other hand, RAS frequencies equal to or slightly higher than each subject's natural cadence seem to be beneficial for gait and stability.