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.

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.

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.

Robotic Surgery in Achalasia: State of the Art.

Introduction: Achalasia is a rare primary esophageal disorder characterized by impaired functioning of the lower esophageal sphincter. The goal of treatment is to reduce symptoms and improve the quality of life. The gold standard of surgical approach is Heller-Dor myotomy. The aim of this review is to describe the use of robotic surgery in patients with achalasia. Methods: The literature review was performed by searching on PubMed, Web of Science, Scopus and EMBASE for all studies on robotic surgery for achalasia, published from January 1, 2001, to December 31, 2022. We focused our attention on randomized controlled trials (RCTs), metaanalysis, systematic reviews, and observational studies on large cohorts of patients. Furthermore, we have identified relevant articles from the reference list. Conclusions: Taking into consideration our review and experience, RHM with partial fundoplication is safe, efficient, comfortable for the surgeon and characterized by a reduction of the intraoperative perforation rate of the esophageal mucosa. This approach may represent the future for the surgical treatment of achalasia especially with a reduction in costs.

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.

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.

Clinical connectome fingerprints of cognitive decline.

Brain connectome fingerprinting is rapidly rising as a novel influential field in brain network analysis. Yet, it is still unclear whether connectivity fingerprints could be effectively used for mapping and predicting disease progression from human brain data. We hypothesize that dysregulation of brain activity in disease would reflect in worse subject identification. We propose a novel framework, Clinical Connectome Fingerprinting, to detect individual connectome features from clinical populations. We show that "clinical fingerprints" can map individual variations between elderly healthy subjects and patients with mild cognitive impairment in functional connectomes extracted from magnetoencephalography data. We find that identifiability is reduced in patients as compared to controls, and show that these connectivity features are predictive of the individual Mini-Mental State Examination (MMSE) score in patients. We hope that the proposed methodology can help in bridging the gap between connectivity features and biomarkers of brain dysfunction in large-scale brain networks.

Functional brain network topology across the menstrual cycle is estradiol dependent and correlates with individual well-being.

The menstrual cycle (MC) is a sex hormone-related phenomenon that repeats itself cyclically during the woman's reproductive life. In this explorative study, we hypothesized that coordinated variations of multiple sex hormones may affect the large-scale organization of the brain functional network and that, in turn, such changes might have psychological correlates, even in the absence of overt clinical signs of anxiety and/or depression. To test our hypothesis, we investigated longitudinally, across the MC, the relationship between the sex hormones and both brain network and psychological changes. We enrolled 24 naturally cycling women and, at the early-follicular, peri-ovulatory, and mid-luteal phases of the MC, we performed: (a) sex hormone dosage, (b) magnetoencephalography recording to study the brain network topology, and (c) psychological questionnaires to quantify anxiety, depression, self-esteem, and well-being. We showed that during the peri-ovulatory phase, in the alpha band, the leaf fraction and the tree hierarchy of the brain network were reduced, while the betweenness centrality (BC) of the right posterior cingulate gyrus (rPCG) was increased. Furthermore, the increase in BC was predicted by estradiol levels. Moreover, during the luteal phase, the variation of estradiol correlated positively with the variations of both the topological change and environmental mastery dimension of the well-being test, which, in turn, was related to the increase in the BC of rPCG. Our results highlight the effects of sex hormones on the large-scale brain network organization as well as on their possible relationship with the psychological state across the MC. Moreover, the fact that physiological changes in the brain topology occur throughout the MC has widespread implications for neuroimaging studies.

Mutations in the SPAST gene causing hereditary spastic paraplegia are related to global topological alterations in brain functional networks.

AIM: Our aim was to describe the rearrangements of the brain activity related to genetic mutations in the SPAST gene. METHODS: Ten SPG4 patients and ten controls underwent a 5 min resting state magnetoencephalography recording and neurological examination. A beamformer algorithm reconstructed the activity of 90 brain areas. The phase lag index was used to estimate synchrony between brain areas. The minimum spanning tree was used to estimate topological metrics such as the leaf fraction (a measure of network integration) and the degree divergence (a measure of the resilience of the network against pathological events). The betweenness centrality (a measure to estimate the centrality of the brain areas) was used to estimate the centrality of each brain area. RESULTS: Our results showed topological rearrangements in the beta band. Specifically, the degree divergence was lower in patients as compared to controls and this parameter related to clinical disability. No differences appeared in leaf fraction nor in betweenness centrality. CONCLUSION: Mutations in the SPAST gene are related to a reorganization of the brain topology.

Effects of Acetylcholine on ß-Amyloid-Induced cPLA2 Activation in the TB Neuroectodermal Cell Line: Implications for the Pathogenesis of Alzheimer's Disease.

The role of ß-amyloid (Aß) in the pathogenesis of Alzheimer's disease (AD) is still considered crucial. The state of Aß aggregation is critical in promoting neuronal loss and neuronal function impairment. Recently, we demonstrated that Acetylcholine (ACh) is neuroprotective against the toxic effects of Aß in the cholinergic LAN-2 cells. In biophysical experiments, ACh promotes the soluble Aß peptide conformation rather than the aggregation-prone ß-sheet conformation. In order to better understand the biological role of ACh in AD, we studied the effect of Aß on the phosphorylation of the cytosolic phospholipase A2 (cPLA2) in the TB neuroectodermal cell line, which differentiates toward a neuronal phenotype when cultured in the presence of retinoic acid (RA). We chose the phosphorylated form of cPLA2 (Ser505, Phospho-cPLA2) as a biomarker to test the influence of ACh on the effects of Aß in both undifferentiated and RA-differentiated TB cells. Our results show that TB cells are responsive to Aß. Moreover, in undifferentiated cells 1 h treatment with Aß induces a 2.5-fold increase of the Phospho-cPLA2 level compared to the control after 24 h in vitro, while no significant difference is observed between Aß-treated and non-treated cells after 4 and 7 days in vitro. The RA-differentiated cells are not sensitive to Aß. In TB cell line ACh is able to blunt the effects of Aß. The ability of ACh to protect non-cholinergic cells against Aß reinforces the hypothesis that, in addition to its role in cholinergic transmission, ACh could also act as a neuroprotective agent.

Neurodegeneration of brain networks in the amyotrophic lateral sclerosis-frontotemporal lobar degeneration (ALS-FTLD) continuum: evidence from MRI and MEG studies.

Brain imaging techniques, especially those based on magnetic resonance imaging (MRI) and magnetoencephalography (MEG), have been increasingly applied to study multiple large-scale distributed brain networks in healthy people and neurological patients. With regard to neurodegenerative disorders, amyotrophic lateral sclerosis (ALS), clinically characterized by the predominant loss of motor neurons and progressive weakness of voluntary muscles, and frontotemporal lobar degeneration (FTLD), the second most common early-onset dementia, have been proven to share several clinical, neuropathological, genetic, and neuroimaging features. Specifically, overlapping or mildly diverging brain structural and functional connectivity patterns, mostly evaluated by advanced MRI techniques-such as diffusion tensor and resting-state functional MRI (DT-MRI, RS-fMRI)-have been described comparing several ALS and FTLD populations. Moreover, though only pioneering, promising clues on connectivity patterns in the ALS-FTLD continuum may derive from MEG investigations. We will herein overview the current state of knowledge concerning the most advanced neuroimaging findings associated with clinical and genetic patterns of neurodegeneration across the ALS-FTLD continuum, underlying the possibility that network-based approaches may be useful to develop novel biomarkers of disease for adequately designing and monitoring more appropriate treatment strategies.

Functional Role of Internal and External Visual Imagery: Preliminary Evidences from Pilates.

The present study investigates whether a functional difference between the visualization of a sequence of movements in the perspective of the first- (internal VMI-I) or third- (external VMI-E) person exists, which might be relevant to promote learning. By using a mental chronometry experimental paradigm, we have compared the time or execution, imagination in the VMI-I perspective, and imagination in the VMI-E perspective of two kinds of Pilates exercises. The analysis was carried out in individuals with different levels of competence (expert, novice, and no-practice individuals). Our results showed that in the Expert group, in the VMI-I perspective, the imagination time was similar to the execution time, while in the VMI-E perspective, the imagination time was significantly lower than the execution time. An opposite pattern was found in the Novice group, in which the time of imagination was similar to that of execution only in the VMI-E perspective, while in the VMI-I perspective, the time of imagination was significantly lower than the time of execution. In the control group, the times of both modalities of imagination were significantly lower than the execution time for each exercise. The present data suggest that, while the VMI-I serves to train an already internalised gesture, the VMI-E perspective could be useful to learn, and then improve, the recently acquired sequence of movements. Moreover, visual imagery is not useful for individuals that lack a specific motor experience. The present data offer new insights in the application of mental training techniques, especially in field of sports. However, further investigations are needed to better understand the functional role of internal and external visual imagery.

Mindfulness Meditation Is Related to Long-Lasting Changes in Hippocampal Functional Topology during Resting State: A Magnetoencephalography Study.

It has been suggested that the practice of meditation is associated to neuroplasticity phenomena, reducing age-related brain degeneration and improving cognitive functions. Neuroimaging studies have shown that the brain connectivity changes in meditators. In the present work, we aim to describe the possible long-term effects of meditation on the brain networks. To this aim, we used magnetoencephalography to study functional resting-state brain networks in Vipassana meditators. We observed topological modifications in the brain network in meditators compared to controls. More specifically, in the theta band, the meditators showed statistically significant (p corrected = 0.009) higher degree (a centrality index that represents the number of connections incident upon a given node) in the right hippocampus as compared to controls. Taking into account the role of the hippocampus in memory processes, and in the pathophysiology of Alzheimer's disease, meditation might have a potential role in a panel of preventive strategies.

Comparative Study of Chemical, Biochemical Characteristic and ATR-FTIR Analysis of Seeds, Oil and Flour of the Edible Fedora Cultivar Hemp (Cannabis sativa L.).

A series of chemical and biochemical parameters of edible hemp resources (seeds, oil, and flour) from the monoecious EU registered hemp genotype Fedora, was determined, including fatty acid profile, phytosterol composition, total phenolics, antioxidant activity, macro- and micro-elements. The fatty acid ω-3/ω-6 approached the nutritionally optimal 3/1 ratio. ß-sitosterol and other phytosterols sterols dominated the unsaponifiable fraction. Hemp seeds, flour, and oil contained 767 ± 41, 744 ± 29, and 21 ± 5 mg GAE kg-1 total polyphenols, respectively. The antioxidant potential of Fedora flour and seeds, evaluated through the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, was higher than that of oil. K and Mg were the most abundant macro-elements, particularly in flour, while the concentration of trace elements was Fe > Cu > Ni > Mn. The presence of an array of bioactive compound candidate Fedora products as health-promoting food matrices. The ATR-FTIR spectra of hemp-derived products indicated the proximate composition of macro-nutrients.

Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies.

We do not all grow older in the same way. Some individuals have a cognitive decline earlier and faster than others who are older in years but cerebrally younger. This is particularly easy to verify in people who have maintained regular physical activity and healthy and cognitively stimulating lifestyle and even in the clinical field. There are patients with advanced neurodegeneration, such as Alzheimer's disease (AD), that, despite this, have mild cognitive impairment. What determines this interindividual difference? Certainly, it cannot be the result of only genetic factors. We are made in a certain manner and what we do acts on our brain. In fact, our genetic basis can be modulated, modified, and changed by our experiences such as education and life events; daily, by sleep schedules and habits; or also by dietary elements. And this can be seen as true even if our experiences are indirectly driven by our genetic basis. In this paper, we will review some current scientific research on how our experiences are able to modulate the structural organization of the brain and how a healthy lifestyle (regular physical activity, correct sleep hygiene, and healthy diet) appears to positively affect cognitive reserve.

Effects of Global Postural Reeducation on gait kinematics in parkinsonian patients: a pilot randomized three-dimensional motion analysis study.

The Global Postural Reeducation (GPR) method is a physical therapy based on the stretching of antigravity muscle chains with the parallel enhancement of the basal tone of antagonistic muscles addressed to improve static and dynamic stability. Through a three-dimensional motion analysis (3DMA) system, our study aims to investigate whether in Parkinson's disease (PD) patients a GPR program results in a more physiological gait pattern. The kinematic parameters of gait of twenty subjects with clinically diagnosed PD were calculated. The patients were randomly assigned to a study (10 or control (10) group. All subjects underwent neurological and 3DMA assessments at entry time (t 0), at 4 weeks (t 1, end of GPR program), and at 8 and 12 weeks (t 2 and t 3, follow-up evaluation). The study group underwent a four-week GPR program, three times a week, for 40 min individual sessions. Kinematic gait parameters of thigh (T), knee (K) and ankle (A) and UPDRS-III scores were evaluated. At the end of the GPR program, we observed an improvement of the kinematic gait pattern, documented by the increase in KΔc and TΔc values that respectively express the flexion amplitude of knee and thigh. The amelioration was persistent at follow-up assessments, with a parallel enhancement in clinical parameters. GPR intervention shows a long-term efficacy on gait pattern in PD patients. Furthermore, we validated 3DMA as a valuable tool to study the kinematics of gait thus refining the understanding of the effects of specific rehabilitation programs.

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.

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.

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.

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.