191 research outputs found
THE IMPACT OF MILD TRAUMATIC BRAIN INJURY ON TIME-FREQUENCY ERP MEASURES AND NEUROPSYCHOLOGICAL FUNCTIONING: A LONGITUDINAL STUDY OF ACUTELY INJURED SERVICE MEMBERS
Traumatic Brain Injury (TBI) is the most common injury in recent military conflicts, with nearly 500,000 service members sustaining a TBI since 2000. Mild TBI (mTBI), or concussion, is by far the most common type of TBI and has been associated with long-term cognitive complaints and functional impairment. While clinical assessment of mTBI (i.e., MRI and performance-based cognitive testing) occasionally captures subtle abnormalities in the acute period following mTBI, these measurements lack the sensitivity to assess the time course of cognitive recovery from mTBI. The current study assessed cognitive changes from the acute to chronic period following mTBI using advanced time-frequency event-related potential (ERP) analysis, which isolates rapid regional brain activity and measures the functional communication within and between brain networks in response to varying task stimuli. The validity of these ERP biomarkers was evaluated with correlations between abnormal ERP findings and widely used clinical measures of cognitive functioning (i.e., neuropsychological tests and self-reported cognitive symptoms). Differences between mTBI caused by blast explosion versus impact to the head were also evaluated. A sample of 173 service members, comprising an mTBI group, an orthopedically-injured control group, and a healthy control group, completed ERP, neuropsychological, and self-report assessments within weeks following injury and again six months later. Results suggested that mTBI leads to cognitive changes that persist in the acute to post-acute period following injury (i.e., up to 12 weeks). These cognitive changes were reflected by alterations in ERP time-frequency amplitude and functional connectivity measures, and they remained apparent even when controlling for psychiatric symptoms. ERP differences were also evident between blast-related and impact-related mTBI. Conversely, neuropsychological test performance was not sensitive to mTBI. Abnormal ERP time-frequency measures were related to self-reported cognitive symptoms, suggesting these ERP measures are valid biomarkers of cognitive difficulties following mTBI. Critically, cognitive functioning as assessed by ERP measures returned to a level indistinguishable from controls 7-9 months following mTBI, even though more than a third of mTBI patients continued to report cognitive symptoms. These persistent cognitive complaints were more related to post-injury psychiatric symptoms than to the direct effects of brain injury
Cognitive Assessment and Rehabilitation of subjects with Traumatic Brain Injury
This thesis regards the study and the development of new cognitive assessment and rehabilitation techniques of subjects with traumatic brain injury (TBI).
In particular, this thesis i) provides an overview about the state of art of this new assessment and rehabilitation technologies, ii) suggests new methods for the assessment and rehabilitation and iii) contributes to the explanation of the neurophysiological mechanism that is involved in a rehabilitation treatment.
Some chapters provide useful information to contextualize TBI and its outcome; they describe the methods used for its assessment/rehabilitation. The other chapters illustrate a series of experimental studies conducted in healthy subjects and TBI patients that suggest new approaches to assessment and rehabilitation. The new proposed approaches have in common the use of electroencefalografy (EEG). EEG was used in all the experimental studies with a different purpose, such as diagnostic tool, signal to command a BCI-system, outcome measure to evaluate the effects of a treatment, etc.
The main achieved results are about: i) the study and the development of a system for the communication with patients with disorders of consciousness. It was possible to identify a paradigm of reliable activation during two imagery task using EEG signal or EEG and NIRS signal; ii) the study of the effects of a neuromodulation technique (tDCS) on EEG pattern. This topic is of great importance and interest. The emerged founding showed that the tDCS can manipulate the cortical network activity and through the research of optimal stimulation parameters, it is possible move the working point of a neural network and bring it in a condition of maximum learning. In this way could be possible improved the performance of a BCI system or to improve the efficacy of a rehabilitation treatment, like neurofeedback
Detection of Mild Cognitive Impairment with MEG Functional Connectivity using Wavelet-based Neuromarkers
Studies on developing effective neuromarkers based on magnetoencephalographic (MEG) signals have been drawing increasing attention in the neuroscience community. This study explores the idea of using source-based magnitude-squared spectral coherence as a spatial indicator for effective regions of interest (ROIs) localization, subsequently discriminating the participants with mild cognitive impairment (MCI) from a group of age-matched healthy control (HC) elderly participants. We found that the cortical regions could be divided into two distinctive groups based on their coherence indices. Compared to HC, some ROIs showed increased connectivity (hyper-connected ROIs) for MCI participants, whereas the remaining ROIs demonstrated reduced connectivity (hypo-connected ROIs). Based on these findings, a series of wavelet-based source-level neuromarkers for MCI detection are proposed and explored, with respect to the two distinctive ROI groups. It was found that the neuromarkers extracted from the hyper-connected ROIs performed significantly better for MCI detection than those from the hypo-connected ROIs. The neuromarkers were classified using support vector machine (SVM) and k-NN classifiers and evaluated through Monte Carlo cross-validation. An average recognition rate of 93.83% was obtained using source-reconstructed signals from the hyper-connected ROI group. To better conform to clinical practice settings, a leave-one-out cross-validation
(LOOCV) approach was also employed to ensure that the data for testing was from a participant that the classifier has never seen. Using LOOCV, we found the best average classification accuracy was reduced to 83.80% using the same set of neuromarkers obtained from the ROI group with functional hyper-connections. This performance surpassed the results reported using wavelet-based features by approximately 15%. Overall, our work suggests that (1) certain ROIs are particularly effective for MCI detection, especially when multi-resolution wavelet biomarkers are employed for such diagnosis; (2) there exists a significant performance difference in system evaluation between research-based
experimental design and clinically accepted evaluation standards
Intrinsic functional brain connectivity changes following aerobic exercise, computerized cognitive training, and their combination in physically inactive healthy late-middle-aged adults: the Projecte Moviment
Lifestyle interventions have positive neuroprotective effects in aging. However, there are still open questions about how changes in resting-state functional connectivity (rsFC) contribute to cognitive improvements. The Projecte Moviment is a 12-week randomized controlled trial of a multimodal data acquisition protocol that investigated the effects of aerobic exercise (AE), computerized cognitive training (CCT), and their combination (COMB). An initial list of 109 participants was recruited from which a total of 82 participants (62% female; age¿=¿58.38¿±¿5.47) finished the intervention with a level of adherence¿>¿80%. Only in the COMB group, we revealed an extended network of 33 connections that involved an increased and decreased rsFC within and between the aDMN/pDMN and a reduced rsFC between the bilateral supplementary motor areas and the right thalamus. No global and especially local rsFC changes due to any intervention mediated the cognitive benefits detected in the AE and COMB groups. Projecte Moviment provides evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Projecte Moviment is a project funded by the Spanish Ministry of Economy and Competitiveness under two grants: Neuroplasticity in the adulthood: physical exercise and cognitive training (PSI2013-47724-P) and Integrative omics study on the neurobiological effects of physical activity and cognitive stimulation (PSI2016-77475-R). It has also been rewarded with three pre-doctoral fellowships (FPU014/01460, FI-2016, and FI-2018). It was supported by the ICREA Academia Program to MM.SID is supported by a Beatriu de Pinós
fellowship (2020 BP 00116). This work was supported by the
Spanish Ministry of Economy and Competitiveness (www.
mineco.gob.es) PID2021-122952OB-I00, Networking Biomedical Research Centre in the subject area of Bioengineering,
Biomaterials and Nanomedicine (CIBER-BBN), initiatives of
Instituto de InvestigaciĂłn Carlos III (ISCIII), and Share4Rare
project (Grant Agreement 780262).Peer ReviewedPostprint (published version
Leveraging Artificial Intelligence to Improve EEG-fNIRS Data Analysis
La spectroscopie proche infrarouge fonctionnelle (fNIRS) est apparue comme une technique de neuroimagerie qui permet une surveillance non invasive et à long terme de l'hémodynamique corticale. Les technologies de neuroimagerie multimodale en milieu clinique permettent d'étudier les maladies neurologiques aiguës et chroniques. Dans ce travail, nous nous concentrons sur l'épilepsie - un trouble chronique du système nerveux central affectant près de 50 millions de personnes dans le monde entier prédisposant les individus affectés à des crises récurrentes. Les crises sont des aberrations transitoires de l'activité électrique du cerveau qui conduisent à des symptômes physiques perturbateurs tels que des changements aigus ou chroniques des compétences cognitives, des hallucinations sensorielles ou des convulsions de tout le corps. Environ un tiers des patients épileptiques sont récalcitrants au traitement pharmacologique et ces crises intraitables présentent un risque grave de blessure et diminuent la qualité de vie globale. Dans ce travail, nous étudions 1. l'utilité des informations hémodynamiques dérivées des signaux fNIRS dans une tâche de détection des crises et les avantages qu'elles procurent dans un environnement multimodal par rapport aux signaux électroencéphalographiques (EEG) seuls, et 2. la capacité des signaux neuronaux, dérivé de l'EEG, pour prédire l'hémodynamique dans le cerveau afin de mieux comprendre le cerveau épileptique. Sur la base de données rétrospectives EEG-fNIRS recueillies auprès de 40 patients épileptiques et utilisant de nouveaux modèles d'apprentissage en profondeur, la première étude de cette thèse suggère que les signaux fNIRS offrent une sensibilité et une spécificité accrues pour la détection des crises par rapport à l'EEG seul. La validation du modèle a été effectuée à l'aide de l'ensemble de données CHBMIT open source documenté et bien référencé avant d'utiliser notre ensemble de données EEG-fNIRS multimodal interne. Les résultats de cette étude ont démontré que fNIRS améliore la détection des crises par rapport à l'EEG seul et ont motivé les expériences ultérieures qui ont déterminé la capacité prédictive d'un modèle d'apprentissage approfondi développé en interne pour décoder les signaux d'état de repos hémodynamique à partir du spectre complet et d'une bande de fréquences neuronale codée spécifique signaux d'état de repos (signaux sans crise). Ces résultats suggèrent qu'un autoencodeur multimodal peut apprendre des relations multimodales pour prédire les signaux d'état de repos. Les résultats suggèrent en outre que des gammes de fréquences EEG plus élevées prédisent l'hémodynamique avec une erreur de reconstruction plus faible par rapport aux gammes de fréquences EEG plus basses. De plus, les connexions fonctionnelles montrent des modèles spatiaux similaires entre l'état de repos expérimental et les prédictions fNIRS du modèle. Cela démontre pour la première fois que l'auto-encodage intermodal à partir de signaux neuronaux peut prédire l'hémodynamique cérébrale dans une certaine mesure. Les résultats de cette thèse avancent le potentiel de l'utilisation d'EEG-fNIRS pour des tâches cliniques pratiques (détection des crises, prédiction hémodynamique) ainsi que l'examen des relations fondamentales présentes dans le cerveau à l'aide de modèles d'apprentissage profond. S'il y a une augmentation du nombre d'ensembles de données disponibles à l'avenir, ces modèles pourraient être en mesure de généraliser les prédictions qui pourraient éventuellement conduire à la technologie EEG-fNIRS à être utilisée régulièrement comme un outil clinique viable dans une grande variété de troubles neuropathologiques.----------ABSTRACT
Functional near-infrared spectroscopy (fNIRS) has emerged as a neuroimaging technique that allows for non-invasive and long-term monitoring of cortical hemodynamics. Multimodal neuroimaging technologies in clinical settings allow for the investigation of acute and chronic neurological diseases. In this work, we focus on epilepsy—a chronic disorder of the central nervous system affecting almost 50 million people world-wide predisposing affected individuals to recurrent seizures. Seizures are transient aberrations in the brain's electrical activity that lead to disruptive physical symptoms such as acute or chronic changes in cognitive skills, sensory hallucinations, or whole-body convulsions. Approximately a third of epileptic patients are recalcitrant to pharmacological treatment and these intractable seizures pose a serious risk for injury and decrease overall quality of life. In this work, we study 1) the utility of hemodynamic information derived from fNIRS signals in a seizure detection task and the benefit they provide in a multimodal setting as compared to electroencephalographic (EEG) signals alone, and 2) the ability of neural signals, derived from EEG, to predict hemodynamics in the brain in an effort to better understand the epileptic brain. Based on retrospective EEG-fNIRS data collected from 40 epileptic patients and utilizing novel deep learning models, the first study in this thesis suggests that fNIRS signals offer increased sensitivity and specificity metrics for seizure detection when compared to EEG alone. Model validation was performed using the documented open source and well referenced CHBMIT dataset before using our in-house multimodal EEG-fNIRS dataset. The results from this study demonstrated that fNIRS improves seizure detection as compared to EEG alone and motivated the subsequent experiments which determined the predictive capacity of an in-house developed deep learning model to decode hemodynamic resting state signals from full spectrum and specific frequency band encoded neural resting state signals (seizure free signals). These results suggest that a multimodal autoencoder can learn multimodal relations to predict resting state signals. Findings further suggested that higher EEG frequency ranges predict hemodynamics with lower reconstruction error in comparison to lower EEG frequency ranges. Furthermore, functional connections show similar spatial patterns between experimental resting state and model fNIRS predictions. This demonstrates for the first time that intermodal autoencoding from neural signals can predict cerebral hemodynamics to a certain extent. The results of this thesis advance the potential of using EEG-fNIRS for practical clinical tasks (seizure detection, hemodynamic prediction) as well as examining fundamental relationships present in the brain using deep learning models. If there is an increase in the number of datasets available in the future, these models may be able to generalize predictions which would possibly lead to EEG-fNIRS technology to be routinely used as a viable clinical tool in a wide variety of neuropathological disorders
Magnetoencephalography for the investigation and diagnosis of Mild Traumatic Brain Injury
Mild Traumatic Brain Injury (mTBI), (or concussion), is the most common type of brain injury. Despite this, it often goes undiagnosed and can cause long term disability—most likely caused by the disruption of axonal connections in the brain. Objective methods for diagnosis and prognosis are needed but clinically available neuroimaging modalities rarely show structural abnormalities, even when patients suffer persisting functional deficits. In the past three decades, new powerful techniques to image brain structure and function have shown promise in detecting mTBI related changes. Magnetoencephalography (MEG), which measures electrical brain activity by detecting magnetic fields outside the head generated by neural currents, is particularly sensitive and has therefore gained interest from researchers. Numerous studies are proposing abnormal low-frequency neural oscillations and functional connectivity—the statistical interdependency of signals from separate brain regions—as potential biomarkers for mTBI. However, typically small sample sizes, the lack of replication between groups, the heterogeneity of the cohorts studied, and the lack of longitudinal studies impedes the adoption of MEG as a clinical tool in mTBI management. In particular, little is known about the acute phase of mTBI.
In this thesis, some of these gaps will be addressed by analysing MEG data from individuals with mTBI, using novel as well as conventional methods. The potential future of MEG in mTBI research will also be addressed by testing the capabilities of a wearable MEG system based on optically pumped magnetometers (OPMs).
The thesis contains three main experimental studies. In study 1, we investigated the signal dynamics underlying MEG abnormalities, found in a cohort of subjects scanned within three months of an mTBI, using a Hidden Markov Model (HMM), as growing evidence suggests that neural dynamics are (in part) driven by transient bursting events. Applying the HMM to resting-state data, we show that previously reported findings of diminished intrinsic beta amplitude and connectivity in individuals with mTBI (compared to healthy controls) can be explained by a reduction in the beta-band content of pan-spectral bursts and a loss in the temporal coincidence of bursts respectively. Using machine learning, we find the functional connections driving group differences and achieve classification accuracies of 98%. In a motor task, mTBI resulted in reduced burst amplitude, altered modulation of burst probability during movement and decreased connectivity in the motor network.
In study 2, we further test our HMM-based method in a cohort of subjects with mTBI and non-head trauma—scanned within two weeks of injury—to ensure specificity of any observed effects to mTBI and replicate our previous finding of reduced connectivity and high classification accuracy, although not the reduction in burst amplitude. Burst statistics were stable over both studies—despite data being acquired at different sites, using different scanners. In the same cohort, we applied a more conventional analysis of delta-band power. Although excess low-frequency power appears to be a promising candidate marker for persistently symptomatic mTBI, insufficient data exist to confirm this pattern in acute mTBI. We found abnormally high delta power to be a sensitive measure for discriminating mTBI subjects from healthy controls, however, similarly elevated delta amplitude was found in the cohort with non-head trauma, suggesting that excess delta may not be specific to mTBI, at least in the acute stage of injury.
Our work highlights the need for longitudinal assessment of mTBI. In addition, there appears to be a need to investigate naturalistic paradigms which can be tailored to induce activity in symptom-relevant brain networks and consequently are likely to be more sensitive biomarkers than the resting state scans used to date. Wearable OPM-MEG makes naturalistic scanning possible and may offer a cheaper and more accessible alternative to cryogenic MEG, however, before deploying OPMs clinically, or in pitch-side assessment for athletes, for example, the reliability of OPM-derived measures needs to be verified. In the third and final study, we performed a repeatability study using a novel motor task, estimating a series of common MEG measures and quantifying the reliability of both activity and connectivity derived from OPM-MEG data. These initial findings—presently limited to a small sample of healthy controls—demonstrate the utility of OPM-MEG and pave the way for this technology to be deployed on patients with mTBI
Advances in Clinical Neurophysiology
Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests
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Network approaches to understanding the functional effects of focal brain lesions
Complex network models of functional connectivity have emerged as a paradigm shift in brain mapping over the past decade. Despite significant attention within the neuroimaging and cognitive neuroscience communities, these approaches have hitherto not been extensively explored in neurosurgery. The aim of this thesis is to investigate how the field of connectomics can contribute to understanding the effects of focal brain lesions and to functional brain mapping in neurosurgery.
This datasets for this thesis include a clinical population with focal brain tumours and a cohort focused on healthy adolescent brain development. Multiple network analyses of increasing complexity are performed based upon resting state functional MRI.
In patients with focal brain tumours, the full complement of resting state networks were apparent, while also suggesting putative patterns of network plasticity. Connectome analysis was able to identify potential signatures of node robustness and connections at risk that could be used to individually plan surgery. Focal lesions induced the formation of new hubs while down regulating previously established hubs. Overall these data are consistent with a dynamic rather than a static response to the presence of focal lesions.
Adolescent brain development demonstrated discrete dynamics with distinct gender specific and age-gender interactions. Network architecture also became more robust, particularly to random removal of nodes and edges. Overall these data provide evidence for the early vulnerability rather than enhanced plasticity of brain networks.
In summary, this thesis presents a combined analysis of pathological and healthy development datasets focused on understanding the functional effects of focal brain lesions at a network level. The coda serves as an introduction to a forthcoming study, known as Connectomics and Electrical Stimulation for Augmenting Resection (CAESAR), which is an evolution of the results and methods herein.MGH is funded by the Wellcome Trust Neuroscience in Psychiatry Network with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre
Magnetoencephalography for the investigation and diagnosis of Mild Traumatic Brain Injury
Mild Traumatic Brain Injury (mTBI), (or concussion), is the most common type of brain injury. Despite this, it often goes undiagnosed and can cause long term disability—most likely caused by the disruption of axonal connections in the brain. Objective methods for diagnosis and prognosis are needed but clinically available neuroimaging modalities rarely show structural abnormalities, even when patients suffer persisting functional deficits. In the past three decades, new powerful techniques to image brain structure and function have shown promise in detecting mTBI related changes. Magnetoencephalography (MEG), which measures electrical brain activity by detecting magnetic fields outside the head generated by neural currents, is particularly sensitive and has therefore gained interest from researchers. Numerous studies are proposing abnormal low-frequency neural oscillations and functional connectivity—the statistical interdependency of signals from separate brain regions—as potential biomarkers for mTBI. However, typically small sample sizes, the lack of replication between groups, the heterogeneity of the cohorts studied, and the lack of longitudinal studies impedes the adoption of MEG as a clinical tool in mTBI management. In particular, little is known about the acute phase of mTBI.
In this thesis, some of these gaps will be addressed by analysing MEG data from individuals with mTBI, using novel as well as conventional methods. The potential future of MEG in mTBI research will also be addressed by testing the capabilities of a wearable MEG system based on optically pumped magnetometers (OPMs).
The thesis contains three main experimental studies. In study 1, we investigated the signal dynamics underlying MEG abnormalities, found in a cohort of subjects scanned within three months of an mTBI, using a Hidden Markov Model (HMM), as growing evidence suggests that neural dynamics are (in part) driven by transient bursting events. Applying the HMM to resting-state data, we show that previously reported findings of diminished intrinsic beta amplitude and connectivity in individuals with mTBI (compared to healthy controls) can be explained by a reduction in the beta-band content of pan-spectral bursts and a loss in the temporal coincidence of bursts respectively. Using machine learning, we find the functional connections driving group differences and achieve classification accuracies of 98%. In a motor task, mTBI resulted in reduced burst amplitude, altered modulation of burst probability during movement and decreased connectivity in the motor network.
In study 2, we further test our HMM-based method in a cohort of subjects with mTBI and non-head trauma—scanned within two weeks of injury—to ensure specificity of any observed effects to mTBI and replicate our previous finding of reduced connectivity and high classification accuracy, although not the reduction in burst amplitude. Burst statistics were stable over both studies—despite data being acquired at different sites, using different scanners. In the same cohort, we applied a more conventional analysis of delta-band power. Although excess low-frequency power appears to be a promising candidate marker for persistently symptomatic mTBI, insufficient data exist to confirm this pattern in acute mTBI. We found abnormally high delta power to be a sensitive measure for discriminating mTBI subjects from healthy controls, however, similarly elevated delta amplitude was found in the cohort with non-head trauma, suggesting that excess delta may not be specific to mTBI, at least in the acute stage of injury.
Our work highlights the need for longitudinal assessment of mTBI. In addition, there appears to be a need to investigate naturalistic paradigms which can be tailored to induce activity in symptom-relevant brain networks and consequently are likely to be more sensitive biomarkers than the resting state scans used to date. Wearable OPM-MEG makes naturalistic scanning possible and may offer a cheaper and more accessible alternative to cryogenic MEG, however, before deploying OPMs clinically, or in pitch-side assessment for athletes, for example, the reliability of OPM-derived measures needs to be verified. In the third and final study, we performed a repeatability study using a novel motor task, estimating a series of common MEG measures and quantifying the reliability of both activity and connectivity derived from OPM-MEG data. These initial findings—presently limited to a small sample of healthy controls—demonstrate the utility of OPM-MEG and pave the way for this technology to be deployed on patients with mTBI
SLEEPING WHILE AWAKE: A NEUROPHYSIOLOGICAL INVESTIGATION ON SLEEP DURING WAKEFULNESS.
Il sonno e la veglia vengono comunemente considerati come due stati distinti. L\u2019alternanza tra essi, la cui presenza \ue8 stata dimostrata in ogni specie animale studiata fino ad oggi, sembra essere una delle caratteristiche che definisce la nostra vita. Allo stesso tempo, per\uf2, le scoperte portate alla luce negli ultimi decenni hanno offuscato i confini tra questi due stati. I meccanismi del sonno hanno sempre affascinato i neurofisiologi, che infatti, nell\u2019ultimo secolo, li hanno caratterizzati in dettaglio: ora sappiamo che all\u2019attivit\ue0 del sonno sottost\ue0 una specifica attivit\ue0 neuronale chiamata slow oscillation. La slow oscillation, che \ue8 costituita da (ancora una volta) un\u2019alternanza tra periodi di attivit\ue0 e periodi di iperpolarizzazione e silenzio neuronale (OFF-periods), \ue8 la modalit\ue0 base di attivazione del cervello dormiente. Questa alternanza \ue8 dovuta alla tendenza dei neuroni surante lo stato di sonno, di passare ad un periodo silente dopo un\u2019attivazione iniziale, una tendenza a cui viene dato il nome di bistabilit\ue0 neuronale. Molti studi hanno dimostrato come la bistabilit\ue0 neuronale tipica del sonno ed i relativi OFF-periods, possano accadere anche durante la veglia in particolari condizioni patologiche, nelle transizioni del sonno e durante le deprivazioni di sonno. Per questo motivo, se accettassimo che la bistabilit\ue0 neuronale e gli OFF-periods rappresentino una caratteristica fondamentale del sonno, allora dovremmo ammettere che stiamo assistendo ad un cambio di paradigma: da una prospettiva neurofisiologica il sonno pu\uf2 intrudere nella veglia. In questa tesi ho analizzato i nuovi -fluidi- confini tra sonno e veglia e le possibili implicazioni di questi nel problema della persistenza personale attraverso il tempo. Inoltre, ho studiato le implicazioni cliniche dell\u2019intrusione di sonno nella veglia in pazienti con lesioni cerebrali focali di natura ischemica. In particolare, i miei obiettivi sono stati: 1) Dimostrare come la bistabilit\ue0 neuronale possa essere responsabile della perdita di funzione nei pazienti affetti da ischemia cerebrale e come questo potrebbe avere implicazioni nello studio della patofisiologia dell\u2019ischemia cerebrale e nella sua terapia; 2) Stabilire le basi per un modello di sonno locale presente nella vita di tutti i giorni: la sensazione di sonnolenza. Infatti, essa potrebbe riflettere la presenza di porzioni di corteccia in stato di sonno, ma durante lo stato di veglia; 3) Difendere il criterio biologico di identit\ue0, che troverebbe nell\u2019attivit\ue0 cerebrale la continuit\ue0 necessaria al mantenimento della nostra identit\ue0 nel tempo.Sleep and wakefulness are considered two mutually exclusive states. The alternation between those two states seems to be a defining characteristic of our life, a ubiquitous phenomenon demonstrated in every animal species investigated so far. However, during the last decade, advances in neurophysiology have blurred the boundaries between those states. The mechanisms of sleep have always intrigued neurophysiologists and great advances have been made over the last century in understanding them: we now know that the defining characteristic underlying sleep activity is a specific pattern of neuronal activity, namely the slow oscillation. The slow oscillation, which is characterized by the periodic alternation between periods of activity (ON-periods) and periods of hyperpolarization and neuronal silence (OFF-periods) is the default mode of activity of the sleeping cortex. This alternation is due to the tendency of neurons to fall into a silent period after an initial activation; such tendency is known as \u201cbistability\u201d. There is accumulating evidence that sleep-like bistability, and the ensuing OFF-periods, may occur locally in the awake human brain in some pathological conditions, in sleep transition, as well as after sleep deprivation. Therefore, to the extent that bistability and OFF periods represents the basic neuronal features of sleep, a paradigm shift is in place: from a neurophysiological perspective sleep can intrude into wakefulness. In this thesis, I explore the fluid boundaries between sleep and wakefulness and investigate their possible implications on the problem of personal persistence over time. Moreover, I study the clinical implications of the intrusion of sleep into wakefulness in patients with focal brain injury due to stroke. Specifically, I aim to: 1) show how the sleep-like bistability can be responsible for the loss of function in stroke patients. This may have implications for understanding the pathophysiology of stroke and helping to foster recovery; 2) establish the basis for a model of local sleep that might be present in the everyday life, id est the sensation of sleepiness. Indeed, sleepiness could reflect islands of sleep during wakefulness; 3) advocate the biological criterion of identity, in which the continuity necessary for maintaining ourselves over time could be represented by never resting activity in the brain
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