790 research outputs found

    Imaging of epileptic activity using EEG-correlated functional MRI.

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    This thesis describes the method of EEG-correlated fMRI and its application to patients with epilepsy. First, an introduction on MRI and functional imaging methods in the field of epilepsy is provided. Then, the present and future role of EEG-correlated fMRI in the investigation of the epilepsies is discussed. The fourth chapter reviews the important practicalities of EEG-correlated fMRI that were addressed in this project. These included patient safety, EEG quality and MRI artifacts during EEG-correlated fMRI. Technical solutions to enable safe, good quality EEG recordings inside the MR scanner are presented, including optimisation of the EEG recording techniques and algorithms for the on-line subtraction of pulse and image artifact. In chapter five, a study applying spike-triggered fMRI to patients with focal epilepsy (n = 24) is presented. Using statistical parametric mapping (SPM), cortical Blood Oxygen Level-Dependent (BOLD) activations corresponding to the presumed generators of the interictal epileptiform discharges (IED) were identified in twelve patients. The results were reproducible in repeated experiments in eight patients. In the remaining patients no significant activation (n = 10) was present or the activation did not correspond to the presumed epileptic focus (n = 2). The clinical implications of this finding are discussed. In a second study it was demonstrated that in selected patients, individual (as opposed to averaged) IED could also be associated with hemodynamic changes detectable with fMRI. Chapter six gives examples of combination of EEG-correlated fMRI with other modalities to obtain complementary information on interictal epileptiform activity and epileptic foci. One study compared spike-triggered fMRI activation maps with EEG source analysis based on 64-channel scalp EEG recordings of interictal spikes using co-registration of both modalities. In all but one patient, source analysis solutions were anatomically concordant with the BOLD activation. Further, the combination of spike- triggered fMRI with diffusion tensor and chemical shift imaging is demonstrated in a patient with localisation-related epilepsy. In chapter seven, applications of EEG-correlated fMRI in different areas of neuroscience are discussed. Finally, the initial imaging findings with the novel technique for the simultaneous and continuous acquisition of fMRI and EEG data are presented as an outlook to future applications of EEG-correlated fMRI. In conclusion, the technical problems of both EEG-triggered fMRI and simultaneous EEG-correlated fMRI are now largely solved. The method has proved useful to provide new insights into the generation of epileptiform activity and other pathological and physiological brain activity. Currently, its utility in clinical epileptology remains unknown

    Functional Magnetic Resonance Imaging as an Assessment Tool in Critically Ill Patients

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    Little is known about whether residual cognitive function occurs in the earliest stages of brain injury. The overarching goal of the work presented in this dissertation was to elucidate the role of functional neuroimaging in assessing brain activity in critically ill patients. The overall objective was addressed in the following four empirical chapters: In Chapter 2, three versions of a hierarchically-designed auditory task were developed and their ability to detect various levels of auditory language processing was assessed in individual healthy participants. The same procedure was then applied in two acutely comatose patients. In Chapter 3, a hierarchical auditory task was employed in a heterogeneous cohort of acutely comatose patients. The results revealed that the level of auditory processing in coma may be predictive of subsequent functional recovery. In Chapter 4, two mental imagery paradigms were utilized to assess covert command-following in coma. The findings demonstrate, for the first time, preserved awareness in an acutely comatose patient. In Chapter 5, functional neuroimaging techniques were used for covert communication with two completely locked-in, critically ill patients. The results suggest that this methodology could be used as an augmentative communication tool to allow patients to be involved in their own medical decision-making. Taken together, the proceeding chapters of this work demonstrate that functional neuroimaging can detect preserved cognitive functions in some acutely comatose patients, which has both diagnostic and prognostic relevance. Moreover, these techniques may be extended even further to be used as a communication tool in critically ill patients

    Using Wavelet Entropy To Demonstrate How Mindfulness Practice Increases Coordination Between Irregular Cerebral And Cardiac Activities

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    In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, statistical parametric mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard mindfulness-based stress reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities

    Multimodal phenotyping of synaptic damage in Alzheimer’s disease : translational perspective with focus on quantitative EEG

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    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Accumulation of AD-associated pathology in the brain may begin a decade or more before the appearance of the first symptoms of the disease. The pathological-clinical “continuum of AD” therefore encompasses time between the initial neuropathological changes and symptoms of advanced disease. Besides cognitively healthy individuals at risk, it includes subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and eventually dementia when the severity of cognitive impairment affects patients’ ability to carry out everyday activities. Timely detection of the disease would therefore recognize patients that are at risk for future cognitive deterioration and provide time window for the prevention and novel therapeutical interventions. Accumulating evidence suggests that degeneration and dysfunction of brain neuronal connections, i.e. synapses, is one of the earliest and best proxies of cognitive deficits in patients along AD continuum. Human electroencephalography (EEG) is a non-invasive and widely available diagnostic method that records real-time large-scale synaptic activity. The commonly used method in research settings is quantitative EEG (qEEG) analysis that provides objective information on EEG recorded at the level of the scalp. Quantitative EEG analysis unravels complex EEG signal and adds relevant information on its spectral components (frequency domain), temporal dynamics (time domain) and topographic estimates (space domain) of brain cortical activity. The general aim of the present thesis was to characterize different aspects of synaptic degeneration in AD, with the focus on qEEG and its relationship to both conventional and novel synaptic markers. In study I, global qEEG measures of power and synchronization were found to correlate with conventional cerebrospinal fluid (CSF) biomarkers of Aβ and tau pathology in patients diagnosed with SCD, MCI and AD, linking the markers of AD pathology to the generalized EEG slowing and reduced brain connectivity in fast frequency bands. In study II, qEEG analysis in the time domain (EEG microstates) revealed alterations in the organization and dynamics of large-scale brain networks in memory clinic patients compared to healthy elderly controls. In study III, topographical qEEG analysis of brain functional connectivity was associated with regionspecific cortical glucose hypometabolism ([18F]Fluorodeoxyglucose positron-emission tomography) in MCI and AD patients. Study IV provided evidence that qEEG measures of global power and synchronization correlate with CSF levels of synaptic marker neurogranin, both modalities being in combination independent predictors of progression to AD dementia in MCI patients. Study V and associated preliminary study introduced in the thesis assessed the translational potential of CSF neurogranin and qEEG as well as their direct relationship to AD neuropathology in App knock-in mouse models of AD. In study V, changes in CSF neurogranin levels and their relationship to conventional CSF markers in App knock-in mice corresponded to the pattern observed in clinical AD cohorts. These findings highlighted the potential use of mouse CSF biomarkers as well as App knock-in mouse models for translational investigation of synaptic dysfunction due to AD. In general, the results of the thesis invite for further clinical validation of multimodal synaptic markers in the context of early AD diagnosis, prognosis, and treatment monitoring in individual patients

    Backtranslation of EEG biomarkers of Alzheimer's disease from patients to mouse model

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    The present Ph.D. thesis has been mainly developed on the data of the project with the short name PharmaCog (2010-2015), granted by the European Framework Programme 7 with about 28 millions of Euro (i.e. Innovative Medicine Initiative, IMI, grant agreement n°115009; www.pharmacog.org). This project involved 15 academic institutions, 12 global pharmaceutical companies, and 5 small and medium sized enterprises (SMEs). The PharmaCog project aimed at improving the pathway of drug discovery in Alzheimer’s disease (AD), based on a major interest of pharma companies, namely the validation of electrophysiological, neuroimaging, and blood biomarkers possibly sensitive to the effect of disease-modifying drugs reducing Ab42 in the brain in AD patients at the prodromal stage of amnesic mild cognitive impairment (aMCI). The core concept of the PharmaCog project was that the pathway of drug discovery in AD may be enhanced by (1) the validation of biomarkers derived from blood, EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) in patients with aMCI due to AD diagnosed by in-vivo measurement of Ab42 and phospho-tau in the brain and (2) the evaluation of the translational value of those human biomarkers in wild type (WT) mice and animal models of AD including transgenic mice with the mutation of PS1 and/or APP (i.e. PDAPP and TASTPM strains). Those genetic factors induce an abnormal accumulation of Ab42 in the brain and related cognitive deficits. The expected results may be (1) the identification of a matrix of biomarkers sensitive to the prodromal AD (aMCI cognitive status) and its progression in patients and (2) the selection of similar biomarkers related to AD neuropathology and cognitive deficits in PDAPP and TASTPM strains. These biomarkers were expected to be very useful in clinical trials testing the efficacy and neurobiological impact of new disease-modifying drugs against prodromal AD. For the development of this Ph.D. thesis, the access to the experiments and the data of the PharmaCog project was allowed by Prof. Claudio Babiloni, leader of an Italian Unit (University of Foggia in 2010-2012 and Sapienza University of Rome in 2013-2015) of the PharmaCog Consortium and coordinator of study activities relative to biomarkers derived from electroencephalographic (EEG) signals recorded from human subjects and animals in that project. Specifically, Prof. Claudio Babiloni was in charge for the centralized qualification and analysis of EEG data recorded from aMCI patients (Work Package 5, WP5) and transgenic mouse models of AD such as PDAPP and TASTPM strains (WP6). The data of the present Ph.D. thesis mostly derived from the WP5 and WP6. This document illustrating the Ph.D. thesis is structured in three main Sections: ▪ An Introductive part illustrating concisely the AD neuropathology, the mouse models of AD used in this thesis, and basic concepts of EEG techniques useful to understand the present study results; ▪ An Experimental part describing the result of the four research studies led in the framework of this Ph.D. project. Two of these studies were published in international journals registered in ISI/PubMed with impact factor, while the other two are being currently under minor revisions in those journals; ▪ A Conclusion section

    Psychophysiological reactivity to auditory Binaural Beats stimulation in the alpha and theta EEG brain-wave frequency bands: A randomized, double–blind and placebo–controlled study in human healthy young adult subjects

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    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Psicología, Departamento de Psicología Biológica y de la Salud. Fecha de lectura: 25-06-2014Binaural beats are an acoustical illusion of the perception of a “virtual” third tone, fluctuating (i.e. beating) in its volume evoked by two carrier–sinusoids of same amplitudes, but slightly different frequencies f1 and f2, presented by stereo-headphones. Although this illusion was discovered as early as 1839 by Dove and, after the discovery of the EEG, visual rhythmic stimulation by stroboscopic flicker was known to evoke photic driving, until today relatively few works with moreover contradictory results have been published searching for specific Binaural Beat effects on the organism. Objective The present investigation aimed, in a highly controlled laboratory study with multimodal measurements, for deciding on the question whether there is or there is not specific psychophysiological reactivity to Binaural Beats auditory stimulation in the EEG alpha and theta frequency bands, striving for the overcoming of unsatisfactory methodology of previous works. If efficacy to specifically decrease psychophysiological arousal levels would be proven, multiple applications in clinical contexts would be feasible. Moreover, the employed stimuli would be useful for basic research trying to better understand the underlying neurocircuitry of arousal, attention and consciousness regulation. Methods After rigorous psychometric screening for bio–psycho–social health, N = 12 young university students (5 females) entered in a within–subject randomized placebo–controlled design, with 50% of the subjects randomly assigned to the presentation order Placebo vs. Verum, and the remaining 50% vice versa. Placebo and Verum sessions took place with more than one week time interval. The 25 min Verum stimulus consisted of Binaural Beats carrier frequencies equivalent to a sweep from 10 Hz to 4 Hz embedded into a special dynamic noise mask, while under Placebo only this mask was presented without Binaural Beats for 25 min. 63–channel EEG, ECG and respiratory flow by nasal cannulae were continuously recorded at 1024 Hz common sample frequency. Pre– vs. post saliva samples were collected by passive drool technique and immediately flash frozen by immersion into liquid nitrogen. Hypnoidal state depth was measured by retrospective psychometry immediately after each experiment using the Phenomenology of Consciousness Inventory (PCI) of Pekala (1991). Results Logit–transformed EEG relative spectral powers showed only under Verum significant change over time with distinguishable scalp topographies, a linear increasing trend in slower vs. a linear decreasing trend in faster EEG frequency bands and meaningful correlations with the psychometric effects in hypnoidal state depth. Significant change over time in the parasympathetic parameter HRV–HF power derived from ECG was only found under Verum. These HRV findings are not confounded by changes in respiratory frequency which showed no significant change over time. Pre– vs. post saliva samples revealed significant increases only under Placebo in stress–related biomarkers (Cortisol, α–Amylase and Salivary Secretory Immunoglobulin A, SIgA), but not under Verum. Significant increases under Verum as compared to Placebo were observed in psychometric hypnoidal state depths with a large effect size of r = .513 and difference scores showed a significant and large Spearman’s rank order correlation of rho = .671 and pexact = .020 with hypnotizability as operationalized as psychometric hypnoidal state depths under Placebo. Hypnotizability is thus a predictor of reactivity magnitudes to Binaural Beat auditory stimulation. Presentation order effects could be excluded for all reported effects. Conclusions Multimodal evidence was found for the searched specific efficacy of Binaural Beats auditory stimulation in the EEG alpha and theta frequency range. Linear trends in EEG relative spectral powers suggest that only the Verum stimulus caused significant decreases in (cortical) arousal. The significant increase of stress–related biomarkers only under Placebo could be interpreted as a sign that the Verum stimulus inhibited processes which naturally occurred under Placebo. Both the Placebo and Verum of the present investigation should be used as a nonverbal culture–free paradigm for neurocientific basic laboratory studies on hypnosis and hypnotizability especially, but also on resting–state networks and related neurocircuitry generally. The ability of the Verum stimulus to decrease arousal levels and induce/boost altered states of consciousness (ASCs) implies applications in several practical–clinical contexts and calls for further field studies.Los pulsos binaurales o Binaural Beats son una ilusión acústica que consiste en la percepción de un tercer tono “virtual” que fluctúa (beating) en volumen, inducido por dos ondas portadoras (f1 y f2 ) de la misma amplitud, pero con frecuencias ligeramente distintas, presentadas en cada uno de los oídos mediante auriculares estéreo. Aunque esta ilusión fue descubierta por Dove en 1838 y después del descubrimiento del EEG se conoce que la estimulación visual por luz estroboscópica provoca photic driving, hasta ahora se han publicado pocos trabajos sobre los efectos de los Binaural Beats en el organismo, y además con resultados contradictorios. Objectivos La investigación en esta tesis tiene como objeto realizar un estudio de laboratorio en condiciones altamente controladas y con registros multimodales para averiguar si hay o no una respuesta psicofisológica a la estimulación auditiva con Binaural Beats en las frecuencias alfa y theta del EEG. La metodología empleada intenta resolver los problemas de investigaciones previas. La demostración de la eficacia de los Binaural Beats para disminuir específicamente los niveles de arousal psicofisiológico daría pie a muchas aplicaciones clínicas. Además, este paradigma de estimulación auditiva puede contribuir a la investigación básica de la neurocircuitería del arousal, de la atención y de la regulación de la consciencia. Métodos Se reclutaron N = 12 jóvenes estudiantes universitarios (5 mujeres) comprobando rigorosamente su salud bio–psico–social. El estudio siguió un diseño intrasujeto–aleatorizado y controlado por Placebo, en que se asignó aleatoriamente a la mitad de los voluntarios un orden de presentación Placebo vs. estímulo con Binaural Beats, mientras a la otra mitad el orden contrario. Estas dos sesiones experimentales se realizaron al menos con una semana de separación temporal. Los 25 minutos del estímulo con Binaural Beats contienen un barrido de 10 Hz a 4 Hz (decreciente) con enmascaramiento auditivo dinámico, mientras que los 25 minutos del Placebo contienen solamente la máscara auditiva. Se registró el EEG con 63 canales, el ECG y el flujo respiratorio mediante cánulas nasales a una frecuencia de muestreo común de 1024 Hz. Se tomaron muestras de saliva pre vs. post mediante la técnica de passive drool que fueron inmediatamente ultracongeladas por inmersión en nitrógeno líquido. El nivel del estado hipnótico se midió por psicometría retrospectiva inmediatamente después de cada sesión experimental con el test Phenomenology of Consciousness Inventory (PCI) de Pekala (1991). Resultados El análisis de la potencia espectral relativa del EEG sometida a la transformación logit mostró que existen cambios significativos en su evolución temporal con topografías espaciales distinguibles solamente bajo la estimulación con Binaural Beats presentes y no bajo Placebo. Además, se observó un incremento de la pendiente de la tendencia lineal en las bandas del EEG más lentas y una bajada de la pendiente en frecuencias más rápidas. Se encuentraron correlaciones significativas y relevantes con los efectos psicométricos del nivel del estado hipnótico. En el parámetro parasimpático HRV–HF power derivado del ECG se encuentron también cambios significativos en su evolución temporal exclusivamente bajo el estímulo con Binaural Beats. Estos cambios no se deben a variaciones en la frecuencia respiratoria puesto que en ella no se apreciaron cambios significativos. En las muestras de la saliva pre vs. post se observaron incrementos significativos en los biomarcadores salivares de estrés (cortisol, α–amylasa e inmunoglobulina A secretora, SIgA) solamente bajo Placebo. Se encuentraron incrementos significativos de los niveles del estado hipnótico con un tamaño del efecto r =.513 solamente bajo el estímulo con Binaural Beats, pero no bajo Placebo. Con un rho de Spearman de .671 y pexact = .020, las puntuaciones de las diferencias de los niveles del estado hipnótico correlacionan altamente con la hipnotizabilidad operacionalizada como nivel del estado hipnótico bajo Placebo. Por tanto, el rasgo hipnotizabilidad se identificó como predictor de las magnitudes de las reacciones a la estimulación con Binaural Beats. Para todos los efectos mencionados, se pudo descartar la influencia del orden de presentación de los estímulos. Conclusiones Esta tesis proporciona evidencia multimodal de la eficacia de la estimulación auditiva con Binaural Beats en las bandas del EEG alfa y theta. Las pendientes de las tendencias lineales en las potencias espectrales relativas del EEG sugieren que esta estimulación causa una disminución del arousal (cortical). El incremento de los biomarcadores de saliva relacionados con el estrés solo en el caso de Placebo sugiere que la estimulación con Binaural Beats inhibe procesos que ocurren naturalmente bajo Placebo. Tanto el Placebo como el estímulo con Binaural Beats pueden emplearse como un paradigma no verbal culture–free en especial para estudios de neurociencia básica respecto a la hipnosis y la hipnotizabilidad, y, en general respecto a resting–state networks y la neurocircuitería relacionada. El hecho de que el estímulo con Binaural Beats puede disminuir el arousal e inducir estados alterados de la consciencia sugiere aplicaciones en múltiples contextos clínicos y futuros estudios de camp

    Presurgical language mapping in children with epilepsy: Clinical usefulness of functional magnetic resonance imaging for the planning of cortical stimulation

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    Purpose: Presurgical language mapping in dominant hemisphere epilepsy to evaluate the risk of postoperative deficit is particularly difficult in children. Extraoperative invasive cortical stimulation can show some areas critical to language, but not all of them, due to scarce sampling, poor cooperation, cortical immaturity, or network reorganization, whereas functional magnetic resonance imaging (fMRI) displays entire networks involved in, but not necessarily critical to, language. In a homogeneous series of children with epilepsy, we compared the contributions of language fMRI and depth electrode stimulations to optimize language mapping. Methods: Eight children (7.5-15.5 years) with left frontal or temporal epilepsy underwent language fMRI and language stimulation with depth electrodes as part of their comprehensive presurgical workup. fMRI data collected during sentence generation were analyzed using statistical parametric mapping (SPM2) (false discovery rate [FDR] p \u3c 0.05). Bipolar stimulations were performed during language production tasks. By coregistering fMRI and postimplantation computed tomography (CT) images, we were able to directly compare the cortical areas identified by both investigations. Key Findings: fMRI during sentence generation robustly showed activation in the whole perisylvian regions with little reorganization (left hemisphere dominant in 7). Of the 184 electrode contacts tested for language, only 8 were positive (language disruption) in three of the seven patients with periictal language impairment and left language dominance. All of the positive contacts colocalized with an fMRI activated cluster, that is, fMRI did not miss any region critical to language (sensitivity = 100%). However, 54 of the 176 negative contacts were within activated clusters (low specificity). Significance: In children with epilepsy, the sensitivity of fMRI during sentence generation allows for the detection of all critical regions displayed by cortical stimulation within the large perisylvian language network, but with a low specificity. It is, therefore, useful to optimize the placement of intracranial electrodes when language mapping is necessary. Systematic planning of the electrode placement according to language fMRI maps should increase the yield of extraoperative cortical stimulation, which appears rather low in children when compared to adults. © 2011 International League Against Epilepsy

    Localization of sources in electroencephalographic registers during working memory tasks

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    Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2020-2021. Director: Albert Compte. Tutor: Santiago Marco.EEG source localization is a non-invasive imaging technique developed to locate the anatomical sources recorded at the scalp during an EEG recording. The reconstruction of the sources can be computed by solving the so-called inverse problem. This is an ill-posed problem which aims in estimating the sources that fit the recorded measurements. There exist several powerful commercial and academic software packages that cover multiple methods on data processing, source localization, and statistical analysis. In this work, the open-source MNE-Python package was selected as the working environment used to address the challenge of characterizing and locating neural activation. This study provides a pipeline with practical steps on the EEG source localization technique. The results obtained in this project have been validated by experts in the Theoretical Neurobiology and Computational Neuroscience fields In this project, the EEG source localization has been computed over a group of encephalitic patients and a control group. The two groups had shown differences regarding the electrical activity in a working memory trial. This study aimed in localizing the anatomical brain regions that were responsible of the electrical differences. It has been observed that instants before the stimulus, the activated sites between control groups and encephalitic groups differ. In the case of the control group, the activated region was located at the frontal lobe of the left hemisphere. Whereas, in the case of the encephalitic group the activated region was located at the temporal lobe of the right hemisphere
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