Análisis de la señal de electroencefalograma mediante distancias espectrales para la ayuda en el diagnóstico de la enfermedad de Alzheimer

En este Trabajo Fin de Máster se ha estudiado la actividad electroencefalográfica (EEG) espontánea en 32 pacientes con la enfermedad de Alzheimer (EA) y en 25 sujetos de control de edad avanzada, utilizando métodos espectrales de procesado de señal. El objetivo de este estudio es determinar si la conectividad cerebral en los registros EEG presenta diferencias entre los enfermos y los controles. Para ello, se ha realizado un análisis de conectividad de la actividad espectral en los distintos sensores del EEG. Los resultados obtenidos muestran que la EA provoca una disminución de la conectividad entre neuronas alejadas entre sí. Mientras que el impacto de la demencia es menor en la conectividad de neuronas en regiones adyacentes o en una misma región cerebral. En conclusión, los resultados obtenidos muestran la capacidad de las distancias espectrales para caracterizar la similitud en el espectro de registros de EEG, así como las alteraciones en los patrones de conectividad provocados por la EA.Teoría de la Señal y las Comunicaciones e Ingeniería TelemáticaMáster en Investigación en Tecnologías de la Información y las Comunicacione

Characterization of dynamical neural activity by means of EEG data: application to schizophrenia

Schizophrenia is a disabling, chronic and severe mental illness characterized by disintegration of the process of thinking, contact with reality and emotional responsiveness. Schizophrenia has been related to an aberrant assignment of salience to external objects and internal representations. In addition, schizophrenia has been identified as a dysconnection syndrome, which is associated with a reduced capacity to integrate information among different brain regions. Relevance attribution likely involves diverse cerebral regions and their interconnections. As a consequence, many efforts have been devoted to identifying abnormalities in the cortical connections and their relation to schizophrenia symptoms and cognitive performance. Neural oscillations are one of the largest contributing mechanism for enabling coordinated activity during normal brain functioning. Alterations in neural oscillations and cognitive processing in schizophrenia have long been assessed using electroencephalographic (EEG) recordings (i.e. time-varying voltages on the human scalp generated by the electrical activity on the cerebral cortex). Event-related potentials (ERP) depict EEG data as a response to a cognitive task. ERP analyses are used to gain further insights into the neural mechanisms underlying cognitive dysfunctions. In this Doctoral Thesis, a 3-stimulus auditory-oddball paradigm was used for examining cognitive processing as response to both relevant and irrelevant stimuli. A total of 69 ERP recordings were analyzed in the research papers included in the Thesis, which comprises 20 chronic schizophrenia patients, 11 first episode patients and 38 healthy controls. This Doctoral Thesis is focused on the study, design and application of biomedical signal processing methodologies in order to facilitate the understanding of cognitive processes altered by the schizophrenia. EEG data were examined using a two-level analysis: (I) local activation studies to quantify functional segregation of the brain network, by means of spectral analysis and by assessing neural source generators of P3a and P3b components; and (II) EEG interactions studies to explore functional integration across brain regions, including pair-wise couplings and exploring hierarchical organization of neural rhythms.Departamento de Teoría de la Señal y Comunicaciones e Ingeniería TelemáticaDoctorado en Tecnologías de la Información y las Telecomunicacione

Effect of infusion tests on the dynamical properties of intracranial pressure in hydrocephalus

Producción CientíficaHydrocephalus comprises a number of conditions characterised by clinical symptoms, dilated ventricles and anomalous cerebrospinal fluid (CSF) dynamics. Infusion tests (ITs) are usually performed to study CSF circulation and in the preoperatory evaluation of patients with hydrocephalus. The study of intracranial pressure (ICP) signals recorded during ITs could be useful to gain insight into the underlying pathophysiology of this condition and to further support treatment decisions. In this study, two wavelet parameters, wavelet turbulence (WT) and wavelet entropy (WE), were analysed in order to characterise the variability, irregularity and similarity in spectral content of ICP signals in hydrocephalus.Ministerio de Economía y Competitividad (TEC2014-53196-R)Junta de Castilla y León (project VA059U13

MEG Analysis of Neural Interactions in Attention-Deficit/Hyperactivity Disorder

Producción CientíficaThe aim of the present study was to explore the interchannel relationships of resting-state brain activity in patients with attentiondeficit/hyperactivity disorder (ADHD), one of the most common mental disorders that develop in children. Magnetoencephalographic (MEG) signals were recorded using a 148-channel whole-head magnetometer in 13 patients with ADHD (range: 8–12 years) and 14 control subjects (range: 8–13 years).Three complementary measures (coherence, phase-locking value, and Euclidean distance) were calculated in the conventionalMEG frequency bands: delta, theta, alpha, beta, and gamma. Our results showed that the interactions among MEG channels are higher for ADHD patients than for control subjects in all frequency bands. Statistically significant differences were observed for short-distance values within right-anterior and central regions, especially at delta, beta, and gamma-frequency bands ( < 0.05; Mann-Whitney test with false discovery rate correction). These frequency bands also showed statistically significant differences in long-distance interactions, mainly among anterior and central regions, as well as among anterior, central, and other areas. These differences might reflect alterations during brain development in children with ADHD. Our results support the role of frontal abnormalities in ADHD pathophysiology, which may reflect a delay in cortical maturation in the frontal cortex.Ministerio de Economía, Industria y Competitividad (TEC2014-53196-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. VA059U1

Auditory P3a and P3b neural generators in schizophrenia: An adaptive sLORETA P300 localization approach

The present study investigates the neural substrates underlying cognitive processing in schizophrenia (Sz) patients. To this end, an auditory 3-stimulus oddball paradigm was used to identify P3a and P3b components, elicited by rare-distractor and rare-target tones, respectively. Event-related potentials (ERP) were recorded from 31 Sz patients and 38 healthy controls. The P3a and P3b brain-source generators were identified by time-averaging of low-resolution brain electromagnetic tomography (LORETA) current density images. In contrast with the commonly used fixed window of interest (WOI), we proposed to apply an adaptive WOI, which takes into account subjects’ P300 latency variability. Our results showed different P3a and P3b source activation patterns in both groups. P3b sources included frontal, parietal and limbic lobes, whereas P3a response generators were localized over bilateral frontal and superior temporal regions. These areas have been related to the discrimination of auditory stimulus and to the inhibition (P3a) or the initiation (P3b) of motor response in a cognitive task. In addition, differences in source localization between Sz and control groups were observed. Sz patients showed lower P3b source activity in bilateral frontal structures and the cingulate. P3a generators were less widespread for Sz patients than for controls in right superior, medial and middle frontal gyrus. Our findings suggest that target and distractor processing involves distinct attentional subsystems, both being altered in Sz. Hence, the study of neuroelectric brain information can provide further insights to understand cognitive processes and underlying mechanisms in Sz.Postprint (author's final draft

Exploring non-stationarity patterns in schizophrenia: neural reorganization abnormalities in the alpha band

Producción CientíficaObjective. The aim of this paper was to characterize brain non-stationarity during an auditory oddball task in schizophrenia (SCH). The level of non-stationarity was measured in the baseline and response windows of relevant tones in SCH patients and healthy controls. Approach. Event-related potentials were recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in the conventional electroencephalography frequency bands by means of Kullback-Leibler divergence (KLD). Relative power (RP) was also computed to assess a possible complementarity with KLD. Main results. Results showed a widespread statistically significant increase in the level of non-stationarity from baseline to response in all frequency bands for both groups. Statistically significant differences in non-stationarity were found between SCH patients and controls in beta-2 and especially in the alpha band. SCH patients showed more non-stationarity in the left parieto-occipital region during the baseline window in the beta-2 band. A leave-one-out cross validation classification study with feature selection based on binary stepwise logistic regression to discriminate between SCH patients and controls provided an accuracy of 89.87% and area under ROC of 0.9510. Significance. KLD can characterize transient neural reorganization during an attentional task in response to novelty and relevance. Our findings suggest anomalous reorganization of neural dynamics in SCH during an oddball task. The abnormal frequency-dependent modulation found in SCH patients during relevant tones is in agreement with the hypothesis of aberrant salience detection in SCH. The increase in non-stationarity in the alpha band during the active task supports the notion that this band is involved in top-down processing. The baseline differences in the beta-2 band suggest that hyperactivation of the default mode network during attention tasks may be related to SCH symptoms. Furthermore, the binary stepwise logistic regression procedure selected features from both KLD and RP, supporting the idea that these measures can be complementary.This research project was supported in part by the projects TEC2014-53196-R of ‘Ministerio de Economía y Competitividad’ and FEDER; the project VA037U16 from the “Consejería de Educación de la Junta de Castilla y León”, the “Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III)” under projects FIS PI11/02203 and PI15/00299; and the “Gerencia Regional de Salud de Castilla y León” under projects GRS 932/A/14 and GRS 1134/A/15. P. Núñez was in receipt of a ‘Promoción de empleo joven e implantación de la Garantía Juvenil en I+D+i’ grant from ‘Ministerio de Economía y Competitividad’ and the University of Valladolid, A. Bachiller and J. Gomez-Pilar were in receipt of a PIF-UVA grant from the University of Valladolid. A. Lubeiro has a predoctoral scholarship from the “Junta de Castilla y León” and European Social Fund

Analysis of the Non-stationarity of Neural Activity during an Auditory Oddball Task in Schizophrenia

Producción CientíficaThe aim of this study was to characterize brain dynamics during an auditory oddball task. For this purpose, a measure of the non-stationarity of a given time-frequency representation (TFR) was applied to electroencephalographic (EEG) signals. EEG activity was acquired from 20 schizophrenic (SCH) patients and 20 healthy controls while they underwent a three-stimulus auditory oddball task. The Degree of Stationarity (DS), a measure of the non-stationarity of the TFR, was computed using the continuous wavelet transform. DS was calculated for both the baseline [-300 0] ms and active task [150 550] ms windows of a P300 auditory oddball task. Results showed a statistically significant increase (p<0.05) in non-stationarity for controls during the cognitive task in the central region, while less widespread statistically significant differences were obtained for SCH patients, especially in the beta-2 and gamma bands. Our findings support the relevance of DS as a means to study cerebral processing in SCH. Furthermore, the lack of statistically significant changes in DS for SCH patients suggests an abnormal reorganization of neural dynamics during an oddball task.Ministerio de Economía y Competitividad (TEC2014-53196-R)Junta de Castilla y León (VA059U13

Analysis of Functional Connectivity during an Auditory Oddball Task in Schizophrenia

Producción CientíficaThe aim of this study was to evaluate neural coupling patterns in schizophrenia (SCH) patients and healthy controls during an auditory oddball task. Two measures of functional connectivity were applied to 28 SCH patients and 51 healthy controls to characterize electroencephalographic (EEG) activity. Specifically, magnitude squared coherence (MSC) and the imaginary part of coherency (ICOH) were computed for five frequency bands: theta, alpha, beta-1, beta-2 and gamma. The results showed a statistically significant modulation increase in MSC and ICOH for controls with respect to SCH in the theta band, and a decrease in ICOH for the beta-2 band. Furthermore, controls showed more significant changes from the baseline and active task windows than SCH patients. Our findings suggest that SCH patients show coupling abnormalities during an auditory oddball task compared to healthy controls.Ministerio de Economía y Competitividad (TEC2014-53196-R)Junta de Castilla y León (VA059U13

Novel Measure of the Weigh Distribution Balance on the Brain Network: Graph Complexity Applied to Schizophrenia

Producción CientíficaThe aim of this study was to assess brain complexity dynamics in schizophrenia (SCH) patients during an auditory oddball task. For that task, we applied a novel graph measure based on the balance of the node weighs distribution. Previous studies applied complexity parameters that were strongly dependent on network topology. This fact could bias the results besides being necessary correction techniques as surrogating process. In the present study, we applied a novel graph complexity measure from the information theory: Shannon Graph Complexity (SGC). Complexity patterns form electroencephalographic recordings of 20 healthy controls and 20 SCH patients during an auditory oddball task were analyzed. Results showed a significantly more pronounced decrease of SGC for controls than for SCH patients during the cognitive task. These findings suggest an important change in the brain configuration towards more balanced networks, mainly in the connections related to long-range interactions. Since these changes are significantly more pronounced in controls, it implies a deficit in the neural network reorganization in SCH patients. In addition, SGC showed a suitable discrimination ability using a leave-one-out cross-validation: 0.725 accuracy and 0.752 area under receiver operating characteristics curve. The novel complexity measure proposed in this study demonstrated to be independent of network topology and, therefore, it complements traditional graph measures to characterize brain networks.Ministerio de Economía y Competitividad (TEC2014-53196-R)Junta de Castilla y León (VA059U13

Influence of the number of trials on evoked motor cortical activity in EEG recordings

The data that support the findings of this study are openly available at the following URL/DOI: https://doi.org/10.1371/journal.pone.0182578.Objective. Improvements in electroencephalography enable the study of the localization of active brain regions during motor tasks. Movement-related cortical potentials (MRCPs), and event-related desynchronization (ERD) and synchronization are the main motor-related cortical phenomena/neural correlates observed when a movement is elicited. When assessing neurological diseases, averaging techniques are commonly applied to characterize motor related processes better. In this case, a large number of trials is required to obtain a motor potential that is representative enough of the subject’s condition. This study aimed to assess the effect of a limited number of trials on motor-related activity corresponding to different upper limb movements (elbow flexion/extension, pronation/supination and hand open/close). Approach. An open dataset consisting on 15 healthy subjects was used for the analysis. A Monte Carlo simulation approach was applied to analyse, in a robust way, different typical time- and frequency-domain features, topography, and low-resolution electromagnetic tomography. Main results. Grand average potentials, and topographic and tomographic maps showed few differences when using fewer trials, but shifts in the localization of motor-related activity were found for several individuals. MRCP and beta ERD features were more robust to a limited number of trials, yielding differences lower than 20% for cases with 50 trials or more. Strong correlations between features were obtained for subsets above 50 trials. However, the inter-subject variability increased as the number of trials decreased. The elbow flexion/extension movement showed a more robust performance for a limited number of trials, both in population and in individual-based analysis. Significance. Our findings suggested that 50 trials can be an appropriate number to obtain stable motor-related features in terms of differences in the averaged motor features, correlation, and changes in topography and tomography.This study has been funded by the Ministry of Science and Innovation (MICINN), Spain, under contract PID2020-117751RB-I00. CIBER-BBN is an initiative of the Instituto de Salud Carlos III, Spain. Marta Borràs gratefully acknowledges the Universitat Politècnica de Catalunya and Banco Santander for the financial support of her predoctoral Grant FPI-UPC. A B is a Serra Hunter Fellow.Peer ReviewedPostprint (published version