Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts

Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the `atoms of thought'.

Frequency-domain source localization shows state-dependent diazepam effects in 47-channel EEG

The topic of this study was to evaluate state-dependent effects of diazepam on the frequency characteristics of 47-channel spontaneous EEG maps. A novel method, the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study effects on the strength and the topography of the maps in the different frequency bands. Map topography was characterized by the 3-dimensional location of the equivalent dipole source and map strength was defined as the spatial standard deviation (the Global Field Power) of the maps of each frequency point. The Global Field Power can be considered as a measure of the amount of energy produced by the system, while the source location gives an estimate of the center of gravity of all sources in the brain that were active at a certain frequency. State-dependency was studied by evaluating the drug effects before and after a continuous performance task of 25 min duration. Clear interactions between drug (diazepam vs. placebo) and time after drug intake (before and after the task) were found, especially in the inferior-superior location of the dipole sources. It supports the hypothesis that diazepam, like other drugs, has different effects on brain functions depending on the momentary functional state of the brain. In addition to the drug effects, clearly different source locations and Global Field Power were found for the different frequency bands, replicating earlier reports (Michel et al., 1992).

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.

Chow–Liu trees are sufficient predictive models for reproducing key features of functional networks of periictal EEG time-series

Seizure freedom in patients suffering from pharmacoresistant epilepsies is still not achieved in 20–30% of all cases. Hence, current therapies need to be improved, based on a more complete understanding of ictogenesis. In this respect, the analysis of functional networks derived from intracranial electroencephalographic (iEEG) data has recently become a standard tool. Functional networks however are purely descriptive models and thus are conceptually unable to predict fundamental features of iEEG time-series, e.g., in the context of therapeutical brain stimulation. In this paper we present some first steps towards overcoming the limitations of functional network analysis, by showing that its results are implied by a simple predictive model of time-sliced iEEG time-series. More specifically, we learn distinct graphical models (so called Chow–Liu (CL) trees) as models for the spatial dependencies between iEEG signals. Bayesian inference is then applied to the CL trees, allowing for an analytic derivation/prediction of functional networks, based on thresholding of the absolute value Pearson correlation coefficient (CC) matrix. Using various measures, the thus obtained networks are then compared to those which were derived in the classical way from the empirical CC-matrix. In the high threshold limit we find (a) an excellent agreement between the two networks and (b) key features of periictal networks as they have previously been reported in the literature. Apart from functional networks, both matrices are also compared element-wise, showing that the CL approach leads to a sparse representation, by setting small correlations to values close to zero while preserving the larger ones. Overall, this paper shows the validity of CL-trees as simple, spatially predictive models for periictal iEEG data. Moreover, we suggest straightforward generalizations of the CL-approach for modeling also the temporal features of iEEG signals.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study is to investigate FAA and its correlation with resting – state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant for reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left – lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients) and in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right – lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Studying functional brain networks with concurrent transcranical alternating current stimulation and EEG

Recently transcranial electric stimulation (tES) has been widely used as a mean to modulate brain activity. The modulatory effects of tES have been studied with the excitability of primary motor cortex. However, tES effects are not limited to the site of stimulation but extended to other brain areas, suggesting a need for the study of functional brain networks. Transcranial alternating current stimulation (tACS) applies sinusoidal current at a specified frequency, presumably modulating brain activity in a frequency-specific manner. At a behavioural level, tACS has been confirmed to modulate behaviour, but its neurophysiological effects are still elusive. In addition, neural oscillations are considered to reflect rhythmic changes in transmission efficacy across brain networks, suggesting that tACS would provide a mean to modulate brain networks. To study neurophysiological effects of tACS, we have been developing a methodological framework by combining transcranial magnetic stimulation (TMS), EEG and tACS. We have developed the optimized concurrent tACS-EEG recording protocol and powerful artefact removal method that allow us to study neurophysiological effects of tACS. We also established the concurrent tACS-TMS-EEG recording to study brain network connectivity while introducing extrinsic oscillatory activity by tACS. We show that tACS modulate brain activity in a phase-dependent manner. Our methodological advancement will open an opportunity to study causal role of oscillatory brain activity in neural transmissions in cortical brain networks.

Brain rhythms alterations and their effect in functional networks: A simultaneous EEG/fMRI study in Fixation-off epilepsy

Fixation-off sensitivity (FOS) denotes the forms of EEG abnormalities, which are elicited by elimination of central vision or fixation. The phenomenon seems to depend on variables that modulate the alpha rhythm, however, the cerebral mechanisms underlying FOS remain unclear [1]. The scarce previous fMRI findings related to FOS have shown activation in extrastriate cortex [2] and also in frontal areas [3][4]. On the other hand, simultaneous EEG-fMRI technique has been used to assess the relationship between spontaneous power fluctuations of electrical rhythms and associated fMRI signal modulations. These studies have identified that lateral frontoparietal networks show a negative correlation with alpha band in healthy subjects. This neuroanatomical pattern is related to attentional processes and cognitive resources. Moreover, a sub-beta band (17-23 Hz) has been identified with posterior cingulate, temporoparietal junction and dorso-medial prefrontal cortex activations, which correspond to the DMN [5][6].

Brain-Computer Interfaces: Desarrollo de un sistema de identificación de estados mentales alfa

En el mundo actual las aplicaciones basadas en sistemas biométricos, es decir, aquellas que miden las señales eléctricas de nuestro organismo, están creciendo a un gran ritmo. Todos estos sistemas incorporan sensores biomédicos, que ayudan a los usuarios a controlar mejor diferentes aspectos de la rutina diaria, como podría ser llevar un seguimiento detallado de una rutina deportiva, o de la calidad de los alimentos que ingerimos. Entre estos sistemas biométricos, los que se basan en la interpretación de las señales cerebrales, mediante ensayos de electroencefalografía o EEG están cogiendo cada vez más fuerza para el futuro, aunque están todavía en una situación bastante incipiente, debido a la elevada complejidad del cerebro humano, muy desconocido para los científicos hasta el siglo XXI. Por estas razones, los dispositivos que utilizan la interfaz cerebro-máquina, también conocida como BCI (Brain Computer Interface), están cogiendo cada vez más popularidad. El funcionamiento de un sistema BCI consiste en la captación de las ondas cerebrales de un sujeto para después procesarlas e intentar obtener una representación de una acción o de un pensamiento del individuo. Estos pensamientos, correctamente interpretados, son posteriormente usados para llevar a cabo una acción. Ejemplos de aplicación de sistemas BCI podrían ser mover el motor de una silla de ruedas eléctrica cuando el sujeto realice, por ejemplo, la acción de cerrar un puño, o abrir la cerradura de tu propia casa usando un patrón cerebral propio. Los sistemas de procesamiento de datos están evolucionando muy rápido con el paso del tiempo. Los principales motivos son la alta velocidad de procesamiento y el bajo consumo energético de las FPGAs (Field Programmable Gate Array). Además, las FPGAs cuentan con una arquitectura reconfigurable, lo que las hace más versátiles y potentes que otras unidades de procesamiento como las CPUs o las GPUs.En el CEI (Centro de Electrónica Industrial), donde se lleva a cabo este TFG, se dispone de experiencia en el diseño de sistemas reconfigurables en FPGAs. Este TFG es el segundo de una línea de proyectos en la cual se busca obtener un sistema capaz de procesar correctamente señales cerebrales, para llegar a un patrón común que nos permita actuar en consecuencia. Más concretamente, se busca detectar cuando una persona está quedándose dormida a través de la captación de unas ondas cerebrales, conocidas como ondas alfa, cuya frecuencia está acotada entre los 8 y los 13 Hz. Estas ondas, que aparecen cuando cerramos los ojos y dejamos la mente en blanco, representan un estado de relajación mental. Por tanto, este proyecto comienza como inicio de un sistema global de BCI, el cual servirá como primera toma de contacto con el procesamiento de las ondas cerebrales, para el posterior uso de hardware reconfigurable sobre el cual se implementarán los algoritmos evolutivos. Por ello se vuelve necesario desarrollar un sistema de procesamiento de datos en una FPGA. Estos datos se procesan siguiendo la metodología de procesamiento digital de señales, y en este caso se realiza un análisis de la frecuencia utilizando la transformada rápida de Fourier, o FFT. Una vez desarrollado el sistema de procesamiento de los datos, se integra con otro sistema que se encarga de captar los datos recogidos por un ADC (Analog to Digital Converter), conocido como ADS1299. Este ADC está especialmente diseñado para captar potenciales del cerebro humano. De esta forma, el sistema final capta los datos mediante el ADS1299, y los envía a la FPGA que se encarga de procesarlos. La interpretación es realizada por los usuarios que analizan posteriormente los datos procesados. Para el desarrollo del sistema de procesamiento de los datos, se dispone primariamente de dos plataformas de estudio, a partir de las cuales se captarán los datos para después realizar el procesamiento: 1. La primera consiste en una herramienta comercial desarrollada y distribuida por OpenBCI, proyecto que se dedica a la venta de hardware para la realización de EEG, así como otros ensayos. Esta herramienta está formada por un microprocesador, un módulo de memoria SD para el almacenamiento de datos, y un módulo de comunicación inalámbrica que transmite los datos por Bluetooth. Además cuenta con el mencionado ADC ADS1299. Esta plataforma ofrece una interfaz gráfica que sirve para realizar la investigación previa al diseño del sistema de procesamiento, al permitir tener una primera toma de contacto con el sistema. 2. La segunda plataforma consiste en un kit de evaluación para el ADS1299, desde la cual se pueden acceder a los diferentes puertos de control a través de los pines de comunicación del ADC. Esta plataforma se conectará con la FPGA en el sistema integrado. Para entender cómo funcionan las ondas más simples del cerebro, así como saber cuáles son los requisitos mínimos en el análisis de ondas EEG se realizaron diferentes consultas con el Dr Ceferino Maestu, neurofisiólogo del Centro de Tecnología Biomédica (CTB) de la UPM. Él se encargó de introducirnos en los distintos procedimientos en el análisis de ondas en electroencefalogramas, así como la forma en que se deben de colocar los electrodos en el cráneo. Para terminar con la investigación previa, se realiza en MATLAB un primer modelo de procesamiento de los datos. Una característica muy importante de las ondas cerebrales es la aleatoriedad de las mismas, de forma que el análisis en el dominio del tiempo se vuelve muy complejo. Por ello, el paso más importante en el procesamiento de los datos es el paso del dominio temporal al dominio de la frecuencia, mediante la aplicación de la transformada rápida de Fourier o FFT (Fast Fourier Transform), donde se pueden analizar con mayor precisión los datos recogidos. El modelo desarrollado en MATLAB se utiliza para obtener los primeros resultados del sistema de procesamiento, el cual sigue los siguientes pasos. 1. Se captan los datos desde los electrodos y se escriben en una tabla de datos. 2. Se leen los datos de la tabla. 3. Se elige el tamaño temporal de la muestra a procesar. 4. Se aplica una ventana para evitar las discontinuidades al principio y al final del bloque analizado. 5. Se completa la muestra a convertir con con zero-padding en el dominio del tiempo. 6. Se aplica la FFT al bloque analizado con ventana y zero-padding. 7. Los resultados se llevan a una gráfica para ser analizados. Llegados a este punto, se observa que la captación de ondas alfas resulta muy viable. Aunque es cierto que se presentan ciertos problemas a la hora de interpretar los datos debido a la baja resolución temporal de la plataforma de OpenBCI, este es un problema que se soluciona en el modelo desarrollado, al permitir el kit de evaluación (sistema de captación de datos) actuar sobre la velocidad de captación de los datos, es decir la frecuencia de muestreo, lo que afectará directamente a esta precisión. Una vez llevado a cabo el primer procesamiento y su posterior análisis de los resultados obtenidos, se procede a realizar un modelo en Hardware que siga los mismos pasos que el desarrollado en MATLAB, en la medida que esto sea útil y viable. Para ello se utiliza el programa XPS (Xilinx Platform Studio) contenido en la herramienta EDK (Embedded Development Kit), que nos permite diseñar un sistema embebido. Este sistema cuenta con: Un microprocesador de tipo soft-core llamado MicroBlaze, que se encarga de gestionar y controlar todo el sistema; Un bloque FFT que se encarga de realizar la transformada rápida Fourier; Cuatro bloques de memoria BRAM, donde se almacenan los datos de entrada y salida del bloque FFT y un multiplicador para aplicar la ventana a los datos de entrada al bloque FFT; Un bus PLB, que consiste en un bus de control que se encarga de comunicar el MicroBlaze con los diferentes elementos del sistema. Tras el diseño Hardware se procede al diseño Software utilizando la herramienta SDK(Software Development Kit).También en esta etapa se integra el sistema de captación de datos, el cual se controla mayoritariamente desde el MicroBlaze. Por tanto, desde este entorno se programa el MicroBlaze para gestionar el Hardware que se ha generado. A través del Software se gestiona la comunicación entre ambos sistemas, el de captación y el de procesamiento de los datos. También se realiza la carga de los datos de la ventana a aplicar en la memoria correspondiente. En las primeras etapas de desarrollo del sistema, se comienza con el testeo del bloque FFT, para poder comprobar el funcionamiento del mismo en Hardware. Para este primer ensayo, se carga en la BRAM los datos de entrada al bloque FFT y en otra BRAM los datos de la ventana aplicada. Los datos procesados saldrán a dos BRAM, una para almacenar los valores reales de la transformada y otra para los imaginarios. Tras comprobar el correcto funcionamiento del bloque FFT, se integra junto al sistema de adquisición de datos. Posteriormente se procede a realizar un ensayo de EEG real, para captar ondas alfa. Por otro lado, y para validar el uso de las FPGAs como unidades ideales de procesamiento, se realiza una medición del tiempo que tarda el bloque FFT en realizar la transformada. Este tiempo se compara con el tiempo que tarda MATLAB en realizar la misma transformada a los mismos datos. Esto significa que el sistema desarrollado en Hardware realiza la transformada rápida de Fourier 27 veces más rápido que lo que tarda MATLAB, por lo que se puede ver aquí la gran ventaja competitiva del Hardware en lo que a tiempos de ejecución se refiere. En lo que al aspecto didáctico se refiere, este TFG engloba diferentes campos. En el campo de la electrónica:  Se han mejorado los conocimientos en MATLAB, así como diferentes herramientas que ofrece como FDATool (Filter Design Analysis Tool).  Se han adquirido conocimientos de técnicas de procesado de señal, y en particular, de análisis espectral.  Se han mejorado los conocimientos en VHDL, así como su uso en el entorno ISE de Xilinx.  Se han reforzado los conocimientos en C mediante la programación del MicroBlaze para el control del sistema.  Se ha aprendido a crear sistemas embebidos usando el entorno de desarrollo de Xilinx usando la herramienta EDK (Embedded Development Kit). En el campo de la neurología, se ha aprendido a realizar ensayos EEG, así como a analizar e interpretar los resultados mostrados en el mismo. En cuanto al impacto social, los sistemas BCI afectan a muchos sectores, donde destaca el volumen de personas con discapacidades físicas, para los cuales, este sistema implica una oportunidad de aumentar su autonomía en el día a día. También otro sector importante es el sector de la investigación médica, donde los sistemas BCIs son aplicables en muchas aplicaciones como, por ejemplo, la detección y estudio de enfermedades cognitivas.

Left-right information flow in the brain during EEG arousals

In disorders such as sleep apnea, sleep is fragmented with frequent EEG-arousal (EEGA) as determined via changes in the sleep-electroencephalogram. EEGA is a poorly understood, complicated phenomenon which is critically important in studying the mysteries of sleep. In this paper we study the information flow between the left and right hemispheres of the brain during the EEGA as manifested through inter-hemispheric asynchrony (IHA) of the surface EEG. EEG data (using electrodes A1/C4 and A2/C3 of international 10-20 system) was collected from 5 subjects undergoing routine polysomnography (PSG). Spectral correlation coefficient (R) was computed between EEG data from two hemispheres for delta-delta(0.5-4 Hz), theta-thetas(4.1-8 Hz), alpha-alpha(8.1-12 Hz) & beta-beta(12.1-25 Hz) frequency bands, during EEGA events. EEGA were graded in 3 levels as (i) micro arousals (3-6 s), (ii) short arousals (6.1-10 s), & (iii) long arousals (10.1-15 s). Our results revealed that in beta band, IHA increases above the baseline after the onset of EEGA and returns to the baseline after the conclusion of event. Results indicated that the duration of EEGA events has a direct influence on the onset of IHA. The latency (L) between the onset of arousals and IHA were found to be L=2plusmn0.5 s (for micro arousals), 4plusmn2.2 s (short arousals) and 6.5plusmn3.6 s (long arousals)

Brain ictal state characterisation through multimodal information integration

This Thesis addresses the problem of automated false-positive free detection of epileptic events by the fusion of information extracted from simultaneously recorded electro-encephalographic (EEG) and the electrocardiographic (ECG) time-series. The approach relies on a biomedical case for the coupling of the Brain and Heart systems through the central autonomic network during temporal lobe epileptic events: neurovegetative manifestations associated with temporal lobe epileptic events consist of alterations to the cardiac rhythm. From a neurophysiological perspective, epileptic episodes are characterised by a loss of complexity of the state of the brain. The description of arrhythmias, from a probabilistic perspective, observed during temporal lobe epileptic events and the description of the complexity of the state of the brain, from an information theory perspective, are integrated in a fusion-of-information framework towards temporal lobe epileptic seizure detection. The main contributions of the Thesis include the introduction of a biomedical case for the coupling of the Brain and Heart systems during temporal lobe epileptic seizures, partially reported in the clinical literature; the investigation of measures for the characterisation of ictal events from the EEG time series towards their integration in a fusion-of-knowledge framework; the probabilistic description of arrhythmias observed during temporal lobe epileptic events towards their integration in a fusion-of-knowledge framework; and the investigation of the different levels of the fusion-of-information architecture at which to perform the combination of information extracted from the EEG and ECG time-series. The performance of the method designed in the Thesis for the false-positive free automated detection of epileptic events achieved a false-positives rate of zero on the dataset of long-term recordings used in the Thesis.

Which physiological components are more suitable for visual ERP based brain-computer interface?:A preliminary MEG/EEG study

We investigated which evoked response component occurring in the first 800 ms after stimulus presentation was most suitable to be used in a classical P300-based brain-computer interface speller protocol. Data was acquired from 275 Magnetoencephalographic sensors in two subjects and from 61 Electroencephalographic sensors in four. To better characterize the evoked physiological responses and minimize the effect of response overlap, a 1000 ms Inter Stimulus Interval was preferred to the short (