Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy

Fixation-off sensitivity (FOS) denotes the forms of epilepsy elicited by elimination of fixation. FOS-IGE patients are rare cases [1]. In a previous work [2] we showed that two FOS-IGE patients had different altered EEG rhythms when closing eyes; only beta band was altered in patient 1 while theta, alpha and beta were altered in patient 2. In the present work, we explain the relationship between the altered brain rhythms in these patients and the disruption in functional brain networks.

Dysfunctional profile for patients in physical neurorehabilitation of upper limb

This paper proposes a first approach to Objective Motor Assessment (OMA) methodology. Also, it introduces the Dysfunctional profile (DP) concept. DP consists of a data matrix characterizing the Upper Limb (UL) physical alterations of a patient with Acquired Brain Injury (ABI) during the rehabilitation process. This research is based on the comparison methology of UL movement between subjects with ABI and healthy subjects as part of OMA. The purpose of this comparison is to classify subjects according to their motor control and subsequently issue a functional assessment of the movement. For this purpose Artificial Neural Networks (ANN) have been used to classify patients. Different network structures are tested. The obtained classification accuracy was 95.65%. This result allows the use of ANNs as a viable option for dysfunctional assessment. This work can be considered a pilot study for further research to corroborate these results.

Brain injury MRI simulator based on theoretical models of neuroanatomic damage

In order to improve the body of knowledge about brain injury impairment is essential to develop image database with different types of injuries. This paper proposes a new methodology to model three types of brain injury: stroke, tumor and traumatic brain injury; and implements a system to navigate among simulated MRI studies. These studies can be used on research studies, to validate new processing methods and as an educational tool, to show different types of brain injury and how they affect to neuroanatomic structures.

A graphical tool for designing interactive video cognitive rehabilitation therapies

Acquired Brain Injury (ABI) has become one of the most common causes of neurological disability in developed countries. Cognitive disorders result in a loss of independence and therefore patients? quality of life. Cognitive rehabilitation aims to promote patients? skills to achieve their highest degree of personal autonomy. New technologies such as interactive video, whereby real situations of daily living are reproduced within a controlled virtual environment, enable the design of personalized therapies with a high level of generalization and a great ecological validity. This paper presents a graphical tool that allows neuropsychologists to design, modify, and configure interactive video therapeutic activities, through the combination of graphic and natural language. The tool has been validated creating several Activities of Daily Living and a preliminary usability evaluation has been performed showing a good clinical acceptance in the definition of complex interactive video therapies for cognitive rehabilitation.

Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment

The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

White matter damage disorganizes brain functional networks in amnestic mild cognitive impairment

Although progressive functional brain network disruption has been one of the hallmarks of Alzheimer?s Dis- ease, little is known about the origin of this functional impairment that underlies cognitive symptoms. We in- vestigated how the loss of white matter (WM) integrity disrupts the organization of the functional networks at different frequency bands. The analyses were performed in a sample of healthy elders and mild cognitive im- pairment (MCI) subjects. Spontaneous brain magnetic activity (measured with magnetoencephalography) was characterized with phase synchronization analysis, and graph theory was applied to the functional networks. We identified WM areas (using diffusion weighted magnetic resonance imaging) that showed a statistical de- pendence between the fractional anisotropy and the graph metrics. These regions are part of an episodic mem- ory network and were also related to cognitive functions. Our data support the hypothesis that disruption of the anatomical networks influences the organization at the functional level resulting in the prodromal dementia syndrome of MCI.

Non-invasive user monitoring in daily tasks for cognitive rehabilitation

El uso de técnicas para la monitorización del movimiento humano generalmente permite a los investigadores analizar la cinemática y especialmente las capacidades motoras en aquellas actividades de la vida cotidiana que persiguen un objetivo concreto como pueden ser la preparación de bebidas y comida, e incluso en tareas de aseo. Adicionalmente, la evaluación del movimiento y el comportamiento humanos en el campo de la rehabilitación cognitiva es esencial para profundizar en las dificultades que algunas personas encuentran en la ejecución de actividades diarias después de accidentes cerebro-vasculares. Estas dificultades están principalmente asociadas a la realización de pasos secuenciales y al reconocimiento del uso de herramientas y objetos. La interpretación de los datos sobre la actitud de este tipo de pacientes para reconocer y determinar el nivel de éxito en la ejecución de las acciones, y para ampliar el conocimiento en las enfermedades cerebrales, sus consecuencias y severidad, depende totalmente de los dispositivos usados para la captura de esos datos y de la calidad de los mismos. Más aún, existe una necesidad real de mejorar las técnicas actuales de rehabilitación cognitiva contribuyendo al diseño de sistemas automáticos para crear una especie de terapeuta virtual que asegure una vida más independiente de estos pacientes y reduzca la carga de trabajo de los terapeutas. Con este objetivo, el uso de sensores y dispositivos para obtener datos en tiempo real de la ejecución y estado de la tarea de rehabilitación es esencial para también contribuir al diseño y entrenamiento de futuros algoritmos que pudieran reconocer errores automáticamente para informar al paciente acerca de ellos mediante distintos tipos de pistas como pueden ser imágenes, mensajes auditivos o incluso videos. La tecnología y soluciones existentes en este campo no ofrecen una manera totalmente robusta y efectiva para obtener datos en tiempo real, por un lado, porque pueden influir en el movimiento del propio paciente en caso de las plataformas basadas en el uso de marcadores que necesitan sensores pegados en la piel; y por otro lado, debido a la complejidad o alto coste de implantación lo que hace difícil pensar en la idea de instalar un sistema en el hospital o incluso en la casa del paciente. Esta tesis presenta la investigación realizada en el campo de la monitorización del movimiento de pacientes para proporcionar un paso adelante en términos de detección, seguimiento y reconocimiento del comportamiento de manos, gestos y cara mediante una manera no invasiva la cual puede mejorar la técnicas actuales de rehabilitación cognitiva para la adquisición en tiempo real de datos sobre el comportamiento del paciente y la ejecución de la tarea. Para entender la importancia del marco de esta tesis, inicialmente se presenta un resumen de las principales enfermedades cognitivas y se introducen las consecuencias que tienen en la ejecución de tareas de la vida diaria. Más aún, se investiga sobre las metodologías actuales de rehabilitación cognitiva. Teniendo en cuenta que las manos son la principal parte del cuerpo para la ejecución de tareas manuales de la vida cotidiana, también se resumen las tecnologías existentes para la captura de movimiento de manos. Una de las principales contribuciones de esta tesis está relacionada con el diseño y evaluación de una solución no invasiva para detectar y seguir las manos durante la ejecución de tareas manuales de la vida cotidiana que a su vez involucran la manipulación de objetos. Esta solución la cual no necesita marcadores adicionales y está basada en una cámara de profundidad de bajo coste, es robusta, precisa y fácil de instalar. Otra contribución presentada se centra en el reconocimiento de gestos para detectar el agarre de objetos basado en un sensor infrarrojo de última generación, y también complementado con una cámara de profundidad. Esta nueva técnica, y también no invasiva, sincroniza ambos sensores para seguir objetos específicos además de reconocer eventos concretos relacionados con tareas de aseo. Más aún, se realiza una evaluación preliminar del reconocimiento de expresiones faciales para analizar si es adecuado para el reconocimiento del estado de ánimo durante la tarea. Por su parte, todos los componentes y algoritmos desarrollados son integrados en un prototipo simple para ser usado como plataforma de monitorización. Se realiza una evaluación técnica del funcionamiento de cada dispositivo para analizar si es adecuada para adquirir datos en tiempo real durante la ejecución de tareas cotidianas reales. Finalmente, se estudia la interacción con pacientes reales para obtener información del nivel de usabilidad del prototipo. Dicha información es esencial y útil para considerar una rehabilitación cognitiva basada en la idea de instalación del sistema en la propia casa del paciente al igual que en el hospital correspondiente. ABSTRACT The use of human motion monitoring techniques usually let researchers to analyse kinematics, especially in motor strategies for goal-oriented activities of daily living, such as the preparation of drinks and food, and even grooming tasks. Additionally, the evaluation of human movements and behaviour in the field of cognitive rehabilitation is essential to deep into the difficulties some people find in common activities after stroke. This difficulties are mainly associated with sequence actions and the recognition of tools usage. The interpretation of attitude data of this kind of patients in order to recognize and determine the level of success of the execution of actions, and to broaden the knowledge in brain diseases, consequences and severity, depends totally on the devices used for the capture of that data and the quality of it. Moreover, there is a real need of improving the current cognitive rehabilitation techniques by contributing to the design of automatic systems to create a kind of virtual therapist for the improvement of the independent life of these stroke patients and to reduce the workload of the occupational therapists currently in charge of them. For this purpose, the use of sensors and devices to obtain real time data of the execution and state of the rehabilitation task is essential to also contribute to the design and training of future smart algorithms which may recognise errors to automatically provide multimodal feedback through different types of cues such as still images, auditory messages or even videos. The technology and solutions currently adopted in the field don't offer a totally robust and effective way for obtaining real time data, on the one hand, because they may influence the patient's movement in case of marker-based platforms which need sensors attached to the skin; and on the other hand, because of the complexity or high cost of implementation, which make difficult the idea of installing a system at the hospital or even patient's home. This thesis presents the research done in the field of user monitoring to provide a step forward in terms of detection, tracking and recognition of hand movements, gestures and face via a non-invasive way which could improve current techniques for cognitive rehabilitation for real time data acquisition of patient's behaviour and execution of the task. In order to understand the importance of the scope of the thesis, initially, a summary of the main cognitive diseases that require for rehabilitation and an introduction of the consequences on the execution of daily tasks are presented. Moreover, research is done about the actual methodology to provide cognitive rehabilitation. Considering that the main body members involved in the completion of a handmade daily task are the hands, the current technologies for human hands movements capture are also highlighted. One of the main contributions of this thesis is related to the design and evaluation of a non-invasive approach to detect and track user's hands during the execution of handmade activities of daily living which involve the manipulation of objects. This approach does not need the inclusion of any additional markers. In addition, it is only based on a low-cost depth camera, it is robust, accurate and easy to install. Another contribution presented is focused on the hand gesture recognition for detecting object grasping based on a brand new infrared sensor, and also complemented with a depth camera. This new, and also non-invasive, solution which synchronizes both sensors to track specific tools as well as recognize specific events related to grooming is evaluated. Moreover, a preliminary assessment of the recognition of facial expressions is carried out to analyse if it is adequate for recognizing mood during the execution of task. Meanwhile, all the corresponding hardware and software developed are integrated in a simple prototype with the purpose of being used as a platform for monitoring the execution of the rehabilitation task. Technical evaluation of the performance of each device is carried out in order to analyze its suitability to acquire real time data during the execution of real daily tasks. Finally, a kind of healthcare evaluation is also presented to obtain feedback about the usability of the system proposed paying special attention to the interaction with real users and stroke patients. This feedback is quite useful to consider the idea of a home-based cognitive rehabilitation as well as a possible hospital installation of the prototype.

In vitro repair of oxidative DNA damage by human nucleotide excision repair system: Possible explanation for neurodegeneration in Xeroderma pigmentosum patients

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20–30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer’s disease

To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzheimer’s disease (AD), the transfer of mtDNA from elderly patients with AD into mtDNA-less (ρ0) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with ρ0 HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in ρ0 HeLa cells. Next, the cybrid clones repopulated with exogenously imported mtDNA from patients with AD were used for examination of respiratory enzyme activity and transfer of mtDNA with the pathogenic mutations that induce mitochondrial dysfunction. The presence of the mutated mtDNA was restricted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as mtDNA donors had detectable mutated mtDNA. However, biochemical analyses showed that all cybrid clones with mtDNA imported from platelets or brain tissues of patients with AD restored mitochondrial respiration activity to almost the same levels as those of cybrid clones with mtDNA from age-matched normal controls, suggesting functional integrity of mtDNA in both platelets and brain tissues of elderly patients with AD. These observations warrant the reassessment of the conventional concept that the accumulation of pathogenic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the development of age-associated neurodegenerative diseases.

Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

Preserved speech abilities and compensation following prefrontal damage.

Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.