Data acquisition and imaging using wavelet transform: a new path for high speed transient force microscopy

The unique ability of Atomic Force Microscopy (AFM) to image, manipulate and characterize materials at the nanoscale has made it a remarkable tool in nanotechnology. In dynamic AFM, acquisition and processing of the photodetector signal originating from probe–sample interaction is a critical step in data analysis and measurements. However, details of such interaction including its nonlinearity and dynamics of the sample surface are limited due to the ultimately bounded bandwidth and limited time scales of data processing electronics of standard AFM. Similarly, transient details of the AFM probe's cantilever signal are lost due to averaging of data by techniques which correlate the frequency spectrum of the captured data with a temporally invariant physical system. Here, we introduce a fundamentally new approach for dynamic AFM data acquisition and imaging based on applying the wavelet transform on the data stream from the photodetector. This approach provides the opportunity for exploration of the transient response of the cantilever, analysis and imaging of the dynamics of amplitude and phase of the signals captured from the photodetector. Furthermore, it can be used for the control of AFM which would yield increased imaging speed. Hence the proposed method opens a pathway for high-speed transient force microscopy

Sistema de predicción epileptogenica en lazo cerrado basado en matrices sub-durales

The human brain is the most complex organ in the human body, which consists of approximately 100 billion neurons. These cells effortlessly communicate over multiple hemispheres to deliver our everyday sensorimotor and cognitive abilities. Although the underlying principles of neuronal communication are not well understood, there is evidence to suggest precise synchronisation and/or de-synchronisation of neuronal clusters could play an important role. Furthermore, new evidence suggests that these patterns of synchronisation could be used as an identifier for the detection of a variety of neurological disorders including, Alzheimers (AD), Schizophrenia (SZ) and Epilepsy (EP), where neural degradation or hyper synchronous networks have been detected. Over the years many different techniques have been proposed for the detection of synchronisation patterns, in the form of spectral analysis, transform approaches and statistical based studies. Nonetheless, most are confined to software based implementations as opposed to hardware realisations due to their complexity. Furthermore, the few hardware implementations which do exist, suffer from a lack of scalability, in terms of brain area coverage, throughput and power consumption. Here we introduce the design and implementation of a hardware efficient algorithm, named Delay Difference Analysis (DDA), for the identification of patient specific synchronisation patterns. The design is remarkably hardware friendly when compared with other algorithms. In fact, we can reduce hardware requirements by as much as 80% and power consumption as much as 90%, when compared with the most common techniques. In terms of absolute sensitivity the DDA produces an average sensitivity of more than 80% for a false positive rate of 0.75 FP/h and indeed up to a maximum of 90% for confidence levels of 95%. This thesis presents two integer-based digital processors for the calculation of phase synchronisation between neural signals. It is based on the measurement of time periods between two consecutive minima. The simplicity of the approach allows for the use of elementary digital blocks, such as registers, counters or adders. In fact, the first introduced processor was fabricated in a 0.18μm CMOS process and only occupies 0.05mm2 and consumes 15nW from a 0.5V supply voltage at a signal input rate of 1024S/s. These low-area and low-power features make the proposed circuit a valuable computing element in closed-loop neural prosthesis for the treatment of neural disorders, such as epilepsy, or for measuring functional connectivity maps between different recording sites in the brain. A second VLSI implementation was designed and integrated as a mass integrated 16-channel design. Incorporated into the design were 16 individual synchronisation processors (15 on-line processors and 1 test processor) each with a dedicated training and calculation module, used to build a specialised epileptic detection system based on patient specific synchrony thresholds. Each of the main processors are capable of calculating the phase synchrony between 9 independent electroencephalography (EEG) signals over 8 epochs of time totalling 120 EEG combinations. Remarkably, the entire circuit occupies a total area of only 3.64 mm2. This design was implemented with a multi-purpose focus in mind. Firstly, as a clinical aid to help physicians detect pathological brain states, where the small area would allow the patient to wear the device for home trials. Moreover, the small power consumption would allow to run from standard batteries for long periods. The trials could produce important patient specific information which could be processed using mathematical tools such as graph theory. Secondly, the design was focused towards the use as an in-vivo device to detect phase synchrony in real time for patients who suffer with such neurological disorders as EP, which need constant monitoring and feedback. In future developments this synchronisation device would make an good contribution to a full system on chip device for detection and stimulation.El cerebro humano es el órgano más complejo del cuerpo humano, que consta de aproximadamente 100 mil millones de neuronas. Estas células se comunican sin esfuerzo a través de ambos hemisferios para favorecer nuestras habilidades sensoriales y cognitivas diarias. Si bien los principios subyacentes de la comunicación neuronal no se comprenden bien, existen pruebas que sugieren que la sincronización precisa y/o la desincronización de los grupos neuronales podrían desempeñar un papel importante. Además, nuevas evidencias sugieren que estos patrones de sincronización podrían usarse como un identificador para la detección de una gran variedad de trastornos neurológicos incluyendo la enfermedad de Alzheimer(AD), la esquizofrenia(SZ) y la epilepsia(EP), donde se ha detectado la degradación neural o las redes hiper sincrónicas. A lo largo de los años, se han propuesto muchas técnicas diferentes para la detección de patrones de sincronización en forma de análisis espectral, enfoques de transformación y análisis estadísticos. No obstante, la mayoría se limita a implementaciones basadas en software en lugar de realizaciones de hardware debido a su complejidad. Además, las pocas implementaciones de hardware que existen, sufren una falta de escalabilidad, en términos de cobertura del área del cerebro, rendimiento y consumo de energía. Aquí presentamos el diseño y la implementación de un algoritmo eficiente de hardware llamado “Delay Difference Aproximation” (DDA) para la identificación de patrones de sincronización específicos del paciente. El diseño es notablemente compatible con el hardware en comparación con otros algoritmos. De hecho, podemos reducir los requisitos de hardware hasta en un 80% y el consumo de energía hasta en un 90%, en comparación con las técnicas más comunes. En términos de sensibilidad absoluta, la DDA produce una sensibilidad promedio de más del 80% para una tasa de falsos positivos de 0,75 PF / hr y hasta un máximo del 90% para niveles de confianza del 95%. Esta tesis presenta dos procesadores digitales para el cálculo de la sincronización de fase entre señales neuronales. Se basa en la medición de los períodos de tiempo entre dos mínimos consecutivos. La simplicidad del enfoque permite el uso de bloques digitales elementales, como registros, contadores o sumadores. De hecho, el primer procesador introducido se fabricó en un proceso CMOS de 0.18μm y solo ocupa 0.05mm2 y consume 15nW de un voltaje de suministro de 0.5V a una tasa de entrada de señal de 1024S/s Estas características de baja área y baja potencia hacen que el procesador propuesto sea un valioso elemento informático en prótesis neurales de circuito cerrado para el tratamiento de trastornos neuronales, como la epilepsia, o para medir mapas de conectividad funcional entre diferentes sitios de registro en el cerebro. Además, se diseñó una segunda implementación VLSI que se integró como un diseño de 16 canales integrado en masa. Se incorporaron al diseño 16 procesadores de sincronización individuales (15 procesadores en línea y 1 procesador de prueba), cada uno con un módulo de entrenamiento y cálculo dedicado, utilizado para construir un sistema de detección epiléptico especializado basado en umbrales de sincronía específicos del paciente. Cada uno de los procesadores principales es capaz de calcular la sincronización de fase entre 9 señales de electroencefalografía (EEG) independientes en 8 épocas de tiempo que totalizan 120 combinaciones de EEG. Cabe destacar que todo el circuito ocupa un área total de solo 3.64 mm2. Este diseño fue implementado teniendo en mente varios propósitos. En primer lugar, como ayuda clínica para ayudar a los médicos a detectar estados cerebrales patológicos, donde el área pequeña permitiría al paciente usar el dispositivo para las pruebas caseras. Además, el pequeño consumo de energía permitiría una carga cero del dispositivo, lo que le permitiría funcionar con baterías estándar durante largos períodos. Los ensayos podrían producir información importante específica para el paciente que podría procesarse utilizando herramientas matemáticas como la teoría de grafos. En segundo lugar, el diseño se centró en el uso como un dispositivo in-vivo para detectar la sincronización de fase en tiempo real para pacientes que sufren trastornos neurológicos como el EP, que necesitan supervisión y retroalimentación constantes. En desarrollos futuros, este dispositivo de sincronización sería una buena base para desarrollar un sistema completo de un dispositivo chip para detección de trastornos neurológicos

ARTIFACT CHARACTERIZATION, DETECTION AND REMOVAL FROM NEURAL SIGNALS

Ph.DDOCTOR OF PHILOSOPH

Brain functional and effective connectivity based on electroencephalography recordings: A review.

Functional connectivity and effective connectivity of the human brain, representing statistical dependence and directed information flow between cortical regions, significantly contribute to the study of the intrinsic brain network and its functional mechanism. Many recent studies on electroencephalography (EEG) have been focusing on modeling and estimating brain connectivity due to increasing evidence that it can help better understand various brain neurological conditions. However, there is a lack of a comprehensive updated review on studies of EEG-based brain connectivity, particularly on visualization options and associated machine learning applications, aiming to translate those techniques into useful clinical tools. This article reviews EEG-based functional and effective connectivity studies undertaken over the last few years, in terms of estimation, visualization, and applications associated with machine learning classifiers. Methods are explored and discussed from various dimensions, such as either linear or nonlinear, parametric or nonparametric, time-based, and frequency-based or time-frequency-based. Then it is followed by a novel review of brain connectivity visualization methods, grouped by Heat Map, data statistics, and Head Map, aiming to explore the variation of connectivity across different brain regions. Finally, the current challenges of related research and a roadmap for future related research are presented

Recent Advances in Signal Processing

The signal processing task is a very critical issue in the majority of new technological inventions and challenges in a variety of applications in both science and engineering fields. Classical signal processing techniques have largely worked with mathematical models that are linear, local, stationary, and Gaussian. They have always favored closed-form tractability over real-world accuracy. These constraints were imposed by the lack of powerful computing tools. During the last few decades, signal processing theories, developments, and applications have matured rapidly and now include tools from many areas of mathematics, computer science, physics, and engineering. This book is targeted primarily toward both students and researchers who want to be exposed to a wide variety of signal processing techniques and algorithms. It includes 27 chapters that can be categorized into five different areas depending on the application at hand. These five categories are ordered to address image processing, speech processing, communication systems, time-series analysis, and educational packages respectively. The book has the advantage of providing a collection of applications that are completely independent and self-contained; thus, the interested reader can choose any chapter and skip to another without losing continuity

Signal Processing Using Non-invasive Physiological Sensors

Non-invasive biomedical sensors for monitoring physiological parameters from the human body for potential future therapies and healthcare solutions. Today, a critical factor in providing a cost-effective healthcare system is improving patients' quality of life and mobility, which can be achieved by developing non-invasive sensor systems, which can then be deployed in point of care, used at home or integrated into wearable devices for long-term data collection. Another factor that plays an integral part in a cost-effective healthcare system is the signal processing of the data recorded with non-invasive biomedical sensors. In this book, we aimed to attract researchers who are interested in the application of signal processing methods to different biomedical signals, such as an electroencephalogram (EEG), electromyogram (EMG), functional near-infrared spectroscopy (fNIRS), electrocardiogram (ECG), galvanic skin response, pulse oximetry, photoplethysmogram (PPG), etc. We encouraged new signal processing methods or the use of existing signal processing methods for its novel application in physiological signals to help healthcare providers make better decisions

Wearable brain computer interfaces with near infrared spectroscopy

Brain computer interfaces (BCIs) are devices capable of relaying information directly from the brain to a digital device. BCIs have been proposed for a diverse range of clinical and commercial applications; for example, to allow paralyzed subjects to communicate, or to improve machine human interactions. At their core, BCIs need to predict the current state of the brain from variables measuring functional physiology. Functional near infrared spectroscopy (fNIRS) is a non-invasive optical technology able to measure hemodynamic changes in the brain. Along with electroencephalography (EEG), fNIRS is the only technique that allows non-invasive and portable sensing of brain signals. Portability and wearability are very desirable characteristics for BCIs, as they allow them to be used in contexts beyond the laboratory, extending their usability for clinical and commercial applications, as well as for ecologically valid research. Unfortunately, due to limited access to the brain, non-invasive BCIs tend to suffer from low accuracy in their estimation of the brain state. It has been suggested that feedback could increase BCI accuracy as the brain normally relies on sensory feedback to adjust its strategies. Despite this, presenting relevant and accurate feedback in a timely manner can be challenging when processing fNIRS signals, as they tend to be contaminated by physiological and motion artifacts. In this dissertation, I present the hardware and software solutions we proposed and developed to deal with these challenges. First, I will talk about ninjaNIRS, the wearable open source fNIRS device we developed in our laboratory, which could help fNIRS neuroscience and BCIs to become more accessible. Next, I will present an adaptive filter strategy to recover the neural responses from fNIRS signals in real-time, which could be used for feedback and classification in a BCI paradigm. We showed that our wearable fNIRS device can operate autonomously for up to three hours and can be easily carried in a backpack, while offering noise equivalent power comparable to commercial devices. Our adaptive multimodal Kalman filter strategy provided a six-fold increase in contrast to noise ratio of the brain signals compared to standard filtering while being able to process at least 24 channels at 400 samples per second using a standard computer. This filtering strategy, along with visual feedback during a left vs right motion imagery task, showed a relative increase of accuracy of 37.5% compared to not using feedback. With this, we show that it is possible to present relevant feedback for fNIRS BCI in real-time. The findings on this dissertation might help improve the design of future fNIRS BCIs, and thus increase the usability and reliability of this technology

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches

Electrophysiologic assessment of (central) auditory processing disorder in children with non-syndromic cleft lip and/or palate

Session 5aPP - Psychological and Physiological Acoustics: Auditory Function, Mechanisms, and Models (Poster Session)Cleft of the lip and/or palate is a common congenital craniofacial malformation worldwide, particularly non-syndromic cleft lip and/or palate (NSCL/P). Though middle ear deficits in this population have been universally noted in numerous studies, other auditory problems including inner ear deficits or cortical dysfunction are rarely reported. A higher prevalence of educational problems has been noted in children with NSCL/P compared to craniofacially normal children. These high level cognitive difficulties cannot be entirely attributed to peripheral hearing loss. Recently it has been suggested that children with NSCLP may be more prone to abnormalities in the auditory cortex. The aim of the present study was to investigate whether school age children with (NSCL/P) have a higher prevalence of indications of (central) auditory processing disorder [(C)APD] compared to normal age matched controls when assessed using auditory event-related potential (ERP) techniques. School children (6 to 15 years) with NSCL/P and normal controls with matched age and gender were recruited. Auditory ERP recordings included auditory brainstem response and late event-related potentials, including the P1-N1-P2 complex and P300 waveforms. Initial findings from the present study are presented and their implications for further research in this area —and clinical intervention—are outlined. © 2012 Acoustical Society of Americapublished_or_final_versio