Functional network and spectral analysis of clinical EEG data to identify quantitative biomarkers and classify brain disorders

Many cognitive and neurological disorders today, such as Autism Spectrum Disorders (ASD) and various forms of epilepsy such as infantile spasms (IS), manifest as changes in voltage activity recorded in scalp electroencephalograms (EEG). Diagnosis of brain disease often relies on the interpretation of complex EEG features through visual inspection by clinicians. Although clinically useful, such interpretation is subjective and suffers from poor inter-rater reliability, which affects clinical care through increased variability and uncertainty in diagnosis. In addition, such qualitative assessments are often binary, and do not parametrically measure characteristics of disease manifestations. Many cognitive disorders are grouped by similar behaviors, but may arise from distinct biological causes, possibly represented by subtle electrophysiological differences. To address this, quantitative analytical tools - such as functional network connectivity, frequency-domain, and time-domain features - are being developed and applied to clinically obtained EEG data to identify electrophysiological biomarkers. These biomarkers enhance a clinician’s ability to accurately diagnose, categorize, and select treatment for various neurological conditions. In the first study, we use spectral and functional network analysis of clinical EEG data recorded from a population of children to propose a cortical biomarker for autism. We first analyze a training set of age-matched (4–8 years) ASD and neurotypical children to develop hypotheses based on power spectral features and measures of functional network connectivity. From the training set of subjects, we derive the following hypotheses: 1) The ratio of the power of the posterior alpha rhythm (8–14 Hz) peak to the anterior alpha rhythm peak is significantly lower in ASD than control subjects. 2) The functional network density is lower in ASD subjects than control subjects. 3) A select group of edges provide a more sensitive and specific biomarker of ASD. We then test these hypotheses in a validation set of subjects and show that both the first and third hypotheses, but not the second, are validated. The validated features successfully classified the data with significant accuracy. These results provide a validated study for EEG biomarkers of ASD based on changes in brain rhythms and functional network characteristics. We next perform a follow-up study that utilizes the same group of ASD and neurotypical subjects, but focuses on differences between these two groups in the sleep state. Motivated by the results from the previous study, we utilize the previously validated biomarkers, including the alpha ratio and the subset of edges found to be a sensitive biomarker of ASD, and test their effectiveness in the sleep state. To complement these frequency domain features, we also investigate the efficacy of several time domain measures. This investigation did not lead to significant findings, which may have important implications for the differences between sleep and wake states in ASD, or perhaps generally for clinical assessment, as well as for the effect of noise on signal in clinically obtained data. Finally, we design a similar analysis framework to investigate a set of clinical EEG data recorded from a population of children with active infantile spasms (IS) (2-16 months), and age-matched neurotypical children, in both wake and sleep states. The goal of this analysis is to develop a quantitative biomarker from the EEG signal, which ultimately we will apply to predict the clinical outcome of children with IS. In addition to spectral and functional network analysis, we calculate time domain features previously found to correlate with seizures. We compare the two populations by each feature individually, test the effects of age on these features, use all features in a linear discriminant model to categorize IS versus neurotypical EEG, and test the findings using a leave-one-out validation test. We find almost every feature tested shows significant population differences between IS and control groups, and that taken together they serve as an effective classifier, with potential to be informative as to disease severity and long-term outcome. Furthermore, analysis of these features reveals two groups, indicating a possibility that these features reflect two distinct qualitative characteristics of IS and seizures

Fully portable and wireless universal brain-machine interfaces enabled by flexible scalp electronics and deep-learning algorithm

Variation in human brains creates difficulty in implementing electroencephalography (EEG) into universal brain-machine interfaces (BMI). Conventional EEG systems typically suffer from motion artifacts, extensive preparation time, and bulky equipment, while existing EEG classification methods require training on a per-subject or per-session basis. Here, we introduce a fully portable, wireless, flexible scalp electronic system, incorporating a set of dry electrodes and flexible membrane circuit. Time domain analysis using convolutional neural networks allows for an accurate, real-time classification of steady-state visually evoked potentials on the occipital lobe. Simultaneous comparison of EEG signals with two commercial systems captures the improved performance of the flexible electronics with significant reduction of noise and electromagnetic interference. The two-channel scalp electronic system achieves a high information transfer rate (122.1 ± 3.53 bits per minute) with six human subjects, allowing for a wireless, real-time, universal EEG classification for an electronic wheelchair, motorized vehicle, and keyboard-less presentation

Data Analytics in Steady-State Visual Evoked Potential-based Brain-Computer Interface: A Review

Electroencephalograph (EEG) has been widely applied for brain-computer interface (BCI) which enables paralyzed people to directly communicate with and control of external devices, due to its portability, high temporal resolution, ease of use and low cost. Of various EEG paradigms, steady-state visual evoked potential (SSVEP)-based BCI system which uses multiple visual stimuli (such as LEDs or boxes on a computer screen) flickering at different frequencies has been widely explored in the past decades due to its fast communication rate and high signal-to-noise ratio. In this paper, we review the current research in SSVEP-based BCI, focusing on the data analytics that enables continuous, accurate detection of SSVEPs and thus high information transfer rate. The main technical challenges, including signal pre-processing, spectrum analysis, signal decomposition, spatial filtering in particular canonical correlation analysis and its variations, and classification techniques are described in this paper. Research challenges and opportunities in spontaneous brain activities, mental fatigue, transfer learning as well as hybrid BCI are also discussed

Decision-Making with Heterogeneous Sensors - A Copula Based Approach

Statistical decision making has wide ranging applications, from communications and signal processing to econometrics and finance. In contrast to the classical one source-one receiver paradigm, several applications have been identified in the recent past that require acquiring data from multiple sources or sensors. Information from the multiple sensors are transmitted to a remotely located receiver known as the fusion center which makes a global decision. Past work has largely focused on fusion of information from homogeneous sensors. This dissertation extends the formulation to the case when the local sensors may possess disparate sensing modalities. Both the theoretical and practical aspects of multimodal signal processing are considered. The first and foremost challenge is to \u27adequately\u27 model the joint statistics of such heterogeneous sensors. We propose the use of copula theory for this purpose. Copula models are general descriptors of dependence. They provide a way to characterize the nonlinear functional relationships between the multiple modalities, which are otherwise difficult to formalize. The important problem of selecting the `best\u27 copula function from a given set of valid copula densities is addressed, especially in the context of binary hypothesis testing problems. Both, the training-testing paradigm, where a training set is assumed to be available for learning the copula models prior to system deployment, as well as generalized likelihood ratio test (GLRT) based fusion rule for the online selection and estimation of copula parameters are considered. The developed theory is corroborated with extensive computer simulations as well as results on real-world data. Sensor observations (or features extracted thereof) are most often quantized before their transmission to the fusion center for bandwidth and power conservation. A detection scheme is proposed for this problem assuming unifom scalar quantizers at each sensor. The designed rule is applicable for both binary and multibit local sensor decisions. An alternative suboptimal but computationally efficient fusion rule is also designed which involves injecting a deliberate disturbance to the local sensor decisions before fusion. The rule is based on Widrow\u27s statistical theory of quantization. Addition of controlled noise helps to \u27linearize\u27 the higly nonlinear quantization process thus resulting in computational savings. It is shown that although the introduction of external noise does cause a reduction in the received signal to noise ratio, the proposed approach can be highly accurate when the input signals have bandlimited characteristic functions, and the number of quantization levels is large. The problem of quantifying neural synchrony using copula functions is also investigated. It has been widely accepted that multiple simultaneously recorded electroencephalographic signals exhibit nonlinear and non-Gaussian statistics. While the existing and popular measures such as correlation coefficient, corr-entropy coefficient, coh-entropy and mutual information are limited to being bivariate and hence applicable only to pairs of channels, measures such as Granger causality, even though multivariate, fail to account for any nonlinear inter-channel dependence. The application of copula theory helps alleviate both these limitations. The problem of distinguishing patients with mild cognitive impairment from the age-matched control subjects is also considered. Results show that the copula derived synchrony measures when used in conjunction with other synchrony measures improve the detection of Alzheimer\u27s disease onset