High-performance detection of epilepsy in seizure-free EEG recordings: A novel machine learning approach using very specific epileptic EEG sub-bands

We applied machine learning to diagnose epilepsy based on the fine-graded spectral analysis of seizure-free (resting state) EEG recordings. Despite using unspecific agglomerated EEG spectra, our fine-graded spectral analysis specifically identified the two EEG resting state sub-bands differentiating healthy people from epileptics (1.5-2 Hz and 11-12.5 Hz). The rigorous evaluation of completely unseen data of 100 EEG recordings (50 belonging to epileptics and the other 50 to healthy people) shows that the approach works successfully, achieving an outstanding accuracy of 99 percent, which significantly outperforms the current benchmark of 70% to 95% by a panel of up to three experienced neurologists. Our epilepsy diagnosis classifier can be implemented in modern EEG analysis devices, especially in intensive care units where early diagnosis and appropriate treatment are decisive in life and death scenarios and where physicians’ error rates are particularly high. Our approach is accurate, robust, fast, and cost-efficient and substantially contributes to Information Systems research in healthcare. The approach is also of high practical and theoretical relevance

Sleep‐related hypermotor epilepsy and non‐rapid eye movement parasomnias: Differences in the periodic and aperiodic component of the electroencephalographic power spectra

Over the last two decades, our understanding of clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviours has improved considerably, although it is far from complete. Indeed, even if many core characteristics of sleep-related hypermotor epilepsy and non-rapid eye movement parasomnias have been clarified, some crucial points remain controversial, and the overlap of the behavioural patterns between these disorders represents a diagnostic challenge. In this work, we focused on segments of multichannel sleep electroencephalogram free from clinical episodes, from two groups of subjects affected by sleep-related hypermotor epilepsy (N = 15) and non-rapid eye movement parasomnias (N = 16), respectively. We examined sleep stages N2 and N3 of the first part of the night (cycles 1 and 2), and assessed the existence of differences in the periodic and aperiodic components of the electroencephalogram power spectra between the two groups, using the Fitting Oscillations & One Over f (FOOOF) toolbox. A significant difference in the gamma frequency band was found, with an increased relative power in sleep-related hypermotor epilepsy subjects, during both N2 (p < .001) and N3 (p < .001), and a significant higher slope of the aperiodic component in non-rapid eye movement parasomnias, compared with sleep-related hypermotor epilepsy, during N3 (p = .012). We suggest that the relative power of the gamma band and the slope extracted from the aperiodic component of the electroencephalogram signal may be helpful to characterize differences between subjects affected by non-rapid eye movement parasomnias and those affected by sleep-related hypermotor epilepsy

Intraoperative Guidance for Pediatric Brain Surgery based on Optical Techniques

For most of the patients with brain tumors and/or epilepsy, surgical resection of brain lesions, when applicable, remains one of the optimal treatment options. The success of the surgery hinges on accurate demarcation of neoplastic and epileptogenic brain tissue. The primary goal of this PhD dissertation is to demonstrate the feasibility of using various optical techniques in conjunction with sophisticated signal processing algorithms to differentiate brain tumor and epileptogenic cortex from normal brain tissue intraoperatively. In this dissertation, a new tissue differentiation algorithm was developed to detect brain tumors in vivo using a probe-based diffuse reflectance spectroscopy system. The system as well as the algorithm were validated experimentally on 20 pediatric patients undergoing brain tumor surgery at Nicklaus Children’s Hospital. Based on the three indicative parameters, which reflect hemodynamic and structural characteristics, the new algorithm was able to differentiate brain tumors from the normal brain with a very high accuracy. The main drawbacks of the probe-based system were its high susceptibility to artifacts induced by hand motion and its interference to the surgical procedure. Therefore, a new optical measurement scheme and its companion spectral interpretation algorithm were devised. The new measurement scheme was evaluated both theoretically with Monte Carlo simulation and experimentally using optical phantoms, which confirms the system is capable of consistently acquiring total diffuse reflectance spectra and accurately converting them to the ratio of reduced scattering coefficient to absorption coefficient (µs’(λ)/µa(λ)). The spectral interpretation algorithm for µs’(λ)/µa(λ) was also validated based on Monte Carlo simulation. In addition, it has been demonstrated that the new measurement scheme and the spectral interpretation algorithm together are capable of detecting significant hemodynamic and scattering variations from the Wistar rats’ somatosensory cortex under forepaw stimulation. Finally, the feasibility of using dynamic intrinsic optical imaging to distinguish epileptogenic and normal cortex was validated in an in vivo study involving 11 pediatric patients with intractable epilepsy. Novel data analysis methods were devised and applied to the data from the study; identification of the epileptogenic cortex was achieved with a high accuracy

Doctor of Philosophy

dissertationRecording the neural activity of human subjects is indispensable for fundamental neuroscience research and clinical applications. Human studies range from examining the neural activity of large regions of the cortex using electroencephalography (EEG) or electrocorticography (ECoG) to single neurons or small populations of neurons using microelectrode arrays. In this dissertation, microscale recordings in the human cortex were analyzed during administration of propofol anesthesia and articulate movements such as speech, finger flexion, and arm reach. Recordings were performed on epilepsy patients who required long-term electrocorticographic monitoring and were implanted with penetrating or surface microelectrode arrays. We used penetrating microelectrode arrays to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, as well as the generation of large amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol anesthesia. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased, and the AP-LFP relationship became more predictable, firing rate encoding capacity was impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness. We also demonstrated that speech, finger, and arm movements can be decoded from LFPs recorded with dense grids of microelectrodes placed on the surface of human cerebral cortex for brain computer interface (BCI) applications using LFPs recorded over face-motor area, vocalized articulations of ten different words and silence were classified on a trial-by-trial basis with 82.4% accuracy. Using LFPs recorded over the hand area of motor cortex, three individual finger movements and rest were classified on a trial-by-trial basis with 62% accuracy. LFPs recorded over the arm area of motor cortex were used to continuously decode the arm trajectory with a maximum correlation coefficient of 0.82 in the x-direction and 0.76 in the y-direction. These findings demonstrate that LFPs recorded by micro-ECoG grids from the surface of the cerebral cortex contain sufficient information to provide rapid and intuitive control a BCI communication or motor prosthesis

The Electrophysiology of Resting State fMRI Networks

Traditional research in neuroscience has studied the topography of specific brain functions largely by presenting stimuli or imposing tasks and measuring evoked brain activity. This paradigm has dominated neuroscience for 50 years. Recently, investigations of brain activity in the resting state, most frequently using functional magnetic resonance imaging (fMRI), have revealed spontaneous correlations within widely distributed brain regions known as resting state networks (RSNs). Variability in RSNs across individuals has found to systematically relate to numerous diseases as well as differences in cognitive performance within specific domains. However, the relationship between spontaneous fMRI activity and the underlying neurophysiology is not well understood. This thesis aims to combine invasive electrophysiology and resting state fMRI in human subjects to better understand the nature of spontaneous brain activity. First, we establish an approach to precisely coregister intra-cranial electrodes to fMRI data (Chapter 2). We then created a novel machine learning approach to define resting state networks in individual subjects (Chapter 3). This approach is validated with cortical stimulation in clinical electrocorticography (ECoG) patients (Chapter 4). Spontaneous ECoG data are then analyzed with respect to fMRI time-series and fMRI-defined RSNs in order to illustrate novel ECoG correlates of fMRI for both local field potentials and band-limited power (BLP) envelopes (Chapter 5). In Chapter 6, we show that the spectral specificity of these resting state ECoG correlates link classic brain rhythms with large-scale functional domains. Finally, in Chapter 7 we show that the frequencies and topographies of spontaneous ECoG correlations specifically recapitulate the spectral and spatial structure of task responses within individual subjects

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis

Coherence analysis: Methods, solutions and problems

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.A coherence function is a measure of the correlation of two signals and may be used as a measure for functional relationship between brain areas. In studying functional relationships, referenced EEG (REEG) coherence analysis yields important new aspects of brain activities, which complement the data obtained by power spectral analysis. However, REEG-based coherence tends to show a false high value due to volume conduction from un correlated sources (VCUS). Existing signal processing methods address this issue using a Fourier coherence function of scalp Laplacian. Although this method has been proved useful to reveal correlation between EEG signals with minimum VCUS effects, it only provides frequency-domain analysis. Since EEG signals are highly non-stationary, it is more appropriate to use time-frequency methods for coherence analysis of scalp Laplacian. Thus this research applies the wavelet transform on coherence analysis of scalp Laplacian. To verify our technique, already recorded EEG data of event related potentials were obtained from a study of two large groups of alcoholic and abstinent alcoholic subjects, performing visual picture-recognition tasks. The proposed coherence method successfully detected time-frequency correlation between EEG signals with minimum VCUS effects. It showed significant spatial specificity and revealed detailed coherence patterns. Some new important results regarding time-frequency characteristics of VCUS effects on wavelet and short-time Fourier transform (STFT) coherence analysis of REEG signals were deduced. The proposed coherence method was also compared to a conventional wavelet coherence method of REEG signals in the study of coherence difference between coherences of alcoholic and abstinent alcoholic EEG signals. Results of this study provided substantial evidence that VCUS effects are not additive and therefore can not be ignored in comparison of different brain states between groups of subjects