Mark G Frei

• Flint Hills Scientific, L.L.C.

Epilepsy, one of the most prevalent neurological disorders, affects approximately 1% (greater than 60 million) of the world's population. In an estimated 20 million of these patients, seizures are not controlled even by multiple anti-seizure drugs, and are extremely difficult to predict. Epilepsy: The Intersection of Neurosciences, Biology, Mathema...

Methods, systems, and apparatus for detecting and/or validating a detection of a state change by matching the shape of one or more of an cardiac data series, a heart rate variability data series, or at least a portion of a heart beat complex, derived from cardiac data, to an appropriate template.

A method of treating a medical condition in a patient using an implantable medical device, comprising providing an electrical signal generator; providing at least a first electrode operatively coupled to the electrical signal generator and to a vagus nerve of the patient; sensing cardiac data of the patient; determining at least a first cardiac par...

Apparatus and method detect a detection cluster that is associated with a neurological event, such as a seizure, of a nervous system disorder and update therapy parameters that are associated with a treatment therapy. The occurrence of the detection cluster is detected when the maximal ratio exceeds an intensity threshold. If the maximal ratio drop...

Apparatuses and methods support multi-modal operation of a medical device system for a nervous system disorder. The medical device system comprises an implanted component and an external component and supports a first feature and a second feature that are associated with the treatment therapy. The medical device system supports both features when t...

Apparatus and method support a neurological event screening for a medical device. The medical device assists a user in determining a configuration of the medical device for delivering an effective treatment for a nervous system disorder. The medical device detects a neurological event, such as a seizure, and reports a neurological event focus locat...

Apparatus and method support the configuration and testing of therapy parameters for a medical device system in the treatment of nervous system disorders. With the embodiment, the medical device system operates in a manual treatment therapy mode, in which the medical device system evaluates a set of information that is indicative of a system config...

A method and system for monitoring and/or controlling a glycemic state of a subject, comprising a housing device having one or more chambers, extendable and retractable sensors, extendable and retractable catheters, insulin reservoir, neuroprotective agent reservoir, release mechanism for releasing insulin and neuroprotective agent into the subject...

One of the goals of the Fourth International Workshop on Seizure Prediction was to provide an opportunity for patients with epilepsy and their caregivers to voice their perspectives on seizure prediction and related matters toward the goal of influencing the design of solutions. In an attempt to fulfill this goal, a survey of patients and caregiver...

The recently convened Fourth International Workshop on Seizure Prediction (IWSP4) brought together a diverse international group of investigators, from academia and industry, including epileptologists, neurosurgeons, neuroscientists, computer scientists, engineers, physicists, and mathematicians who are conducting interdisciplinary research on the...

Debates on six controversial topics were held during the Fourth International Workshop on Seizure Prediction (IWSP4) convened in Kansas City, KS, USA, July 4-7, 2009. The topics were (1) Ictogenesis: Focus versus Network? (2) Spikes and Seizures: Step-relatives or Siblings? (3) Ictogenesis: A Result of Hyposynchrony? (4) Can Focal Seizures Be Cause...

A dynamical analogy supported by five scale-free statistics (the Gutenberg-Richter distribution of event sizes, the distribution of interevent intervals, the Omori and inverse Omori laws, and the conditional waiting time until the next event) is shown to exist between two classes of seizures ("focal" in humans and generalized in animals) and earthq...

Relevant and timely questions such as regarding the predictability of seizures and their capacity to trigger more seizures remain the subject of debate in epileptology. The present study endeavors to gain insight into these dynamic issues by adopting a non-reductionist approach and via the use of mathematical tools. Probability distribution functio...

Substantive advances in clinical epileptology may be realized through the judicious use of real-time automated seizure detection, quantification, warning, and delivery of therapy in subjects with pharmacoresistant seizures. Materialization of these objectives is likely to elevate epileptology to the level of a mature clinical science.

Topological approaches for seizure abatement have received scarce attention. The ability to reset the phase of biological oscillations has been widely exploited in cardiology, as evidenced in part by the usefulness of implantable of defibrillators, but not in epileptology. The aim of this work is to investigate the feasibility of seizure blockage u...

Epilepsy, a common neurological disorder, manifests with seizures that occur suddenly, cyclically but aperiodically, features that enhance its disabling power. This chapter reviews the results of correlation dimension analysis from an extensive clinical database—over 2,000 total hours of continuous ECoG from 20 subjects with epilepsy. It examines t...

IntroductionModalitySeizure Generation and ModelsAcademia and IndustryThe Question of Seizure Prediction and its PrioritizationSummaryAcknowledgement

Seizures and Neuronal Synchronization: Increased or Decreased Relative to Interictal Values?The ‘Focus’ (‘Ictio-centric’) vs the Network Theory in IctiogenesisReferences

Epileptic seizures show a certain degree of rhythmicity, a feature of heuristic and practical interest. In this paper, we introduce a simple model of this type of behavior, and suggest a measure for detecting and quantifying it. To evaluate our method, we develop a set of test segments that incorporate rhythmicity features, and present results from...

Probability density functions and the probability of Sz occurrence conditional upon the time elapsed from the previous Sz were estimated using the energy and intervals of SZ in prolonged recordings from subjects with localization- related pharmaco-resistant epilepsy, undergoing surgical evaluation. Clinical and subclinical seizure E and ISI distrib...

The concept of universality proposes that dynamical systems with the same power law behaviors are equivalent at large scales. We test this hypothesis on the Earth's crust and the epileptic brain, and discover that power laws also govern the distributions of seizure energies and recurrence times. This robust correspondence is extended over seven sta...

The time-varying dynamics of epileptic seizures and the high inter-individual variability make their detection difficult. Osorio et al. [Osorio, I, Frei, MG, Wilkinson, SB. Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset. Epilepsia 1998;39(6):615-27] developed an algorithm that has had...

The possibility that seizures may be intercorrelated has not been sufficiently investigated. A handful of studies, the majority based on patient seizure diaries, provide disparate results: some claim that seizures are serially correlated and others that they are random events. This study investigates the effect that a seizure may have on the time o...

Measurement of synchrony in networks of complex or high-dimensional, nonstationary, and noisy systems such as the mammalian brain is technically difficult. We present a general method to analyze synchrony from multichannel time series. The idea is to calculate the phase-synchronization times and to construct a matrix. We develop a random-matrix-bas...

Estimation of the Hurst parameter provides information about the memory range orcorrelations (long vs. short) of processes (time-series). A new application for the Hurst parameter, real-time event detection, is identified. Hurst estimates using rescaled range, dispersional and bridgedetrended scaled windowed variance analyses of seizure time-series...

We introduce a new algorithm, the intrinsic time-scale decomposition (ITD), for efficient and precise time–frequency–energy (TFE) analysis of signals. The ITD method overcomes many of the limitations of both classical (e.g. Fourier transform or wavelet transform based) and more recent (empirical mode decomposition based) approaches to TFE analysis...

We propose a general framework for detecting and characterizing phase synchronization from noisy, nonstationary time series. For detection, we propose to use the average phase-synchronization time and show that it is extremely sensitive to parameter changes near the onset of phase synchronization. To characterize the degree of temporal phase synchr...

Epilepsy is the most prevalent neurological disorder affecting both adults and children. Over two-and-one-half million individuals in the United States have epilepsy and 25% of them do not respond to drugs. A significant focus of current research efforts is the development of a fully implantable device for real-time seizure detection and automated...

Reports in the literature have indicated potential value of the correlation integral and dimension for prediction of epileptic seizures up to several minutes before electrographic onset. We apply these measures to over 2000 total hours of continuous electrocortiogram, taken from 20 patients with epilepsy, examine their sensitivity to quantifiable p...

To examine the seizure prediction and detection abilities of the accumulated energy on multi-center data submitted to the First International Collaborative Workshop on Seizure Prediction. The accumulated energy (AE), windowed average power, and FHS seizure detection algorithm were applied to a single channel of ECoG data taken from the data sets co...

The need for novel, efficacious, antiseizure therapies is widely acknowledged. This study investigates in humans the feasibility, safety, and efficacy of high-frequency electrical stimulation (HFES; 100-500 Hz) triggered by automated seizure detections. Eight patients were enrolled in this study, which consisted of a control and an experimental pha...

A Reply to the Comment by Leonidas D. Iasemidis et al.

Lyapunov exponents are a set of fundamental dynamical invariants characterizing a system's sensitive dependence on initial conditions. For more than a decade, it has been claimed that the exponents computed from electroencephalogram (EEG) or electrocorticogram (ECoG) signals can be used for prediction of epileptic seizures minutes or even tens of m...

To investigate the potential for improving the performance of the Osorio-Frei seizure detection algorithm (OFA) by incorporating multiple FIR filters operating in parallel and Gaussian mixture models (GMM) for ECoG features distributions, thus creating "hybrid" system. The "hybrid" algorithm decomposes the signal into four subbands, using wavelets,...

It has been claimed that Lyapunov exponents computed from electroencephalogram or electrocorticogram (ECoG) time series are useful for early prediction of epileptic seizures. We show, by utilizing a paradigmatic chaotic system, that there are two major obstacles that can fundamentally hinder the predictive power of Lyapunov exponents computed from...

The removal of ocular artifact from scalp electroencephalograms (EEGs) is of con-siderable importance for both the automated and visual analysis of underlying brainwave activity. Traditionally, subtraction techniques use linear regression to estimate the influence of eye movements on the electrodes of interest. These methods are based on the assump...

Automated seizure detection and blockage requires highly sensitive and specific algorithms. This study reassessed the performance of an algorithm by using a more extensive database than that of a previous study and its suitability for safety/efficacy closed-loop studies to block seizures in humans. Up to eight electrocorticography (EcoG) channels f...

We focus on an anomalous scaling region in correlation integral [C(epsilon)] analysis of electrocorticogram in epilepsy patients. We find that epileptic seizures typically are accompanied by wide fluctuations in the slope of this scaling region. An explanation, based on analyzing the interplay between the autocorrelation and C(epsilon), is provided...

The time-varying dynamics and non-stationarity of epileptic seizures makes their detection difficult. Osorio et. al. in ([1]) proposed an adaptable seizure detection algorithm (‘SDA’), however, that has had great success. In this presentation, we begin with an overview of the original detection algorithm’s architecture, describing its degrees of fr...

Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over c...

The authors describe an integrated bedside system for real-time seizure detection and automated delivery of electrical stimulation directly to the brain of subjects undergoing invasive epilepsy surgery evaluation. These stimulations were triggered by specific detections following a prespecified pattern. The system uses a commercially available EEG...

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chem...

in its predictive application. Specifically, chaos holds great allure to epileptologists, because the aperiodic and unstable behavior of the epileptic human brain seems ideally suited to investigation by tools that would allow precise tracking of its temporal evolution. For the first time in the history of epilepsy, a systematic and readily accessi...

Purpose: The purpose of this study was to determine if stimulation of the left vagus nerve (LVNS) with the neurocybernetic prosthesis (NCP) in humans is, as claimed in the literature, without cardiac chronotropic actions. Methods: We analyzed 228 h of ECG recorded from five subjects with intractable epilepsy who had not benefited from LVNS, for eff...

The authors reexamine the correlation integral and the related correlation dimension in the context of EEG analysis with application to seizure prediction. They identify dependencies of the correlation integral and the correlation dimension on frequency and amplitude of the signal, which may result in a reinterpretation of the dynamic importance of...

Most seizure prediction methods are based on nonlinear dynamic techniques, which are highly computationally expensive, thus limiting their clinical usefulness. The authors propose a different approach for prediction that uses a stochastic Markov chain model. Seizure (Ts) and interictal (Ti) durations were measured from 11 rats treated with 3-mercap...

A family of finite impulse-response (FIR) filters is derived which estimate the second derivative or "acceleration" of a digitized signal. The acceleration is obtained from parabolas that are continuously fit to the signal using a least squares optimization criterion. A closed-form solution for the filter coefficients is obtained. The general appro...

A family of finite impulse-response (FIR) filters is derived which estimate the second derivative or "acceleration" of a digitized signal. The acceleration is obtained from parabolas that are continuously fit to the signal using a least squares optimization criterion. A closed-form solution for the filter coefficients is obtained. The general appro...

The algorithm for computing coefficients of nonrecursive (finite impulse response) two-dimensional smoothing and/or differentiating weighted Savitzky-Golay digital filters is described. The algorithm is numerically accurate for arbitrary order filters and can be easily extended to more dimensions. Savitzky-Golay filters combine noise reduction with...

An analog device for automated real-time detection and short-term prediction of epileptic seizures is described. In its basic form, the device utilizes a non-sorting analog percentile filtering to implement in analog form the FHS numerical seizure detection algorithm. The extensions and enhancements of the basic version of the device include (1) ad...

Purpose: We describe an algorithm for rapid realtime detection, quantitation, localization of seizures, and prediction of their clinical onset. Methods: Advanced digital signal processing techniques used in time-frequency localization, image processing, and identification of time-varying stochastic systems were used to develop the algorithm, which...

Summary form only given. Automated seizure detection with high specificity and sensitivity is a highly desirable but elusive goal. The failure to develop a reliable system despite decades of effort is due in part to the non-stationary and noise in the EEG/ECoG signals, as well as to the rudimentary mathematical treatment it has received. We have de...

Thesis (M.S.)--University of Southern California, 1986. Bibliography: leaf 36.