William C Stacey

University of Michigan | U-M · Department of Neurology

Seeing the face of a speaker facilitates speech recognition in challenging listening environments. Prior work has shown that visual speech contains timing information to aid auditory speech processing, yet how these signals are integrated within the auditory system during audiovisual speech perception remains poorly understood. Observation of prepa...

In drug-resistant focal epilepsy, planning surgical resection may involve presurgical intracranial EEG recordings (iEEG) to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcom...

Introduction: Bilateral absent cortical N20 somatosensory evoked potentials (SSEPs) at 12 and 24 hours after return of spontaneous circulation (ROSC) can predict poor neurologic outcome in cardiac arrest patients. However, it remains unknown if early SSEPs can be used to assess the efficacy of neuroprotective therapies after cardiac arrest. We hypo...

Background and objectives: Participants with treatment-resistant epilepsy who are randomized to add-on placebo and remain in a trial for the typical 3 to 5-month maintenance period may be at increased risk of adverse outcomes. A novel trial design has been suggested, time to prerandomization monthly seizure count (T-PSC), which would limit partici...

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular “no-reflow” is l...

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone (EZ) compared to other leading interictal biomarkers in a multicenter, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied...

High frequency oscillations are a promising biomarker of outcome in intractable epilepsy. Prior high frequency oscillation work focused on counting high frequency oscillations on individual channels, and it is still unclear how to translate those results into clinical care. We show that high frequency oscillations arise as network discharges that h...

Circular statistics and Rayleigh tests are important tools for analyzing cyclic events. However, current methods are not robust to significant measurement bias, especially incomplete or otherwise non-uniform sampling. One example is studying 24-cyclicity but having data not recorded uniformly over the full 24-hour cycle. Our objective is to present...

Epileptic seizures are characterized by abnormal synchronous bursting of neurons. This is commonly attributed to an imbalance between excitatory and inhibitory neurotransmission. We introduce compartmental models from epidemiology to study this interaction between excitatory and inhibitory populations of neurons in the context of epilepsy. Neurons...

Electrical stimulation is an increasingly popular method to terminate epileptic seizures, yet it is not always successful. A potential reason for inconsistent efficacy is that stimuli are applied empirically without considering the underlying dynamical properties of a given seizure. We use a computational model of seizure dynamics to show that diff...

Objective This study was undertaken to evaluate how the challenges in the recruitment and retention of participants in clinical trials for focal onset epilepsy have changed over time. Methods In this systematic analysis of randomized clinical trials of adjunct antiseizure medications for medication‐resistant focal onset epilepsy, we evaluated how...

Unlabelled: Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during E...

Objective We evaluated whether the combination of epileptiform spikes and ripples (spike ripples) outperformed other leading biomarkers in identifying the epileptogenic zone across subjects in a multicenter international study. Methods We validated and applied an automated spike ripple detector on intracranial EEG recordings in subjects from 4 cen...

The search for valid biomarkers to aid in epilepsy diagnosis and management is a major goal of the Epilepsy Research Benchmarks. Many papers and grants answer this call by searching for new biomarkers from a wide range of disciplines. However, the academic use of the word “biomarker” is often imprecise. Without proper definition, such work is not w...

Electroencephalography (EEG) has been the primary diagnostic tool in clinical epilepsy for nearly a century. Its review is performed using qualitative clinical methods that have changed little over time. However, the intersection of higher resolution digital EEG and analytical tools developed in the past decade invites a re‐exploration of relevant...

A lot of mileage has been made recently on the long and winding road toward seizure forecasting. Here we briefly review some selected milestones passed along the way, which were discussed at the International Conference for Technology and Analysis of Seizures—ICTALS 2022—convened at the University of Bern, Switzerland. Major impetus was gained rece...

Human brain cellular assemblies generate emergent oscillations up to very high frequencies that can exceed the known firing rates of individual neurons. Using advanced intracranial microEEG recordings in a cohort of patients with epilepsy, we identified short-lasting local field oscillations with frequencies between 2 and 8 kHz. These ultra fast os...

Watching a speaker’s face improves speech perception accuracy. These benefits are owed, in part, to implicit lipreading abilities present in the general population. While it is established that lipreading can alter the perception of a heard word, it is unknown how information that is extracted from lipread words is transformed into a neural code th...

Background and objective. Circular statistics and Rayleigh tests are important tools for analyzing the occurrence of cyclic events. However, current methods fail in the presence of measurement bias, such as incomplete or otherwise non-uniform sampling. Consider, for example, studying 24-cyclicity but having data not recorded uniformly over the full...

Purpose Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS...

In drug-resistant focal epilepsy, interictal high-frequency oscillations (HFOs) recorded from intracranial EEG (iEEG) may provide clinical information for delineating epileptogenic brain tissue. The iEEG electrode contacts that contain HFO are hypothesized to delineate the epileptogenic zone; their resection should then lead to postsurgical seizure...

Introduction Patients with refractory epilepsy are often evaluated with intracranial electrodes prior to resection. While depth electrodes can be placed through small burr-holes, grids and strips generally require large craniotomies. We have observed many differences in patient experience between these two populations. As sleep is crucial for many...

Sounds enhance our ability to detect, localize, and respond to co-occurring visual targets. Research suggests that sounds improve visual processing by resetting the phase of ongoing oscillations in visual cortex. However, it remains unclear what information is relayed from the auditory system to visual areas and if sounds modulate visual activity e...

Speech perception is a central component of social communication. Although principally an auditory process, accurate speech perception in everyday settings is supported by meaningful information extracted from visual cues. Visual speech modulates activity in cortical areas subserving auditory speech perception including the superior temporal gyrus...

High Frequency Oscillations are very brief events that are a well-established biomarker of the epileptogenic zone, but are rare and comprise only a tiny fraction of the total recorded EEG. We hypothesize that the interictal high frequency “background” data, which has received little attention but represents the majority of the EEG record, also may...

Objective Functional seizures often are managed incorrectly as a diagnosis of exclusion. However, a significant minority of patients with functional seizures may have abnormalities on neuroimaging that typically are associated with epilepsy, leading to diagnostic confusion. We evaluated the rate of epilepsy-associated findings on MRI, FDG-PET, and...

Objective: To compare the performance of different ictal quantitative biomarkers of the seizure onset zone (SOZ) across many seizures in a cohort of consecutive patients with a variety of seizure onset patterns. Methods: The Epileptogenicity Index (EI, a measure of fast activity) and Slow Polarizing Shift index (SPS, a measure of infraslow activ...

Study objective Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency departmen...

Motivation: There is an ongoing search for definitive and reliable biomarkers to forecast or predict imminent seizure onset, but to date most research has been limited to EEG with sampling rates <1,000 Hz. High-frequency oscillations (HFOs) have gained acceptance as an indicator of epileptic tissue, but few have investigated the temporal properties...

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is promising but is unproven, and outcomes are strongly dependent on time to initiation of therapy. Expedited transport may facilitate opportunities for ECPR in clinical practice and future trials. Hypotheses: We hypothesized that a real-time...

Objective: Conventional neural signal analysis methods assume that features of interest are linear, time-invariant signals confined to well-delineated spectral bands. However, new evidence suggests that neural signals exhibit important non-stationary characteristics with ill-defined spectral distributions. These features pose a need for signal pro...

Objective High‐frequency oscillations (HFOs) have shown promising utility in the spatial localization of the seizure onset zone for patients with focal refractory epilepsy. Comparatively few studies have addressed potential temporal variations in HFOs, or their role in the preictal period. Here, we introduce a novel evaluation of the instantaneous...

Objective: High frequency oscillations (HFOs) are a promising biomarker of tissue that instigates seizures. However, ambiguous data and random background fluctuations can cause any HFO detector (human or automated) to falsely label non-HFO data as an HFO (a false positive detection). The objective of this paper was to identify quantitative feature...

Speech perception is a central component of social communication. While principally an auditory process, accurate speech perception in everyday settings is supported by meaningful information extracted from visual cues (e.g., speech content, timing, and speaker identity). Previous research has shown that visual speech modulates activity in cortical...

Optimizing antiepileptic drug therapy is very challenging due to the absence of a reliable method to assess how brain activity changes between seizures. This work uses the Taxonomy of Seizure Dynamics (Saggio et al. , 2020) to investigate how anticonvulsants influence seizure onset dynamotypes. The no Mg ²⁺ /high K ⁺ mouse brain-slice seizure model...

Seizures are a disruption of normal brain activity present across a vast range of species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory. The ‘dynamotype’ of a seizure is the dynamic composition that defines its observable characteristics, includi...

Seizures are a disruption of normal brain activity present across a vast range of species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory. The ‘dynamotype’ of a seizure is the dynamic composition that defines its observable characteristics, includi...

Seizures are a disruption of normal brain activity present across a vast range of species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory. The ‘dynamotype’ of a seizure is the dynamic composition that defines its observable characteristics, includi...

There is a crucial need to identify biomarkers of epileptogenesis that will help predict later development of seizures. This work identifies two novel electrophysiological biomarkers that quantify epilepsy progression in a rat model of epileptogenesis. The long-term tetanus toxin rat model was used to show the development and remission of epilepsy...

Seizures are a disruption of normal brain activity present across a vast range of species, diseases, and conditions. Here we introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory, and applied it to the analysis of EEG data. The “dynamotype” of a seizure is the part of its...

This scientific commentary refers to ‘Virtual resection predicts surgical outcome for drug-resistant epilepsy’ by Kini et al. (doi:10.1093/brain/awz303).

Signals encoded in one sensory modality can enhance cortical sensitivity for co-occurring signals in another modality. Previous research has demonstrated that this facilitation occurs through crossmodal modulations of cortical oscillatory activity. However, the source and content of the information conveyed by this mechanism remain poorly understoo...

Objective: High Frequency Oscillations (HFOs) are a promising biomarker of epilepsy. HFOs are typically acquired on intracranial electrodes, but contamination from muscle artifacts is still problematic in HFO analysis. This paper evaluates the effect of myogenic artifacts on intracranial HFO detection and how to remove them. Methods: Intracrania...

Co-occurring sounds can facilitate perception of spatially and temporally correspondent visual events. Separate lines of research have identified two putatively distinct neural mechanisms underlying two types of crossmodal facilitations: Whereas crossmodal phase resetting is thought to underlie enhancements based on temporal correspondences, latera...

Epilepsy produces chronic chemical changes induced by altered cellular structures, and acute ones produced by conditions leading into individual seizures. Here, we aim to quantify 24 molecules simultaneously at baseline and during periods of lowered seizure threshold in rats. Using serial hippocampal microdialysis collections starting two weeks aft...

The rate of interictal high frequency oscillations (HFOs) is a promising biomarker of the seizure onset zone, though little is known about its consistency over hours to days. Here we test whether the highest HFO-rate channels are consistent across different 10-min segments of EEG during sleep. An automated HFO detector and blind source separation a...

Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable...

Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable...

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

The random nature of seizures poses difficult challenges for epilepsy research. There is great need for a reliable method to control the pathway to seizure onset, which would allow investigation of the mechanisms of ictogenesis and optimization of treatments. Our hypothesis is that increased random afferent synaptic activity (i.e. synaptic noise) w...

Electroencephalography (EEG)—the direct recording of the electrical activity of populations of neurons—is a tremendously important tool for diagnosing, treating, and researching epilepsy. Although standard procedures for recording and analyzing human EEG exist and are broadly accepted, there are no such standards for research in animal models of se...

Objective Recent research suggests that high frequency intracranial EEG (iEEG) may improve localization of epileptic networks. This study aims to determine whether recording macroelectrode iEEG with higher sampling rates improves seizure localization in clinical practice. Methods 14 iEEG seizures from 10 patients recorded with >2000 Hz sampling ra...

Abstract of poster presentation at OCNS-2017

Objectives: High-dose valproic acid in combination with hypothermic-targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest. This study investigated the potential synergistic mechanisms. Design: Prospective, randomized, experimental study. Setting: University research institution....

High-frequency oscillations (HFOs) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFOs with epileptogenic tissue and ictogenesis, understanding their cellular and network mechanisms could provide valuable information about the organization of epileptogenic network...

Objective: Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passiv...

Presentation on "25th Annual Computational Neuroscience Meeting: CNS-2016 " BMC Neuroscience 17, 112-113 (2016).

Previous experimental studies have demonstrated the emergence of narrowband local field potential oscillations during epileptic seizures in which the underlying neural activity appears to be completely asynchronous. We derive a mathematical model explaining how this counterintuitive phenomenon may occur, showing that a population of independent, co...

Objective: High Frequency Oscillations (HFOs) are being studied as a biomarker of epilepsy, yet it is unknown how various acquisition parameters at different centers affect detection and analysis of HFOs. This paper specifically quantifies effects of sampling rate (FS) and anti-aliasing filter (AAF) positions on automated HFO detection. Methods:...

The Epilepsy Benchmark goals in Area III focus on making progress in understanding and controlling seizures and related conditions as well as on developing biomarkers and new therapies that will reduce seizures and improve outcomes for individuals with epilepsy. Area III emphasizes a need to better understand the ways in which seizures start, propa...

High frequency oscillations (HFOs) are a promising biomarker of epileptic brain tissue and activity. HFOs additionally serve as a prototypical example of challenges in the analysis of discrete events in high-temporal resolution, intracranial EEG data. Two primary challenges are 1) dimensionality reduction, and 2) assessing feasibility of classifica...

ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experiment Ion channels are fundamental constituents determining the function of single neurons and neuronal circuits. To understand their complex interactions, the field of computational modeling has proven essential: since its emergence, thousands...

We investigate the possibility that narrowband oscillations may emerge from completely asynchronous, independent neural firing. We find that a population of asynchronous neurons may produce narrowband oscillations if each neuron fires quasi-periodically, and we deduce bounds on the degree of variability in neural spike-timing which will permit the...

Objective: Reliable early prognostication of neurologic recovery in comatose cardiac arrest (CA) survivors remains a major clinical challenge. We hypothesized that continuous somatosensory evoked potentials (SSEP) in the immediate post-CA period could enable early quantification of cortical recovery. Methods: Pigs were instrumented for hemodynamic...

Introduction: Hypothermic targeted temperature management (TTM) has greatly improved post-cardiac arrest patient outcomes, but also makes prognostication more difficult. In this study, we tested the hypothesis that early continuous EEG biomarkers are associated with neurologic outcome in post-cardiac arrest rats treated with normothermic and hypoth...