Stimulating Solutions for Intractable Epilepsy.

Implantable devices for controlling medically intractable seizures nondestructively are rapidly advancing. These offer reversible, potentially, restorative options beyond traditional, surgical procedures, which rely, largely on resection or ablation of selected brain sites. Several lines of, investigation aimed at improving efficacy of these devices are discussed, ranging from identifying novel subcortical, white matter, or cell-type specific targets to engineering advances for adaptive techniques based- on continuous, dynamic system analysis.

Design of optimal multi-site brain stimulation protocols via neuro-inspired epilepsy models for abatement of interictal discharges.

. Electrical brain stimulation is recognized as a promising therapeutic approach for treating brain disorders such as epilepsy. However, the use of this technique is still largely empirical, since stimulation parameters and targets are chosen using a trial-and-error approach.

Reconstruction of post-synaptic potentials by reverse modeling of local field potentials.

Objective: Among electrophysiological signals, local field potentials (LFPs) are extensively used to study brain activity, either in vivo or in vitro. LFPs are recorded with extracellular electrodes implanted in brain tissue. They reflect intermingled excitatory and inhibitory processes in neuronal assemblies.

Noise-Assisted Multivariate EMD-Based Mean-Phase Coherence Analysis to Evaluate Phase-Synchrony Dynamics in Epilepsy Patients.

Spatiotemporal evolution of synchrony dynamics among neuronal populations plays an important role in decoding complicated brain function in normal cognitive processing as well as during pathological conditions such as epileptic seizures. In this paper, a non-linear analytical methodology is proposed to quantitatively evaluate the phase-synchrony dynamics in epilepsy patients. A set of finite neuronal oscillators was adaptively extracted from a multi-channel electrocorticographic (ECoG) dataset utilizing noise-assisted multivariate empirical mode de-composition (NA-MEMD).

EMD-Based, Mean-Phase Coherence Analysis to Assess Instantaneous Phase-Synchrony Dynamics in Epilepsy Patients.

In this paper, an adaptive, non-linear, analytical methodology is proposed in order to quantitatively evaluate the instantaneous phase-synchrony dynamics in epilepsy patients. A group of finite neuronal oscillators is extracted from a multichannel electrocorticographic (ECoG) data, using the empirical mode decomposition (EMD). The instantaneous phases of the extracted oscillators are measured using the Hilbert transform in order to be utilized in the mean-phase coherence analysis.

Using Interictal HFOs to Improve the Identification of Epileptogenic Zones in Preparation for Epilepsy Surgery.

For the more than 15 million patients who have drug-resistant epilepsy, surgical resection of the region where seizure arise is often the only alternative therapy. However, the identification of this epileptogenic zone (EZ) is often imprecise. Generally, insufficient EZ identification and resection may cause seizures to continue and too much resection may lead to unnecessary neurological deficits.

Should stimulation parameters be individualized to stop seizures: Evidence in support of this approach.

Objective: Deep-brain electrical stimulation (DBS) is a treatment modality being explored for many neurologic diseases and is a potentially potent means of disrupting the aberrant rhythms that arise during the epileptic seizures that afflict >1% of the population. However, current DBS protocols typically employed are formulated a priori and do not reflect the electrophysiologic dynamics within the brain as seizures arise, which may underlie their limited efficacy. This study investigates how the efficacy of DBS could be improved using endogenous dynamics to inform stimulation protocols.

Evaluation of Cortical Thickness after Traumatic Brain Injury in Military Veterans.

Military service members frequently sustain traumatic brain injuries (TBI) while on active duty, a majority of which are related to explosive blasts and are mild in severity. Studies evaluating the cortical gray matter in persons with injuries of this nature remain scarce. The purpose of this study was to assess cortical thickness in a sample of military veterans with chronic blast-related TBI.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation.

Objective: Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response.

Electrical control of epilepsy.

Epilepsy afflicts approximately 1-2% of the world's population. The mainstay therapy for treating the chronic recurrent seizures that are emblematic of epilepsy are drugs that manipulate levels of neuronal excitability in the brain. However, approximately one-third of all epilepsy patients get little to no clinical relief from this therapeutic regimen.

PET-based confirmation of orientation sensitivity of TMS-induced cortical activation in humans.

Background: Currently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks.

Rapid onset of a kainate-induced mirror focus in rat hippocampus is mediated by contralateral AMPA receptors.

The development of an epileptic "mirror" focus in an area of the brain contralateral to the primary epileptic focus typically evolves over days in the experimental setting after status epilepticus or electrical kindling of the primary focal region. In contrast, we observed the rapid development of an apparent mirror focus in the contralateral hippocampus following microinjection of kainic acid (KA) in the ipsilateral hippocampus in rats. Using multisite intracranial recordings, local field potentials were recorded in anesthetized adult male rats using electrodes implanted in the CA3 region of both hippocampi and in the anteromedial nucleus of the thalamus.

Synchrony dynamics across brain structures in limbic epilepsy vary between initiation and termination phases of seizures.

Neuronal populations in the brain achieve levels of synchronous electrophysiological activity during both normal brain function and pathological states such as epileptic seizures. Understanding how the dynamics of neuronal oscillators in the brain evolve from normal to diseased states is a critical component toward decoding such complex behaviors. In this study, we sought to develop a more in-depth understanding of multisite dynamics underlying seizure evolution in limbic epilepsy by analyzing oscillators in recordings of local field potentials from three brain structures (bilateral hippocampi and anteromedial thalamus) in a kainic acid in vivo rat model of temporal lobe epilepsy extracted using the empirical mode decomposition (EMD) technique.

A study of multi-site brain dynamics during limbic seizures.

Neuronal populations in the brain achieve levels of synchronous electrophysiological activity as a consequence of both normal brain functions as well as during pathological states such as in epileptic seizures. Understanding the nature of this synchrony and the dynamics of neuronal oscillators in the brain is a critical component towards decoding such complex behaviors. We have sought to achieve a more in-depth understanding of the dynamics underlying the evolution of seizures in limbic epilepsy by analyzing recordings of local field potentials from three subcortical nuclei that are part of the circuit of Papez in a kainic acid rat model of temporal lobe epilepsy using the empirical mode decomposition technique.

Optimal spacing of surface electrode arrays for brain-machine interface applications.

Brain-machine interfaces (BMIs) use signals recorded directly from the brain to control an external device, such as a computer cursor or a prosthetic limb. These control signals have been recorded from different levels of the brain, from field potentials at the scalp or cortical surface to single neuron action potentials. At present, the more invasive recordings have better signal quality, but also lower stability over time.

Using increased structural detail of the cortex to improve the accuracy of modeling the effects of transcranial magnetic stimulation on neocortical activation.

Transcranial magnetic stimulation (TMS) is a noninvasive technique that can alter brain activation by inducing electrical current in neurons using dynamic magnetic fields. Because of its painless nature, clinical usage has expanded to diagnostic purposes and therapeutic treatments. However, several issues and challenges still exist for TMS.

Modulation of instantaneous synchrony during seizures by deep brain stimulation.

Epileptic seizures were experimentally induced in the CA3 region of rat hippocampus in vivo. Recordings of seizure activity were made in both hippocampi as well as anteromedial region of the thalamus in order to analyze the instantaneous activity for synchronous oscillators. A new method is introduced for detecting this synchrony which combines empirical mode decomposition, the Hilbert analytic signal method and eigenvalue decomposition.

Assessing instantaneous synchrony of nonlinear nonstationary oscillators in the brain.

Neuronal populations throughout the brain achieve levels of synchronous electrophysiological activity as a consequence of both normal brain function as well as during pathological states such as in epileptic seizures. Understanding this synchrony and being able to quantitatively assess the dynamics with which neuronal oscillators across the brain couple their activity is a critical component toward decoding such complex behavior. Commonly applied techniques to resolve relationships between oscillators typically make assumptions of linearity and stationarity that are likely not to be valid for complex neural signals.

A structurally detailed finite element human head model for simulation of transcranial magnetic stimulation.

Computational studies of the head utilizing finite element models (FEMs) have been used to investigate a wide variety of brain-electromagnetic (EM) field interaction phenomena including magnetic stimulation of the head using transcranial magnetic stimulation (TMS), direct electric stimulation of the brain for electroconvulsive therapy, and electroencephalography source localization. However, no human head model of sufficient complexity for studying the biophysics under these circumstances has been developed which utilizes structures at both the regional and cellular levels and provides well-defined smooth boundaries between tissues of different conductivities and orientations. The main barrier for building such accurate head models is the complex modeling procedures that include 3D object reconstruction and optimized meshing.

Neuronal desynchronization as a trigger for seizure generation.

Experimental reports have appeared which challenge the dogma that epileptic seizures arise as a consequence of neuronal hypersynchronization. We sought to explore what mechanisms that desynchronize neuronal firing could induce epileptic seizures. A computer model of connections in a mammalian hippocampal slice preparation was constructed including two recently-reported distinct inhibitory feedback circuits.

Proportional feedback stimulation for seizure control in rats.

Purpose: A responsive electrical brain stimulation system using control feedback was investigated for the treatment of seizures.

Methods: A proportional feedback stimulation system was designed. Penicillin-induced episodic seizures were created in rat primary motor cortex.

Electrical control of epileptic seizures.

Epilepsy is among the most common neurologic disorders, yet it is estimated that about one third of patients do not respond favorably to currently available drug treatments and up to 50% experience major side effects of these treatments. Although surgical resection of seizure foci can provide reduction or cessation of seizure incidents, a significant fraction of pharmacologically intractable seizure patients are not considered viable candidates for such procedures. Research advances in applying electrical stimulation as an alternative treatment for intractable epilepsy have been reported.

Computer-assisted intraaneurysmal thrombus visualization.

Objective: Improved visualization of intraaneurysmal thrombi can contribute to understanding their impact on clinical courses and treatments. Digital subtraction angiography (DSA) demonstrates the hemodynamic portion of aneurysm domes and vasculature structures and has been considered by many to be the principal technique used for aneurysm diagnosis. An intraaneurysmal thrombus may be visualized as a filling defect on DSA, but DSA does not reliably indicate the presence of an intraaneurysmal thrombus or its details.

Manipulating epileptiform bursting in the rat hippocampus using chaos control and adaptive techniques.

Epilepsy is a relatively common disease, afflicting 1%-2% of the population, yet many epileptic patients are not sufficiently helped by current pharmacological therapies. Recent reports have suggested that chaos control techniques may be useful for electrically manipulating epileptiform bursting behavior in vitro and could possibly lead to an alternative method for preventing seizures. We implemented chaos control of spontaneous bursting in the rat hippocampal slice using robust control techniques: stable manifold placement (SMP) and an adaptive tracking (AT) algorithm designed to overcome nonstationarity.