Ultra Broad Band Neural Activity Portends Seizure Onset in a Rat Model of Epilepsy

Abstract An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson–Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network’s predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons’ responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.

Download Full-text

Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures

PLoS ONE ◽

10.1371/journal.pone.0211847 ◽

2019 ◽

Vol 14 (7) ◽

pp. e0211847 ◽

Cited By ~ 1

Author(s):

Timothée Proix ◽

Mehdi Aghagolzadeh ◽

Joseph R. Madsen ◽

Rees Cosgrove ◽

Emad Eskandar ◽

...

Keyword(s):

Neural Activity ◽

Seizure Onset ◽

Focal Seizures

Download Full-text

Quantifying epileptogenesis in rats with spontaneous and responsive brain state dynamics

Brain Communications ◽

10.1093/braincomms/fcaa048 ◽

2020 ◽

Vol 2 (1) ◽

Cited By ~ 3

Author(s):

Dakota N Crisp ◽

Warwick Cheung ◽

Stephen V Gliske ◽

Alan Lai ◽

Dean R Freestone ◽

...

Keyword(s):

Electrical Stimulation ◽

Rat Model ◽

Tetanus Toxin ◽

Brain State ◽

Induced Responses ◽

Spontaneous Seizure ◽

Seizure Onset ◽

Theoretical Predictions ◽

Over Time

Abstract 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 over several weeks. We measured the response to periodic electrical stimulation and features of spontaneous seizure dynamics over several weeks. Both biomarkers showed dramatic changes during epileptogenesis. Electrically induced responses began to change several days before seizures began and continued to change until seizures resolved. These changes were consistent across animals and allowed development of an algorithm that could differentiate which animals would later develop epilepsy. Once seizures began, there was a progression of seizure dynamics that closely follows recent theoretical predictions, suggesting that the underlying brain state was changing over time. This research demonstrates that induced electrical responses and seizure onset dynamics are useful biomarkers to quantify dynamical changes in epileptogenesis. These tools hold promise for robust quantification of the underlying epileptogenicity and prediction of later development of seizures.

Download Full-text

Application of adaptive nonlinear Granger causality: Disclosing network changes before and after absence seizure onset in a genetic rat model

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2014.01.028 ◽

2014 ◽

Vol 226 ◽

pp. 33-41 ◽

Cited By ~ 26

Author(s):

Marina V. Sysoeva ◽

Evgenia Sitnikova ◽

Ilya V. Sysoev ◽

Boris P. Bezruchko ◽

Gilles van Luijtelaar

Keyword(s):

Granger Causality ◽

Rat Model ◽

Absence Seizure ◽

Seizure Onset ◽

Before And After

Download Full-text

Case Report: Aperiodic Fluctuations of Neural Activity in the Ictal MEG of a Child With Drug-Resistant Fronto-Temporal Epilepsy

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.646426 ◽

2021 ◽

Vol 15 ◽

Author(s):

Saskia van Heumen ◽

Jeremy T. Moreau ◽

Elisabeth Simard-Tremblay ◽

Steffen Albrecht ◽

Roy WR. Dudley ◽

...

Keyword(s):

Neural Activity ◽

Brain Activity ◽

Diagnostic Methods ◽

Drug Resistant ◽

Seizure Onset ◽

Source Imaging ◽

Temporal Epilepsy ◽

Aperiodic Component ◽

Temporal Neocortex ◽

Control Regions

Successful surgical treatment of patients with focal drug-resistant epilepsy remains challenging, especially in cases for which it is difficult to define the area of cortex from which seizures originate, the seizure onset zone (SOZ). Various diagnostic methods are needed to select surgical candidates and determine the extent of resection. Interictal magnetoencephalography (MEG) with source imaging has proven to be useful for presurgical evaluation, but the use of ictal MEG data remains limited. The purpose of the present study was to determine whether pre-ictal variations of spectral properties of neural activity from ictal MEG recordings are predictive of SOZ location.We performed a 4 h overnight MEG recording in an 8-year-old child with drug-resistant focal epilepsy of suspected right fronto-temporal origin and captured one ~45-s seizure. The patient underwent a right temporal resection from the anterior temporal neocortex and amygdala to the mid-posterior temporal neocortex, sparing the hippocampus proper. She remains seizure-free 21 months postoperatively. The histopathological assessment confirmed frank focal cortical dysplasia (FCD) type IIa in the MEG-defined SOZ, which was based on source imaging of averaged ictal spikes at seizure onset. We investigated temporal changes (inter-ictal, pre-ictal, and ictal periods) together with spatial differences (SOZ vs. control regions) in spectral parameters of background brain activity, namely the aperiodic broadband offset and slope, and assessed how they confounded the interpretation of apparent variations of signal power in typical electrophysiological bands. Our data show that the SOZ was associated with a higher aperiodic offset and exponent during the seizure compared to control regions. Both parameters increased in all regions from 2 min before the seizure onwards. Regions anatomically closer to the SOZ also expressed higher values compared to contralateral regions, potentially indicating ictal spread. We also show that narrow-band power changes were caused by these fluctuations in the aperiodic component of ongoing brain activity. Our results indicate that the broadband aperiodic component of ongoing brain activity cannot be reduced to background noise of no physiological interest, and rather may be indicative of the neuropathophysiology of the SOZ. We believe these findings will inspire future studies of ictal MEG cases and confirm their significance.

Download Full-text

The Temporal Course of the Masking of Tinnitus as a Basis for Inferring Its Origin

Journal of Speech Language and Hearing Research ◽

10.1044/jshr.2402.257 ◽

1981 ◽

Vol 24 (2) ◽

pp. 257-261 ◽

Cited By ~ 23

Author(s):

M. J. Penner ◽

Steven Brauth ◽

Linda Hood

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Neural Activity ◽

Broad Band ◽

Sensorineural Hearing ◽

Eighth Nerve ◽

Band Noise ◽

Minute Period ◽

Temporal Course

For patients with tinnitus and sensorineural hearing loss, the intensity of broad-band noise required to mask the tinnitus increases by as much as 45 dB during a 30-minute period if the patient is exposed to noise. In contrast, the intensity required to mask an external tone remains nearly constant. Some speculations which might account for this result are offered. Excess neural activity is posited to be the physiological determinant of tinnitus and to be central, generated in the brainstem postsynaptic to the, eighth nerve.

Download Full-text

Phase shift in the 24-hour rhythm of hippocampal EEG spiking activity in a rat model of temporal lobe epilepsy

Journal of Neurophysiology ◽

10.1152/jn.00911.2012 ◽

2013 ◽

Vol 110 (5) ◽

pp. 1070-1086 ◽

Cited By ~ 6

Author(s):

David A. Stanley ◽

Sachin S. Talathi ◽

Mansi B. Parekh ◽

Daniel J. Cordiner ◽

Junli Zhou ◽

...

Keyword(s):

Phase Shift ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Rat Model ◽

Neural Activity ◽

Core Body Temperature ◽

Epileptic Seizures ◽

Medial Septum ◽

State Transitions ◽

Hippocampal Eeg

For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction.

Download Full-text

Reduced Reach-Related Modulation of Motor Thalamus Neural Activity in a Rat Model of Parkinson's Disease

Journal of Neuroscience ◽

10.1523/jneurosci.0893-14.2014 ◽

2014 ◽

Vol 34 (48) ◽

pp. 15836-15850 ◽

Cited By ~ 15

Author(s):

C. Bosch-Bouju ◽

R. A. Smither ◽

B. I. Hyland ◽

L. C. Parr-Brownlie

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rat Model ◽

Neural Activity ◽

Motor Thalamus

Download Full-text

Chronic Laser Exposure Effects on Rabbit Retina

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100093523 ◽

1972 ◽

Vol 30 ◽

pp. 54-55

Author(s):

Burton B. Silver ◽

Theodore Lawwill

Keyword(s):

Laser Irradiation ◽

Laser Light ◽

Broad Band ◽

Argon Laser ◽

Atropine Sulfate ◽

Ultrastructural Changes ◽

Laser Exposure ◽

Rabbit Retina ◽

Histological Changes ◽

Threshold Doses

Dutch-belted 1 to 2.5 kg anesthetized rabbits were exposed to either xenon or argon laser light administered in a broad band, designed to cover large areas of the retina. For laser exposure, the pupil was dilated with atropine sulfate 1% and pheny lephrine 10%. All of the laser generated power was within a band centered at 5145.0 Anstroms. Established threshold for 4 hour exposures to laser irradiation are in the order of 25-35 microwatts/cm2. Animals examined for ultrastructural changes received 4 hour threshold doses. These animals exhibited ERG, opthalmascopic, and histological changes consistent with threshold damage.One month following exposure the rabbits were killed with pentobarbitol. The eyes were immediately enucleated and dissected while bathed in 3% phosphate buffered gluteraldehyde.

Download Full-text

Real-ear Masking Calibration for Portable Pure-Tone Audiometers

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.1504.289 ◽

1984 ◽

Vol 15 (4) ◽

pp. 289-294

Author(s):

Martin S. Robinette ◽

Robert H. Brey

Keyword(s):

Pure Tone ◽

Broad Band ◽

Resistive Network ◽

Many Instruments

A transformer mixing network is described which allows the calibration of broad-band masking for portable audiometers that lack a built-in mixing network. For many instruments the transformer network is preferable to the resistive network previously published.

Download Full-text