Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies.

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Vagus nerve stimulation outcome prediction: from simple parameters to advanced models.

Since its approval as an adjunct treatment for refractory partial epilepsy, the positive effects of vagus nerve stimulation (VNS) on seizure frequency and severity have been supported by many studies. Seizure reduction of more than 50 % can be expected in at least 50 % of patients. However, a complete post-VNS seizure freedom is rarely achieved and 25 % of patients do not benefit from VNS. Our study provides an overview of the potential predictors of VNS response, from the most simple and basic data to sophisticated EEG processing studies and functional imaging studying brain connectivity. The data support better outcomes in younger patients with early VNS implantation, in patients with posttraumatic epilepsy or tuberous sclerosis, and in patients without bilateral interictal epileptiform discharges. The variability of heart activity has also been studied with some promising results. Because the generally accepted hypothesis of the VNS mechanism is the modulation of synaptic activity in multiple cortical and subcortical regions of the brain, the studies of brain response to external stimulation and/or of brain connectivity were used for models predicting the effect of VNS in individual patients. Although the predictive value of these models is high, the required special equipment and sophisticated mathematical tools limit their routine use (Ref. 58). Keywords: epilepsy, vagus nerve stimulation, response predictor, EEG.

Insights into déjà vu: Associations between the frequency of experience and amplitudes of low-frequency oscillations in resting-state functional magnetic resonance imaging.

The phenomenon of déjà vu (DV) has intrigued scientists for decades, yet its neurophysiological underpinnings remain elusive. Brain regions have been identified in which morphometry differs between healthy individuals according to the frequency of their DV experiences. This study built upon these findings by assessing if and how neural activity in these and other brain regions also differ with respect to DV experience. Resting-state fMRI was performed on 68 healthy volunteers, 44 of whom reported DV experiences (DV group) and 24 who did not (NDV group). Using multivariate analyses, we then assessed the (fractional) amplitude of low-frequency fluctuations (fALFF/ALFF), a metric that is believed to index brain tissue excitability, for five discrete frequency bands within sets of brain regions implicated in DV and those comprising the default mode network (DMN). Analyses revealed significantly lower values of fALFF/ALFF for specific frequency bands in the DV relative to the NDV group, particularly within mesiotemporal structures, bilateral putamina, right caudatum, bilateral superior frontal cortices, left lateral parietal cortex, dorsal and ventral medial prefrontal cortex, and the posterior cingulate cortex. The pattern of differences in fALFF/ALFF measures between the brains of individuals who have experienced DV and those who have not provides new neurophysiological insights into this phenomenon, including the potential role of the DMN. We suggest that the erroneous feeling of familiarity arises from a temporary disruption of cortico-subcortical circuitry together with the upregulation of cortical excitability.

Immunoaffinity carrier prepared by immobilization of antibody via Co3+-chelate.

A method for the immobilization of antibodies to inert matrix represents an important factor that affects results of immunoaffinity chromatography. Binding antibodies to immobilized metal ions is an example of oriented immobilization that avoids a random coupling of a protein. Preparation of a stable immunoaffinity sorbent using immobilized metal ions was described. Antibodies were bound to chelated Co3+ ions that were prepared by oxidation of Co2+-iminodiacetic acid agarose using hydrogen peroxide. The formation of a stable complex of the antibody with immobilized Co3+ ions was proved. Antibodies bound by this way were not released with solutions of 50 mM EDTA, 6 M urea, 3 M NaCl, 20% v/v dioxane, 0.1 M imidazole and buffers of pH 2.5 and pH 11.0. If needed, antibody could be released from the carrier by the reduction of Co3+ ions with a reducing agent (e.g. dithiotreitol or 2-mercaptoethanol). Antibody released from the carrier could be then replaced by another antibody. The method described in this paper was used for the immobilization of polyclonal rabbit anti-ovalbumin antibody or egg yolk antibody (IgY) produced in chicken. In a model experiment, immobilized polyclonal rabbit antibodies were used for the separation of ovalbumin from egg white and conditions of chromatography were described.

Separation of cobalt binding proteins by immobilized metal affinity chromatography.

Cobalt binding proteins from mouse liver, which were expressed in response to CoCl2 poisoning, were separated using gel permeation chromatography and then immobilised metal ion affinity chromatography (IMAC) with immobilized cobalt ions. Conditions used in IMAC-Co2+ were optimised. The fractions eluted with 60 mM imidazole were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Differences between the samples were also evaluated by a two-dimensional electrophoresis. Samples from the Co2+-treated mice provided higher number of electrophoretic spots than those from the untreated mice. Relative molecular masses of these proteins are appropriately 37,000; 32,000 and 26,000 and their isoelectric points (pI) are 6.5-7.5.