Algorithm for automatic detection of pentylenetetrazole-induced seizures in rats.

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation (TFS) system through our novel concentric ring electrodes to control seizures. Here we report on the development of a seizure detecting algorithm to be used for automatic application of TFS. A cumulative sum (CUSUM) algorithm was evaluated that detected the electrographic seizure activity in all experiments well in advance of the behavioral seizure activity.

Development of a tri-polar concentric ring electrode for acquiring accurate Laplacian body surface potentials.

Potentials recorded on the body surface from the heart are of a spatial and temporal function. The 12-lead electrocardiogram (ECG) provides a useful means of global temporal assessment; however, it yields limited spatial information due to the smoothing effect caused by the volume conductor. In an attempt to circumvent the smoothing problem, researchers have used the five-point method (FPM) to numerically estimate the analytical solution of the Laplacian with an array of monopolar electrodes. Researchers have also developed a bipolar concentric ring electrode system to estimate the analytical Laplacian, and others have used a quasi-bipolar electrode configuration. In a search to find an electrode configuration with a close approximation to the analytical Laplacian, development of a tri-polar concentric ring electrode based on the nine-point method (NPM) was conducted. A comparison of the NPM, FPM, and discrete form of the quasi-bipolar configuration was performed over a 400 x 400 mesh with 1/400 spacing by computer modeling. Different properties of bipolar, quasi-bipolar and tri-polar concentric ring electrodes were evaluated and compared, and verified with tank experiments. One-way analysis of variance (ANOVA) with post hoc t-test and Bonferroni corrections were performed to compare the performance of the various methods and electrode configurations. It was found that the tri-polar electrode has significantly improved accuracy and local sensitivity. This paper also discusses the development of an active sensor using the tri-polar electrode configuration. A 1-cm active Laplacian tri-polar sensor based on the NPM was tested and deemed feasible for acquiring Laplacian cardiac surface potentials.

Mutual information of tri-polar concentric ring electrodes.

Electroencephalography (EEG) signals are spatio-temporal. EEG has very good temporal resolution but typically doesn't possess high spatial resolution. The surface Laplacian enhances the spatial resolution and selectivity of the surface electrical activity. Concentric ring electrodes have been shown to estimate the surface Laplacian directly with significantly better spatial resolution than conventional electrodes and possess spatial filtering characteristics. Movement Related potentials (MRP) were recorded using tri-polar and bipolar concentric ring electrodes as well as conventional disc EEG electrodes while the subjects were pressing a micro-switch. The electrodes were placed in an array of 35 encompassing the area between Fz-Cz-Pz-P3-T5-T3-T7-F3. Mutual information (MI) of the MRP signals recorded with the different electrode systems was compared. The MRP signals recorded with the tri-polar concentric ring electrode system have significantly less MI between locations than the other two electrode configurations tested. The decrease in MI should increase the total information available by pooling of information from independent tri-polar concentric ring electrodes. These characteristics should make tri-polar concentric electrodes beneficial for EEG applications.

Computer simulation and tank experimental verification of concentric ring electrodes.

Brain activity generates electrical potentials that are spatio-temporal in nature. EEG is the least costly and most widely used non-invasive technique for diagnosing many problems related to the brain. It has very good temporal resolution, but does not poses high spatial resolution primarily due to the blurring affects of the volume conductor. The surface Laplacian enhances the spatial resolution and selectivity of the surface electrical activity as it takes the second spatial derivative of the potential. In an attempt to increase the localization and spatial selectivity a five point finite difference method has recently been used in a bipolar electrode configuration. Here we report on a nine point finite difference method as a model for the tripolar electrode configuration. We have designed a computer simulation to model electrode properties and a dipole at various depths below the electrode surface. A tank experimental was setup to verify the computer simulated potentials. In the simulation and tank experiment, a concentric ring electrode of 2 cm diameter was used. We found that the tripolar electrode configuration has significantly better localization and signal to noise ratio than the bipolar and quasi-bipolar configurations.

Polymorphic glutathione S-transferase M1 is a risk factor of primary open-angle glaucoma among Estonians.

Primary open-angle glaucoma, the most common form of glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and is usually associated with elevated intraocular pressure. The etiology and genetic risk factors of primary open-angle glaucoma are mostly unknown. The aim of this study was to find out whether the polymorphism at GSTM1, GSTM3, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma, because these polymorphic enzymes are susceptibility candidates for several diseases, including such eye disease as cataract. The phenotype of GSTM1 and GSTT1 was determined by ELISA and the genotype of GSTM3 and GSTP1 was detected by polymerase chain reaction. Four hundred and fifty two Estonians (250 glaucomas and 202 controls) participated in a case-control study. A significant association of the GSTM1 polymorphism with glaucoma was observed. The frequency of the GSTM1 positive individuals among the glaucoma group was significantly higher than in controls (60 vs. 45.0%) with odds ratio of 1.83 (95% CI 1.26-2.66;P = 0.002). The risk among the GSTM1 positive individuals of developing glaucoma was even higher in the case of smoking: 62.7% of smokers were GSTM1 positive in the glaucoma group while only 33.3% of smokers had GSTM1 positive phenotype in controls (OR = 3.36; 95% CI 1.49-7.56;P = 0.012). An association with a lower level of significance was also found with the GSTM3 gene. Four% of the 250 patients with POAG were identified as carriers of the GSTM3 BB genotype, a proportion which was slightly higher than the 1.0% for the controls (OR = 4.17; 95% CI 0. 90-19.24;P = 0.144). The frequencies of the GSTT1 and GSTP1 genotypes in both groups were not statistically different. The present study suggests that the GSTM1 polymorphism may be associated with increased risk of development of primary open-angle glaucoma.

Polymorphic glutathione S-transferases as genetic risk factors for senile cortical cataract in Estonians.

PURPOSE: To investigate the possible association between glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age-related cataracts in Estonian patients. METHODS: Patients with cortical (155), nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme-linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain reaction. RESULTS: The frequency of the GSTM1-positive phenotype was significantly higher in the cortical cataract group (60.6%) than in the controls (45.0%) with odds ratio of 1.88 (95% CI, 1.23-2.94; P = 0.004). The cortical cataract risk associated with the GSTM1-positive phenotype was increased in carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95% CI, 1.30-3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28; 95% CI, 1.51-3.73; P < 0.001). The highest risk of cortical cataract was observed in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59-4.11; P < 0.001). Also, a significant interaction between the presence of the GSTP1* A allele and cortical cataract was found with prevalence of the GSTP1* A allele among the cortical cataract cases compared with the controls. Ninety-five percent of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype, whereas in controls 87% of persons had a genotype with GSTP1*A allele (OR = 3.1; 95% CI, 1.31-7.35; P = 0.007). In contrast to the GSTP1*A allele, the presence of the GSTP1*B allele in one or two copies leads to decreased cortical cataract risk (OR = 0.09 for GSTP1 BB genotype). CONCLUSIONS. The GSTM1-positive phenotype as well as the presence of the GSTP1*A allele may be a genetic risk factor for development of cortical cataract.