Transcranial focal electrical stimulation via tripolar concentric ring electrodes does not modify the short- and long-term memory formation in rats evaluated in the novel object recognition test.

Noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been under development as an alternative/complementary therapy for seizure control. Transcranial focal electrical stimulation has shown efficacy in attenuating penicillin-, pilocarpine-, and pentylenetetrazole-induced acute seizures in rat models. This study evaluated the effects of TFS via TCREs on the memory formation of healthy rats as a safety test of TFS. Short- and long-term memory formation was tested after the application of TFS using the novel object recognition (NOR) test. The following independent groups were used: naïve, control (without TFS), and TFS (treated). The naïve, control, and stimulated groups spent more time investigating the new object than the familiar one during the test phase. Transcranial focal electrical stimulation via TCREs given once does not modify the short- and long-term memory formation in rats in the NOR test. Results provide an important step towards a better understanding for the safe usage of TFS via TCREs.

Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

PURPOSE: To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. METHODS: The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. RESULTS: In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. CONCLUSIONS: TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia.

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.

The effects of concentric ring electrode electrical stimulation on rat skin.

Surface electrodes are commonly used electrodes clinically, in applications such as functional electrical stimulation for the restoration of motor functions, pain relief, transcutaneous electrical nerve stimulation, electrocardiographic monitoring, defibrillation, surface cardiac pacing, and advanced drug delivery systems. Common to these applications are occasional reports of pain, tissue damage, rash, or burns on the skin at the point where electrodes are placed. In this study, we quantitatively analyzed the effects of acute noninvasive electrical stimulation from concentric ring electrodes (CRE) to determine the maximum safe current limit. We developed a three-dimensional multi-layer model and calculated the temperature profile under the CRE and the corresponding energy density with electrical-thermal coupled field analysis. Infrared thermography was used to measure skin temperature during electrical stimulation to verify the computer simulations. We also performed histological analysis to study cell morphology and characterize any resulting tissue damage. The simulation results are accurate for low energy density distributions. It can also be concluded that as long as the specified energy density applied is kept below 0.92 (A2/cm4.s(-1)), the maximum temperature will remain within the safe limits. Future work should focus on the effects of the electrode paste.

Computer simulation comparison of tripolar, bipolar, and spline Laplacian electrocadiogram estimators.

A comparison of the performance of the tripolar and bipolar concentric as well as spline Laplacian electrocardiograms (LECGs) and body surface Laplacian mappings (BSLMs) for localizing and imaging the cardiac electrical activation has been investigated based on computer simulation. In the simulation a simplified eccentric heart-torso sphere-cylinder homogeneous volume conductor model were developed. Multiple dipoles with different orientations were used to simulate the underlying cardiac electrical activities. Results show that the tripolar concentric ring electrodes produce the most accurate LECG and BSLM estimation among the three estimators with the best performance in spatial resolution.

Improved separability of dipole sources by tripolar versus conventional disk electrodes: a modeling study using independent component analysis.

Tripolar electrodes have been shown to have less mutual information and higher spatial resolution than disc electrodes. In this work, a four-layer anisotropic concentric spherical head computer model was programmed, then four configurations of time-varying dipole signals were used to generate the scalp surface signals that would be obtained with tripolar and disc electrodes, and four important EEG artifacts were tested: eye blinking, cheek movements, jaw movements, and talking. Finally, a fast fixed-point algorithm was used for signal independent component analysis (ICA). The results show that signals from tripolar electrodes generated better ICA separation results than from disc electrodes for EEG signals with these four types of artifacts.

An optimal spatial filtering electrode for brain computer interface.

There are millions of people in the U.S. and many more worldwide who could benefit from a noninvasive-based electroencephalography (EEG) brain computer interface (BCI). A BCI is an alternative or augmentative communication method for people with severe motor disabilities. However, EEG suffers from poor spatial resolution and signal-to-noise ratio (SNR). To improve the spatial resolution and SNR many researchers have turned to implantable electrodes. We have previously reported on significant improvements in BCI recognition rates using tripolar concentric ring electrodes compared to disc electrodes. We now report on a optimal method for combining the outputs from the independent elements of the tripolar concentric ring electrodes to improve the spatial resolution further. We used minimum variance distortionless look (MVDL), a beamformer, on simulated data to compare the spatial sensitivity of the optimal combination to disc electrodes and the tripolar concentric ring electrode surface Laplacian. The optimal combination shows the highest spatial sensitivity with the Laplacian a close second and disc electrodes resulting in a distant third. Further analysis is necessary with a more realistic computer model and then real signals. however it appears that the optimal combination may improve the spatial resolution of EEG further which in turn can be utilized to improve noninvasive EEG-based BCIs.

Tripolar Laplacian electrocardiogram and moment of activation isochronal mapping.

The electrocardiogram (ECG) provides useful global temporal assessment of the cardiac activity, but has limited spatial capabilities. The Laplacian electrocardiogram (LECG), an improvement over the ECG, provides high spatiotemporal distributed information about cardiac electrical activation. We designed and developed LECG tripolar concentric ring electrode active sensors based on the finite element algorithm 'nine-point method' (NPM). The active sensors were used in an array of 6 by 12 (72) locations to record bipolar and tripolar LECG from the body surface over the anterolateral chest. Compared to bipolar LECG, tripolar LECG showed significantly higher spatial selectivity which may be helpful in inferring information about cardiac activations detected on the body surface. In this study the moment of activation (MOA), an indicator of a depolarization wave passing below the active sensors, was used to surmise possible timing information of the cardiac electrical activation below the active sensors' recording sites. The MOA on the body surface was used to generate isochronal maps that may some day be used by clinicians in diagnosing arrhythmias and assessing the efficacy of therapies.

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.

Non-invasive Laplacian electrocardiography and moment of activation mapping.

Laplacian Electrocardiogram (LECG) is a non-invasive approach providing high spatiotemporal distributed information of cardiac electrical activity. Recently researchers have recorded surface potentials from monopolar disc electrodes to estimate the Laplacian using finite difference algorithms or spline surface Laplacian estimators. Bipolar and quasi-bipolar electrodes have also been used to record LECG directly. Here based on the "Nine Point Method" (NPM), Laplacian tripolar concentric ring electrode active sensors were designed. High spatiotemporal resolution body surface LECG using the new tripolar active sensors was recorded. Moment of activation (MOA) isochronal maps used to detect cardiac electrical activation patterns exhibited on the body surface was also generated.

Analysis of skin-electrode impedance using concentric ring electrode.

A significant contributor to artefact generation in surface electromyography (sEMG) and, functional electrical stimulation (FES) intensity is the skin-to-electrode impedance (Z(S/E)). While using electrolytic gels may initially lower Z(S/E), the impedance may not remain stable. It can vary over time due to changes in underlying structures such as sweat glands and physical deformations due to movements. An experiment seeking to identify major factors in the reduction of Z(S/E), and therefore mitigate these artefacts, was performed by varying a series of control factors on the concentric ring electrode (CRE). Unlike conventional disc electrodes, CREs have small surface areas which may exacerbate Z(S/E) changes. The factors tested were electrode material, electrode size, skin preparation, and surface pressure. This work analyzes how these factors in their various combinations effect changes in Z(S/E) and suggests protocols for improving recording or stimulation with CREs via lowered and consistent Z(S/E).

Development of the triple ring body surface laplacian sensor and its experimental study.

The Laplacian of the body surface potentials (Laplacian ECG--LECG) is a new approach to resolve spatially distributed bioelectric sources. LECG is a weak signal so an LECG sensor needs a good signal-to-noise ratio (SNR) and high common mode rejection ratio (CMRR). In this paper, we discuss a LECG sensor, which integrated tripolar concentric ring electrodes and signal conditioning circuit on a printed circuit board. The experimental results are in agreement with the theoretical calculations suggesting the feasibility of measuring the surface Laplacian. This lays the foundation for using such a device to assist in heart disease diagnoses.

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.

Comparison of bipolar vs. tripolar concentric ring electrode Laplacian estimates.

Potentials on the body surface from the heart are of a spatial and temporal function. The 12-lead electrocardiogram (ECG) provides useful global temporal assessment, but it yields limited spatial information due to the smoothing effect caused by the volume conductor. The smoothing complicates identification of multiple simultaneous bioelectrical events. In an attempt to circumvent the smoothing problem, some researchers used a five-point method (FPM) to numerically estimate the analytical solution of the Laplacian with an array of monopolar electrodes. The FPM is generalized to develop a bi-polar concentric ring electrode system. We have developed a new Laplacian ECG sensor, a trielectrode sensor, based on a nine-point method (NPM) numerical approximation of the analytical Laplacian. For a comparison, the NPM, FPM and compact NPM were calculated over a 400 x 400 mesh with 1/400 spacing. Tri and bi-electrode sensors were also simulated and their Laplacian estimates were compared against the analytical Laplacian. We found that tri-electrode sensors have a much-improved accuracy with significantly less relative and maximum errors in estimating the Laplacian operator. Apart from the higher accuracy, our new electrode configuration will allow better localization of the electrical activity of the heart than bi-electrode configurations.

Fractionated premotor, motor, and ankle dorsiflexion reaction times in hemiplegia.

Ten hemiplegic subjects completed 20 rapid dorsiflexions of their afflicted and nonafflicted limbs. Electrodes were attached to the tibialis anterior and the gastrocnemius muscles and electromyograms were recorded for their premotor time, motor time, and simple reaction time during ankle dorsiflexion and plantar flexion of their lower limbs. The fractionated components of reaction time, namely, premotor time and motor time, of both legs were statistically compared. It was found that the premotor time of the subject's stroke-affected limb was significantly slower than the premotor time of the nonaffected limb (control), with no differences between their associated mean motor times. These results supported the hypothesis that a stroke has a deleterious affect upon the central, premotor time processing centers and has no disruptive influence upon the peripheral motor time. Comparing the fractionated components of reaction time (premotor time and motor time), with simple reaction time, the former provided a more sensitive and valid method to detect possible injurious side effects of a stroke upon the brain's neuromotor transmission centers and subcenters, and their peripheral, stimulus, response network.