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PURPOSE High-density EEG (HD-EEG) systems and electrical source imaging techniques have revolutionized our ability to assess the potential sources of epileptiform activity and other EEG features. Nonetheless, clinical use of HD-EEG is hampered by the lack of a standardized electrode nomenclature system and the inherent difficulties encountered in visually reviewing recordings. Inefficient visual review of HD-EEG remains a major barrier to incorporating these techniques into routine clinical care. METHODS Extension of the 10-10 is first defined by the addition of 2 reference curves: the -10% and -20% axial reference curves. Electrode positions over the face are named based on facial bony structures (N = nasion, Z = zygomatic prominence, M = mandible) and over the back of the head on posterior landmarks (I = inion, S = subinion, B = Base). Then, following the 10% incremental distance rule, we define additional electrode positions. Electrodes with nonstandard positions are clustered around the closest 10-10 electrode, deemed their cardinal point. RESULTS The 256-electrode Geodesic Sensor Net mapped to 96 of the 120 extended 10-10 cardinal electrodes. CONCLUSIONS Electrode position nomenclature that builds upon the international standard 10-10 system allows electroencephalographers to identify spatial areas of interest in HD-EEG relative to positions in routine use. A standard viewing montage for HD-EEG and its application with electrical source imaging boost efficiency when reviewing data and improve accuracy in recognizing epileptiform discharges. Additionally, our proposed system is not limited to a specific HD-EEG system, electrode count, or electrode layout.

Introduction High density EEG (hdEEG) systems and Electrical Source Imaging (ESI) techniques have revolutionized our ability to assess the potential sources of epileptiform activity and other EEG features. HdEEG interpretation is limited by lack of standardized electrode position nomenclature and montages. Inefficient visual review of hdEEG remains a major barrier to incorporating these techniques into clinical care. The aim of this project is to propose an electrode map and nomenclature with digitized electrode locations for easy integration with neuroimaging studies and ESI. Methods The 256 channel EEG net (Geodesic Sensor Net, Electrical Geodesics, Inc.) includes electrode locations approximating the International 10–20 and 10–10 systems, but intervening electrodes do not have a standardized location, and many electrodes over the cheeks and face do not have positions defined by the 10–10 or 10–5 systems. We co-registered average 256 channel EEG net electrode positions to the 10–10 positions based on the Montreal Neurologic Institute using Curry 7.0 software. then clustered the 256 electrode locations to their closest 10–10 electrodes tested several channel layouts (montages) allowing rapid transition from global views (all head regions) to focal views (subregions corresponding to 10–10 electrode coordinates). Results 256 electrode locations were successfully clustered around their closest 10–10 electrode, deemed its cardinal point. All 256 electrodes within a cluster received the same initial letters according to the 10–10 electrode at its center. Within a cluster, the first subscript identified its position either anterior (a) or posterior (p) to the cardinal 10–10 electrode. The second subscript identified its position either superior (s) or inferior (i) to the cardinal 10–10 electrode. The last subscript, numerical, identified the proximity of the nonstandard electrode relative to the cardinal 10–10 electrode, compared to the other nonstandard electrodes in that cluster. Therefore, the closest nonstandard electrode would have the subscript as 1, and each subscript would increase in numeric value as distance from the cardinal 10–10 electrode increases. Conclusion Electrode position nomenclature which builds upon the international standard 10–10 system allows electroencephalographers to identify spatial areas of interest in hdEEG relative to positions in routine use. A standard viewing montage for hdEEG and its application with ESI both boosts efficiency when reviewing data, and also improves accuracy in recognizing epileptiform discharges. Furthermore, combining the montage with electrode geopositions will provide greater continuity and ease of use across analysis techniques that would potentially increase adoption of source analysis in clinical care. Our proposed system could also be expanded to higher numbers of electrodes or additional positions on the face or head and is not limited to a specific hdEEG system or electrode count.

The rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON–OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.

Introduction Despite major advances in using high density EEG (hdEEG) and electrical source imaging (ESI) for analysis of interictal activity, research demonstrating its utility in examining ictal activity is still lacking. This may be a result of technical challenges associated with capturing epileptic seizures on scalp hdEEG recordings (physical constraints, such as high number of sensors, lack of standardization in review, comfort, etc.). Furthermore, the value of using interictal discharges as a valid estimate of seizure onset zone (SOZ) still remains disputable. The aim of this study is to use electrical source imaging (ESI) to evaluate the co-localization of ictal and interictal activity through the use of high density scalp EEG. Methods A retrospective analysis was performed on 5 patients with intractable focal temporal and extratemporal lobe epilepsy. EEG scalp recordings were obtained using high density 256 Geodesic Sensory Net (Geodesic Sensor Net, Electrical Geodesic Inc.). ESI was performed using two different commercially available ESI systems, Curry 7.0 (Compumedics) and MIPEGI (Electrical Geodesic Inc.). Sensor locations were determined using the Geodesic Photogrammetry System (GPS) and Geosource 3 (Electrical Geodesic Inc), Realistic geometric individualized head models were constructed from patient specific MRIs using the boundary element model and the finite difference model. Source reconstruction was based on distributed source models and dipole models. The concordance of irritative and ictal onset zones was estimated by the distance between maximal ictal and interictal source activity. Results ESI identified the seizure onset and irritative zones in all 5 patients. There was good concordance between the estimated seizure onset zone and irritative zone on the sub-lobar level. Similar results were obtained through the use of the boundary element and finite difference models. Conclusion The results provide insight into whether interictal discharges provide accurate estimate of SOZ. Furthermore, these results assess similarity of source reconstruction obtained through two different types of individual head models that are commercially available.

Action potentials were recorded from rat retinal ganglion cell fibers in the presence of a uniform field, and the maintained discharge pattern was characterized. Spike trains recorded under ketamine–xylazine anesthesia were generally stationary, while those recorded under urethane anesthesia often showed slow, undriven, quasiperiodic fluctuations in firing rate. In light of these nonstationarities, interspike interval distributions and power spectral densities are reported for data collected primarily under ketamine–xylazine. The majority of cells had multimodal interval distributions, with the first peak in the range of 25.0–38.5 ms and the subsequent peaks occurring at integer multiples of the first peak. Cells with unimodal distributions were fit well by a gamma distribution function. Interval and spike count statistics showed that ON cells tended to fire faster than OFF cells and that cells with higher rates fired in a more regular manner, with the coefficient of variation covering a wide range of values across all cells (0.43–0.97). Both ON and OFF cells show serial correlations between adjacent interspike intervals, while ON cells also showed second-order correlations. Cells with multimodal interval distribution showed a strong peak at high frequencies in the power spectra in the range of 28.9–41.4 Hz. Oscillations were present under both anesthetic conditions and persisted in the dark at a slightly lower frequency, implying that the oscillations are generated independent of any light stimulus but can be modulated by light level. The oscillation frequency varied slightly between cells of the same type and in the same eye, suggesting that multiple oscillatory generating mechanisms exist within the retina. Cells with high-frequency oscillations were described well by an integrate-and-fire model with the input consisting of Gaussian noise plus a sinusoid where the phase was jittered randomly to account for the bandwidth present in the oscillations.

Regeneration in the peripheral nervous system is impaired after prolonged periods of denervation. Currently, no interventions exist to alter the outcome after prolonged denervation. To examine the role of transplanted neural stem cells (NSC), we prepared chronically denervated distal tibial nerve segments. After 6 months of chronic denervation, we transplanted vehicle, C17.2 mouse NSCs, or C17.2 mouse NSCs engineered to overexpress GDNF to the distal tibial nerve and performed a peroneal nerve cross-suture. In animals transplanted with the NSCs, there was better regeneration of the peroneal axons into the tibial nerve as measured by counting the number of axons and by the emergence of compound motor action potentials in the tibial innervated foot muscles. Improved regeneration correlated with a reduction of chondroitin sulphate proteoglycan (CSPG) immunoreactivity in the extracellular matrix (ECM). In vitro, supernatant from C17.2 NSCs contained large quantities of secreted matrix metalloprotease-2 (MMP-2), degraded the CSPGs on chronically denervated tibial nerve sections, and reversed the CSPG-induced inhibition of neuritic outgrowth of DRG neurons. This reversal was inhibited by selective MMP-2 inhibitors. This is the first successful demonstration of regeneration through a chronically denervated nerve. These findings suggest that improved regeneration in the PNS can be accomplished by combining neurotrophic factor support and removal of axon growth inhibitory components in the extracellular matrix.

Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3–5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of NBS cells to survive γ irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients.

Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer1. The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to γ-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by γ-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after γ-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage.

Information about the visual world is transmitted to the brain in sequences of action potentials in retinal ganglion cell axons that make up the optic nerve. In vivo recordings of ganglion cell spike trains in several animal models have revealed much of what is known about how the early visual system processes and encodes visual information. However, such recordings have been rare in one of the most common animal models, the rat, possibly owing to difficulty in detecting spikes fired by small diameter axons. The many retinal disease models involving rats motivate a need for characterizing the functional properties of ganglion cells without disturbing the eye, as with intraocular or in vitro recordings. Here, we demonstrate a method for recording ganglion cell spike trains from the optic chiasm of the anesthetized rat. We first show how to fabricate tungsten-in-glass electrodes that can pick up electrical activity from single ganglion cell axons in rat. The electrodes outperform all commercial ones that we have tried. We then illustrate our custom-designed stereotaxic system for in vivo visual neurophysiology experiments and our procedures for animal preparation and reliable and stable electrode placement in the optic chiasm.

The BRCA1 gene product plays a multifunctional role in controlling genome integrity. Embryonic stem cells lacking BRCA1 are reportedly defective in transcription-coupled repair of oxidative DNA damage ([1][1]). Cells lacking intact BRCA1 also manifest a mitotic-checkpoint defect and are more likely