Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation.

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1 week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (≈1/day) persisted to the end of the experiment at 4 weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spikes, a significant but modest increase in seizure occurrence and changes in EEG frequency band power. Taken together, findings suggest that the hippocampus regains relative homeostasis-with occasional breakthrough seizures-in the face of an extensive and abrupt loss of interneurons.

Spatial and Temporal Comparisons of Calcium Channel and Intrinsic Signal Imaging During in Vivo Cortical Spreading Depolarizations in Healthy and Hypoxic Brains.

BACKGROUND: Spreading depolarizations (SDs) can be viewed at a cellular level using calcium imaging (CI), but this approach is limited to laboratory applications and animal experiments. Optical intrinsic signal imaging (OISI), on the other hand, is amenable to clinical use and allows viewing of large cortical areas without contrast agents. A better understanding of the behavior of OISI-observed SDs under different brain conditions is needed. METHODS: We performed simultaneous calcium and OISI of SDs in GCaMP6f mice. SDs propagate through the cortex as a pathological wave and trigger a neurovascular response that can be imaged with both techniques. We imaged both mechanically stimulated SDs (sSDs) in healthy brains and terminal SDs (tSDs) induced by system hypoxia and cardiopulmonary failure. RESULTS: We observed a lag in the detection of SDs in the OISI channels compared with CI. sSDs had a faster velocity than tSDs, and tSDs had a greater initial velocity for the first 400 µm when observed with CI compared with OISI. However, both imaging methods revealed similar characteristics, including a decrease in the sSD (but not tSD) velocities as the wave moved away from the site of initial detection. CI and OISI also showed similar spatial propagation of the SD throughout the image field. Importantly, only OISI allowed regional ischemia to be detected before tSDs occurred. CONCLUSIONS: Altogether, data indicate that monitoring either neural activity or intrinsic signals with high-resolution optical imaging can be useful to assess SDs, but OISI may be a clinically applicable way to predict, and therefore possibly mitigate, hypoxic-ischemic tSDs.

Evaluation of smartphone-integrated magnetometers in detection of safe electromagnetic devices for use near programmable shunt valves: a proof-of-concept study.

OBJECTIVE: External magnetic forces can have an impact on programmable valve mechanisms and potentially alter the opening pressure. As wearable technology has begun to permeate mainstream living, there is a clear need to provide information regarding safety of these devices for use near a programmable valve (PV). The aim of this study was to evaluate the magnetic fields of reference devices using smartphone-integrated magnetometers and compare the results with published shunt tolerances. METHODS: Five smartphones from different manufacturers were used to evaluate the magnetic properties of various commonly used (n = 6) and newer-generation (n = 10) devices using measurements generated from the internal smartphone magnetometers. PV tolerance testing using calibrated magnets of varying field strengths was also performed by smartphone magnetometers. RESULTS: All tested smartphone-integrated magnetometers had a factory sensor saturation point at around 5000 µT or 50 Gauss (G). This is well below the threshold at which a magnet can potentially deprogram a shunt, based on manufacturer reports as well as the authors' experimental data with a threshold of more than 300 G. While many of the devices did saturate the smartphone sensors at the source, the magnetic flux density of the objects decreases significantly at 2 inches. CONCLUSIONS: The existence of an upper limit on the magnetometers of all the smartphones used, although well below the published deprogramming threshold for modern programmable valves, does not allow us to give precise recommendations on those devices that saturate the sensor. Based on the authors' experimental data using smartphone-integrated magnetometers, they concluded that devices that measure < 40 G can be used safely close to a PV.