Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning.

Seizure prediction is the grand challenge of epileptology. However, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long-lasting local field potential (LFP) recordings containing several hundred generalized spike and wave discharges (SWDs), acquired at eight locations in the cortico-thalamic system of absence epileptic rats, were iteratively analyzed in all possible combinations of either two or three recording sites, by a wavelet-based algorithm, calculating the product of the wavelet-energy signaling increases in synchronicity. Sensitivity and false alarm rate of prediction were compared between various combinations, and wavelet spectra of true and false positive predictions were fed to a random forest machine learning algorithm to further differentiate between them. Wavelet analysis of intracortical and cortico-thalamic LFP traces showed a significantly smaller number of false alarms compared with intrathalamic combinations, while predictions based on recordings in Layers IV, V, and VI of the somatosensory-cortex significantly outreached all other combinations in terms of prediction sensitivity. In 24-h out-of-sample recordings of nine Genetic Absence Epilepsy Rats from Strasbourg (GAERS), containing diurnal fluctuations of SWD occurrence, classification of true and false positives by the trained random forest further reduced the false alarm rate by 71%, although at some trade-off between false alarms and sensitivity of prediction, as reflected in relatively low F1 score values. Results provide support for the cortical-focus theory of absence epilepsy and allow the conclusion that SWDs are predictable to some degree. The latter paves the way for the development of closed-loop SWD prediction-prevention systems. Suggestions for a possible translation to human data are outlined.

Modulation of Hyperpolarization-Activated Inward Current and Thalamic Activity Modes by Different Cyclic Nucleotides.

The hyperpolarization-activated inward current, Ih, plays a key role in the generation of rhythmic activities in thalamocortical (TC) relay neurons. Cyclic nucleotides, like 3',5'-cyclic adenosine monophosphate (cAMP), facilitate voltage-dependent activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels by shifting the activation curve of Ih to more positive values and thereby terminating the rhythmic burst activity. The role of 3',5'-cyclic guanosine monophosphate (cGMP) in modulation of Ih is not well understood. To determine the possible role of the nitric oxide (NO)-sensitive cGMP-forming guanylyl cyclase 2 (NO-GC2) in controlling the thalamic Ih, the voltage-dependency and cGMP/cAMP-sensitivity of Ih was analyzed in TC neurons of the dorsal part of the lateral geniculate nucleus (dLGN) in wild type (WT) and NO-GC2-deficit (NO-GC2-/-) mice. Whole cell voltage clamp recordings in brain slices revealed a more hyperpolarized half maximal activation (V1/2) of Ih in NO-GC2-/- TC neurons compared to WT. Different concentrations of 8-Br-cAMP/8-Br-cGMP induced dose-dependent positive shifts of V1/2 in both strains. Treatment of WT slices with lyase enzyme (adenylyl and guanylyl cyclases) inhibitors (SQ22536 and ODQ) resulted in further hyperpolarized V1/2. Under current clamp conditions NO-GC2-/- neurons exhibited a reduction in the Ih-dependent voltage sag and reduced action potential firing with hyperpolarizing and depolarizing current steps, respectively. Intrathalamic rhythmic bursting activity in brain slices and in a simplified mathematical model of the thalamic network was reduced in the absence of NO-GC2. In freely behaving NO-GC2-/- mice, delta and theta band activity was enhanced during active wakefulness (AW) as well as rapid eye movement (REM) sleep in cortical local field potential (LFP) in comparison to WT. These findings indicate that cGMP facilitates Ih activation and contributes to a tonic activity in TC neurons. On the network level basal cGMP production supports fast rhythmic activity in the cortex.

Expectations as a key to understanding actor strategies in the field of fuel cell and hydrogen vehicles.

Due to its environmental impact, the mobility system is increasingly under pressure. The challenges to cope with climate change, air quality, depleting fossil resources imply the need for a transition of the current mobility system towards a more sustainable one. Expectations and visions have been identified as crucial in the guidance of such transitions, and more specifically of actor strategies. Still, it remained unclear why the actors involved in transition activities appear to change their strategies frequently and suddenly. The empirical analysis of the expectations and strategies of three actors in the field of hydrogen and fuel cell technology indicates that changing actor strategies can be explained by rather volatile expectations related to different levels. Our case studies of the strategies of two large car manufacturers and the German government demonstrate that the car manufacturers refer strongly to expectations about the future regime, while expectations related to the socio-technical landscape level appear to be crucial for the strategy of the German government.