Lung clearance index predicts persistence of preschool wheeze.

Background: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze.

Altered neocortical oscillations and cellular excitability in an in vitro Wwox knockout mouse model of epileptic encephalopathy.

Loss of function mutations of the WW domain-containing oxidoreductase (WWOX) gene are associated with severe and fatal drug-resistant pediatric epileptic encephalopathy. Epileptic seizures are typically characterized by neuronal hyperexcitability; however, the specific contribution of WWOX to that hyperexcitability has yet to be investigated. Using a mouse model of neuronal Wwox-deletion that exhibit spontaneous seizures, in vitro whole-cell and field potential electrophysiological characterization identified spontaneous bursting activity in the neocortex, a marker of the underlying network hyperexcitability.

Neuronal deletion of Wwox, associated with WOREE syndrome, causes epilepsy and myelin defects.

WWOX-related epileptic encephalopathy (WOREE) syndrome caused by human germline bi-allelic mutations in WWOX is a neurodevelopmental disorder characterized by intractable epilepsy, severe developmental delay, ataxia and premature death at the age of 2-4 years. The underlying mechanisms of WWOX actions are poorly understood. In the current study, we show that specific neuronal deletion of murine Wwox produces phenotypes typical of the Wwox-null mutation leading to brain hyperexcitability, intractable epilepsy, ataxia and postnatal lethality.

Delta-gamma phase-amplitude coupling as a biomarker of postictal generalized EEG suppression.

Postictal generalized EEG suppression is the state of suppression of electrical activity at the end of a seizure. Prolongation of this state has been associated with increased risk of sudden unexpected death in epilepsy, making characterization of underlying electrical rhythmic activity during postictal suppression an important step in improving epilepsy treatment. Phase-amplitude coupling in EEG reflects cognitive coding within brain networks and some of those codes highlight epileptic activity; therefore, we hypothesized that there are distinct phase-amplitude coupling features in the postictal suppression state that can provide an improved estimate of this state in the context of patient risk for sudden unexpected death in epilepsy.

Transitions between neocortical seizure and non-seizure-like states and their association with presynaptic glutamate release.

The transition between seizure and non-seizure states in neocortical epileptic networks is governed by distinct underlying dynamical processes. Based on the gamma distribution of seizure and inter-seizure durations, over time, seizures are highly likely to self-terminate; whereas, inter-seizure durations have a low chance of transitioning back into a seizure state. Yet, the chance of a state transition could be formed by multiple overlapping, unknown synaptic mechanisms.

Glial Modulation of Electrical Rhythms in a Neuroglial Network Model of Epilepsy.

Objective: An important EEG-based biomarker for epilepsy is the phase-amplitude cross-frequency coupling (PAC) of electrical rhythms; however, the underlying pathways of these pathologic markers are not always clear. Since glial cells have been shown to play an active role in neuroglial networks, it is likely that some of these PAC markers are modulated via glial effects.

Methods: We developed a 4-unit hybrid model of a neuroglial network, consisting of 16 sub-units, that combines a mechanistic representation of neurons with an oscillator-based Cognitive Rhythm Generator (CRG) representation of glial cells-astrocytes and microglia.