Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate

17 Apr

Blind deconvolution decreases requirements on temporal resolution of DCE-MRI: Application to 2nd generation pharmacokinetic modeling

Purpose: Dynamic Contrast-Enhanced (DCE) MRI with 2nd generation pharmacokinetic models provides estimates of plasma flow and permeability surface-area product in contrast to the broadly used 1st generation models (e.g. the Tofts models). However, the use of 2nd generation models requires higher frequency with which the dynamic images are acquired (around 1.5 s per image). Blind deconvolution can decrease the demands on temporal resolution as shown previously for one of the 1st generation models. Here, the temporal-resolution requirements achievable for blind deconvolution with a 2nd generation model are studied.

Methods: The 2nd generation model is formulated as the distributed-capillary adiabatic-tissue-homogeneity (DCATH) model. Blind deconvolution is based on Parker's model of the arterial input function. The accuracy and precision of the estimated arterial input functions and the perfusion parameters is evaluated on synthetic and real clinical datasets with different levels of the temporal resolution.

Results: The estimated arterial input functions remained unchanged from their reference high-temporal-resolution estimates (obtained with the sampling interval around 1 s) when increasing the sampling interval up to about 5 s for synthetic data and up to 3.6-4.8 s for real data. 

17 Apr

Weak coupling of neurons enables very high-frequency and ultra-fast oscillations through the interplay of synchronized phase shifts

Recently, in the past decade, high-frequency oscillations (HFOs), very high-frequency oscillations (VHFOs), and ultra-fast oscillations (UFOs) were reported in epileptic patients with drug-resistant epilepsy. However, to this day, the physiological origin of these events has yet to be understood. Our study establishes a mathematical framework based on bifurcation theory for investigating the occurrence of VHFOs and UFOs in depth EEG signals of patients with focal epilepsy, focusing on the potential role of reduced connection strength between neurons in an epileptic focus. We demonstrate that synchronization of a weakly coupled network can generate very and ultra high-frequency signals detectable by nearby microelectrodes. In particular, we show that a bistability region enables the persistence of phase-shift synchronized clusters of neurons. This phenomenon is observed for different hippocampal neuron models, including Morris-Lecar, Destexhe-Paré, and an interneuron model. The mechanism seems to be robust for small coupling, and it also persists with random noise affecting the external current. Our findings suggest that weakened neuronal connections could contribute to the production of oscillations with frequencies above 1000 Hz, which could advance our understanding of epilepsy pathology and potentially improve treatment strategies.