Inferring Parameters of Pyramidal Neuron Excitability in Mouse Models of Alzheimer's Disease Using Biophysical Modeling and Deep Learning.

Alzheimer's disease (AD) is believed to occur when abnormal amounts of the proteins amyloid beta and tau aggregate in the brain, resulting in a progressive loss of neuronal function. Hippocampal neurons in transgenic mice with amyloidopathy or tauopathy exhibit altered intrinsic excitability properties. We used deep hybrid modeling (DeepHM), a recently developed parameter inference technique that combines deep learning with biophysical modeling, to map experimental data recorded from hippocampal CA1 neurons in transgenic AD mice and age-matched wildtype littermate controls to the parameter space of a conductance-based CA1 model. Although mechanistic modeling and machine learning methods are by themselves powerful tools for approximating biological systems and making accurate predictions from data, when used in isolation these approaches suffer from distinct shortcomings: model and parameter uncertainty limit mechanistic modeling, whereas machine learning methods disregard the underlying biophysical mechanisms. DeepHM addresses these shortcomings by using conditional generative adversarial networks to provide an inverse mapping of data to mechanistic models that identifies the distributions of mechanistic modeling parameters coherent to the data. Here, we demonstrated that DeepHM accurately infers parameter distributions of the conductance-based model on several test cases using synthetic data generated with complex underlying parameter structures. We then used DeepHM to estimate parameter distributions corresponding to the experimental data and infer which ion channels are altered in the Alzheimer's mouse models compared to their wildtype controls at 12 and 24 months. We found that the conductances most disrupted by tauopathy, amyloidopathy, and aging are delayed rectifier potassium, transient sodium, and hyperpolarization-activated potassium, respectively.

Graph Trilateration for Indoor Localization in Sparsely Distributed Edge Computing Devices in Complex Environments Using Bluetooth Technology.

Spatial navigation patterns in indoor space usage can reveal important cues about the cognitive health of participants. In this work, we present a low-cost, scalable, open-source edge computing system using Bluetooth low energy (BLE) beacons for tracking indoor movements in a large, 1700 m2 facility used to carry out therapeutic activities for participants with mild cognitive impairment (MCI). The facility is instrumented with 39 edge computing systems, along with an on-premise fog server. The participants carry a BLE beacon, in which BLE signals are received and analyzed by the edge computing systems. Edge computing systems are sparsely distributed in the wide, complex indoor space, challenging the standard trilateration technique for localizing subjects, which assumes a dense installation of BLE beacons. We propose a graph trilateration approach that considers the temporal density of hits from the BLE beacon to surrounding edge devices to handle the inconsistent coverage of edge devices. This proposed method helps us tackle the varying signal strength, which leads to intermittent detection of beacons. The proposed method can pinpoint the positions of multiple participants with an average error of 4.4 m and over 85% accuracy in region-level localization across the entire study area. Our experimental results, evaluated in a clinical environment, suggest that an ordinary medical facility can be transformed into a smart space that enables automatic assessment of individuals' movements, which may reflect health status or response to treatment.

The emergence of polyglot entrainment responses to periodic inputs in vicinities of Hopf bifurcations in slow-fast systems.

Several distinct entrainment patterns can occur in the FitzHugh-Nagumo (FHN) model under external periodic forcing. Investigating the FHN model under different types of periodic forcing reveals the existence of multiple disconnected 1:1 entrainment segments for constant, low enough values of the input amplitude when the unforced system is in the vicinity of a Hopf bifurcation. This entrainment structure is termed polyglot to distinguish it from the single 1:1 entrainment region (monoglot) structure typically observed in Arnold tongue diagrams. The emergence of polyglot entrainment is then explained using phase-plane analysis and other dynamical system tools. Entrainment results are investigated for other slow-fast systems of neuronal, circadian, and glycolytic oscillations. Exploring these models, we found that polyglot entrainment structure (multiple 1:1 regions) is observed when the unforced system is in the vicinity of a Hopf bifurcation and the Hopf point is located near a knee of a cubic-like nullcline.