Variational Autoencoder Modular Bayesian Networks for Simulation of Heterogeneous Clinical Study Data.

In the area of Big Data, one of the major obstacles for the progress of biomedical research is the existence of data "silos" because legal and ethical constraints often do not allow for sharing sensitive patient data from clinical studies across institutions. While federated machine learning now allows for building models from scattered data of the same format, there is still the need to investigate, mine, and understand data of separate and very differently designed clinical studies that can only be accessed within each of the data-hosting organizations. Simulation of sufficiently realistic virtual patients based on the data within each individual organization could be a way to fill this gap. In this work, we propose a new machine learning approach [Variational Autoencoder Modular Bayesian Network (VAMBN)] to learn a generative model of longitudinal clinical study data. VAMBN considers typical key aspects of such data, namely limited sample size coupled with comparable many variables of different numerical scales and statistical properties, and many missing values. We show that with VAMBN, we can simulate virtual patients in a sufficiently realistic manner while making theoretical guarantees on data privacy. In addition, VAMBN allows for simulating counterfactual scenarios. Hence, VAMBN could facilitate data sharing as well as design of clinical trials.

Comparison of view-based and reconstruction-based models of human navigational strategy.

There is good evidence that simple animals, such as bees, use view-based strategies to return to a familiar location, whereas humans might use a 3-D reconstruction to achieve the same goal. Assuming some noise in the storage and retrieval process, these two types of strategy give rise to different patterns of predicted errors in homing. We describe an experiment that can help distinguish between these models. Participants wore a head-mounted display to carry out a homing task in immersive virtual reality. They viewed three long, thin, vertical poles and had to remember where they were in relation to the poles before being transported (virtually) to a new location in the scene from where they had to walk back to the original location. The experiment was conducted in both a rich-cue scene (a furnished room) and a sparse scene (no background and no floor or ceiling). As one would expect, in a rich-cue environment, the overall error was smaller, and in this case, the ability to separate the models was reduced. However, for the sparse-cue environment, the view-based model outperforms the reconstruction-based model. Specifically, the likelihood of the experimental data is similar to the likelihood of samples drawn from the view-based model (but assessed under both models), and this is not true for samples drawn from the reconstruction-based model.

Transition between encoding and consolidation/replay dynamics via cholinergic modulation of CAN current: A modeling study.

Hippocampal place cells that are activated sequentially during active waking get reactivated in a temporally compressed (5-20 times) manner during slow-wave-sleep and quiet waking. The two-stage model of the hippocampus suggests that neural activity during awaking supports encoding function while temporally compressed reactivation (replay) supports consolidation. However, the mechanisms supporting different neural activity with different temporal scales during encoding and consolidation remain unclear. Based on the idea that acetylcholine modulates functional transition between encoding and consolidation, we tested whether the cholinergic modulation may adjust intrinsic network dynamics to support different temporal scales for these two modes of operation. Simulations demonstrate that cholinergic modulation of the calcium activated non-specific cationic (CAN) current and the synaptic transmission may be sufficient to switch the network dynamics between encoding and consolidation modes. When the CAN current is active and the synaptic transmission is suppressed, mimicking the high acetylcholine condition during active waking, a slow propagation of multiple spikes is evident. This activity resembles the firing pattern of place cells and time cells during active waking. On the other hand, when CAN current is suppressed and the synaptic transmission is intact, mimicking the low acetylcholine condition during slow-wave-sleep, a time compressed fast (∼10 times) activity propagation of the same set of cells is evident. This activity resembles the time compressed firing pattern of place cells during replay and pre-play, achieving a temporal compression factor in the range observed in vivo (5-20 times). These observations suggest that cholinergic system could adjust intrinsic network dynamics suitable for encoding and consolidation through the modulation of the CAN current and synaptic conductance in the hippocampus.