Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays

Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.

Recollections on the Origins and Development of the Prosomeric Model

The prosomeric model was postulated jointly by L. Puelles and J. L. R. Rubenstein in 1993 and has been developed since by means of minor changes and a major update in 2012. This article explains the progressive academic and scientific antecedents leading LP to this collaboration and its subsequent developments. Other antecedents due to earlier neuroembryologists that also proposed neuromeric brain models since the late 19th century, as well as those who defended the alternative columnar model, are presented and explained. The circumstances that apparently caused the differential success of the neuromeric models in the recent neurobiological field are also explored.

Towards an Efficient Validation of Dynamical Whole-brain Models

Simulating the resting-state brain dynamics via mathematical whole-brain models requires an optimal selection of parameters, which determine the model’s capability to replicate empirical data. Since the parameter optimization via a grid search (GS) becomes unfeasible for high-dimensional models, we evaluate several alternative approaches to maximize the correspondence between simulated and empirical functional connectivity. A dense GS serves as a benchmark to assess the performance of four optimization schemes: Nelder-Mead Algorithm (NMA), Particle Swarm Optimization (PSO), Covariance Matrix Adaptation Evolution Strategy (CMAES) and Bayesian Optimization (BO). To compare them, we employ an ensemble of coupled phase oscillators built upon individual empirical structural connectivity of 105 healthy subjects. We determine optimal model parameters from two- and three-dimensional parameter spaces and show that the overall fitting quality of the tested methods can compete with the GS. There are, however, marked differences in the required computational resources and stability properties, which we also investigate before proposing CMAES and BO as efficient alternatives to a high-dimensional GS. For the three-dimensional case, these methods generated similar results as the GS, but within less than 6% of the computation time. Our results contribute to an efficient validation of models for personalized simulations of brain dynamics.

Multilayer Network Approach in EEG Motor Imagery with an Adaptive Threshold

The brain has been understood as an interconnected neural network generally modeled as a graph to outline the functional topology and dynamics of brain processes. Classic graph modeling is based on single-layer models that constrain the traits conveyed to trace brain topologies. Multilayer modeling, in contrast, makes it possible to build whole-brain models by integrating features of various kinds. The aim of this work was to analyze EEG dynamics studies while gathering motor imagery data through single-layer and multilayer network modeling. The motor imagery database used consists of 18 EEG recordings of four motor imagery tasks: left hand, right hand, feet, and tongue. Brain connectivity was estimated by calculating the coherence adjacency matrices from each electrophysiological band (δ, θ, α and β) from brain areas and then embedding them by considering each band as a single-layer graph and a layer of the multilayer brain models. Constructing a reliable multilayer network topology requires a threshold that distinguishes effective connections from spurious ones. For this reason, two thresholds were implemented, the classic fixed (average) one and Otsu’s version. The latter is a new proposal for an adaptive threshold that offers reliable insight into brain topology and dynamics. Findings from the brain network models suggest that frontal and parietal brain regions are involved in motor imagery tasks.