Transcriptome and epigenome landscape of human cortical development modeled in organoids

Science

The human cerebral cortex has undergone an extraordinary increase in size and complexity during mammalian evolution. Cortical cell lineages are specified in the embryo, and genetic and epidemiological evidence implicates early cortical development in the etiology of neuropsychiatric disorders such as autism spectrum disorder (ASD), intellectual disabilities, and schizophrenia. Most of the disease-implicated genomic variants are located outside of genes, and the interpretation of noncoding mutations is lagging behind owing to limited annotation of functional elements in the noncoding genome. We set out to discover gene-regulatory elements and chart their dynamic activity during prenatal human cortical development, focusing on enhancers, which carry most of the weight upon regulation of gene expression. We longitudinally modeled human brain development using human induced pluripotent stem cell (hiPSC)–derived cortical organoids and compared organoids to isogenic fetal brain tissue. Fetal fibroblast–derived hiPSC lines were used to generate cortically patterned organoids and to compare oganoids' epigenome and transcriptome to that of isogenic fetal brains and external datasets. Organoids model cortical development between 5 and 16 postconception weeks, thus enabling us to study transitions from cortical stem cells to progenitors to early neurons. The greatest changes occur at the transition from stem cells to progenitors. The regulatory landscape encompasses a total set of 96,375 enhancers linked to target genes, with 49,640 enhancers being active in organoids but not in mid-fetal brain, suggesting major roles in cortical neuron specification. Enhancers that gained activity in the human lineage are active in the earliest stages of organoid development, when they target genes that regulate the growth of radial glial cells. Parallel weighted gene coexpression network analysis (WGCNA) of transcriptome and enhancer activities defined a number of modules of coexpressed genes and coactive enhancers, following just six and four global temporal patterns that we refer to as supermodules, likely reflecting fundamental programs in embryonic and fetal brain. Correlations between gene expression and enhancer activity allowed stratifying enhancers into two categories: activating regulators (A-regs) and repressive regulators (R-regs).


Towards a Quantum-Like Cognitive Architecture for Decision-Making

arXiv.org Artificial Intelligence

We propose an alternative and unifying framework for decision-making that, by using quantum mechanics, provides more generalised cognitive and decision models with the ability to represent more information than classical models. This framework can accommodate and predict several cognitive biases reported in Lieder & Griffiths without heavy reliance on heuristics nor on assumptions of the computational resources of the mind. Expected utility theory and classical probabilities tell us what people should do if employing traditionally rational thought, but do not tell us what people do in reality (Machina, 2009). Under this principle, L&G propose an architecture for cognition that can serve as an intermediary layer between Neuroscience and Computation. Whilst instances where large expenditures of cognitive resources occur are theoretically alluded to, the model primarily assumes a preference for fast, heuristic-based processing.


An Affective Robot Companion for Assisting the Elderly in a Cognitive Game Scenario

arXiv.org Artificial Intelligence

Being able to recognize emotions in human users is considered a highly desirable trait in Human-Robot Interaction (HRI) scenarios. However, most contemporary approaches rarely attempt to apply recognized emotional features in an active manner to modulate robot decision-making and dialogue for the benefit of the user. In this position paper, we propose a method of incorporating recognized emotions into a Reinforcement Learning (RL) based dialogue management module that adapts its dialogue responses in order to attempt to make cognitive training tasks, like the 2048 Puzzle Game, more enjoyable for the users.