Bobby Thomas

We study the wisdom of the crowd in three sequential decision‐making tasks: the Balloon Analogue Risk Task (BART), optimal stopping problems, and bandit problems. We consider a behavior‐based approach, using majority decisions to determine crowd behavior and show that this approach performs poorly in the BART and bandit tasks. The key problem is that the crowd becomes progressively more extreme as the decision sequence progresses, because the diversity of opinion that underlies the wisdom of the crowd is lost. We also consider model‐based approaches to each task. This involves inferring cognitive models for each individual based on their observed behavior, and using these models to predict what each individual would do in any possible task situation. We show that this approach performs robustly well for all three tasks and has the additional advantage of being able to generalize to new problems for which there are no behavioral data. We discuss potential applications of the model‐based approach to real‐world sequential decision problems and discuss how our approach contributes to the understanding of collective intelligence.

The transcription factor Nrf2 is the master regulator of cellular stress response, facilitating the expression of cytoprotective genes, including those responsible for drug detoxification, immunomodulation, and iron metabolism. FDA‐approved Nrf2 activators, Tecfidera and Skyclarys for patients with multiple sclerosis and Friedreich's ataxia, respectively, are non‐specific alkylating agents exerting side effects. Nrf2 is under feedback regulation through its target gene, transcriptional repressor Bach1. Specifically, in Parkinson's disease and other neurodegenerative diseases with Bach1 dysregulation, excessive Bach1 accumulation interferes with Nrf2 activation. Bach1 is a heme sensor protein, which, upon heme binding, is targeted for proteasomal degradation, relieving the repression of Nrf2 target genes. Ideally, a combination of Nrf2 stabilization and Bach1 inhibition is necessary to achieve the full therapeutic benefits of Nrf2 activation. Here, we discuss recent advances and future perspectives in developing small molecule inhibitors of Bach1, highlighting the significance of the Bach1/Nrf2 signaling pathway as a promising neurotherapeutic strategy.