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Biology subjects

Wu, Y. E.

Publications and source records attributed to Wu, Y. E..

2 recordsLinked to original sources

Task-space dimensions guide human exploration in complex environments

Efficient exploration is essential for rapid learning in high-dimensional environments, where rewards depend on a sparse and unknown subset of task dimensions. Here, we developed a multidimensional value-learning task in which participants explored without explicit knowledge of the underlying structure. Across multiple task designs, participants consistently demonstrated successful learning under structural uncertainty. Behavioral analyses revealed that over half of participants adopted a structured exploration strategy--Full Dimension Scan (FDS)--with three key properties. First, participants systematically isolated and sampled one candidate dimension at a time, effectively reducing search complexity. Second, FDS was temporally persistent within dimensions while maintaining diverse sampling of feature values, enabling efficient local inference. Third, participants sequentially deployed FDS across dimensions, achieving broad coverage of the task space. Importantly, this strategy transferred across tasks: prior experience in lower-dimensional environments promoted stronger FDS use and improved performance in higher-dimensional settings. Consistent with these findings, a dimension-guided exploration model incorporating dimension-level attentional control best captured human behavior. Together, these results identify dimension-guided exploration as a core principle that transforms high-dimensional search into tractable, structured learning, providing new insight into adaptive behavior in complex environments.

animal behavior and cognition↗

Broad transcriptomic dysregulation across the cerebral cortex in ASD

Classically, psychiatric disorders have been considered to lack defining pathology, but recent work has demonstrated consistent disruption at the molecular level, characterized by transcriptomic and epigenetic alterations.1-3 In ASD, upregulation of microglial, astrocyte, and immune signaling genes, downregulation of specific synaptic genes, and attenuation of regional gene expression differences are observed.1,2,4-6 However, whether these changes are limited to the cortical association areas profiled is unknown. Here, we perform RNA-sequencing (RNA-seq) on 725 brain samples spanning 11 distinct cortical areas in 112 ASD cases and neurotypical controls. We identify substantially more genes and isoforms that differentiate ASD from controls than previously observed. These alterations are pervasive and cortex-wide, but vary in magnitude across regions, roughly showing an anterior to posterior gradient, with the strongest signal in visual cortex, followed by parietal cortex and the temporal lobe. We find a notable enrichment of ASD genetic risk variants among cortex-wide downregulated synaptic plasticity genes and upregulated protein folding gene isoforms. Finally, using snRNA-seq, we determine that regional variation in the magnitude of transcriptomic dysregulation reflects changes in cellular proportion and cell-type-specific gene expression, particularly impacting L3/4 excitatory neurons. These results highlight widespread, genetically-driven neuronal dysfunction as a major component of ASD pathology in the cerebral cortex, extending beyond association cortices to involve primary sensory regions.

neuroscience↗