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Park, H.-B.

Publications and source records attributed to Park, H.-B..

2 recordsLinked to original sources

Fast Capture, Slow Shift: How Working Memory Guides Perception

The top-down influence of working memory (WM) can manifest as both attentional capture and small systematic biases in perceptual judgment (i.e., "tinted lens" effect). Yet it remains unclear whether these influences arise from a single mechanism or reflect functionally distinct processes operating over different timescales. Across two experiments, we embedded a perceptual estimation task during the delay interval of a WM task and recorded time-resolved mouse trajectories during both perceptual matching and subsequent WM tests. Hierarchical Bayesian mixture modeling revealed robust bidirectional attraction between memory and perception. Time-resolved analyses of mouse trajectories further revealed two distinct components: an early, endpoint-inconsistent deviation that varied with movement onset latency, and a slower, endpoint-consistent drift that closely tracked biases in the final report. This pattern is consistent with a fast, capture-like influence of the WM template, and a sustained bias in the evolving decision, respectively. Notably, the prospective influence of WM on perception expressed both early deviation and sustained drift, whereas the retrospective influence of perception on WM primarily involved the sustained component. These findings indicate that WM shapes perceptual decisions through at least two temporally distinct contributions, and illustrate how time-resolved trajectories can reveal the dynamic structure of top-down influences within single trials.

neuroscience↗

Targeted degradation of pathologic tau aggregates via AUTOTAC ameliorates tauopathy

The pathogenesis of tauopathies including Alzheimers disease (AD) and progressive supranuclear palsy (PSP) involves the misfolding and aggregation of tau. Here, we employed AUTOTAC to induce the lysosomal degradation of intraneuronal tau aggregates. ATB2005A is a 734-Da chimera that simultaneously binds {beta}-sheet-rich tau aggregates and the autophagic receptor p62/SQSTM1, leading to autophagosomal sequestration and lysosomal co-degradation. In mouse models of tauopathies, orally administered ATB2005A lowered intraneuronal tau aggregates and exerted the therapeutic efficacy in neuroinflammation as well as cognition, behavior, and muscle movements. A Phase 2 clinical trial (U34401-4/2023/14) with companion dogs carrying canine cognitive dysfunction (CCD) demonstrated the efficacy of ATB2005A, as a veterinary medicine, to reverse the disease progression. ATB2005A is under Phase 1 clinical trial with human participants in Korea (202300697). These results validate AUTOTAC as a versatile platform for developing therapeutics to eradicate toxic protein aggregates in a wide range of proteinopathies.

neuroscience↗