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Applebaum, A.

Publications and source records attributed to Applebaum, A..

2 recordsLinked to original sources

The Body Knows Better: Sensorimotor signals reveal "Suboptimal" inference of the Sense of Agency in the human mind

Sense of Agency (SoA) is the feeling of control over our actions. SoA has been suggested to arise from both implicit sensorimotor integration as well as higher-level decision processes. SoA is typically measured by collecting participants subjective judgments, conflating both implicit and explicit processing. Consequently, the interplay between implicit sensorimotor processing and explicit agency judgments is not well understood. Here, we evaluated in one exploratory and one preregistered experiment (N=60), using a machine learning approach, the relation between a well-known mechanism of implicit sensorimotor adaptation and explicit SoA judgments. Specifically, we examined whether subjective judgments of SoA and sensorimotor conflicts could be inferred from hand kinematics in a sensorimotor task using a virtual hand (VH). In both experiments participants performed a hand movement and viewed a virtual hand making a movement that could either be synchronous with their action or include a parametric temporal delay. After each movement, participants judged whether their actual movement was congruent with the movement they observed. Our results demonstrated that sensorimotor conflicts could be inferred from implicit motor kinematics on a trial by trial basis. Moreover, detection of sensorimotor conflicts from machine learning models of kinematic data provided more accurate classification of sensorimotor congruence than participants explicit judgments. These results were replicated in a second, preregistered, experiment. These findings show evidence of diverging implicit and explicit processing for SoA and suggest that the brain holds high-quality information on sensorimotor conflicts that is not fully utilized in the inference of conscious agency.

neuroscience↗

Huntingtin fibrils with different toxicity, structure, and seeding potential can be reversibly interconverted

The first exon of the huntingtin protein (HTTex1) important in Huntingtons Disease (HD) can form cross-{beta} fibrils of varying toxicity. We find that the difference between these fibrils is the degree of entanglement and dynamics of the C-terminal proline-rich domain (PRD) in a mechanism analogous to polyproline film formation. In contrast to fibril strains found for other cross-{beta} fibrils, these HTTex1 fibril types can be reversibly interconverted. This is because the structure of their polyQ fibril core remains unchanged. Further, we find that more toxic fibrils of low entanglement have higher affinities for protein interactors and are more effective seeds for recombinant HTTex1 and HTTex1 in cells. Together these data show how the structure of a framing sequence at the surface of a fibril can modulate seeding, protein-protein interactions, and thereby toxicity in neurodegenerative disease.

biophysics↗