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Biology subjects

Guy, N.

Publications and source records attributed to Guy, N..

3 recordsLinked to original sources

Visual and auditory deep learning models capture neural representations of naturalistic social interaction in the superior temporal sulcus

The superior temporal sulcus (STS) is selectively responsive to multimodal social interactions. Yet studies so far have relied on pre-defined, simplified stimuli or features to uncover the type of information that drives STS activity. We hypothesized that high-dimensional representations from visual and auditory deep learning models would better predict STS responses to naturalistic social interactions. We used self-supervised visual and auditory deep learning models to extract representations of movie frames and audio, respectively, of a TV series participants watched during fMRI scanning. Voxel-wise encoding models of a joint visual-auditory representation outperformed human-made social-affective annotations in predicting STS. Variance partition further revealed visual-auditory posterior-to-anterior gradient within the STS. To interpret what these models encode, we applied Principal Component Analysis to the encoding model weights. In both the visual and auditory models the first dimension tracked social interaction and peaked in the STS, indicating that social interaction is a dominant dimension of STS representation across both modalities. We conclude that the STS represents naturalistic social interaction in a multimodal manner, integrating visual and auditory information, and that visual and auditory deep learning models capture key representational properties of these responses.

neuroscience↗

Concurrent emergence of view invariance, sensitivity to critical features, and identity face classification through visual experience: Insights from deep learning algorithms

Visual experience is known to play a critical role in face recognition. This experience is believed to enable the formation of a view-invariant representation, by learning which features are critical for face identification across views. Discovering these critical features and the type of experience that is needed to uncover them is challenging. We have recently revealed a subset of facial features that are critical for human face recognition. We further revealed that deep convolutional neural networks (DCNNs) that are trained on face classification, but not on object categorization, are sensitive to these facial features, highlighting the importance of experience with faces for the system to reveal these critical features. These findings enable us now to ask what type of experience with faces is required for the network to become sensitive to these human-like critical features and whether it is associated with the formation of a view-invariant representation and face classification performance. To that end, we systematically manipulated the number of within-identity and between-identity face images and examined its effect on the network performance on face classification, view-invariant representation, and sensitivity to human-like critical facial features. Results show that increasing the number of images per identity as well as the number of identities were both required for the simultaneous development of a view-invariant representation, sensitivity to human-like critical features, and successful identity classification. The concurrent emergence of sensitivity to critical features, view invariance and classification performance through experience implies that they depend on similar features. Overall, we show how systematic manipulation of the training diet of DCNNs can shed light on the role of experience on the generation of human-like representations.

neuroscience↗

Management of Hsp90-Dependent Protein Folding by Small Molecule Targeting the Aha1 Co-Chaperone

The core cytosolic Hsp90 chaperone/co-chaperone complex plays a critical role in proteostasis management of human health and disease. To identify novel compounds that alter the ability of the Hsp90 co-chaperone Aha1 to modulate the ATPase activity found in multiple folding diseases ranging from steroid hormone receptor (SHR) sensitive prostate cancer to tauopathies associated with neurodegenerative diseases, we employed a high throughput screening (HTS) assay to monitor selectively Aha1-stimulated Hsp90 (ASH) ATPase activity. The ASH assay identified SEW04784 (SEW), a small molecule that disrupts ASH activity without inhibiting the basal Hsp90 ATPase activity. NMR analysis reveals that SEW binds to the C-terminal domain of Aha1 to disrupt its asymmetric binding to Hsp90 leading to abrogation of its chaperoning activity of Hsp90. SEW exhibits therapeutic potential by blocking the transcriptional activity of prostate cancer (PCa) associated variants of the androgen receptor (AR) in a cell-based model of PCa. Additionally, SEW exhibits the ability to clear toxic, phosphorylated tau aggregated species associated with tauopathies. By not directly impacting the basal ATPase function of the abundant and ubiquitous Hsp90, SEW could provide a therapeutic approach for mitigation of client-specific proteostatic disease.

biochemistry↗