Neurons and Cognition (q-bio.NC)

Abstract: Under the framework of network-based neurodegeneration, brain functional connectome (FC)-based Graph Neural Networks (GNN) have emerged as a valuable tool for the diagnosis and prognosis of neurodegenerative diseases such as Alzheimer's disease (AD). However, these models are tailored for brain FC at a single time point instead of characterizing FC trajectory. Discerning how FC evolves with disease progression, particularly at the predementia stages such as cognitively normal individuals with amyloid deposition or individuals with mild cognitive impairment (MCI), is crucial for delineating disease spreading patterns and developing effective strategies to slow down or even halt disease advancement. In this work, we proposed the first interpretable framework for brain FC trajectory embedding with application to neurodegenerative disease diagnosis and prognosis, namely Brain Tokenized Graph Transformer (Brain TokenGT). It consists of two modules: 1) Graph Invariant and Variant Embedding (GIVE) for generation of node and spatio-temporal edge embeddings, which were tokenized for downstream processing; 2) Brain Informed Graph Transformer Readout (BIGTR) which augments previous tokens with trainable type identifiers and non-trainable node identifiers and feeds them into a standard transformer encoder to readout. We conducted extensive experiments on two public longitudinal fMRI datasets of the AD continuum for three tasks, including differentiating MCI from controls, predicting dementia conversion in MCI, and classification of amyloid positive or negative cognitively normal individuals. Based on brain FC trajectory, the proposed Brain TokenGT approach outperformed all the other benchmark models and at the same time provided excellent interpretability. The code is available at https://github.com/ZijianD/Brain-TokenGT.git

Abstract: The topological organization and feature preferences of primate visual area V4 have been primarily studied using artificial stimuli. Here, we combined large-scale calcium imaging with deep learning methods to characterize and understand how V4 processes natural images. By fitting a deep learning model to an unprecedentedly large dataset of columnar scale cortical responses to tens of thousands of natural stimuli and using the model to identify the images preferred by each cortical pixel, we obtained a detailed V4 topographical map of natural stimulus preference. The map contains distinct functional domains preferring a variety of natural image features, ranging from surface-related features such as color and texture to shape-related features such as edge, curvature, and facial features. These predicted domains were verified by additional widefield calcium imaging and single-cell resolution two-photon imaging. Our study reveals the systematic topological organization of V4 for encoding image features in natural scenes.