An explainable deep learning framework for characterizing and interpreting human brain states.

Deep learning approaches have been widely adopted in the medical image analysis field. However, a most of existing deep learning approaches focus on achieving promising performances such as classification, detection, and segmentation, and much less effort is devoted to the explanation of the designed models. Similarly, in the brain imaging field, many deep learning approaches have been designed and applied to characterize and predict human brain states. However, these models lack interpretation. In response, we propose a novel domain knowledge informed self-attention graph pooling-based (SAGPool) graph convolutional neural network to study human brain states. Specifically, the dense individualized and common connectivity-based cortical landmarks system (DICCCOL, structural brain connectivity profiles) and holistic atlases of functional networks and interactions system (HAFNI, functional brain connectivity profiles) are integrated with the SAGPool model to better characterize and interpret the brain states. Extensive experiments are designed and carried out on the large-scale human connectome project (HCP) Q1 and S1200 dataset. Promising brain state classification performances are observed (e.g., an average of 93.7% for seven-task classification and 100% for binary classification). In addition, the importance of the brain regions, which contributes most to the accurate classification, is successfully quantified and visualized. A thorough neuroscientific interpretation suggests that these extracted brain regions and their importance calculated from self-attention graph pooling layer offer substantial explainability.

Modeling spatio-temporal patterns of holistic functional brain networks via multi-head guided attention graph neural networks (Multi-Head GAGNNs).

Mounting evidence has demonstrated that complex brain function processes are realized by the interaction of holistic functional brain networks which are spatially distributed across specific brain regions in a temporally dynamic fashion. Therefore, modeling spatio-temporal patterns of holistic functional brain networks plays an important role in understanding brain function. Compared to traditional modeling methods such as principal component analysis, independent component analysis, and sparse coding, superior performance has been achieved by recent deep learning methodologies. However, there are still two limitations of existing deep learning approaches for functional brain network modeling. They either (1) merely modeled a single targeted network and ignored holistic ones at one time, or (2) underutilized both spatial and temporal features of fMRI during network modeling, and the spatial/temporal accuracy was thus not warranted. To address these limitations, we proposed a novel Multi-Head Guided Attention Graph Neural Network (Multi-Head GAGNN) to simultaneously model both spatial and temporal patterns of holistic functional brain networks. Specifically, a spatial Multi-Head Attention Graph U-Net was first adopted to model the spatial patterns of multiple brain networks, and a temporal Multi-Head Guided Attention Network was then introduced to model the corresponding temporal patterns under the guidance of modeled spatial patterns. Based on seven task fMRI datasets from the public Human Connectome Project and resting state fMRI datasets from the public Autism Brain Imaging Data Exchange I of 1448 subjects, the proposed Multi-Head GAGNN showed superior ability and generalizability in modeling both spatial and temporal patterns of holistic functional brain networks in individual brains compared to other state-of-the-art (SOTA) models. Furthermore, the modeled spatio-temporal patterns of functional brain networks via the proposed Multi-Head GAGNN can better predict the individual cognitive behavioral measures compared to the other SOTA models. This study provided a novel and powerful tool for brain function modeling as well as for understanding the brain-cognitive behavior associations.

The effects of lutein and zeaxanthin on resting state functional connectivity in older Caucasian adults: a randomized controlled trial.

The carotenoids lutein (L) and zeaxanthin (Z) accumulate in retinal regions of the eye and have long been shown to benefit visual health. A growing literature suggests cognitive benefits as well, particularly in older adults. The present randomized controlled trial sought to investigate the effects of L and Z on brain function using resting state functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation would (1) improve intra-network integrity of default mode network (DMN) and (2) reduce inter-network connectivity between DMN and other resting state networks. 48 community-dwelling older adults (mean age = 72 years) were randomly assigned to receive a daily L (10 mg) and Z (2 mg) supplement or a placebo for 1 year. Resting state fMRI data were acquired at baseline and post-intervention. A dictionary learning and sparse coding computational framework, based on machine learning principles, was used to investigate intervention-related changes in functional connectivity. DMN integrity was evaluated by calculating spatial overlap rate with a well-established DMN template provided in the neuroscience literature. Inter-network connectivity was evaluated via time series correlations between DMN and nine other resting state networks. Contrary to expectation, results indicated that L and Z significantly increased rather than decreased inter-network connectivity (Cohen's d = 0.89). A significant intra-network effect on DMN integrity was not observed. Rather than restoring what has been described in the available literature as a "youth-like" pattern of intrinsic brain activity, L and Z may facilitate the aging brain's capacity for compensation by enhancing integration between networks that tend to be functionally segregated earlier in the lifespan.

Joint representation of connectome-scale structural and functional profiles for identification of consistent cortical landmarks in macaque brain.

Discovery and representation of common structural and functional cortical architectures has been a significant yet challenging problem for years. Due to the remarkable variability of structural and functional cortical architectures in human brain, it is challenging to jointly represent a common cortical architecture which can comprehensively encode both structure and function characteristics. In order to better understand this challenge and considering that macaque monkey brain has much less variability in structure and function compared with human brain, in this paper, we propose a novel computational framework to apply our DICCCOL (Dense Individualized and Common Connectivity-based Cortical Landmarks) and HAFNI (Holistic Atlases of Functional Networks and Interactions) frameworks on macaque brains, in order to jointly represent structural and functional connectome-scale profiles for identification of a set of consistent and common cortical landmarks across different macaque brains based on multimodal DTI and resting state fMRI (rsfMRI) data. Experimental results demonstrate that 100 consistent and common cortical landmarks are successfully identified via the proposed framework, each of which has reasonably accurate anatomical, structural fiber connection pattern, and functional correspondences across different macaque brains. This set of 100 landmarks offer novel insights into the structural and functional cortical architectures in macaque brains.

Decoding Auditory Saliency from Brain Activity Patterns during Free Listening to Naturalistic Audio Excerpts.

In recent years, natural stimuli such as audio excerpts or video streams have received increasing attention in neuroimaging studies. Compared with conventional simple, idealized and repeated artificial stimuli, natural stimuli contain more unrepeated, dynamic and complex information that are more close to real-life. However, there is no direct correspondence between the stimuli and any sensory or cognitive functions of the brain, which makes it difficult to apply traditional hypothesis-driven analysis methods (e.g., the general linear model (GLM)). Moreover, traditional data-driven methods (e.g., independent component analysis (ICA)) lack quantitative modeling of stimuli, which may limit the power of analysis models. In this paper, we propose a sparse representation based decoding framework to explore the neural correlates between the computational audio features and functional brain activities under free listening conditions. First, we adopt a biologically-plausible auditory saliency feature to quantitatively model the audio excerpts and meanwhile develop sparse representation/dictionary learning method to learn an over-complete dictionary basis of brain activity patterns. Then, we reconstruct the auditory saliency features from the learned fMRI-derived dictionaries. After that, a group-wise analysis procedure is conducted to identify the associated brain regions and networks. Experiments showed that the auditory saliency feature can be well decoded from brain activity patterns by our methods, and the identified brain regions and networks are consistent and meaningful. At last, our method is evaluated and compared with ICA method and experimental results demonstrated the superiority of our methods.

Holistic atlases of functional networks and interactions reveal reciprocal organizational architecture of cortical function.

For decades, it has been largely unknown to what extent multiple functional networks spatially overlap/interact with each other and jointly realize the total cortical function. Here, by developing novel sparse representation of whole-brain fMRI signals and by using the recently publicly released large-scale Human Connectome Project high-quality fMRI data, we show that a number of reproducible and robust functional networks, including both task-evoked and resting state networks, are simultaneously distributed in distant neuroanatomic areas and substantially spatially overlapping with each other, thus forming an initial collection of holistic atlases of functional networks and interactions (HAFNIs). More interestingly, the HAFNIs revealed two distinct patterns of highly overlapped regions and highly specialized regions and exhibited that these two patterns of areas are reciprocally localized, revealing a novel organizational principle of cortical function.