A Learnable Counter-Condition Analysis Framework for Functional Connectivity-Based Neurological Disorder Diagnosis.

To understand the biological characteristics of neurological disorders with functional connectivity (FC), recent studies have widely utilized deep learning-based models to identify the disease and conducted post-hoc analyses via explainable models to discover disease-related biomarkers. Most existing frameworks consist of three stages, namely, feature selection, feature extraction for classification, and analysis, where each stage is implemented separately. However, if the results at each stage lack reliability, it can cause misdiagnosis and incorrect analysis in afterward stages. In this study, we propose a novel unified framework that systemically integrates diagnoses (i.e., feature selection and feature extraction) and explanations. Notably, we devised an adaptive attention network as a feature selection approach to identify individual-specific disease-related connections. We also propose a functional network relational encoder that summarizes the global topological properties of FC by learning the inter-network relations without pre-defined edges between functional networks. Last but not least, our framework provides a novel explanatory power for neuroscientific interpretation, also termed counter-condition analysis. We simulated the FC that reverses the diagnostic information (i.e., counter-condition FC): converting a normal brain to be abnormal and vice versa. We validated the effectiveness of our framework by using two large resting-state functional magnetic resonance imaging (fMRI) datasets, Autism Brain Imaging Data Exchange (ABIDE) and REST-meta-MDD, and demonstrated that our framework outperforms other competing methods for disease identification. Furthermore, we analyzed the disease-related neurological patterns based on counter-condition analysis.

EAG-RS: A Novel Explainability-Guided ROI-Selection Framework for ASD Diagnosis via Inter-Regional Relation Learning.

Deep learning models based on resting-state functional magnetic resonance imaging (rs-fMRI) have been widely used to diagnose brain diseases, particularly autism spectrum disorder (ASD). Existing studies have leveraged the functional connectivity (FC) of rs-fMRI, achieving notable classification performance. However, they have significant limitations, including the lack of adequate information while using linear low-order FC as inputs to the model, not considering individual characteristics (i.e., different symptoms or varying stages of severity) among patients with ASD, and the non-explainability of the decision process. To cover these limitations, we propose a novel explainability-guided region of interest (ROI) selection (EAG-RS) framework that identifies non-linear high-order functional associations among brain regions by leveraging an explainable artificial intelligence technique and selects class-discriminative regions for brain disease identification. The proposed framework includes three steps: (i) inter-regional relation learning to estimate non-linear relations through random seed-based network masking, (ii) explainable connection-wise relevance score estimation to explore high-order relations between functional connections, and (iii) non-linear high-order FC-based diagnosis-informative ROI selection and classifier learning to identify ASD. We validated the effectiveness of our proposed method by conducting experiments using the Autism Brain Imaging Database Exchange (ABIDE) dataset, demonstrating that the proposed method outperforms other comparative methods in terms of various evaluation metrics. Furthermore, we qualitatively analyzed the selected ROIs and identified ASD subtypes linked to previous neuroscientific studies.

Module of Axis-based Nexus Attention for weakly supervised object localization.

Weakly supervised object localization tasks remain challenging to identify and segment an entire object rather than only discriminative parts of the object. To tackle this problem, corruption-based approaches have been devised, which involve the training of non-discriminative regions by corrupting (e.g., erasing) the input images or intermediate feature maps. However, this approach requires an additional hyperparameter, the corrupting threshold, to determine the degree of corruption and can unfavorably disrupt training. It also tends to localize object regions coarsely. In this paper, we propose a novel approach, Module of Axis-based Nexus Attention (MoANA), which helps to adaptively activate less discriminative regions along with the class-discriminative regions without an additional hyperparameter, and elaborately localizes an entire object. Specifically, MoANA consists of three mechanisms (1) triple-view attentions representation, (2) attentions expansion, and (3) features calibration mechanism. Unlike other attention-based methods that train a coarse attention map with the same values across elements in feature maps, MoANA trains fine-grained values in an attention map by assigning different attention values to each element. We validated MoANA by comparing it with various methods. We also analyzed the effect of each component in MoANA and visualized attention maps to provide insights into the calibration.

Site-Invariant Meta-Modulation Learning for Multisite Autism Spectrum Disorders Diagnosis.

Large amounts of fMRI data are essential to building generalized predictive models for brain disease diagnosis. In order to conduct extensive data analysis, it is often necessary to gather data from multiple organizations. However, the site variation inherent in multisite resting-state functional magnetic resonance imaging (rs-fMRI) leads to unfavorable heterogeneity in data distribution, negatively impacting the identification of biomarkers and the diagnostic decision. Several existing methods have alleviated this shift of domain distribution (i.e., multisite problem). Statistical tuning schemes directly regress out site disparity factors from the data prior to model training. Such methods have a limitation in processing data each time through variance estimation according to the added site. In the model adjustment approaches, domain adaptation (DA) methods adjust the features or models of the source domain according to the target domain during model training. Thus, it is inevitable that it needs updating model parameters according to the samples of a target site, causing great limitations in practical applicability. Meanwhile, the approach of domain generalization (DG) aims to create a universal model that can be quickly adapted to multiple domains. In this study, we propose a novel framework for disease diagnosis that alleviates the multisite problem by adaptively calibrating site-specific features into site-invariant features. Specifically, it applies directly to samples from unseen sites without the need for fine-tuning. With a learning-to-learn strategy that learns how to calibrate the features under the various domain shift environments, our novel modulation mechanism extracts site-invariant features. In our experiments over the Autism Brain Imaging Data Exchange (ABIDE I and II) dataset, we validated the generalization ability of the proposed network by improving diagnostic accuracy in both seen and unseen multisite samples.

Long-term renal outcomes of patients with non-proliferative lupus nephritis.

BACKGROUND/AIMS: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. METHODS: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. RESULTS: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI 0.949-0.991; p = 0.014) was significantly associated with poor renal outcomes. CONCLUSION: Poor renal outcomes occurred in approximately 30% of patients with non-proliferative LN after long-term follow-up. More active management may be needed for non-proliferative LN, especially for patients with eGFR < 60 mL/ min/1.73 m2 at 6 months follow-up after LN diagnosis.

Altered functional connectivity in psychotic disorder not otherwise specified.

BACKGROUND: Few studies have investigated functional connectivity (FC) in patients with psychotic disorder not otherwise specified (PNOS). We sought to identify distinct FC differentiating PNOS from schizophrenia (SZ). METHODS: In total, 49 patients with PNOS, 42 with SZ, and 55 healthy controls (HC) matched for age, sex, and education underwent functional magnetic resonance imaging (fMRI) brain scans and clinical evaluation. Using six functional networks consisting of 40 regions of interest (ROIs), we conducted ROI to ROI and intra- and inter-network FC analyses using resting-state fMRI (rs-fMRI) data. Correlations of altered FC with symptomatology were explored. RESULTS: We found common brain connectomics in PNOS and SZ including thalamo-cortical (especially superior temporal gyrus) hyperconnectivity, thalamo-cerebellar hypoconnectivity, and reduced within-thalamic connectivity compared to HC. Additionally, features differentiating the two patient groups included hyperconnectivity between the thalamic subregion and anterior cingulate cortex in PNOS compared to SZ and hyperconnectivity of the thalamic subregions with the posterior cingulate cortex and precentral gyrus in SZ compared to PNOS. CONCLUSIONS: These findings suggest that PNOS and SZ exhibit both common and differentiating changes in neuronal connectivity. Furthermore, they may support the hypothesis that PNOS should be treated as a separate clinical syndrome with distinct neural connectomics.

A unified framework for personalized regions selection and functional relation modeling for early MCI identification.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely adopted to investigate functional abnormalities in brain diseases. Rs-fMRI data is unsupervised in nature because the psychological and neurological labels are coarse-grained, and no accurate region-wise label is provided along with the complex co-activities of multiple regions. To the best of our knowledge, most studies regarding univariate group analysis or multivariate pattern recognition for brain disease identification have focused on discovering functional characteristics shared across subjects; however, they have paid less attention to individual properties of neural activities that result from different symptoms or degrees of abnormality. In this work, we propose a novel framework that can identify subjects with early-stage mild cognitive impairment (eMCI) and consider individual variability by learning functional relations from automatically selected regions of interest (ROIs) for each subject concurrently. In particular, we devise a deep neural network composed of a temporal embedding module, an ROI selection module, and a disease-identification module. Notably, the ROI selection module is equipped with a reinforcement learning mechanism so it adaptively selects ROIs to facilitate the learning of discriminative feature representations from a temporally embedded blood-oxygen-level-dependent signals. Furthermore, our method allows us to capture the functional relations of a subject-specific ROI subset through the use of a graph-based neural network. Our method considers individual characteristics for diagnosis, as opposed to most conventional methods that identify the same biomarkers across subjects within a group. Based on the ADNI cohort, we validate the effectiveness of our method by presenting the superior performance of our network in eMCI identification. Furthermore, we provide insightful neuroscientific interpretations by analyzing the regions selected for the eMCI classification.

Modeling regional dynamics in low-frequency fluctuation and its application to Autism spectrum disorder diagnosis.

With the advent of neuroimaging techniques, many studies in the literature have validated the use of resting-state fMRI (rs-fMRI) for understanding functional mechanisms of the brain, as well as for identifying brain disorders or diseases. One of the main streams in recent studies of modeling and analyzing rs-fMRI data is to account for the dynamic characteristics of a brain. In this study, we propose a novel method that directly models the regional temporal BOLD fluctuations in a stochastic manner and estimates the dynamic characteristics in the form of likelihoods. Specifically, we modeled temporal BOLD fluctuation of individual Regions Of Interest (ROIs) by means of Hidden Markov Models (HMMs), and then estimated the 'goodness-of-fit' of each ROI's BOLD signals to the corresponding trained HMM in terms of a likelihood. Using estimated likelihoods of the ROIs over the whole brain as features, we built a classifier that can discriminate subjects with Autism Spectrum Disorder (ASD) from Typically Developing (TD) controls at an individual level. In order to interpret the trained HMMs and a classifier from a neuroscience perspective, we also conducted model analysis. First, we investigated the learned weight coefficients of a classifier by transforming them into activation patterns, from which we could identify the ROIs that are highly associated with ASD and TD groups. Second, we explored the characteristics of temporal BOLD signals in terms of functional networks by clustering them based on sequences of the hidden states decoded with the trained HMMs. We validated the effectiveness of the proposed method by achieving the state-of-the-art performance on the ABIDE dataset and observed insightful patterns related to ASD.