A Generative-Discriminative Basis Learning Framework to Predict Clinical Severity from Resting State Functional MRI Data

We propose a matrix factorization technique that decomposes the resting state fMRI (rs-fMRI) correlation matrices for a patient population into a sparse set of representative subnetworks, as modeled by rank one outer products. The subnetworks are combined using patient specific non-negative coefficients; these coefficients are also used to model, and subsequently predict the clinical severity of a given patient via a linear regression. Our generative-discriminative framework is able to exploit the structure of rs-fMRI correlation matrices to capture group level effects, while simultaneously accounting for patient variability. We employ ten fold cross validation to demonstrate the predictive power of our model on a cohort of fifty eight patients diagnosed with Autism Spectrum Disorder. Our method outperforms classical semi-supervised frameworks, which perform dimensionality reduction on the correlation features followed by non-linear regression to predict the clinical scores

Spatial parcellations, spectral filtering, and connectivity measures in fMRI: Optimizing for discrimination.

The analysis of Functional Connectivity (FC) is a key technique of fMRI, having been used to distinguish brain states and conditions. While many approaches to calculating FC are available, there have been few assessments of their differences, making it difficult to choose approaches and compare results. Here, we assess the impact of methodological choices on discriminability, using a fully controlled dataset of continuous active states involving basic visual and motor tasks, providing robust localized FC changes. We tested a range of anatomical and functional parcellations, including the AAL atlas, parcellations derived from the Human Connectome Project and Independent Component Analysis (ICA) of many dimensionalities. We measure amplitude, covariance, correlation and regularized partial correlation under different temporal filtering choices. We evaluate features derived from these methods for discriminating states using MVPA. We find that multidimensional parcellations derived from functional data performed similarly, outperforming an anatomical atlas, with correlation and partial correlation (p<0.05, FDR). Partial correlation, with appropriate regularization, outperformed correlation. Amplitude and covariance generally discriminated less well, although gave good results with high-dimensionality ICA. We found that discriminative FC properties are frequency specific; higher frequencies performed surprisingly well under certain configurations of atlas choices and dependency measures, with ICA-based parcellations revealing greater discriminability at high frequencies compared to other parcellations. Methodological choices in FC analyses can have a profound impact on results and can be selected to optimize accuracy, interpretability, and sharing of results. This work contributes to a basis for consistent selection of approaches to estimating and analyzing FC

Machine Learning Methods for Depression Detection Using SMRI and RS-FMRI Images

Major Depression Disorder (MDD) is a common disease throughout the world that negatively influences people’s lives. Early diagnosis of MDD is beneficial, so detecting practical biomarkers would aid clinicians in the diagnosis of MDD. Having an automated method to find biomarkers for MDD is helpful even though it is difficult. The main aim of this research is to generate a method for detecting discriminative features for MDD diagnosis based on Magnetic Resonance Imaging (MRI) data. In this research, representational similarity analysis provides a framework to compare distributed patterns and obtain the similarity/dissimilarity of brain regions. Regions are obtained by either data-driven or model-driven methods such as cubes and atlases respectively. For structural MRI (sMRI) similarity of voxels of spatial cubes (data-driven) are explored. For resting-state fMRI (rs-fMRI) images, the similarity of the time series of both cubes (data-driven) and atlases (model-driven) are examined. Moreover, the similarity method of the inverse of Minimum Covariant Determinant is applied that excludes outliers from patterns and finds conditionally independent regions given the rest of regions. Next, a statistical test that is robust to outliers, identifies discriminative similarity features between two groups of MDDs and controls. Therefore, the key contribution is the way to get discriminative features that include obtaining similarity of voxel’s cubes/time series using the inverse of robust covariance along with the statistical test. The experimental results show that obtaining these features along with the Bernoulli Naïve Bayes classifier achieves superior performance compared with other methods. The performance of our method is verified by applying it to three imbalanced datasets. Moreover, the similarity-based methods are compared with deep learning and regional-based approaches for detecting MDD using either sMRI or rs-fMRI. Given that depression is famous to be a connectivity disorder problem, investigating the similarity of the brain’s regions is valuable to understand the behavior of the brain. The combinations of structural and functional brain similarities are explored to investigate the brain’s structural and functional properties together. Moreover, the combination of data-driven (cube) and model-driven (atlas) similarities of rs-fMRI are looked over to evaluate how they affect the performance of the classifier. Besides, discriminative similarities are visualized for both sMRI and rs-fMRI. Also, to measure the informativeness of a cube, the relationship of atlas regions with overlapping cubes and vise versa (cubes with overlapping regions) are explored and visualized. Furthermore, the relationship between brain structure and function has been probed through common similarities between structural and resting-state functional networks

The Expert Knowledge combined with AI outperforms AI Alone in Seizure Onset Zone Localization using resting state fMRI

We evaluated whether integration of expert guidance on seizure onset zone (SOZ) identification from resting state functional MRI (rs-fMRI) connectomics combined with deep learning (DL) techniques enhances the SOZ delineation in patients with refractory epilepsy (RE), compared to utilizing DL alone. Rs-fMRI were collected from 52 children with RE who had subsequently undergone ic-EEG and then, if indicated, surgery for seizure control (n = 25). The resting state functional connectomics data were previously independently classified by two expert epileptologists, as indicative of measurement noise, typical resting state network connectivity, or SOZ. An expert knowledge integrated deep network was trained on functional connectomics data to identify SOZ. Expert knowledge integrated with DL showed a SOZ localization accuracy of 84.8& and F1 score, harmonic mean of positive predictive value and sensitivity, of 91.7%. Conversely, a DL only model yielded an accuracy of less than 50% (F1 score 63%). Activations that initiate in gray matter, extend through white matter and end in vascular regions are seen as the most discriminative expert identified SOZ characteristics. Integration of expert knowledge of functional connectomics can not only enhance the performance of DL in localizing SOZ in RE, but also lead toward potentially useful explanations of prevalent co-activation patterns in SOZ. RE with surgical outcomes and pre-operative rs-fMRI studies can yield expert knowledge most salient for SOZ identification.Comment: Accepted in Frontiers in Neurology journal, section Artificial Intelligenc

High Classification Accuracy for Schizophrenia with Rest and Task fMRI Data

We present a novel method to extract classification features from functional magnetic resonance imaging (fMRI) data collected at rest or during the performance of a task. By combining a two-level feature identification scheme with kernel principal component analysis (KPCA) and Fisher’s linear discriminant analysis (FLD), we achieve high classification rates in discriminating healthy controls from patients with schizophrenia. Experimental results using leave-one-out cross-validation show that features extracted from the default mode network (DMN) lead to a classification accuracy of over 90% in both data sets. Moreover, using a majority vote method that uses multiple features, we achieve a classification accuracy of 98% in auditory oddball (AOD) task and 93% in rest data. Several components, including DMN, temporal, and medial visual regions, are consistently present in the set of features that yield high classification accuracy. The features we have extracted thus show promise to be used as biomarkers for schizophrenia. Results also suggest that there may be different advantages to using resting fMRI data or task fMRI data

Combination of Resting State fMRI, DTI, and sMRI Data to Discriminate Schizophrenia by N-way MCCA + jICA

Multimodal brain imaging data have shown increasing utility in answering both scientifically interesting and clinically relevant questions. Each brain imaging technique provides a different view of brain function or structure, while multimodal fusion capitalizes on the strength of each and may uncover hidden relationships that can merge findings from separate neuroimaging studies. However, most current approaches have focused on pair-wise fusion and there is still relatively little work on N-way data fusion and examination of the relationships among multiple data types. We recently developed an approach called “mCCA + jICA” as a novel multi-way fusion method which is able to investigate the disease risk factors that are either shared or distinct across multiple modalities as well as the full correspondence across modalities. In this paper, we applied this model to combine resting state fMRI (amplitude of low-frequency fluctuation, ALFF), gray matter (GM) density, and DTI (fractional anisotropy, FA) data, in order to elucidate the abnormalities underlying schizophrenia patients (SZs, n = 35) relative to healthy controls (HCs, n = 28). Both modality-common and modality-unique abnormal regions were identified in SZs, which were then used for successful classification for seven modality-combinations, showing the potential for a broad applicability of the mCCA + jICA model and its results. In addition, a pair of GM-DTI components showed significant correlation with the positive symptom subscale of Positive and Negative Syndrome Scale (PANSS), suggesting that GM density changes in default model network along with white-matter disruption in anterior thalamic radiation are associated with increased positive PANSS. Findings suggest the DTI anisotropy changes in frontal lobe may relate to the corresponding functional/structural changes in prefrontal cortex and superior temporal gyrus that are thought to play a role in the clinical expression of SZ

Learning and comparing functional connectomes across subjects

Functional connectomes capture brain interactions via synchronized fluctuations in the functional magnetic resonance imaging signal. If measured during rest, they map the intrinsic functional architecture of the brain. With task-driven experiments they represent integration mechanisms between specialized brain areas. Analyzing their variability across subjects and conditions can reveal markers of brain pathologies and mechanisms underlying cognition. Methods of estimating functional connectomes from the imaging signal have undergone rapid developments and the literature is full of diverse strategies for comparing them. This review aims to clarify links across functional-connectivity methods as well as to expose different steps to perform a group study of functional connectomes

SEARCHING NEUROIMAGING BIOMARKERS IN MENTAL DISORDERS WITH GRAPH AND MULTIMODAL FUSION ANALYSIS OF FUNCTIONAL CONNECTIVITY

Mental disorders such as schizophrenia (SZ), bipolar (BD), and major depression disorders (MDD) can cause severe symptoms and life disruption. They share some symptoms, which can pose a major clinical challenge to their differentiation. Objective biomarkers based on neuroimaging may help to improve diagnostic accuracy and facilitate optimal treatment for patients. Over the last decades, non-invasive in-vivo neuroimaging techniques such as magnetic resonance imaging (MRI) have been increasingly applied to measure structure and function in human brains. With functional MRI (fMRI) or structural MRI (sMRI), studies have identified neurophysiological deficits in patients’ brain from different perspective. Functional connectivity (FC) analysis is an approach that measures functional integration in brains. By assessing the temporal coherence of the hemodynamic activity among brain regions, FC is considered capable of characterizing the large-scale integrity of neural activity. In this work, we present two data analysis frameworks for biomarker detection on brain imaging with FC, 1) graph analysis of FC and 2) multimodal fusion analysis, to better understand the human brain. Graph analysis reveals the interaction among brain regions based on graph theory, while the multimodal fusion framework enables us to utilize the strength of different imaging modalities through joint analysis. Four applications related to FC using these frameworks were developed. First, FC was estimated using a model-based approach, and revealed altered the small-world network structure in SZ. Secondly, we applied graph analysis on functional network connectivity (FNC) to differentiate BD and MDD during resting-state. Thirdly, two functional measures, FNC and fractional amplitude of low frequency fluctuations (fALFF), were spatially overlaid to compare the FC and spatial alterations in SZ. And finally, we utilized a multimodal fusion analysis framework, multi-set canonical correlation analysis + joint independent component analysis (mCCA+jICA) to link functional and structural abnormalities in BD and MDD. We also evaluated the accuracy of predictive diagnosis through classifiers generated on the selected features. In summary, via the two frameworks, our work has made several contributions to advance FC analysis, which improves our understanding of underlying brain function and structure, and our findings may be ultimately useful for the development of biomarkers of mental disease