Multi-Scale Graph Theoretical Analysis of Resting-State fMRI for Classification of Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
University of Bojnord（博季努尔德大学）；Munster Technological University（芒斯特理工大学）
Alzheimer's disease (AD) is a neurodegenerative disorder marked by memory loss and cognitive decline, making early detection vital for timely intervention. However, early diagnosis is challenging due to the heterogeneous presentation of symptoms. Resting-state functional magnetic resonance imaging (rs-fMRI) captures spontaneous brain activity and functional connectivity, which are known to be disrupted in AD and mild cognitive impairment (MCI). Traditional methods, such as Pearson's correlation, have been used to calculate association matrices, but these approaches often overlook the dynamic and non-stationary nature of brain activity. In this study, we introduce a novel method that integrates discrete wavelet transform (DWT) and graph theory to model the dynamic behavior of brain networks. Our approach captures the time-frequency representation of brain activity, allowing for a more nuanced analysis of the underlying network dynamics. Machine learning was employed to automate the discrimination of different stages of AD based on learned patterns from brain network at different frequency bands. We applied our method to a dataset of rs-fMRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, demonstrating its potential as an early diagnostic tool for AD and for monitoring disease progression. Our statistical analysis identifies specific brain regions and connections that are affected in AD and MCI, at different frequency bands, offering deeper insights into the disease's impact on brain function.
Deep Learning Inductive Biases for fMRI Time Series Classification during Resting-state and Movie-watching
School of Electrical and Computer Engineering, University of Tehran（埃特瓦尔大学电气与计算机工程学院）；School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM)（基础科学研究所（IPM）认知科学学院）
This paper describes an approach of using dynamic Structural Equation Modeling (SEM) analysis to estimate the connectivity networks from resting-state fMRI data measured by a multiband EPI sequence. Two structural equation models were estimated at each voxel with respect to the sensory-motor network and default-mode network. The resulting connectivity maps indicate that supplementary motor area has significant connections to left/right primary motor areas, and medial prefrontal cortex link significantly with posterior cingulate cortex and inferior parietal lobules. The results imply that high …
A recent Editorial by Slotnick (2017) reconsiders the findings of our paper on the accuracy of false positive rate control with cluster inference in fMRI (Eklund et al, 2016), in particular criticising our use of resting state fMRI data as a source for null data in the evaluation of task fMRI methods. We defend this use of resting fMRI data, as while there is much structure in this data, we argue it is representative of task data noise and as such analysis software should be able to accommodate this noise. We also discuss a potential problem with Slotnick's own method.
Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy. While it is characterized by an epileptogenic focus in the mesial temporal lobe, it is increasingly understood as a network disorder. Hence, understanding the nature of impairments on a network level is essential for its diagnosis and treatment. In this work, we review recent works that apply resting-state functional MRI to provide key insights into the impairments to the functional architecture in mTLE. We discuss changes on both regional and global scales. Finally, we describe how Machine Learning can be applied to rs-…
National Technical University of Athens（雅典国立理工大学）；Università degli Studi di Napoli Federico II（那不勒斯费德里科二世大学）
We construct embedded functional connectivity networks (FCN) from benchmark resting-state functional magnetic resonance imaging (rsfMRI) data acquired from patients with schizophrenia and healthy controls based on linear and nonlinear manifold learning algorithms, namely, Multidimensional Scaling (MDS), Isometric Feature Mapping (ISOMAP) and Diffusion Maps. Furthermore, based on key global graph-theoretical properties of the embedded FCN, we compare their classification potential using machine learning techniques. We also assess the performance of two metrics that are widely used for the const…
Functional Brain Network Identification in Opioid Use Disorder Using Machine Learning Analysis of Resting-State fMRI BOLD Signals
Old Dominion University（奥多明尼昂大学）；Institute of Drug and Alcohol Studies（药物与酒精研究所）；Virginia Commonwealth University（弗吉尼亚联邦大学）；C. Kenneth and Dianne Wright Center for Clinical and Translational Research（C.肯尼斯和黛安·赖特临床与转化研究中心）；Data Science Institute（数据科学研究所）
Searching for biomarkers has been a chief pursuit of the field of psychiatry. Toward this end, studies have catalogued candidate resting-state biomarkers in nearly all forms of mental disorder. However, it is becoming increasingly clear that these biomarkers lack specificity, limiting their capacity to yield clinical impact. We discuss three avenues of research that are overcoming this limitation: (i) the adoption of transdiagnostic research designs, which involve studying and explicitly comparing multiple disorders from distinct diagnostic axes of psychiatry; (ii) dimensional models of psycho…
VarCoNet: A variability-aware self-supervised framework for functional connectome extraction from resting-state fMRI
Department of Biomedical Engineering and Biotechnology, and the Health Engineering Innovation Group (HEIG), Khalifa University（生物医学工程与生物技术系，以及健康工程创新小组（HEIG），卡利法大学）；Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki（电气与计算机工程系，阿尔基洛斯大学）
To explain individual differences in development, behavior, and cognition, most previous studies focused on projecting resting-state functional MRI (fMRI) based functional connectivity (FC) data into a low-dimensional space via linear dimensionality reduction techniques, followed by executing analysis operations. However, linear dimensionality analysis techniques may fail to capture nonlinearity of brain neuroactivity. Moreover, besides resting-state FC, FC based on task fMRI can be expected to provide complementary information. Motivated by these considerations, we nonlinearly fuse resting-st…
Deep learning methods are increasingly being used with neuroimaging data like structural and function magnetic resonance imaging (MRI) to predict the diagnosis of neuropsychiatric and neurological disorders. For psychiatric disorders in particular, it is believed that one of the most promising modality is the resting-state functional MRI (rsfMRI), which captures the intrinsic connectivity between regions in the brain. Because rsfMRI data points are inherently high-dimensional (~1M), it is impossible to process the entire input in its raw form. In this paper, we propose a very simple transforma…
The study of hierarchy in networks of the human brain has been of significant interest among the researchers as numerous studies have pointed out towards a functional hierarchical organization of the human brain. This paper provides a novel method for the extraction of hierarchical connectivity components in the human brain using resting-state fMRI. The method builds upon prior work of Sparse Connectivity Patterns (SCPs) by introducing a hierarchy of sparse overlapping patterns. The components are estimated by deep factorization of correlation matrices generated from fMRI. The goal of the pape…
Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distor…
A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response func…
We present a computational framework for analysis and visualization of non-linear functional connectivity in the human brain from resting state functional MRI (fMRI) data for purposes of recovering the underlying network community structure and exploring causality between network components. Our proposed methodology of non-linear mutual connectivity analysis (MCA) involves two computational steps. First, the pair-wise cross-prediction performance between resting state fMRI pixel time series within the brain is evaluated. The underlying network structure is subsequently recovered from the affin…
Fractals are self-similar and scale-invariant patterns found ubiquitously in nature. A lot of evidences implying fractal properties such as 1/f power spectrums have been also observed in resting state fMRI time series. To explain the fractal behavior in rs-fMRI, we have proposed the fractal-based model of resting state hemodynamic response function (rs-HRF) whose properties can be summarized by a fractal exponent. Here we show, through a simulation studies, that the fractal behavior of cerebral hemodynamics may cause significant distortion of network properties between neuronal activities and …
University of Regensburg（雷根斯堡大学）；Universidade de Aveiro（阿威罗大学）
Independent component analysis (ICA), as a data driven method, has shown to be a powerful tool for functional magnetic resonance imaging (fMRI) data analysis. One drawback of this multivariate approach is, that it is not compatible to the analysis of group data in general. Therefore various techniques have been proposed in order to overcome this limitation of ICA. In this paper a novel ICA-based work-flow for extracting resting state networks from fMRI group studies is proposed. An empirical mode decomposition (EMD) is used to generate reference signals in a data driven manner, which can be in…
Functional connectivity, as estimated using resting state fMRI, has shown potential in bridging the gap between pathophysiology and cognition. However, clinical use of functional connectivity biomarkers is impeded by unreliable estimates of individual functional connectomes and lack of generalizability of models predicting cognitive outcomes from connectivity. To address these issues, we combine the frameworks of connectome predictive modeling and differential identifiability. Using the combined framework, we show that enhancing the individual fingerprint of resting state functional connectome…
Circadian rhythms synchronize a variety of physiological processes ranging from neural activity and hormone secretion to sleep cycles and feeding habits. Despite significant diurnal variation, time-of-day (TOD) is rarely recorded or analyzed in human brain research. Moreover, sleep-wake patterns, diurnal preferences, and daytime alertness vary across individuals, known as sleep chronotypes. Here, we performed graph-theory network analysis on resting-state functional MRI (rs-fMRI) data to explore topological differences in whole-brain functional networks between morning and evening sessions (TO…
Brain regions are often topographically connected: nearby locations within one brain area connect with nearby locations in another area. Mapping these connection topographies, or 'connectopies' in short, is crucial for understanding how information is processed in the brain. Here, we propose principled, fully data-driven methods for mapping connectopies using functional magnetic resonance imaging (fMRI) data acquired at rest by combining spectral embedding of voxel-wise connectivity 'fingerprints' with a novel approach to spatial statistical inference. We applied the approach in human primary …
Parkinson's disease (PD) is a common and complex neurodegenerative disorder with 5 stages in the Hoehn and Yahr scaling. Given the heterogeneity of PD, it is challenging to classify early stages 1 and 2 and detect brain function alterations. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. Some machine learning approaches like support vector machine and logistic regression have been successfully applied in the early diagnosis of PD using fMRI data, which outperform classifiers based on manual…
Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analysis consortium (ENIGMA), combine data collected by independent studies worldwide to achieve more accurate estimates of effect sizes and more reliable and reproducible outcomes. Such efforts require harmonized analyses protocols to consistently extract phenotypes. Even so, challenges include wide variability of fMRI protocols and scanner platforms; this leads to site-to-site variance in quality, resolution and temporal signal-to-noise ratio (tSNR). An effective harmonization should provide optimal measures for da…
Automatic identification and categorization of Alzheimer's patients and the ability to distinguish between different levels of this disease can be very helpful to the research community in this field, since other non-automatic approaches are very time-consuming and are highly dependent on experts' experience. Herein, we propose the utility of cerebral instantaneous phase and envelope information in order to discriminate between Alzheimer's patients, MCI subjects and healthy normal individuals from functional magnetic resonance imaging (fMRI) data. To this end, after performing the region-of-in…
We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer's disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related…
Adaptive behavior, cognition and emotion are the result of a bewildering variety of brain spatiotemporal activity patterns. An important problem in neuroscience is to understand the mechanism by which the human brain's 100 billion neurons and 100 trillion synapses manage to produce this large repertoire of cortical configurations in a flexible manner. In addition, it is recognized that temporal correlations across such configurations cannot be arbitrary, but they need to meet two conflicting demands: while diverse cortical areas should remain functionally segregated from each other, they must …
Objectives: We develop a framework for the analysis of synergy and redundancy in the pattern of information flow between subsystems of a complex network. Methods: The presence of redundancy and/or synergy in multivariate time series data renders difficult to estimate the neat flow of information from each driver variable to a given target. We show that adopting an unnormalized definition of Granger causality one may put in evidence redundant multiplets of variables influencing the target by maximizing the total Granger causality to a given target, over all the possible partitions of the set of…
The human brain exhibits large-scale spontaneous fluctuations that account for most of its total energy metabolism. Independent of any overt function, this immense ongoing activity likely creates or maintains a potential functional brain reserve to facilitate normal brain function. An important property of spontaneous brain activity is the long-range temporal coherence, which can be characterized by resting state fMRI-based brain entropy mapping (BEN), a relatively new method that has gained increasing research interest. The purpose of this study was to leverage the large resting state fMRI an…
The continuous interaction between brain regions "at rest" defines the so-called resting state networks (RSN) which can be reconstructed from the analysis of functional magnetic resonance imaging (fMRI) data. What dynamical mechanism allows for a flexible large-scale organization of the RSN still remains an important challenge. Here, three key novel properties of the RSN are uncovered. First, the correlation length (i.e., the length at which correlation between two regions vanishes) diverges with the cluster's size considered. Second, this divergence it is observed also for measures of mutual …
Functional magnetic resonance imaging (fMRI) techniques have contributed significantly to our understanding of brain function. Current methods are based on the analysis of \emph{gradual and continuous} changes in the brain blood oxygenated level dependent (BOLD) signal. Departing from that approach, recent work has shown that equivalent results can be obtained by inspecting only the relatively large amplitude BOLD signal peaks, suggesting that relevant information can be condensed in \emph{discrete} events. This idea is further explored here to demonstrate how brain dynamics at resting state c…
Johns Hopkins University（约翰斯·霍普金斯大学）；Microsoft（微软公司）；Johns Hopkins School of Medicine（约翰斯·霍普金斯医学院）；Malone Center for Engineering in Healthcare（马龙医疗保健工程中心）
a Division of Medical Informatics, Department of Biomedical Engineering b Division of Statistics \& Machine Learning, Department of Computer；Information Science c Center for Medical Image Science；Visualization (CMIV) \ \" o ping University, Sweden
Classifying subjects as healthy or diseased using neuroimaging data has gained a lot of attention during the last 10 years. Here we apply deep learning to derivatives from resting state fMRI data, and investigate how different 3D augmentation techniques affect the test accuracy. Specifically, we use resting state derivatives from 1,112 subjects in ABIDE preprocessed to train a 3D convolutional neural network (CNN) to perform the classification. Our results show that augmentation only provide minor improvements to the test accuracy.
Analysis of brain activity in resting-state is of fundamental importance in identifying functional characteristics of neuronal system. Although resting brain has been extensively investigated for low frequency synchrony between brain regions, namely Functional Connectivity (FC), the other main stream of brain connectivity analysis that seeks causal interactions between brain regions, Effective Connectivity (EC), has been little explored in spontaneous brain oscillations. Inherent complexity of brain activities in resting-state, as is observed in BOLD (Blood Oxygenation-Level Dependant) fluctua…
Autism spectrum disorder (ASD) is one of the major developmental disorders affecting children. Recently, it has been hypothesized that ASD is associated with atypical brain connectivities. A substantial body of researches use Pearson's correlation coefficients, mutual information, or partial correlation to investigate the differences in brain connectivities between ASD and typical controls from functional Magnetic Resonance Imaging (fMRI). However, correlation or partial correlation does not directly reveal causal influences - the information flow - between brain regions. Comparing to correlat…
Accurate early diagnosis and monitoring of neurodegenerative conditions is essential for effective disease management and delivery of medication and treatment. This research develops automatic methods for detecting brain imaging preclinical biomarkers for Parkinson's disease (PD) by considering the novel application of evolutionary algorithms. A fundamental novel element of this work is the use of evolutionary algorithms to both map and predict the functional connectivity in patients using resting state functional MRI data taken from the PPMI to identify PD progression biomarkers. Specifically…
Columbia University（哥伦比亚大学）；Stanford University（斯坦福大学）
We propose a hierarchical Bayesian recurrent state space model for modeling switching network connectivity in resting state fMRI data. Our model allows us to uncover shared network patterns across disease conditions. We evaluate our method on the ADNI2 dataset by inferring latent state patterns corresponding to altered neural circuits in individuals with Mild Cognitive Impairment (MCI). In addition to states shared across healthy and individuals with MCI, we discover latent states that are predominantly observed in individuals with MCI. Our model outperforms current state of the art deep learn…
University of Rajshahi（拉杰沙希大学）；Hajee Mohammad Danesh Science and Technology University（哈吉·穆罕默德·达内什科技大学）；Deakin University（迪肯大学）；COMSATS University Islamabad（伊斯兰堡COMSATS大学）；Charles Sturt University（查尔斯特大学）
In the last two decades, functional magnetic resonance imaging (fMRI) has emerged as one of the most effective technologies in clinical research of the human brain. fMRI allows researchers to study healthy and pathological brains while they perform various neuropsychological functions. Beyond task-related activations, the human brain has some intrinsic activity at a task-negative (resting) state that surprisingly consumes a lot of energy to support communication among neurons. Recent neuroimaging research has also seen an increase in modeling and analyzing brain activity in terms of a graph or…
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）
Cross-modal fusion of different types of neuroimaging data has shown great promise for predicting the progression of Alzheimer's Disease(AD). However, most existing methods applied in neuroimaging can not efficiently fuse the functional and structural information from multi-modal neuroimages. In this work, a novel cross-modal transformer generative adversarial network(CT-GAN) is proposed to fuse functional information contained in resting-state functional magnetic resonance imaging (rs-fMRI) and structural information contained in Diffusion Tensor Imaging (DTI). The developed bi-attention mech…
INESC-ID（里斯本系统与计算机工程研究所）；Instituto Superior Técnico（高等技术学院）
Topographical structures represent connections between entities and provide a comprehensive design of complex systems. Currently these structures are used to discover correlates of neuronal and haemodynamical activity. In this work, we incorporate them with neural processing techniques to perform regression, using electrophysiological activity to retrieve haemodynamics. To this end, we use Fourier features, attention mechanisms, shared space between modalities and incorporation of style in the latent representation. By combining these techniques, we propose several models that significantly ou…
