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Martin J. McKeown

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JBHI Journal 2026 Journal Article

A Novel Eigen-Volume-based Co-Activation Pattern Framework for Dynamic Functional Biomarkers of Multiple Sclerosis

  • Fatemeh Valipour
  • Maryam Mohebbi
  • Mani Garousi
  • Maryam S. Mirian
  • Anthony L. Traboulsee
  • Shannon Kolind
  • Martin J. McKeown

Imaging biomarkers are essential for monitoring multiple sclerosis (MS), wand resting-state functional MRI (rs-fMRI) offers functional insights that complement structural imaging. This study investigates whether a novel co-activation pattern (CAP) approach for dynamic rs-fMRI can function as a dual-purpose biomarker in MS, aiding diagnosis and tracking disease severity. RS-fMRI scans from 25 relapsing-remitting MS patients and 41 healthy controls (HCs) were analyzed using a novel CAP-based approach. CAPs derived from individual time frames to capture dynamic brain activity patterns incorporated a bivariate similarity assessment, eigen volume-based dimensionality reduction, and consensus clustering. We evaluated the framework in two analyses: (1) a diagnostic evaluation, using dynamic CAP features—dwell time, persistence, and transition probabilities—for group comparisons and classification; and (2) a severity-prediction analysis, relating these CAP-derived measures to clinical disability (EDSS) in MS using LASSO regression. Method performance was benchmarked against standard CAP and sliding-window (SW) approaches. It revealed significant differences in brain activity between MS and HCs, within the default mode, sensorimotor, and language networks (p 0. 75) and yielded better classification performance than standard CAP and SW approaches in classifying MS from HCs. These results suggest that dynamic brain activity patterns are altered in MS and linked to clinical disability. The proposed CAP provided improved performance in distinguishing MS patients, offering enhanced clinical monitoring. Transition probabilities emerged as a potential biomarker for tracking MS progression, with network shifts reflecting disease severity. As MS advances, increased transitions toward sensory, motor, and executive networks suggest compensatory recruitment. Conversely, reduced transitions from default mode and salience networks to sensorimotor and frontoparietal systems were associated with greater disability and diminished adaptive reorganization.

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JBHI Journal 2022 Journal Article

A Joint Constrained CCA Model for Network-Dependent Brain Subregion Parcellation

  • Qinrui Ling
  • Aiping Liu
  • Yu Li
  • Xueyang Fu
  • Xun Chen
  • Martin J. McKeown
  • Feng Wu

Connectivity-based brain region parcellation from functional magnetic resonance imaging (fMRI) data is complicated by heterogeneity among aged and diseased subjects, particularly when the data are spatially transformed to a common space. Here, we propose a group-guided functional brain region parcellation model capable of obtaining subregions from a target region with consistent connectivity profiles across multiple subjects, even when the fMRI signals are kept in their native spaces. The model is based on a joint constrained canonical correlation analysis (JC-CCA) method that achieves group-guided parcellation while allowing the data dimension of the parcellated regions for each subject to vary. We performed extensive experiments on synthetic and real data to demonstrate the superiority of the proposed model compared to other classical methods. When applied to fMRI data of subjects with and without Parkinson's disease (PD) to estimate the subregions in the Putamen, significant between-group differences were found in the derived subregions and the connectivity patterns. Superior classification and regression results were obtained, demonstrating its potential in clinical practice.

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JBHI Journal 2021 Journal Article

Striatal Subdivisions Estimated via Deep Embedded Clustering With Application to Parkinson's Disease

  • Yu Li
  • Aiping Liu
  • Taomian Mi
  • Runyu Yang
  • Piu Chan
  • Martin J. McKeown
  • Xun Chen
  • Feng Wu

Recent fMRI connectivity-based parcellation (CBP) methods have been developed to obtain homogeneous and functionally coherent brain parcels. However, most of these studies utilize traditional clustering methods that neglect hidden nonlinear features. To enhance parcellation performance, here we propose a deep embedded connectivity-based parcellation (DECBP) framework and apply it to determine functional subdivisions of the striatum in public resting state fMRI data sets. This framework integrates fMRI connectivity features into deep embedded clustering (DEC), a deep neural network based on a stacked autoencoder. Compared to three prevalent clustering methods and their combinations with principal component analysis (PCA), the DECBP exhibited a significantly higher similarity between scans, individuals, and groups, indicating enhanced reproducibility. The generated reliable parcellations were also largely consistent with other public atlases. We further explored the functional subunits in the striatum in a data set from 23 Parkinson's disease (PD) subjects and 27 age-matched healthy controls (HC). All putaminal subregions of PD demonstrated lower interhemispheric connectivity than those of HC, which might reflect imbalance in the pathological progression of PD. Such hypo-connectivity was also observed between putaminal subregions and other brain regions, reflecting neuroimaging manifestations of the altered cortico-striato-thalamo-cortical circuit. These observed weaker couplings were associated with PD severity and duration. Our results support the utilization of the DECBP framework and suggest that abnormal connectivity in putaminal subregions may be a potential indicator of PD.

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IJCAI Conference 2020 Conference Paper

A Gamified Assessment Platform for Predicting the Risk of Dementia +Parkinson’s disease (DPD) Co-Morbidity

  • Zhiwei Zeng
  • Hongchao Jiang
  • Yanci Zhang
  • Zhiqi Shen
  • Jun Ji
  • Martin J. McKeown
  • Jing Jih Chin
  • Cyril Leung

Population aging is becoming an increasingly important issue around the world. As people live longer, they also tend to suffer from more challenging medical conditions. Currently, there is a lack of a holistic technology-powered solution for providing quality care at affordable cost to patients suffering from co-morbidity. In this paper, we demonstrate a novel AI-powered solution to provide early detection of the onset of Dementia + Parkinson's disease (DPD) co-morbidity, a condition which severely limits a senior's ability to live actively and independently. We investigate useful in-game behaviour markers which can support machine learning-based predictive analytics on seniors' risk of developing DPD co-morbidity.

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JBHI Journal 2019 Journal Article

Dynamic Graph Theoretical Analysis of Functional Connectivity in Parkinson's Disease: The Importance of Fiedler Value

  • Jiayue Cai
  • Aiping Liu
  • Taomian Mi
  • Saurabh Garg
  • Wade Trappe
  • Martin J. McKeown
  • Z. Jane Wang

Graph theoretical analysis is a powerful tool for quantitatively evaluating brain connectivity networks. Conventionally, brain connectivity is assumed to be temporally stationary, whereas increasing evidence suggests that functional connectivity exhibits temporal variations during dynamic brain activity. Although a number of methods have been developed to estimate time-dependent brain connectivity, there is a paucity of studies examining the utility of brain dynamics for assessing brain disease states. Therefore, this paper aims to assess brain connectivity dynamics in Parkinson's disease (PD) and determine the utility of such dynamic graph measures as potential components to an imaging biomarker. Resting-state functional magnetic resonance imaging data were collected from 29 healthy controls and 69 PD subjects. Time-varying functional connectivity was first estimated using a sliding windowed sparse inverse covariance matrix. Then, a collection of graph measures, including the Fiedler value, were computed and the dynamics of the graph measures were investigated. The results demonstrated that PD subjects had a lower variability in the Fiedler value, modularity, and global efficiency, indicating both abnormal dynamic global integration and local segregation of brain networks in PD. Autoregressive models fitted to the dynamic graph measures suggested that Fiedler value, characteristic path length, global efficiency, and modularity were all less deterministic in PD. With canonical correlation analysis, the altered dynamics of functional connectivity networks, and particularly dynamic Fiedler value, were shown to be related with disease severity and other clinical variables including age. Similarly, Fiedler value was the most important feature for classification. Collectively, our findings demonstrate altered dynamic graph properties, and in particular the Fiedler value, provide an additional dimension upon which to non-invasively and quantitatively assess PD.

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JBHI Journal 2014 Journal Article

A Three-Step Multimodal Analysis Framework for Modeling Corticomuscular Activity With Application to Parkinson’s Disease

  • Xun Chen
  • Z. Jane Wang
  • Martin J. McKeown

Corticomuscular coupling analysis based on multiple datasets such as electroencephalography (EEG) and electromyography (EMG) signals provides a useful tool for understanding human motor control systems. A popular conventional method to assess corticomuscular coupling has been the pair-wise magnitude-squared coherence (MSC) between EEG and concomitant EMG recordings. However, there are certain limitations associated with the MSC, including the difficulty in robustly assessing group inference, only dealing with two types of datasets simultaneously and the biologically implausible assumption of pair-wise interactions. To overcome such limitations, in this paper, we propose assessing corticomuscular coupling by combining multiset canonical correlation analysis (M-CCA) and joint independent component analysis (jICA). The proposed method takes advantage of the M-CCA and jICA to ensure that the extracted components are maximally correlated across multiple datasets and meanwhile statistically independent within each dataset. Simulations were performed to illustrate the performance of the proposed method. We also applied the proposed method to concurrent EEG, EMG, and behavior data collected in a Parkinson's disease (PD) study. The results reveal highly correlated temporal patterns among the three types of signals and corresponding spatial activation patterns. In addition to the expected motor areas, the corresponding spatial activation patterns demonstrate enhanced occipital connectivity in the PD subjects, consistent with previous medical findings.

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