Moo K. Chung

YNIMG Journal 2023 Journal Article

Unified topological inference for brain networks in temporal lobe epilepsy using the Wasserstein distance

• Moo K. Chung
• Camille Garcia Ramos
• Felipe Branco de Paiva
• Jedidiah Mathis
• Vivek Prabhakaran
• Veena A. Nair
• Mary E. Meyerand
• Bruce P. Hermann

Persistent homology offers a powerful tool for extracting hidden topological signals from brain networks. It captures the evolution of topological structures across multiple scales, known as filtrations, thereby revealing topological features that persist over these scales. These features are summarized in persistence diagrams, and their dissimilarity is quantified using the Wasserstein distance. However, the Wasserstein distance does not follow a known distribution, posing challenges for the application of existing parametric statistical models. To tackle this issue, we introduce a unified topological inference framework centered on the Wasserstein distance. Our approach has no explicit model and distributional assumptions. The inference is performed in a completely data driven fashion. We apply this method to resting-state functional magnetic resonance images (rs-fMRI) of temporal lobe epilepsy patients collected from two different sites: the University of Wisconsin-Madison and the Medical College of Wisconsin. Importantly, our topological method is robust to variations due to sex and image acquisition, obviating the need to account for these variables as nuisance covariates. We successfully localize the brain regions that contribute the most to topological differences. A MATLAB package used for all analyses in this study is available at https://github.com/laplcebeltrami/PH-STAT.

YNIMG Journal 2019 Journal Article

Altered dynamic electroencephalography connectome phase-space features of emotion regulation in social anxiety

• Mengqi Xing
• Hyekyoung Lee
• Zachery Morrissey
• Moo K. Chung
• K. Luan Phan
• Heide Klumpp
• Alex Leow
• Olusola Ajilore

Emotion regulation deficits are commonly observed in social anxiety disorder (SAD). We used manifold-learning to learn the phase-space connectome manifold of EEG brain dynamics in twenty SAD participants and twenty healthy controls. The purpose of the present study was to utilize manifold-learning to understand EEG brain dynamics associated with emotion regulation processes. Our emotion regulation task (ERT) contains three conditions: Neutral, Maintain and Reappraise. For all conditions and subjects, EEG connectivity data was converted into series of temporally-consecutive connectomes and aggregated to yield this phase-space manifold. As manifold geodesic distances encode intrinsic geometry, we visualized this space using its geodesic-informed minimum spanning tree and compared neurophysiological dynamics across conditions and groups using the corresponding trajectory length. Results showed that SAD participants had significantly longer trajectory lengths during Neutral and Maintain. Further, trajectory lengths during Reappraise were significantly associated with the habitual use of reappraisal strategies, while Maintain trajectory lengths were significantly associated with the negative affective state during Maintain. In sum, an unsupervised connectome manifold-learning approach can reveal emotion regulation associated phase-space features of brain dynamics.

YNIMG Journal 2015 Journal Article

Multi-resolution statistical analysis of brain connectivity graphs in preclinical Alzheimer's disease

• Won Hwa Kim
• Nagesh Adluru
• Moo K. Chung
• Ozioma C. Okonkwo
• Sterling C. Johnson
• Barbara B. Bendlin
• Vikas Singh

There is significant interest, both from basic and applied research perspectives, in understanding how structural/functional connectivity changes can explain behavioral symptoms and predict decline in neurodegenerative diseases such as Alzheimer's disease (AD). The first step in most such analyses is to encode the connectivity information as a graph; then, one may perform statistical inference on various ‘global’ graph theoretic summary measures (e. g. , modularity, graph diameter) and/or at the level of individual edges (or connections). For AD in particular, clear differences in connectivity at the dementia stage of the disease (relative to healthy controls) have been identified. Despite such findings, AD-related connectivity changes in preclinical disease remain poorly characterized. Such preclinical datasets are typically smaller and group differences are weaker. In this paper, we propose a new multi-resolution method for performing statistical analysis of connectivity networks/graphs derived from neuroimaging data. At the high level, the method occupies the middle ground between the two contrasts — that is, to analyze global graph summary measures (global) or connectivity strengths or correlations for individual edges similar to voxel based analysis (local). Instead, our strategy derives a Wavelet representation at each primitive (connection edge) which captures the graph context at multiple resolutions. We provide extensive empirical evidence of how this framework offers improved statistical power by analyzing two distinct AD datasets. Here, connectivity is derived from diffusion tensor magnetic resonance images by running a tractography routine. We first present results showing significant connectivity differences between AD patients and controls that were not evident using standard approaches. Later, we show results on populations that are not diagnosed with AD but have a positive family history risk of AD where our algorithm helps in identifying potentially subtle differences between patient groups. We also give an easy to deploy open source implementation of the algorithm for use within studies of connectivity in AD and other neurodegenerative disorders.

YNIMG Journal 2014 Journal Article

Multi-resolutional shape features via non-Euclidean wavelets: Applications to statistical analysis of cortical thickness

• Won Hwa Kim
• Vikas Singh
• Moo K. Chung
• Chris Hinrichs
• Deepti Pachauri
• Ozioma C. Okonkwo
• Sterling C. Johnson

Statistical analysis on arbitrary surface meshes such as the cortical surface is an important approach to understanding brain diseases such as Alzheimer's disease (AD). Surface analysis may be able to identify specific cortical patterns that relate to certain disease characteristics or exhibit differences between groups. Our goal in this paper is to make group analysis of signals on surfaces more sensitive. To do this, we derive multi-scale shape descriptors that characterize the signal around each mesh vertex, i. e. , its local context, at varying levels of resolution. In order to define such a shape descriptor, we make use of recent results from harmonic analysis that extend traditional continuous wavelet theory from the Euclidean to a non-Euclidean setting (i. e. , a graph, mesh or network). Using this descriptor, we conduct experiments on two different datasets, the Alzheimer's Disease NeuroImaging Initiative (ADNI) data and images acquired at the Wisconsin Alzheimer's Disease Research Center (W-ADRC), focusing on individuals labeled as having Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. In particular, we contrast traditional univariate methods with our multi-resolution approach which show increased sensitivity and improved statistical power to detect a group-level effects. We also provide an open source implementation.

YNIMG Journal 2014 Journal Article

Tracing the evolution of multi-scale functional networks in a mouse model of depression using persistent brain network homology

• Arshi Khalid
• Byung Sun Kim
• Moo K. Chung
• Jong Chul Ye
• Daejong Jeon

Many brain diseases or disorders, such as depression, are known to be associated with abnormal functional connectivity in neural networks in the brain. Some bivariate measures of electroencephalography (EEG) for coupling analysis have been used widely in attempts to explain abnormalities related with depression. However, brain network evolution based on persistent functional connections in EEG signals could not be easily unveiled. For a geometrical exploration of brain network evolution, here, we used persistent brain network homology analysis with EEG signals from a corticosterone (CORT)-induced mouse model of depression. EEG signals were obtained from eight cortical regions (frontal, somatosensory, parietal, and visual cortices in each hemisphere). The persistent homology revealed a significantly different functional connectivity between the control and CORT model, but no differences in common coupling measures, such as cross correlation and coherence, were apparent. The CORT model showed a more localized connectivity and decreased global connectivity than the control. In particular, the somatosensory and parietal cortices were loosely connected in the CORT model. Additionally, the CORT model displayed altered connections among the cortical regions, especially between the frontal and somatosensory cortices, versus the control. This study demonstrates that persistent homology is useful for brain network analysis, and our results indicate that the CORT-induced depression mouse model shows more localized and decreased global connectivity with altered connections, which may facilitate characterization of the abnormal brain network underlying depression.

YNIMG Journal 2013 Journal Article

Bessel Fourier Orientation Reconstruction (BFOR): An analytical diffusion propagator reconstruction for hybrid diffusion imaging and computation of q-space indices

• A. Pasha Hosseinbor
• Moo K. Chung
• Yu-Chien Wu
• Andrew L. Alexander

The ensemble average propagator (EAP) describes the 3D average diffusion process of water molecules, capturing both its radial and angular contents. The EAP can thus provide richer information about complex tissue microstructure properties than the orientation distribution function (ODF), an angular feature of the EAP. Recently, several analytical EAP reconstruction schemes for multiple q-shell acquisitions have been proposed, such as diffusion propagator imaging (DPI) and spherical polar Fourier imaging (SPFI). In this study, a new analytical EAP reconstruction method is proposed, called Bessel Fourier Orientation Reconstruction (BFOR), whose solution is based on heat equation estimation of the diffusion signal for each shell acquisition, and is validated on both synthetic and real datasets. A significant portion of the paper is dedicated to comparing BFOR, SPFI, and DPI using hybrid, non-Cartesian sampling for multiple b-value acquisitions. Ways to mitigate the effects of Gibbs ringing on EAP reconstruction are also explored. In addition to analytical EAP reconstruction, the aforementioned modeling bases can be used to obtain rotationally invariant q-space indices of potential clinical value, an avenue which has not yet been thoroughly explored. Three such measures are computed: zero-displacement probability (Po), mean squared displacement (MSD), and generalized fractional anisotropy (GFA).

YNIMG Journal 2010 Journal Article

General multivariate linear modeling of surface shapes using SurfStat

• Moo K. Chung
• Keith J. Worsley
• Brendon M. Nacewicz
• Kim M. Dalton
• Richard J. Davidson

Although there are many imaging studies on traditional ROI-based amygdala volumetry, there are very few studies on modeling amygdala shape variations. This paper presents a unified computational and statistical framework for modeling amygdala shape variations in a clinical population. The weighted spherical harmonic representation is used to parameterize, smooth out, and normalize amygdala surfaces. The representation is subsequently used as an input for multivariate linear models accounting for nuisance covariates such as age and brain size difference using the SurfStat package that completely avoids the complexity of specifying design matrices. The methodology has been applied for quantifying abnormal local amygdala shape variations in 22 high functioning autistic subjects.

YNIMG Journal 2009 Journal Article

A study of diffusion tensor imaging by tissue-specific, smoothing-compensated voxel-based analysis

• Jee Eun Lee
• Moo K. Chung
• Mariana Lazar
• Molly B. DuBray
• Jinsuh Kim
• Erin D. Bigler
• Janet E. Lainhart
• Andrew L. Alexander

Voxel-based analysis (VBA) is commonly used for statistical analysis of image data, including the detection of significant signal differences between groups. Typically, images are co-registered and then smoothed with an isotropic Gaussian kernel to compensate for image misregistration, to improve the signal-to-noise ratio (SNR), to reduce the number of multiple comparisons, and to apply random field theory. Problems with typical implementations of VBA include poor tissue specificity from image misregistration and smoothing. In this study, we developed a new tissue-specific, smoothing-compensated (T-SPOON) method for the VBA of diffusion tensor imaging (DTI) data with improved tissue specificity and compensation for image misregistration and smoothing. When compared with conventional VBA methods, the T-SPOON method introduced substantially less errors in the normalized and smoothed DTI maps. Another confound of the conventional DTI-VBA is that it is difficult to differentiate between differences in morphometry and DTI measures that describe tissue microstructure. T-SPOON VBA decreased the effects of differential morphometry in the DTI VBA studies. T-SPOON and conventional VBA were applied to a DTI study of white matter in autism. T-SPOON VBA results were found to be more consistent with region of interest (ROI) measurements in the corpus callosum and temporal lobe regions. The T-SPOON method may be also applicable to other quantitative imaging maps such as T1 or T2 relaxometry, magnetization transfer, or PET tracer maps.

YNIMG Journal 2009 Journal Article

Spatially augmented LPboosting for AD classification with evaluations on the ADNI dataset

• Chris Hinrichs
• Vikas Singh
• Lopamudra Mukherjee
• Guofan Xu
• Moo K. Chung
• Sterling C. Johnson

Structural and functional brain images are playing an important role in helping us understand the changes associated with neurological disorders such as Alzheimer's disease (AD). Recent efforts have now started investigating their utility for diagnosis purposes. This line of research has shown promising results where methods from machine learning (such as Support Vector Machines) have been used to identify AD-related patterns from images, for use in diagnosing new individual subjects. In this paper, we propose a new framework for AD classification which makes use of the Linear Program (LP) boosting with novel additional regularization based on spatial “smoothness” in 3D image coordinate spaces. The algorithm formalizes the expectation that since the examples for training the classifier are images, the voxels eventually selected for specifying the decision boundary must constitute spatially contiguous chunks, i. e. , “regions” must be preferred over isolated voxels. This prior belief turns out to be useful for significantly reducing the space of possible classifiers and leads to substantial benefits in generalization. In our method, the requirement of spatial contiguity (of selected discriminating voxels) is incorporated within the optimization framework directly. Other methods have made use of similar biases as a pre- or post-processing step, however, our model incorporates this emphasis on spatial smoothness directly into the learning step. We report on extensive evaluations of our algorithm on MR and FDG-PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and discuss the relationship of the classification output with the clinical and cognitive biomarker data available within ADNI.

YNIMG Journal 2007 Journal Article

Integrating VBM into the General Linear Model with voxelwise anatomical covariates

• Terrence R. Oakes
• Andrew S. Fox
• Tom Johnstone
• Moo K. Chung
• Ned Kalin
• Richard J. Davidson

A current limitation for imaging of brain function is the potential confound of anatomical differences or registration error, which may manifest via apparent functional “activation” for between-subject analyses. With respect to functional activations, underlying tissue mismatches can be regarded as a nuisance variable. We propose adding the probability of gray matter at a given voxel as a covariate (nuisance variable) in the analysis of voxelwise multisubject functional data using standard statistical techniques. A method is presented to assess the extent to which a functional activation can reliably be explained by underlying anatomical differences, and simultaneously, to assess the component of the functional activation which cannot be attributed to anatomical difference and thus is likely due to functional difference alone. Extension of the method to other intermodal imaging applications is discussed. Two exemplary data sets, one PET and one fMRI, are used to demonstrate the implementation and utility of this method, which apportions the relative contributions of anatomy and function for an apparent functional activation. The examples show two distinct types of results. First, a so-called functional activation may actually be caused by a systematic anatomical difference which, when modeled, diminishes the functional effect. In the second result type, including the anatomical differences in the model can account for a large component of otherwise unmodeled variance, yielding an increase in the functional effect cluster size and/or magnitude. In either case, ignoring the readily available structural information can lead to misinterpretation of functional results.

YNIMG Journal 2005 Journal Article

Cortical thickness analysis in autism with heat kernel smoothing

• Moo K. Chung
• Steven M. Robbins
• Kim M. Dalton
• Richard J. Davidson
• Andrew L. Alexander
• Alan C. Evans

We present a novel data smoothing and analysis framework for cortical thickness data defined on the brain cortical manifold. Gaussian kernel smoothing, which weights neighboring observations according to their 3D Euclidean distance, has been widely used in 3D brain images to increase the signal-to-noise ratio. When the observations lie on a convoluted brain surface, however, it is more natural to assign the weights based on the geodesic distance along the surface. We therefore develop a framework for geodesic distance-based kernel smoothing and statistical analysis on the cortical manifolds. As an illustration, we apply our methods in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children via random field based multiple comparison correction that utilizes the new smoothing technique.

YNIMG Journal 2004 Journal Article

Less white matter concentration in autism: 2D voxel-based morphometry

• Moo K. Chung
• Kim M. Dalton
• Andrew L. Alexander
• Richard J. Davidson

Autism is a neurodevelopmental disorder affecting behavioral and social cognition, but there is little understanding about the link between the functional deficit and its underlying neuroanatomy. We applied a 2D version of voxel-based morphometry (VBM) in differentiating the white matter concentration of the corpus callosum for the group of 16 high functioning autistic and 12 normal subjects. Using the white matter density as an index for neural connectivity, autism is shown to exhibit less white matter concentration in the region of the genu, rostrum, and splenium removing the effect of age based on the general linear model (GLM) framework. Further, it is shown that the less white matter concentration in the corpus callosum in autism is due to hypoplasia rather than atrophy.

YNIMG Journal 2003 Journal Article

Deformation-based surface morphometry applied to gray matter deformation

• Moo K. Chung
• Keith J. Worsley
• Steve Robbins
• Tomáš Paus
• Jonathan Taylor
• Jay N. Giedd
• Judith L. Rapoport
• Alan C. Evans

We present a unified statistical approach to deformation-based morphometry applied to the cortical surface. The cerebral cortex has the topology of a 2D highly convoluted sheet. As the brain develops over time, the cortical surface area, thickness, curvature, and total gray matter volume change. It is highly likely that such age-related surface changes are not uniform. By measuring how such surface metrics change over time, the regions of the most rapid structural changes can be localized. We avoided using surface flattening, which distorts the inherent geometry of the cortex in our analysis and it is only used in visualization. To increase the signal to noise ratio, diffusion smoothing, which generalizes Gaussian kernel smoothing to an arbitrary curved cortical surface, has been developed and applied to surface data. Afterward, statistical inference on the cortical surface will be performed via random fields theory. As an illustration, we demonstrate how this new surface-based morphometry can be applied in localizing the cortical regions of the gray matter tissue growth and loss in the brain images longitudinally collected in the group of children and adolescents.

YNIMG Journal 2001 Journal Article

Diffusion smoothing on the cortical surface

• Moo K. Chung
• Keith J. Worsley
• Jonathan Taylor
• Jim Ramsay
• Steve Robbinsf
• Alan C. Evanst

YNIMG Journal 2001 Journal Article

Statistical analysis of cortical surface area change, with an application to brain growth

• Moo K. Chung
• Keith J. Worsley
• Steve Robbins
• T. Paus
• Jonathan Taylor
• Jay N. Giedd
• Judith L. Rapoport
• Alan C. Evans