Browsing by Author "Lindquist, Martin A."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Assessing uncertainty in dynamic functional connectivity
    (Elsevier, 2017-04-01) Kudela, Maria; Harezlak, Jaroslaw; Lindquist, Martin A.; Biostatistics, School of Public Health
    Functional connectivity (FC) - the study of the statistical association between time series from anatomically distinct regions (Friston, 1994, 2011) - has become one of the primary areas of research in the field surrounding resting state functional magnetic resonance imaging (rs-fMRI). Although for many years researchers have implicitly assumed that FC was stationary across time in rs-fMRI, it has recently become increasingly clear that this is not the case and the ability to assess dynamic changes in FC is critical for better understanding of the inner workings of the human brain (Hutchison et al., 2013; Chang and Glover, 2010). Currently, the most common strategy for estimating these dynamic changes is to use the sliding-window technique. However, its greatest shortcoming is the inherent variation present in the estimate, even for null data, which is easily confused with true time-varying changes in connectivity (Lindquist et al., 2014). This can have serious consequences as even spurious fluctuations caused by noise can easily be confused with an important signal. For these reasons, assessment of uncertainty in the sliding-window correlation estimates is of critical importance. Here we propose a new approach that combines the multivariate linear process bootstrap (MLPB) method and a sliding-window technique to assess the uncertainty in a dynamic FC estimate by providing its confidence bands. Both numerical results and an application to rs-fMRI study are presented, showing the efficacy of the proposed method.
  • Thumbnail Image
    Item
    Differences in functional connectivity distribution after transcranial direct-current stimulation: A connectivity density point of view
    (Wiley, 2023) Tang, Bohao; Zhao, Yi; Venkataraman, Archana; Tsapkini, Kyrana; Lindquist, Martin A.; Pekar, James; Caffo, Brian; Biostatistics, School of Public Health
    In this manuscript, we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting-state functional magnetic resonance imaging association with an intervention. The method uses the estimated density of connectivity between nodes of interest as a functional covariate. Moreover, we demonstrate the utility of the procedure in an instance where connectivity is naturally considered an outcome by reversing the predictor/response relationship using case/control methodology. The method utilizes the density quantile, the density evaluated at empirical quantiles, instead of the empirical density directly. This improved the performance of the method by highlighting tail behavior, though we emphasize that by being flexible and non-parametric, the technique can detect effects related to the central portion of the density. To demonstrate the method in an application, we consider 47 primary progressive aphasia patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, transcranial direct-current stimulation and language therapy versus sham (language therapy only), in a clinical trial. We use the method to analyze the effect of direct stimulation on functional connectivity. As such, we estimate the density of correlations among the regions of interest and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. The new approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared with edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.
  • Thumbnail Image
    Item
    Regression models for partially localized fMRI connectivity analyses
    (Frontiers Media, 2023-11-13) Smith, Bonnie B.; Zhao, Yi; Lindquist, Martin A.; Caffo, Brian; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background: Brain functional connectivity analysis of resting-state functional magnetic resonance imaging (fMRI) data is typically performed in a standardized template space assuming consistency of connections across subjects. Analysis methods can come in the form of one-edge-at-a-time analyses or dimension reduction/decomposition methods. Common to these approaches is an assumption that brain regions are functionally aligned across subjects; however, it is known that this functional alignment assumption is often violated. Methods: In this paper, we use subject-level regression models to explain intra-subject variability in connectivity. Covariates can include factors such as geographic distance between two pairs of brain regions, whether the two regions are symmetrically opposite (homotopic), and whether the two regions are members of the same functional network. Additionally, a covariate for each brain region can be included, to account for the possibility that some regions have consistently higher or lower connectivity. This style of analysis allows us to characterize the fraction of variation explained by each type of covariate. Additionally, comparisons across subjects can then be made using the fitted connectivity regression models, offering a more parsimonious alternative to edge-at-a-time approaches. Results: We apply our approach to Human Connectome Project data on 268 regions of interest (ROIs), grouped into eight functional networks. We find that a high proportion of variation is explained by region covariates and network membership covariates, while geographic distance and homotopy have high relative importance after adjusting for the number of predictors. We also find that the degree of data repeatability using our connectivity regression model-which uses only partial location information about pairs of ROI's-is comparably as high as the repeatability obtained using full location information. Discussion: While our analysis uses data that have been transformed into a common template-space, we also envision the method being useful in multi-atlas registration settings, where subject data remains in its own geometry and templates are warped instead. These results suggest the tantalizing possibility that fMRI connectivity analysis can be performed in subject-space, using less aggressive registration, such as simple affine transformations, multi-atlas subject-space registration, or perhaps even no registration whatsoever.