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Identification of Effective Connectivity Subregions

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 Publication date 2019
and research's language is English




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Standard fMRI connectivity analyses depend on aggregating the time series of individual voxels within regions of interest (ROIs). In certain cases, this spatial aggregation implies a loss of valuable functional and anatomical information about smaller subsets of voxels that drive the ROI level connectivity. We use two recently published graphical search methods to identify subsets of voxels that are highly responsible for the connectivity between larger ROIs. To illustrate the procedure, we apply both methods to longitudinal high-resolution resting state fMRI data from regions in the medial temporal lobe from a single individual. Both methods recovered similar subsets of voxels within larger ROIs of entorhinal cortex and hippocampus subfields that also show spatial consistency across different scanning sessions and across hemispheres. In contrast to standard functional connectivity methods, both algorithms applied here are robust against false positive connections produced by common causes and indirect paths (in contrast to Pearsons correlation) and common effect conditioning (in contrast to partial correlation based approaches). These algorithms allow for identification of subregions of voxels driving the connectivity between regions of interest, recovering valuable anatomical and functional information that is lost when ROIs are aggregated. Both methods are specially suited for voxelwise connectivity research, given their running times and scalability to big data problems.



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Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity, related to the more elusive question Which areas cause the present activity of which others?. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that a dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal [...] Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer [...] Going beyond these early proposals, we advance here that dynamic interactions between brain rhythms provide as well the basis for the self-organized control of this communication-through-coherence, making thus possible a fast on-demand reconfiguration of global information routing modalities.
The estimation of causal network architectures in the brain is fundamental for understanding cognitive information processes. However, access to the dynamic processes underlying cognition is limited to indirect measurements of the hidden neuronal activity, for instance through fMRI data. Thus, estimating the network structure of the underlying process is challenging. In this article, we embed an adaptive importance sampler called Adaptive Path Integral Smoother (APIS) into the Expectation-Maximization algorithm to obtain point estimates of causal connectivity. We demonstrate on synthetic data that this procedure finds not only the correct network structure but also the direction of effective connections from random initializations of the connectivity matrix. In addition--motivated by contradictory claims in the literature--we examine the effect of the neuronal timescale on the sensitivity of the BOLD signal to changes in the connectivity and on the maximum likelihood solutions of the connectivity. We conclude with two warnings: First, the connectivity estimates under the assumption of slow dynamics can be extremely biased if the data was generated by fast neuronal processes. Second, the faster the time scale, the less sensitive the BOLD signal is to changes in the incoming connections to a node. Hence, connectivity estimation using realistic neural dynamics timescale requires extremely high-quality data and seems infeasible in many practical data sets.
181 - G. Wu , W.Liao , S. Stramaglia 2012
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 function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the differences between BOLD and deconvolved BOLD level effective networks and draw some conclusions.
Mild traumatic brain injury (mTBI) is a complex syndrome that affects up to 600 per 100,000 individuals, with a particular concentration among military personnel. About half of all mTBI patients experience a diverse array of chronic symptoms which persist long after the acute injury. Hence, there is an urgent need for better understanding of the white matter and gray matter pathologies associated with mTBI to map which specific brain systems are impacted and identify courses of intervention. Previous works have linked mTBI to disruptions in white matter pathways and cortical surface abnormalities. Herein, we examine these hypothesized links in an exploratory study of joint structural connectivity and cortical surface changes associated with mTBI and its chronic symptoms. Briefly, we consider a cohort of 12 mTBI and 26 control subjects. A set of 588 cortical surface metrics and 4,753 structural connectivity metrics were extracted from cortical surface regions and diffusion weighted magnetic resonance imaging in each subject. Principal component analysis (PCA) was used to reduce the dimensionality of each metric set. We then applied independent component analysis (ICA) both to each PCA space individually and together in a joint ICA approach. We identified a stable independent component across the connectivity-only and joint ICAs which presented significant group differences in subject loadings (p<0.05, corrected). Additionally, we found that two mTBI symptoms, slowed thinking and forgetfulness, were significantly correlated (p<0.05, corrected) with mTBI subject loadings in a surface-only ICA. These surface-only loadings captured an increase in bilateral cortical thickness.
Functional magnetic resonance imaging (fMRI) is a crucial technology for gaining insights into cognitive processes in humans. Data amassed from fMRI measurements result in volumetric data sets that vary over time. However, analysing such data presents a challenge due to the large degree of noise and person-to-person variation in how information is represented in the brain. To address this challenge, we present a novel topological approach that encodes each time point in an fMRI data set as a persistence diagram of topological features, i.e. high-dimensional voids present in the data. This representation naturally does not rely on voxel-by-voxel correspondence and is robust to noise. We show that these time-varying persistence diagrams can be clustered to find meaningful groupings between participants, and that they are also useful in studying within-subject brain state trajectories of subjects performing a particular task. Here, we apply both clustering and trajectory analysis techniques to a group of participants watching the movie Partly Cloudy. We observe significant differences in both brain state trajectories and overall topological activity between adults and children watching the same movie.

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