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Combining multiple connectomes improves predictive modeling of phenotypic measures.

ABSTRACT: Resting-state and task-based functional connectivity matrices, or connectomes, are powerful predictors of individual differences in phenotypic measures. However, most of the current state-of-the-art algorithms only build predictive models based on a single connectome for each individual. This approach neglects the complementary information contained in connectomes from different sources and reduces prediction performance. In order to combine different task connectomes into a single predictive model in a principled way, we propose a novel prediction framework, termed multidimensional connectome-based predictive modeling. Two specific algorithms are developed and implemented under this framework. Using two large open-source datasets with multiple tasks-the Human Connectome Project and the Philadelphia Neurodevelopmental Cohort, we validate and compare our framework against performing connectome-based predictive modeling (CPM) on each task connectome independently, CPM on a general functional connectivity matrix created by averaging together all task connectomes for an individual, and CPM with a naïve extension to multiple connectomes where each edge for each task is selected independently. Our framework exhibits superior performance in prediction compared with the other competing methods. We found that different tasks contribute differentially to the final predictive model, suggesting that the battery of tasks used in prediction is an important consideration. This work makes two major contributions: First, two methods for combining multiple connectomes from different task conditions in one predictive model are demonstrated; Second, we show that these models outperform a previously validated single connectome-based predictive model approach.

SUBMITTER: Gao S

PROVIDER: S-EPMC6765422 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Combining multiple connectomes improves predictive modeling of phenotypic measures.

Gao Siyuan S Greene Abigail S AS Constable R Todd RT Scheinost Dustin D

NeuroImage 20190720

Resting-state and task-based functional connectivity matrices, or connectomes, are powerful predictors of individual differences in phenotypic measures. However, most of the current state-of-the-art algorithms only build predictive models based on a single connectome for each individual. This approach neglects the complementary information contained in connectomes from different sources and reduces prediction performance. In order to combine different task connectomes into a single predictive mo ...[more]

PMID: 31336188

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Project description:BackgroundWhile graph measures are used increasingly to characterize human connectomes, uncertainty remains in how to use these metrics in a quantitative and reproducible manner. Specifically, there is a lack of community consensus regarding the number of streamlines needed to generate connectomes.PurposeThe purpose was to define the relationship between streamline count and graph-measure value, reproducibility, and repeatability.Study typeRetrospective analysis of previously prospective study.PopulationTen healthy subjects, 70% female, aged 25.3 ± 5.9 years.Field strength/sequenceA 3-T, T1-weighted sequences and diffusion-weighted imaging (DWI) with two gradient strengths (b-values = 1200 and 3000 sec/mm2 , echo time [TE] = 68 msec, repetition time [TR] = 5.4 seconds, 120 slices, field of view = 188 mm2 ).AssessmentA total of 13 graph-theory measures were derived for each subject by generating probabilistic whole-brain tractography from DWI and mapping the structural connectivity to connectomes. The streamline count invariance from changes in mean, repeatability, and reproducibility were derived.Statistical testsPaired t-test with P value <0.05 was used to compare graph-measure means with a reference, intraclass correlation coefficient (ICC) to measure repeatability, and concordance correlation coefficient (CCC) to measure reproducibility.ResultsModularity and global efficiency converged to their reference mean with ICC > 0.90 and CCC > 0.99. Edge count, small-worldness, randomness, and average betweenness centrality converged to the reference mean, with ICC > 0.90 and CCC > 0.95. Assortativity and average participation coefficient converged with ICC > 0.75 and CCC > 0.90. Density, average node strength, average node degree, characteristic path length, average local efficiency, and average clustering coefficient did not converge, though had ICC > 0.90 and CCC > 0.99. For these measures, alternate definitions that converge a reference mean are provided.Data conclusionModularity and global efficiency are streamline count invariant for greater than 6 million and 100,000 streamlines, respectively. Density, average node strength, average node degree, characteristic path length, average local efficiency, and average clustering coefficient were strongly dependent on streamline count.Evidence level1.Technical efficacyStage 1.

Project description:Functional connectivity has been shown to be a very promising tool for studying the large-scale functional architecture of the human brain. In network research in fMRI, functional connectivity is considered as a set of pair-wise interactions between the nodes of the network. These interactions are typically operationalized through the full or partial correlation between all pairs of regional time series. Estimating the structure of the latent underlying functional connectome from the set of pair-wise partial correlations remains an open research problem though. Typically, this thresholding problem is approached by proportional thresholding, or by means of parametric or non-parametric permutation testing across a cohort of subjects at each possible connection. As an alternative, we propose a data-driven thresholding approach for network matrices on the basis of mixture modeling. This approach allows for creating subject-specific sparse connectomes by modeling the full set of partial correlations as a mixture of low correlation values associated with weak or unreliable edges in the connectome and a sparse set of reliable connections. Consequently, we propose to use alternative thresholding strategy based on the model fit using pseudo-False Discovery Rates derived on the basis of the empirical null estimated as part of the mixture distribution. We evaluate the method on synthetic benchmark fMRI datasets where the underlying network structure is known, and demonstrate that it gives improved performance with respect to the alternative methods for thresholding connectomes, given the canonical thresholding levels. We also demonstrate that mixture modeling gives highly reproducible results when applied to the functional connectomes of the visual system derived from the n-back Working Memory task in the Human Connectome Project. The sparse connectomes obtained from mixture modeling are further discussed in the light of the previous knowledge of the functional architecture of the visual system in humans. We also demonstrate that with use of our method, we are able to extract similar information on the group level as can be achieved with permutation testing even though these two methods are not equivalent. We demonstrate that with both of these methods, we obtain functional decoupling between the two hemispheres in the higher order areas of the visual cortex during visual stimulation as compared to the resting state, which is in line with previous studies suggesting lateralization in the visual processing. However, as opposed to permutation testing, our approach does not require inference at the cohort level and can be used for creating sparse connectomes at the level of a single subject.

Project description:Although major depressive disorder (MDD) is associated with altered functional coupling between disparate neural networks, the degree to which such measures are ameliorated by antidepressant treatment is unclear. It is also unclear whether functional connectivity can be used as a predictive biomarker of treatment response. Here, we used whole-brain functional connectivity analysis to identify neural signatures of remission following antidepressant treatment, and to identify connectomic predictors of treatment response. 163 MDD and 62 healthy individuals underwent functional MRI during pre-treatment baseline and 8-week follow-up sessions. Patients were randomized to escitalopram, sertraline or venlafaxine-XR antidepressants and assessed at follow-up for remission. Baseline measures of intrinsic functional connectivity between each pair of 333 regions were analyzed to identify pre-treatment connectomic features that distinguish remitters from non-remitters. We then interrogated these connectomic differences to determine if they changed post-treatment, distinguished patients from controls, and were modulated by medication type. Irrespective of medication type, remitters were distinguished from non-remitters by greater connectivity within the default mode network (DMN); specifically, between the DMN, fronto-parietal and somatomotor networks, the DMN and visual, limbic, auditory and ventral attention networks, and between the fronto-parietal and somatomotor networks with cingulo-opercular and dorsal attention networks. This baseline hypo-connectivity for non-remitters also distinguished them from controls and increased following treatment. In contrast, connectivity for remitters was higher than controls at baseline and also following remission, suggesting a trait-like connectomic characteristic. Increased functional connectivity within and between large-scale intrinsic brain networks may characterize acute recovery with antidepressants in depression.

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Combining multiple connectomes improves predictive modeling of phenotypic measures.

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Combining multiple connectomes improves predictive modeling of phenotypic measures.

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