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Schizophrenia is a severe brain disorder with serious symptoms including delusions, disorganized speech, and hallucinations that can have a long-term detrimental impact on different aspects of a patient's life. It is still unclear what the main cause of schizophrenia is, but a combination of altered brain connectivity and structure may play a role. Neuroimaging data has been useful in characterizing schizophrenia, but there has been very little work focused on voxel-wise changes in multiple brain networks over time, despite evidence that functional networks exhibit complex spatiotemporal changes over time within individual subjects. Recent studies have primarily focused on static (average) features of functional data or on temporal variations between fixed networks; however, such approaches are not able to capture multiple overlapping networks which change at the voxel level. In this work, we employ a deep residual convolutional neural network (CNN) model to extract 53 different spatiotemporal networks each of which captures dynamism within various domains including subcortical, cerebellar, visual, sensori-motor, auditory, cognitive control, and default mode. We apply this approach to study spatiotemporal brain dynamism at the voxel level within multiple functional networks extracted from a large functional magnetic resonance imaging (fMRI) dataset of individuals with schizophrenia (N= 708) and controls (N= 510). Our analysis reveals widespread group level differences across multiple networks and spatiotemporal features including voxel-wise variability, magnitude, and temporal functional network connectivity in widespread regions expected to be impacted by the disorder. We compare with typical average spatial amplitude and show highly structured and neuroanatomically relevant results are missed if one does not consider the voxel-wise spatial dynamics. Importantly, our approach can summarize static, temporal dynamic, spatial dynamic, and spatiotemporal dynamics features, thus proving a powerful approach to unify and compare these various perspectives. In sum, we show the proposed approach highlights the importance of accounting for both temporal and spatial dynamism in whole brain neuroimaging data generally, shows a high-level of sensitivity to schizophrenia highlighting global but spatially unique dynamics showing group differences, and may be especially important in studies focused on the development of brain-based biomarkers.
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Path analysis: A method to estimate altered pathways in time-varying graphs of neuroimaging data
Abstract Graph-theoretical methods have been widely used to study human brain networks in psychiatric disorders. However, the focus has primarily been on global graphic metrics with little attention to the information contained in paths connecting brain regions. Details of disruption of these paths may be highly informative for understanding disease mechanisms. To detect the absence or addition of multistep paths in the patient group, we provide an algorithm estimating edges that contribute to these paths with reference to the control group. We next examine where pairs of nodes were connected through paths in both groups by using a covariance decomposition method. We apply our method to study resting-state fMRI data in schizophrenia versus controls. Results show several disconnectors in schizophrenia within and between functional domains, particularly within the default mode and cognitive control networks. Additionally, we identify new edges generating additional paths. Moreover, although paths exist in both groups, these paths take unique trajectories and have a significant contribution to the decomposition. The proposed path analysis provides a way to characterize individuals by evaluating changes in paths, rather than just focusing on the pairwise relationships. Our results show promise for identifying path-based metrics in neuroimaging data.
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- Award ID(s):
- 2112455
- PAR ID:
- 10375009
- Publisher / Repository:
- DOI PREFIX: 10.1162
- Date Published:
- Journal Name:
- Network Neuroscience
- Volume:
- 6
- Issue:
- 3
- ISSN:
- 2472-1751
- Format(s):
- Medium: X Size: p. 634-664
- Size(s):
- p. 634-664
- Sponsoring Org:
- National Science Foundation
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