The concept of resting state functional magnetic resonance imaging (fMRI) is built onto an original finding in 1995 that brain hemispheres present synchronous signal fluctuations with distinct patterns. fMRI measurements rely on blood oxygenation changes that indirectly mirror neural activity. Therefore, the origin of certain functional connectivity patterns, resting state networks (RSNs), has been a widely debated research question and numerous contributing factors have been identified. According to current understanding the fluctuations reflect maintenance of the system integrity in addition to spontaneous thought and action processes in the resting state. A popular method to study the functional connectivity in resting state fMRI is spatial independent component analysis (ICA) that decomposes signal sources into statistically independent components. The dichotomy of functional specialization versus functional integration has a correspondence in fMRI studies where RSNs play the integrative viewpoint of brain function. Although canonical large-scale RSNs are broadly distributed they also express modularity that can be accomplished by ICA with a high number of estimated components. The characteristics of high ICA dimensionality are broadly investigated in the thesis. An enduring issue in resting state research has been the confounding noise sources like motion and cardiorespiratory processes which may hamper the analysis. In this thesis the ability of ICA to separate these noise sources from the default mode network, a major RSN, is studied. Additionally, the suitability of ICA for full frequency spectrum analysis, a relatively rare setting in biosignal analysis, is investigated. The results of the thesis support the viewpoint of ICA as a robust analysis method for functional connectivity analysis. Cardiorespiratory and motion induced noise did not confound the functional connectivity analyses with ICA. High dimensional ICA provided better signal source separation, revealed the modular structure of the RSNs and pinpointed the specific aberrations in the autism spectrum disorder population. ICA was also found applicable for fully explorative analysis in both the spatial and temporal domains and indicated functional connectivity changes induced by transcranial bright light stimulation.
Resting-state networks (RSNs) can be reliably and reproducibly detected using independent component analysis (ICA) at both individual subject and group levels. Altering ICA dimensionality (model order) estimation can have a significant impact on the spatial characteristics of the RSNs as well as their parcellation into sub-networks. Recent evidence from several neuroimaging studies suggests that the human brain has a modular hierarchical organization which resembles the hierarchy depicted by different ICA model orders. We hypothesized that functional connectivity between-group differences measured with ICA might be affected by model order selection. We investigated differences in functional connectivity using so-called dual-regression as a function of ICA model order in a group of unmedicated seasonal affective disorder (SAD) patients compared to normal healthy controls. The results showed that the detected disease-related differences in functional connectivity alter as a function of ICA model order. The volume of between-group differences altered significantly as a function of ICA model order reaching maximum at model order 70 (which seems to be an optimal point that conveys the largest between-group difference) then stabilized afterwards. Our results show that fine-grained RSNs enable better detection of detailed disease-related functional connectivity changes. However, high model orders show an increased risk of false positives that needs to be overcome. Our findings suggest that multilevel ICA exploration of functional connectivity enables optimization of sensitivity to brain disorders.
Recent evidence on resting-state networks in functional (connectivity) magnetic resonance imaging (fcMRI) suggests that there may be significant spatial variability of activity foci over time. This study used a sliding time window approach with the spatial domain–independent component analysis (SliTICA) to detect spatial maps of resting-state networks over time. The study hypothesis was that the spatial distribution of a functionally connected network would present marked variability over time. The spatial stability of successive sliding-window maps of the default mode network (DMN) from fcMRI data of 12 participants imaged in the resting state was analyzed. Control measures support previous findings on the stability of independent component analysis in measuring sliding-window sources accurately. The spatial similarity of successive DMN maps varied over time at low frequencies and presented a 1/f power spectral pattern. SliTICA maps show marked temporal variation within the DMN; a single voxel was detected inside a group DMN map in maximally 82% of time windows. Mapping of incidental connectivity reveals centrifugally increasing connectivity to the brain cortex outside the DMN core areas. In conclusion, SliTICA shows marked spatial variance of DMN activity in time, which may offer a more comprehensive measurement of the overall functional activity of a network.
