Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future.

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by dysfunction in distributed functional brain networks. Previous studies have reported abnormal changes in static functional connectivity using resting-state functional magnetic resonance imaging (fMRI). However, the dynamic characteristics of brain networks in PD is still poorly understood. This study aimed to quantify the characteristics of dynamic functional connectivity in PD patients at nodal, intra- and inter-subnetwork levels. Resting-state fMRI data of a total of 42 PD patients and 40 normal controls (NCs) were investigated from the perspective of the temporal variability on the connectivity profiles across sliding windows. The results revealed that PD patients had greater nodal variability in precentral and postcentral area (in sensorimotor network, SMN), middle occipital gyrus (in visual network), putamen (in subcortical network) and cerebellum, compared with NCs. Furthermore, at the subnetwork level, PD patients had greater intra-network variability for the subcortical network, salience network and visual network, and distributed changes of inter-network variability across several subnetwork pairs. Specifically, the temporal variability within and between subcortical network and other cortical subnetworks involving SMN, visual, ventral and dorsal attention networks as well as cerebellum was positively associated with the severity of clinical symptoms in PD patients. Additionally, the increased inter-network variability of cerebellum-auditory pair was also correlated with clinical severity of symptoms in PD patients. These observations indicate that temporal variability can detect the distributed abnormalities of dynamic functional network of PD patients at nodal, intra- and inter-subnetwork scales, and may provide new insights into understanding PD.

42Neuroimaging evidence suggests that the aging brain relies on a more distributed set of cortical 43 regions than younger adults in order to maintain successful levels of performance during demanding 44 cognitive tasks. However, it remains unclear how task demands give rise to this age-related expansion 45 in cortical networks. To investigate this issue, we used functional magnetic resonance imaging to 46 measure univariate activity, network connectivity, and cognitive performance in younger and older 47 adults during a working memory (WM) task. In the WM task investigated, participants hold letters online 48 (maintenance) while reordering them alphabetically (manipulation). WM load was titrated to obtain four 49 individualized difficulty levels. Network integration-defined as the ratio of within-versus between-50 network connectivity-was linked to individual differences in WM capacity. The study yielded three 51 main findings. First, as task difficulty increased, network integration decreased in younger adults, 52whereas it increased in older adults. Second, age-related increases in network integration were driven 53 by increases in right hemispheric connectivity to both left and right cortical regions, a finding that helps 54 to reconcile extant theories of compensatory recruitment in aging to address the multivariate dynamics 55 of global network functioning. Lastly, older adults with higher WM capacity demonstrated higher levels 56 of network integration in the most difficult condition. These results shed light on the mechanisms of 57 age-related network reorganization by suggesting that changes in network connectivity may act as an 58 adaptive form of compensation, with older adults recruiting a more distributed cortical network as task 59 demands increase. 60 61 3 Significance statement 62 Older adults often activate brain regions not engaged by younger adults, but the circumstances 63 under which this widespread network emerges are unclear. Here, we examined the effects of aging on 64 network connectivity between task regions recruited during a working memory (WM) manipulation task, 65 and the rest of the brain. We found an age-related increase in the more global network integration in 66 older adults, and an association between this integration and working memory capacity in older 67 adults. The findings are generally consistent with the compensatory interpretation of these effects. 68 adults is beneficial for performance (Park and Reuter-Lorenz, 2009;Cabeza and Dennis, 2012; Cabeza 103 and Dennis, 2013), and both CRUNCH and HAROLD effects have been interpreted as compensatory. 104However, the evidence for compensation has been mostly based on univariate activity and evidence 105 that network changes in older adults contribute to cognitive performance is largely missing (however, 106 see Monge et al., 2018). We hypothesized that age-related WM network integration would be 107 associated with WM ability in older adults (Hypothesis 3). 108To test these hypotheses, participants completed a verbal WM man...