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Brain parcellation divides the brain’s spatial domain into small regions, which are represented by nodes within the network analysis framework. While template-based parcellations are widely used, the parcels on the template do not necessarily match individual’s functional nodes. A new method is developed to overcome the inconsistent network analysis results by by-passing the difficulties of parcellating the brain into functionally meaningful areas. First, roughly equal-sized parcellations are obtained. Second, these random parcellations are applied to individual subjects multiple times and a pseudo-bootstrap (PBS) of the network is obtained for statistical inferences. It was found that the variation of mean global network metrics from PBS sampling is smaller compared with inter-subject variation or within-subject variation between two diffusion MRI scans. Using the mean global network metrics from PBS sampling, the intra-class correlation is always higher than the average obtained from using a single random parcellation. As one application, the PBS method was tested on the Human Connectome Project resting state dataset to identify individuals across scan sessions based on the mean functional connectivity (FC)—a trivial network property that has little information about the connectivity between nodes. An accuracy rate of ∼90% was achieved by simply finding the maximum correlation of mean FC of PBS samples between two scan sessions.

Alzheimer's disease is considered a disconnection syndrome, motivating the use of brain network measures to detect changes in whole-brain resting state functional connectivity (FC). We investigated changes in FC within and among resting state networks (RSN) across four different stages in the Alzheimer's disease continuum. FC changes were examined in two independent cohorts of individuals (84 and 58 individuals, respectively) each comprising control, subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia groups. For each participant, FC was computed as a matrix of Pearson correlations between pairs of time series from 278 gray matter brain regions. We determined significant differences in FC modular organization with two distinct approaches, network contingency analysis and multiresolution consensus clustering. Network contingency analysis identified RSN sub-blocks that differed significantly across clinical groups. Multiresolution consensus clustering identified differences in the stability of modules across multiple spatial scales. Significant modules were further tested for statistical association with memory and executive function cognitive domain scores. Across both analytic approaches and in both participant cohorts, the findings converged on a pattern of FC that varied systematically with diagnosis within the frontoparietal network (FP) and between the FP network and default mode network (DMN). Disturbances of modular organization were manifest as greater internal coherence of the FP network and stronger coupling between FP and DMN, resulting in less segregation of these two networks. Our findings suggest that the pattern of interactions within and between specific RSNs offers new insight into the functional disruption that occurs across the Alzheimer's disease spectrum. Keywords: Alzheimer's disease, Resting state, Brain networks, Functional connectivity, Connectomics

Graph theoretical analysis has played a key role in characterizing global features of the topology of complex networks, describing diverse systems such as protein interactions, food webs, social relations and brain connectivity. How system elements communicate with each other depends not only on the structure of the network, but also on the nature of the system's dynamics which are constrained by the amount of knowledge and resources available for communication processes. Complementing widely used measures that capture efficiency under the assumption that communication preferentially follows shortest paths across the network ("routing"), we define analytic measures directed at characterizing network communication when signals flow in a random walk process ("diffusion"). The two dimensions of routing and diffusion efficiency define a morphospace for complex networks, with different network topologies characterized by different combinations of efficiency measures and thus occupying different regions of this space. We explore the relation of network topologies and efficiency measures by examining canonical network models, by evolving networks using a multi-objective optimization strategy, and by investigating real-world network data sets. Within the efficiency morphospace, specific aspects of network topology that differentially favor efficient communication for routing and diffusion processes are identified. Charting regions of the morphospace that are occupied by canonical, evolved or real networks allows inferences about the limits of communication efficiency imposed by connectivity and dynamics, as well as the underlying selection pressures that have shaped network topology.

AbstractCommunication models describe the flow of signals among nodes of a network. In neural systems, communication models are increasingly applied to investigate network dynamics across the whole brain, with the ultimate aim to understand how signal flow gives rise to brain function. Communication models range from diffusion-like processes to those related to infectious disease transmission and those inspired by engineered communication systems like the internet. This Focus Feature brings together novel investigations of a diverse range of mechanisms and strategies that could shape communication in mammal whole-brain networks.