Pathological perturbations of the brain are rarely confined to a single locus; instead, they often spread via axonal pathways to influence other regions. Patterns of such disease propagation are constrained by the extraordinarily complex, yet highly organized, topology of the underlying neural architecture; the so-called connectome. Thus, network organization fundamentally influences brain disease, and a connectomic approach grounded in network science is integral to understanding neuropathology. Here, we consider how brain-network topology shapes neural responses to damage, highlighting key maladaptive processes (such as diaschisis, transneuronal degeneration and dedifferentiation), and the resources (including degeneracy and reserve) and processes (such as compensation) that enable adaptation. We then show how knowledge of network topology allows us not only to describe pathological processes but also to generate predictive models of the spread and functional consequences of brain disease.

Neuronal dynamics display a complex spatiotemporal structure involving the precise, context-dependent coordination of activation patterns across a large number of spatially distributed regions. Functional magnetic resonance imaging (fMRI) has played a central role in demonstrating the nontrivial spatial and topological structure of these interactions, but thus far has been limited in its capacity to study their temporal evolution. Here, using highresolution resting-state fMRI data obtained from the Human Connectome Project, we mapped time-resolved functional connectivity across the entire brain at a subsecond resolution with the aim of understanding how nonstationary fluctuations in pairwise interactions between regions relate to large-scale topological properties of the human brain. We report evidence for a consistent set of functional connections that show pronounced fluctuations in their strength over time. The most dynamic connections are intermodular, linking elements from topologically separable subsystems, and localize to known hubs of default mode and frontoparietal systems. We found that spatially distributed regions spontaneously increased, for brief intervals, the efficiency with which they can transfer information, producing temporary, globally efficient network states. Our findings suggest that brain dynamics give rise to variations in complex network properties over time, possibly achieving a balance between efficient information-processing and metabolic expenditure.network efficiency | dynamic connectivity | time-dependent network T he coordination of brain activity between disparate neural populations is a dynamic and context-dependent process (1-3). Although dynamic patterns of neural synchronization may be evident in time-dependent measures of functional connectivity (4, 5), the temporal stability of high-level topological properties is unknown. The topology of large-scale cortical activity-such as its efficient network layout (6), community structure (7), network hubs (8), rich-club organization (9, 10), and small worldness (11, 12)-may reflect fundamental aspects of cortical computation. Temporal fluctuations in these graph-theoretic measures may hence speak to adaptive properties of neuronal information processing.With international connectome mapping consortia such as the Human Connectome Project (HCP) (13) and the developing Human Connectome Project in full swing, resting-state functional magnetic resonance imaging (rsfMRI) data of unprecedented temporal resolution are now available to map the time-resolved properties of functional brain networks. Imaging the brain at rest reveals spontaneous low-frequency fluctuations in brain activity that are temporally correlated between functionally related regions (14-17). Interregional correlations are referred to as functional connections, and they collectively form a complex network (18). Functional brain networks are typically mapped in a timeaveraged sense, based on the assumption that functional connections remain relatively static (stationary)...

Estimates of functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) are sensitive to artefacts caused by in-scanner head motion. This susceptibility has motivated the development of numerous denoising methods designed to mitigate motion-related artefacts. Here, we compare popular retrospective rs-fMRI denoising methods, such as regression of head motion parameters and mean white matter (WM) and cerebrospinal fluid (CSF) (with and without expansion terms), aCompCor, volume censoring (e.g., scrubbing and spike regression), global signal regression and ICA-AROMA, combined into 19 different pipelines. These pipelines were evaluated across five different quality control benchmarks in four independent datasets associated with varying levels of motion. Pipelines were benchmarked by examining the residual relationship between in-scanner movement and functional connectivity after denoising; the effect of distance on this residual relationship; whole-brain differences in functional connectivity between high- and low-motion healthy controls (HC); the temporal degrees of freedom lost during denoising; and the test-retest reliability of functional connectivity estimates. We also compared the sensitivity of each pipeline to clinical differences in functional connectivity in independent samples of people with schizophrenia and obsessive-compulsive disorder. Our results indicate that (1) simple linear regression of regional fMRI time series against head motion parameters and WM/CSF signals (with or without expansion terms) is not sufficient to remove head motion artefacts; (2) aCompCor pipelines may only be viable in low-motion data; (3) volume censoring performs well at minimising motion-related artefact but a major benefit of this approach derives from the exclusion of high-motion individuals; (4) while not as effective as volume censoring, ICA-AROMA performed well across our benchmarks for relatively low cost in terms of data loss; (5) the addition of global signal regression improved the performance of nearly all pipelines on most benchmarks, but exacerbated the distance-dependence of correlations between motion and functional connectivity; and (6) group comparisons in functional connectivity between healthy controls and schizophrenia patients are highly dependent on preprocessing strategy. We offer some recommendations for best practice and outline simple analyses to facilitate transparent reporting of the degree to which a given set of findings may be affected by motion-related artefact.