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)...

Multielectrode recordings have revealed zero time lag synchronization among remote cerebral cortical areas. However, the axonal conduction delays among such distant regions can amount to several tens of milliseconds. It is still unclear which mechanism is giving rise to isochronous discharge of widely distributed neurons, despite such latencies. Here, we investigate the synchronization properties of a simple network motif and found that, even in the presence of large axonal conduction delays, distant neuronal populations self-organize into lag-free oscillations. According to our results, cortico-cortical association fibers and certain corticothalamo-cortical loops represent ideal circuits to circumvent the phase shifts and time lags associated with conduction delays.thalamocortical system ͉ isochronous oscillations ͉ phase locking ͉ long-range synchronization ͉ axonal latency C ells in the visual cortex of mammals tend to fire simultaneously when activated by related features of a visual stimulus (1-4). This observation provided some of the early evidence that the nervous system may use an internal temporal code to process information. Since then, multicell electrophysiological studies have revealed the synchronous discharge of neurons distributed in different structures of the cerebral cortex, hippocampal formation, and thalamus (5, 6). Its biological significance derives from the observation that such precise and coordinated spike timing correlates with perception and behavioral performance (7-10). Remarkably, synchrony of neuronal activity is not limited to short-range interactions within a cortical patch. Interareal synchronization across cortical regions including interhemispheric areas has been observed in several tasks (7,9,(11)(12)(13)(14). The topological specificity and temporal unfolding of the synchrony reported in such studies are in agreement with its assumed role of subserving the effective ''coupling'' of the neuronal dynamics of the respective regions (9, 15).Beyond its functional relevance, the zero time lag synchrony among such distant neuronal ensembles must be established by mechanisms that are able to compensate for the delays involved in the neuronal communication. Latencies in conducting nerve impulses down axonal processes can amount to delays of several tens of milliseconds between the generation of a spike in a presynaptic cell and the elicitation of a postsynaptic potential (16). The question is how, despite such temporal delays, the reciprocal interactions between two brain regions can lead to the associated neural populations to fire in unison.Direct cortico-cortical fibers are major pathways of transareal communication and thus one principal substrate for the establishment of long-range synchrony. For instance, severing the corpus callosum was observed to disrupt the interhemispheric synchrony among homotopic cortical areas 17 in the cat (17). However, it is not clear whether direct excitatory corticocortical connections alone can mediate the zero phase synchronization of reciproca...

No abstract