Author Summary Neuronal circuits exhibit homeostatic plasticity mechanisms to cope with perturbations or damage. A central mechanism is ‘synaptic scaling,’ a self-organized response in which the strength of neurons’ excitatory synapses is adjusted to compensate for activity variations. Here we present experiments in which the excitatory connectivity of in vitro cortical networks is progressively weakened through chemical action. The spontaneous activity and effective connectivity of the whole network is monitored as degradation progresses, and the capacity of the network for broad information communication is quantified through the global efficiency. We observed that the network responded to the perturbation by strengthening the effective connectivity, reaching a hyperefficient state for moderate perturbations. The study proves the importance of ‘synaptic scaling’ as a driver for functional reorganization and network-wide resilience. Abstract An elusive phenomenon in network neuroscience is the extent of neuronal activity remodeling upon damage. Here, we investigate the action of gradual synaptic blockade on the effective connectivity in cortical networks in vitro. We use two neuronal cultures configurations—one formed by about 130 neuronal aggregates and another one formed by about 600 individual neurons—and monitor their spontaneous activity upon progressive weakening of excitatory connectivity. We report that the effective connectivity in all cultures exhibits a first phase of transient strengthening followed by a second phase of steady deterioration. We quantify these phases by measuring G EFF , the global efficiency in processing network information. We term hyperefficiency the sudden strengthening of G EFF upon network deterioration, which increases by 20–50% depending on culture type. Relying on numerical simulations we reveal the role of synaptic scaling , an activity–dependent mechanism for synaptic plasticity, in counteracting the perturbative action, neatly reproducing the observed hyperefficiency. Our results demonstrate the importance of synaptic scaling as resilience mechanism.

A key question in modern neuroscience is how cognitive changes in a human brain can be quantified and captured by functional connectivity (FC). A systematic approach to measure pairwise functional distance at different brain states is lacking. This would provide a straightforward way to quantify differences in cognitive processing across tasks; also, it would help in relating these differences in task-based FCs to the underlying structural network. Here we propose a framework, based on the concept of Jensen-Shannon divergence, to map the task-rest connectivity distance between tasks and resting-state FC. We show how this information theoretical measure allows for quantifying connectivity changes in distributed and centralized processing in functional networks. We study resting state and seven tasks from the Human Connectome Project dataset to obtain the most distant links across tasks. We investigate how these changes are associated with different functional brain networks, and use the proposed measure to infer changes in the information-processing regimes. Furthermore, we show how the FC distance from resting state is shaped by structural connectivity, and to what extent this relationship depends on the task. This framework provides a well-grounded mathematical quantification of connectivity changes associated with cognitive processing in large-scale brain networks. Author Summary A key question in modern neuroscience is how cognitive changes in a human brain can be quantified and captured by functional connectivity (FC). Here we propose a framework, based on Jensen-Shannon divergence, to define “connectivity distance” and to infer about brain network reconfiguration across different tasks with respect to resting state, and to explore changes in centralized and distributed processing in FCs. Three functional networks (dorsal attention, frontoparietal and DMN) showed major changes in distributed processing and minor changes in centralized processing. Changes in centralized processing depend on the underlying structural connectivity weights and structural path “hiddenness.” These findings suggest that the cognitive “switch” between resting state and task states is a complex interplay between maximally and minimally distant functional connections, and the underlying structure.