On Global Brain Reconfiguration after Local Manipulations

Understanding how localized brain interventions translate into whole-brain dynamics is crucial for deciphering neural function and tailoring therapeutic strategies. Combining mouse experimental datasets of focal interventions (thalamic lesion and chemogenetic silencing of cortical hubs), we demonstrate both local and global effects. Using whole-brain simulations of experimental data, we not only confirm the distributed nature of local manipulations but also offer mechanistic insights into these processes. Our simulations predict specific alterations in firing rates and spectral characteristics across specific brain networks, leading to structured changes in functional connectivity patterns. Some of these predictions have been empirically validated. Notably, the affected brain subnetworks—and their resultant’signatures’ of change—are contingent on the original intervention site, suggesting a method to accurately localize the source of alteration. Our results provide a general framework for interpreting localized intervention effects, offering insights that could refine clinical interventions for focal brain disorders by enabling targeted circuit-level neuromodulation strategies.