Similar structural area modulates local inhibitioninitiating post-lesion adaptive mechanism

The focal lesion, a form of biological perturbation damaging anatomical architecture, reasonably alters the normative healthy functional pattern but may recover over time. Nevertheless, how the brain counters deterioration in structure by global reshaping of functional connectivity (FC) after a lesion is largely unknown. We propose a novel equivalence principle based on structural and dynamic similarity analysis to predict specific compensatory areas initiating lost excitatory-inhibitory (E-I) regulation after lesion. We hypothesize that similar structural areas (SSAs) and dynamically similar areas (DSAs) corresponding to a lesioned site are the crucial dynamical units to restore lost homeostatic balance within the surviving cortical brain regions. SSAs and DSAs are independent measures, one based on structural similarity properties measured by Jaccard Index and the other based on post-lesion recovery time. Thereafter, a large-scale mean field model is deployed on top of a virtually lesioned structural connectome for characterizing the global brain dynamics and functional connectivity at the level of individual subjects. Despite inter-individual variability in SSAs, we found a general normative pattern in functional re-organization within the ipsi- and contra-lesional regions. The study demonstrates how SSAs and DSAs largely predict overlapping brain regions for different lesion centers/sites irrespective of the complexity of the lesion recovery process. The proposed computational framework captures the improvement of large-scale cortical cohesion by re-adjusting local inhibition. Our results further suggest that the predicted brain areas participating in recovery are not randomly distributed and widespread over the brain. Instead, the predicted brain areas are predominantly recruited from the ipsilesional hemisphere, barring a few regions from contra, suggesting that wiring proximity and similarity are the two major guiding principles of compensation-related utilization of hemisphere (CRUH) in the post-lesion FC re-organization process. Our finding further suggests that the re-organization of FC arises from the interplay between the underlying structural connectivity profile and the local inhibitory weights influencing compensatory coordinated brain dynamics during post-lesion recovery.