Pathological Neural Attractor Dynamics in Slowly Growing Gliomas Supports an Optimal Time Frame for White Matter Plasticity

Abstract

Neurological function in patients with slowly growing brain tumors can be preserved even after extensive tumor resection. However, the global process of cortical reshaping and cerebral redistribution cannot be understood without taking into account the white matter tracts. The aim of this study was to predict the functional consequences of tumor-induced white matter damage by computer simulation. A computational model was proposed, incorporating two cortical patches and the white matter connections of the uncinate fasciculus. Tumor-induced structural changes were modeled such that different aspects of the connectivity were altered, mimicking the biological heterogeneity of gliomas. The network performance was quantified by comparing memory pattern recall and the plastic compensatory capacity of the network was analyzed. The model predicts an optimal level of synaptic conductance boost that compensates for tumor-induced connectivity loss. Tumor density appears to change the optimal plasticity regime, but tumor size does not. Compensatory conductance values that are too high lead to performance loss in the network and eventually to epileptic activity. Tumors of different configurations show differences in memory recall performance with slightly lower plasticity values for dense tumors compared to more diffuse tumors. Simulation results also suggest an optimal noise level that is capable of increasing the recall performance in tumor-induced white matter damage. In conclusion, the model presented here is able to capture the influence of different tumor-related parameters on memory pattern recall decline and provides a new way to study the functional consequences of white matter invasion by slowly growing brain tumors.