Abstract

The mystery behind the origin of the pain and the difficulty to propose methodologies for its quantitative characterization fascinated philosophers (and then scientists) from the dawn of our modern society. Nowadays, studying patterns of information flow in mesoscale activity of brain networks is a valuable strategy to offer answers in computational neuroscience. In this paper, complex network analysis was performed on the time-varying brain functional connectomes of a rat model of persistent peripheral neuropathic pain, obtained by means of local field potential and spike train analysis. A wide range of topological network measures (14 in total, the code is publicly released at: https://github.com/biomedical-cybernetics/topological_measures_wide_analysis) was employed to quantitatively investigate the rewiring mechanisms of the brain regions responsible for development and upkeep of pain along time, from three hours to 16 days after nerve injury. The time trend (across the days) of each network measure was correlated with a behavioural test for rat pain, and surprisingly we found that the rewiring mechanisms associated with two local topological measure, the local-community-paradigm and the power-lawness, showed very high statistical correlations (higher than 0.9, being the maximum value 1) with the behavioural test. We also disclosed clear functional connectivity patterns that emerged in association with chronic pain in the primary somatosensory cortex (S1) and ventral posterolateral (VPL) nuclei of thalamus. This study represents a pioneering attempt to exploit network science models in order to elucidate the mechanisms of brain region re-wiring and engram formations that are associated with chronic pain in mammalians. We conclude that the local-community-paradigm is a model of complex network organization that triggers a local learning rule, which seems associated to processing, learning and memorization of chronic pain in the brain functional connectivity. This rule is based exclusively on the network topology, hence was named epitopological learning.

Highlights

  • Life promotes changes to facilitate adaptability in environments subject to modifications

  • We admit that it is crucial to control this degree of uncertainty. For such reason we offer below two different methodologies to assess and quantify how far from this risk are the values of correlation that we obtained using the interpolated signals

  • We found that the standard error was very small in comparison to the mean value of each measure, and for this reason we concluded that all the measures were converging to a correct mean value

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Summary

Introduction

Life promotes changes to facilitate adaptability in environments subject to modifications. For each defined topological measure we can obtain a curve that progressively varies over the time steps, the ensemble of these curves represent different markers of topological features of the rewiring correlates of pain in the brain time-varying functional connectomes of the rat model after CCI.

Results
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