CNS*2020 Online

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74885079714
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2998779


Carlos Coronel, Patricio Orio, Rodrigo Cofré

In the brain, at the macroscale level, two organizational principles participate in the processing of information: segregation and integration. While segregation allows the processing of information in specific brain regions, integration coordinates the activity of these regions to generate a behavioral response [1]. Recent studies suggest that the cholinergic system promotes segregated states and the noradrenergic system promotes integrated states, both measured using graph theoretical tools over the functional connectivity (FC) matrices [2,3]. We extended this neuromodulatory framework by including the noradrenergic system (filter gain), and the effect of the cholinergic system in the excitatory and inhibitory circuits separately (excitatory and inhibitory gain). The neuromodulatory framework was tested using the Jansen Rit neural mass model [4], built from real human structural connectivity matrices and heterogeneous transmission delays for long-range connections (Fig. 1). The fMRI-BOLD signals were simulated using a generalized hemodynamic function model, and features such as the global phase synchronization, oscillatory frequency and SNR were measured. On the other hand, FC matrices were built using pairwise Pearson’s correlation from the simulated BOLD signals. Thresholded FC matrices were analyzed with graph theoretical tools for computing segregation and integration. Our results suggest that functional integration is possible only with the suppression of the feedback excitation, mediated by the inhibitory gain, and follows a sigmoid or inverted U-shaped function, depending of the noise intensity levels. Also, the integration is accompanied by an increase in signal to noise ratio and regularity of EEG signals. The results suggest a mechanistic interpretation. We propose that the cholinergic system neuromodulation on the excitatory connections increases SNR locally, and the effect of that system on the inhibitory interneurons suppresses the local cortico-cortical transmission, increasing the responsivity of pyramidal neurons to stimulus from distant regions. Finally, the noradrenergic system coordinates long-range neural activity promoting integration. This framework constitutes a new set of tools and ideas to test how neural gain mechanisms mediate the balance between integration and segregation in the brain.

[1] Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: uses and interpretations. _Neuroimage, 52(3)_ , 1059-1069.

[2] Shine, J. M., Aburn, M. J., Breakspear, M., & Poldrack, R. A. (2018). The modulation of neural gain facilitates a transition between functional segregation and integration in the brain. _Elife, 7_ , e31130.

[3] Shine, J. M. (2019). Neuromodulatory influences on integration and segregation in the brain. _Trends in cognitive sciences_.

[4] Jansen, B. H., & Rit, V. G. (1995). Electroencephalogram and visual evoked potential generation in a mathematical model of coupled cortical columns. _Biological cybernetics, 73(4)_ , 357-366.