Biology subjects

Pascoa dos Santos, F.

Publications and source records attributed to Pascoa dos Santos, F..

4 recordsLinked to original sources

bioRxiv2024

Metastable Dynamics Emerge from Local Excitatory-Inhibitory Homeostasis in the Cortex at Rest

The dynamics of the human cortex are highly metastable, driving the spontaneous exploration of network states. This metastability depends on circuit-level edge-of-bifurcation dynamics, which emerge from firing-rate control through multiple mechanisms of excitatory-inhibitory (E-I) homeostasis. However, it is unclear how these contribute to the metastability of cortical networks. We propose that individual mechanisms of E-I homeostasis contribute uniquely to the emergence of resting-state dynamics and test this hypothesis in a large-scale model of the human cortex. We show that empirical connectivity and dynamics can only be reproduced when accounting for multiple mechanisms of E-I homeostasis. More specifically, while the homeostasis of excitation and inhibition enhances metastability, the regulation of intrinsic excitability ensures moderate synchrony, maximizing functional complexity. Furthermore, the modulation bifurcation modulation by the homeostasis of excitation and intrinsic excitability compensates for strong input fluctuations in connector hubs. Importantly, this only occurs in models accounting for local gamma oscillations, suggesting a relationship between E-I balance, gamma rhythms, and metastable dynamics. Altogether, our results show that cortical networks self-organize toward maximal metastability through the multi-factor homeostasis of E-I balance. Therefore, the benefits of combining multiple homeostatic mechanisms transcend the circuit level, supporting the metastable dynamics of large-scale cortical networks.

neuroscience↗

bioRxiv2024

Excitatory-Inhibitory Homeostasis and Bifurcation Control in the Wilson-Cowan Model of Cortical Dynamics

Although the primary function of excitatory-inhibitory (E-I) homeostasis is the maintenance of mean firing rates, the conjugation of multiple homeostatic mechanisms is thought to be pivotal to ensuring edge-of-bifurcation dynamics in cortical circuits. However, computational studies on E-I homeostasis have focused solely on the plasticity of inhibition, neglecting the impact of different modes of E-I homeostasis on cortical dynamics. Therefore, we investigate how oscillations and edge-of-bifurcation dynamics are shaped by the diverse mechanisms of E-I homeostasis employed by cortical networks. Using the Wilson-Cowan model, we explore how distinct modes of E-I homeostasis maintain stable firing rates in models with varying levels of input and how it affects circuit dynamics. Our results confirm that E-I homeostasis can be leveraged to control edge-of-bifurcation dynamics and that some modes of homeostasis maintain mean firing rates under higher levels of input by modulating the distance to the bifurcation. Additionally, relying on multiple modes of homeostasis ensures stable activity while keeping oscillation frequencies within a physiological range. Our findings tie relevant features of cortical networks, such as E-I balance, the generation of gamma oscillations, and edge-of-bifurcation dynamics, under the framework of firing-rate homeostasis, providing a mechanistic explanation for the heterogeneity in the distance to the bifurcation found across cortical areas. In addition, we reveal the functional benefits of relying upon different homeostatic mechanisms, providing a robust method to regulate network dynamics with minimal perturbation to the generation of gamma rhythms and explaining the correlation between inhibition and gamma frequencies found in cortical networks. Author summaryWe study how excitatory-inhibitory (E-I) homeostasis controls edge-of-bifurcation dynamics in cortical networks and how it impacts the generation of gamma oscillations. Importantly, while previous studies have limited E-I homeostasis to the plasticity of inhibition, we explore the wide range of mechanisms employed by cortical networks and, more importantly, how they interact. Here, we derive the mathematical solution for the Wilson-Cowan model under distinct modes of homeostasis and study how they shape model dynamics and the generation of gamma oscillations. That said, we demonstrate that E-I homeostasis, particularly of excitation and intrinsic excitability, modulates model dynamics relative to the bifurcation between damped and sustained oscillations in a manner previously unaccounted for, providing a mechanism for the implementation of heterogeneous distances to the bifurcation across cortical areas. Furthermore, our results stress the functional benefits of relying on multiple modes of homeostasis, allowing for the control of firing rates and circuit dynamics while ensuring that gamma oscillations remain within a physiological range and explaining the relationship between inhibition and gamma frequencies found in empirical data. With these results, we unify E-I balance, edge-of-bifurcation dynamics, and gamma oscillations under the lens of firing-rate homeostasis.

neuroscience↗

bioRxiv2022

Multi-modal and multi-model interrogation of large-scale functional brain networks

Current whole-brain models are generally tailored to the modelling of a particular modality of data (e.g., fMRI or MEG/EEG). Although different imaging modalities reflect different aspects of neural activity, we hypothesise that this activity arises from common network dynamics. Building on the universal principles of self-organising delay-coupled nonlinear systems, we aim to link distinct electromagnetic and metabolic features of brain activity to the dynamics on the brains macroscopic structural connectome. To jointly predict dynamical and functional connectivity features of distinct signal modalities, we consider two large-scale models generating local short-lived 40 Hz oscillations with various degrees of realism - namely Stuart Landau (SL) and Wilson and Cowan (WC) models. To this end, we measure features of functional connectivity and metastable oscillatory modes (MOMs) in fMRI and MEG signals - and compare them against simulated data. We show that both models can represent MEG functional connectivity (FC) and functional connectivity dynamics (FCD) to a comparable degree, by varying global coupling and mean conduction time delay. For both models, the omission of delays dramatically decreased the performance. For fMRI, the SL model performed worse for FCD, highlighting the importance of balanced dynamics for the emergence of spatiotemporal patterns of ultra-slow dynamics. Notably, optimal working points varied across modalities and no model was able to achieve a correlation with empirical FC higher than 0.45 across modalities for the same set of parameters. Nonetheless, both displayed the emergence of FC patterns beyond the anatomical framework. Finally, we show that both models can generate MOMs with empirical-like properties. Our results demonstrate the emergence of static and dynamic properties of neural activity at different timescales from networks of delay-coupled oscillators at 40 Hz. Given the higher dependence of simulated FC on the underlying structural connectivity, we suggest that mesoscale heterogeneities in neural circuitry may be critical for the emergence of parallel cross-modal functional networks and should be accounted for in future modelling endeavours.

neuroscience↗

bioRxiv2022

Multiscale Effects of Excitatory-Inhibitory Homeostasis in Lesioned Cortical Networks: A Computational Study

Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesion-dependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic pain. In summary, our results show that the effects of E-I homeostasis extend beyond local E-I balance, driving the restoration of global properties of FC, and relating to post-stroke symptomatology. Therefore, we suggest the framework of E-I homeostasis as a relevant theoretical foundation for the study of stroke recovery and for understanding the emergence of meaningful features of FC from local dynamics.

neuroscience↗