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

Existing whole-brain models are generally tailored to the modelling of a particular data modality (e.g., fMRI or MEG/EEG). We propose that despite the differing aspects of neural activity each modality captures, they originate from shared network dynamics. Building on the universal principles of self-organising delay-coupled nonlinear systems, we aim to link distinct features of brain activity - captured across modalities - to the dynamics unfolding on a macroscopic structural connectome. To jointly predict connectivity, spatiotemporal and transient features of distinct signal modalities, we consider two large-scale models - the Stuart Landau and Wilson and Cowan models - which generate short-lived 40 Hz oscillations with varying levels of realism. 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), functional connectivity dynamics (FCD) and generate MOMs to a comparable degree. This is achieved by adjusting the global coupling and mean conduction time delay and, in the WC model, through the inclusion of balance between excitation and inhibition. For both models, the omission of delays dramatically decreased the performance. For fMRI, the SL model performed worse for FCD and MOMs, highlighting the importance of balanced dynamics for the emergence of spatiotemporal and transient 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 0.4 across modalities for the same set of parameters. Nonetheless, both displayed the emergence of FC patterns that extended beyond the constraints of the anatomical structure. Finally, we show that both models can generate MOMs with empirical-like properties such as size (number of brain regions engaging in a mode) and duration (continuous time interval during which a mode appears). 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

The impact of regional heterogeneity in whole-brain dynamics in the presence of oscillations

Large variability exists across brain regions in health and disease, considering their cellular and molecular composition, connectivity and function. Large-scale whole-brain models comprising coupled brain regions provide insights into the underlying dynamics that shape complex patterns of spontaneous brain activity. In particular, biophysically grounded mean-field whole-brain models in the asynchronous regime were used to demonstrate the dynamical consequences of including regional variability. Nevertheless, the role of heterogeneities when brain dynamics are supporting by synchronous oscillating state, which is a ubiquitous phenomenon in brain, remains poorly understood. Here, we implemented two models capable of presenting oscillatory behaviour with different levels of abstraction: a phenomenological Stuart Landau model and an exact mean-field model. The fit of these models informed by structural-to-functional–weighted MRI signal (T1w/T2w) allowed to explore the implication of the inclusion of heterogeneities for modelling resting-state fMRI recordings from healthy participants. We found that disease-specific regional functional heterogeneity imposed dynamical consequences within the oscillatory regime in fMRI recordings from neurodegeneration with specific impacts in brain atrophy/structure (Alzheimer patients). Overall, we found that models with oscillations perform better when structural and functional regional heterogeneities are considered showing that phenomenological and biophysical models behave similarly at the brink of the Hopf bifurcation.Fil: Sanz Perl Hernandez, Yonatan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Universidad de San Andrés; Argentina. Universitat Pompeu Fabra; EspañaFil: Zamora Lopez, Gorka. Universitat Pompeu Fabra; EspañaFil: Montbrió, Ernest. Universitat Pompeu Fabra; EspañaFil: Monge Asensio, Martí. Universitat Pompeu Fabra; EspañaFil: Vohryzek, Jakub. Universitat Pompeu Fabra; España. University of Oxford; Reino UnidoFil: Fittipaldi, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College; IrlandaFil: Gonzalez Campo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Moguilner, Sebastian Gabriel. University of California; Estados Unidos. Trinity College; Irlanda. Universidad Adolfo Ibañez; ChileFil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College; Irlanda. Universidad Adolfo Ibañez; ChileFil: Tagliazucchi, Enzo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Universidad de San Andrés; Argentina. Universidad Adolfo Ibañez; ChileFil: Yeo, B. T. Thomas. National University of Singapore; SingapurFil: Kringelbach, Morten L.. University of Oxford; Reino Unido. University Aarhus; Dinamarca. Universidade do Minho; PortugalFil: Deco, Gustavo. Universitat Pompeu Fabra; España. Max Planck Institute for Human Cognitive and Brain Sciences; Alemania. Monash University; Australi

The impact of regional heterogeneity in whole-brain dynamics in the presence of oscillations

AbstractLarge variability exists across brain regions in health and disease, considering their cellular and molecular composition, connectivity, and function. Large-scale whole-brain models comprising coupled brain regions provide insights into the underlying dynamics that shape complex patterns of spontaneous brain activity. In particular, biophysically grounded mean-field whole-brain models in the asynchronous regime were used to demonstrate the dynamical consequences of including regional variability. Nevertheless, the role of heterogeneities when brain dynamics are supported by synchronous oscillating state, which is a ubiquitous phenomenon in brain, remains poorly understood. Here, we implemented two models capable of presenting oscillatory behavior with different levels of abstraction: a phenomenological Stuart–Landau model and an exact mean-field model. The fit of these models informed by structural- to functional-weighted MRI signal (T1w/T2w) allowed us to explore the implication of the inclusion of heterogeneities for modeling resting-state fMRI recordings from healthy participants. We found that disease-specific regional functional heterogeneity imposed dynamical consequences within the oscillatory regime in fMRI recordings from neurodegeneration with specific impacts on brain atrophy/structure (Alzheimer’s patients). Overall, we found that models with oscillations perform better when structural and functional regional heterogeneities are considered, showing that phenomenological and biophysical models behave similarly at the brink of the Hopf bifurcation

Understanding brain states across spacetime informed by whole-brain modelling

In order to survive in a complex environment, the human brain relies on the ability to flexibly adapt ongoing behaviour according to intrinsic and extrinsic signals. This capability has been linked to specific whole-brain activity patterns whose relative stability (order) allows for consistent functioning, supported by sufficient intrinsic instability needed for optimal adaptability. The emergent, spontaneous balance between order and disorder in brain activity over spacetime underpins distinct brain states. For example, depression is characterized by excessively rigid, highly ordered states, while psychedelics can bring about more disordered, sometimes overly flexible states. Recent developments in systems, computational and theoretical neuroscience have started to make inroads into the characterization of such complex dynamics over space and time. Here, we review recent insights drawn from neuroimaging and whole-brain modelling motivating using mechanistic principles from dynamical system theory to study and characterize brain states. We show how different healthy and altered brain states are associated to characteristic spacetime dynamics which in turn may offer insights that in time can inspire new treatments for rebalancing brain states in disease.M.L.K. is supported by the ERC Consolidator Grant CAREGIVING (grant no. 615539); Center for Music in the Brain, funded by the Danish National Research Foundation (grant no. DNRF117) and Centre for Eudaimonia and Human Flourishing funded by the Pettit Foundation and Carlsberg Foundation. G.D. is supported by the Spanish Research Project (PID2019–105772GB-I00 AEI FEDER EU), funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI) and European Regional Development Funds (FEDER); HBP SGA3 Human Brain Project Specific Grant Agreement 3 (grant agreement 945539), funded by the EU H2020 FET Flagship programme; and SGR Research Support Group (2017 SGR 1545), funded by the Catalan Agency for Management of University and Research Grants (AGAUR). J.C. is funded by the Portuguese Foundation for Science and Technology (FCT), projects UIDB/50026/2020, UIDP/50026/2020. P.V. is supported by Center for Music in the Brain, funded by the Danish National Research Foundation (grant no. DNRF117). G.D. and J.V. are supported by the EU H2020 project Neurotwin Grant agreement ID: 101017716

Ghost attractors in spontaneous brain activity: recurrent excursions into functionally-relevant BOLD phase-locking states

Functionally relevant network patterns form transiently in brain activity during rest, where a given subset of brain areas exhibits temporally synchronized BOLD signals. To adequately assess the biophysical mechanisms governing intrinsic brain activity, a detailed characterization of the dynamical features of functional networks is needed from the experimental side to constrain theoretical models. In this work, we use an open-source fMRI dataset from 100 healthy participants from the Human Connectome Project and analyze whole-brain activity using Leading Eigenvector Dynamics Analysis (LEiDA), which serves to characterize brain activity at each time point by its whole-brain BOLD phase-locking pattern. Clustering these BOLD phase-locking patterns into a set of k states, we demonstrate that the cluster centroids closely overlap with reference functional subsystems. Borrowing tools from dynamical systems theory, we characterize spontaneous brain activity in the form of trajectories within the state space, calculating the Fractional Occupancy and the Dwell Times of each state, as well as the Transition Probabilities between states. Finally, we demonstrate that within-subject reliability is maximized when including the high frequency components of the BOLD signal (>0.1 Hz), indicating the existence of individual fingerprints in dynamical patterns evolving at least as fast as the temporal resolution of acquisition (here TR = 0.72 s). Our results reinforce the mechanistic scenario that resting-state networks are the expression of erratic excursions from a baseline synchronous steady state into weakly-stable partially-synchronized states – which we term ghost attractors. To better understand the rules governing the transitions between ghost attractors, we use methods from dynamical systems theory, giving insights into high-order mechanisms underlying brain function.This work has been funded by FEDER through the Competitiveness Factors Operational Program (COMPETE), by National funds through the Foundation for Science and Technology (FCT) under the scope of the project UID/Multi/50026; and by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). JC was supported by Portuguese Foundation for Science and Technology CEECIND/03325/2017, Portugal. GD acknowledges funding from the European Union’s Horizon 2020 FET Flagship Human Brain Project under Grant Agreement 785907 HBP SGA2, the Spanish Ministry Project PSI2016-75688-P (AEI/FEDER) and the Catalan Research Group Support 2017 SGR 1545. MK was supported by the European Research Council Consolidator Grant: CAREGIVING (615539), Pettit Foundation, Carlsberg Foundation and Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). BC was supported by the French Government through the UCA-Jedi project managed by the National Research Agency (ANR-15-IDEX-01) and, in particular, by the interdisciplinary Institute for Modeling in Neuroscience and Cognition (NeuroMod) of the Université Côte d’Azur

Moving from phenomenological to predictive modelling: Progress and pitfalls of modelling brain stimulation in-silico

Brain stimulation is an increasingly popular neuromodulatory tool used in both clinical and research settings; however, the effects of brain stimulation, particularly those of non-invasive stimulation, are variable. This variability can be partially explained by an incomplete mechanistic understanding, coupled with a combinatorial explosion of possible stimulation parameters. Computational models constitute a useful tool to explore the vast sea of stimulation parameters and characterise their effects on brain activity. Yet the utility of modelling stimulation in-silico relies on its biophysical relevance, which needs to account for the dynamics of large and diverse neural populations and how underlying networks shape those collective dynamics. The large number of parameters to consider when constructing a model is no less than those needed to consider when planning empirical studies. This piece is centred on the application of phenomenological and biophysical models in non-invasive brain stimulation. We first introduce common forms of brain stimulation and computational models, and provide typical construction choices made when building phenomenological and biophysical models. Through the lens of four case studies, we provide an account of the questions these models can address, commonalities, and limitations across studies. We conclude by proposing future directions to fully realise the potential of computational models of brain stimulation for the design of personalized, efficient, and effective stimulation strategies

Dynamic spatiotemporal patterns of brain connectivity reorganize across development

Late human development is characterized by the maturation of high-level functional processes, which rely on reshaping of white matter connections, as well as synaptic density. However, the relationship between the whole-brain dynamics and the underlying white matter networks in neurodevelopment is largely unknown. In this study, we focused on how the structural connectome shapes the emerging dynamics of cerebral development between the ages of 6 and 33 years, using functional and diffusion magnetic resonance imaging combined into a spatiotemporal connectivity framework. We defined two new measures of brain dynamics, namely the system diversity and the spatiotemporal diversity, which quantify the level of integration/segregation between functional systems and the level of temporal self-similarity of the functional patterns of brain dynamics, respectively. We observed a global increase in system diversity and a global decrease and local refinement in spatiotemporal diversity values with age. In support of these findings, we further found an increase in the usage of long-range and inter-system white matter connectivity and a decrease in the usage of short-range connectivity with age. These findings suggest that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age. These functional changes are supported by a greater involvement of long-range and inter-system axonal pathways.AUTHOR SUMMARYMaturation in human development is represented by changes in both functional dynamics and structural connectivity in the human brain. By constructing a spatiotemporal connectome for a cohort of 81 subjects ranging from 6 to 33 years of age, we demonstrate how these changes can be studied in a unified framework. We do so by defining two new measures of brain dynamics, namely the spatiotemporal diversity, mapping the level of temporal self-similarity of the functional patterns of brain dynamics, and system diversity, quantifying the level of integration/segregation between functional systems. These measures, we argue, represent a novel way of looking at brain dynamics constraints by structural connectivity. Using these measures, we show that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age