Demian Battaglia, Christopher W. Lynn, Danielle S. Bassett, Lia Papadopoulos, University of Pennsylvania [Philadelphia], Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santa Fe Institute, This work was primarily supported by National Science Foundation BCS-1631550, Army Research Office W911NF-18-1-0244, and National Institutes of Health R01-MH -116920. DSB, LP, and CWL would like to acknowledge additional support from the John D. and Catherine T. MacArthur Foundation, the Alfred P. Sloan Foundation, the ISI Foundation, the Paul Allen Foundation, the Army Research Laboratory (W911NF-10-2-0022), the Army Research Office (Bassett-W911NF-14-1-0679, Grafton-W911NF-16-1-0474, DCIST-W911NF-17-2-0181), the Office of Naval Research, the National Institute of Mental Health (2-R01-DC-009209-11, R01-MH112847, R01-MH107235, R21-M MH-106799), the National Institute of Child Health and Human Development (1R01HD086888-01), National Institute of Neurological Disorders and Stroke (R01 NS099348), and the National Science Foundation (BCS-1441502, BCS-1430087, and NSF PHY-1554488). LP was also supported by a Graduate Research Fellowship from the National Science Foundation for part of this work. DB acknowledges support from the EU i-Innovative Training Network 'i-CONN' (H2020 MSCA ITN 859937) and the French Agence Nationale pour la Recherche ('ERMUNDY', ANR-18-CE37-0014-02)., ANR-18-CE37-0014,ERMUNDY,Réduction exacte de la dynamique neuronale multi-échelle(2018), Bodescot, Myriam, APPEL À PROJETS GÉNÉRIQUE 2018 - Réduction exacte de la dynamique neuronale multi-échelle - - ERMUNDY2018 - ANR-18-CE37-0014 - AAPG2018 - VALID, and University of Pennsylvania
At the macroscale, the brain operates as a network of interconnected neuronal populations, which display coordinated rhythmic dynamics that support interareal communication. Understanding how stimulation of different brain areas impacts such activity is important for gaining basic insights into brain function and for further developing therapeutic neurmodulation. However, the complexity of brain structure and dynamics hinders predictions regarding the downstream effects of focal stimulation. More specifically, little is known about how the collective oscillatory regime of brain network activity—in concert with network structure—affects the outcomes of perturbations. Here, we combine human connectome data and biophysical modeling to begin filling these gaps. By tuning parameters that control collective system dynamics, we identify distinct states of simulated brain activity and investigate how the distributed effects of stimulation manifest at different dynamical working points. When baseline oscillations are weak, the stimulated area exhibits enhanced power and frequency, and due to network interactions, activity in this excited frequency band propagates to nearby regions. Notably, beyond these linear effects, we further find that focal stimulation causes more distributed modifications to interareal coherence in a band containing regions’ baseline oscillation frequencies. Importantly, depending on the dynamical state of the system, these broadband effects can be better predicted by functional rather than structural connectivity, emphasizing a complex interplay between anatomical organization, dynamics, and response to perturbation. In contrast, when the network operates in a regime of strong regional oscillations, stimulation causes only slight shifts in power and frequency, and structural connectivity becomes most predictive of stimulation-induced changes in network activity patterns. In sum, this work builds upon and extends previous computational studies investigating the impacts of stimulation, and underscores the fact that both the stimulation site, and, crucially, the regime of brain network dynamics, can influence the network-wide responses to local perturbations., Author summary Stimulation can be used to alter brain activity and is a therapeutic option for certain neurological conditions. However, predicting the distributed effects of local perturbations is difficult. Previous studies show that responses to stimulation depend on anatomical (or structural) coupling. In addition to structure, here we consider how stimulation effects also depend on the brain’s collective dynamical (or functional) state, arising from the coordination of rhythmic activity across large-scale networks. In a whole-brain computational model, we show that global responses to regional stimulation can indeed be contingent upon and differ across various dynamical working points. Notably, depending on the network’s oscillatory regime, stimulation can accelerate the activity of the stimulated site, and lead to widespread effects at both the new, excited frequency, as well as in a much broader frequency range including areas’ baseline frequencies. While structural connectivity is a good predictor of “excited band” changes, in some states “baseline band” effects can be better predicted by functional connectivity, which depends upon the system’s oscillatory regime. By integrating and extending past efforts, our results thus indicate that dynamical—in additional to structural—brain organization plays a role in governing how focal stimulation modulates interactions between distributed network elements.