An overarching goal of neuroscience research is to understand how heterogeneous neuronal ensembles cohere into networks of coordinated activity to support cognition. To investigate how local activity harmonizes with global signals, we measured electroencephalography (EEG) while single pulses of transcranial magnetic stimulation (TMS) perturbed occipital and parietal cortices. We estimate the rapid network reconfigurations in dynamic network communities within specific frequency bands of the EEG, and characterize two distinct features of network reconfiguration, flexibility and allegiance, among spatially distributed neural sources following TMS. Using distance from the stimulation site to infer local and global effects, we find that alpha activity (8-12 Hz) reflects concurrent local and global effects on network dynamics. Pairwise allegiance of brain regions to communities on average increased near the stimulation site, whereas TMS-induced changes to flexibility were generally invariant to distance and stimulation site. In contrast, communities within the beta (13-20 Hz) band demonstrated a high level of spatial specificity, particularly within a cluster comprising paracentral areas. Together, these results suggest that focal magnetic neurostimulation to distinct cortical sites can help identify both local and global effects on brain network dynamics, and highlight fundamental differences in the manifestation of network reconfigurations within alpha and beta frequency bands.

Objective

Current brain stimulation paradigms are largely empirical rather than theoretical. An opportunity exists to improve upon their modest effectiveness in closed-loop control strategies with the development of theoretically grounded, model-based designs.

Approach

Inspired by this need, here we couple experimental data and mathematical modeling with a control-theoretic strategy for seizure termination. We begin by exercising a dynamical systems approach to model seizures (n = 94) recorded using intracranial EEG (iEEG) from 21 patients with medication-resistant, localization-related epilepsy.

Main results

Although each patient's seizures displayed unique spatial and temporal patterns, their evolution can be parsimoniously characterized by the same model form. Idiosyncracies of the model can inform individualized intervention strategies, specifically in iEEG samples with well-localized seizure onset zones. Temporal fluctuations in the spatial profiles of the oscillatory modes show that seizure onset marks a transition into a regime in which the underlying system supports prolonged rhythmic and focal activity. Based on these observations, we propose a control-theoretic strategy that aims to stabilize ictal activity using static output feedback for linear time-invariant switching systems. Finally, we demonstrate in silico that our proposed strategy allows us to dampen the emerging focal oscillatory sources using only a small set of electrodes.

Significance

Our integrative study informs the development of modulation and control algorithms for neurostimulation that could improve the effectiveness of implantable, closed-loop anti-epileptic devices.