Temporally Targeted Interactions With Pathologic Oscillations as Therapeutical Targets in Epilepsy and Beyond

Abstract

Self-organized neuronal oscillations rely on precisely orchestrated ensemble activity in reverberating neuronal networks. Chronic, non-malignant disorders of the brain are often coupled to pathological neuronal activity patterns. In addition to the characteristic behavioral symptoms, these disturbances are giving rise to both transient and persistent changes of various brain rhythms. Increasing evidence support the causal role of these “oscillopathies” in the phenotypic emergence of the disease symptoms, identifying neuronal network oscillations as potential therapeutic targets. While the kinetics of pharmacological therapy is not suitable to compensate the disease related fine-scale disturbances of network oscillations, external biophysical modalities (e.g., electrical stimulation) can alter spike timing in a temporally precise manner. These perturbations can warp rhythmic oscillatory patterns via resonance or entrainment. Properly timed phasic stimuli can even switch between the stable states of networks acting as multistable oscillators, substantially changing the emergent oscillatory patterns. Novel transcranial electric stimulation (TES) approaches offer more reliable neuronal control by allowing higher intensities with tolerable side-effect profiles. This precise temporal steerability combined with the non- or minimally invasive nature of these novel TES interventions make them promising therapeutic candidates for functional disorders of the brain. Here we review the key experimental findings and theoretical background concerning various pathological aspects of neuronal network activity leading to the generation of epileptic seizures. The conceptual and practical state of the art of temporally targeted brain stimulation is discussed focusing on the prevention and early termination of epileptic seizures.

Resonance Scanning as an Efficiency Enhancer for EEG-Guided Adaptive Neurostimulation

“…Similar positive effects were achieved in our study after only a single treatment procedure. This advantage permits us to consider a combination of resonance scanning with EEG-guided adaptive neurostimulation as a newly developed kind of oscillotherapeutics [ 22 , 23 ] that can effectively reduce stress and quickly produce the signs of cognitive rehabilitation in persons under exam stress via identifying neuronal network oscillations as potential therapeutic targets.…”

Manipulating single-unit theta phase-locking with PhaSER: An open-source tool for real-time phase estimation and manipulation

“…From both a clinical and basic-research perspective there is strong interest in acquiring a better understanding of how the timing of manipulations relative to endogenous oscillations and brain states impacts their effectiveness for treating psychiatric and neurological symptoms. By enhancing our knowledge of the precise impacts of phase-specific manipulations, we can inform how clinical stimulation strategies can complement, rather than compete with, the brain’s ongoing activity and improve these therapeutic interventions (Földi et al, 2021; Krause et al, 2022).…”

Putative cause of seizure-induced cognitive alterations: The oscillatory reconfiguration of seizure network

“…Oscillations arise from neuronal interactions that promote communication and information processing between regions of a functional neural network ( Engel et al, 2001 ; Buzsaki and Draguhn, 2004 ; Wang et al, 2020 ; Földi et al, 2021 ). Recent studies have shown that network oscillations temporally link neurons and enhance synaptic plasticity, supporting long-term information consolidation and is a cognitive process necessary for learning and memory ( Goltsev et al, 2013 ; Holmes, 2015 ; Sadaghiani and Kleinschmidt, 2016 ).…”