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.
Highlights
PHYSIOLOGICAL AND PATHOLOGICAL BRAIN OSCILLATIONSNeuronal oscillations are rhythmic neuronal activities that synchronize different operations within and across neuronal networks (Buzsáki, 2009)
Of signal fluctuations occurring at the hippocampal seizure focus in patients with Temporal lobe epilepsy (TLE) might contribute to disruptions in physiological functional connectivity (FC) network dynamics that contribute to decreases in static hippocampal FC on fMRI scans (Morgan et al, 2020a)
We have previously shown that closed-loop electrical stimulation of the medial septum can quickly terminate intrahippocampal seizures while suppressing their secondary generalization in a rat kindling model (Takeuchi et al, 2021)
Summary
Neuronal oscillations are rhythmic neuronal activities that synchronize different operations within and across neuronal networks (Buzsáki, 2009). An epileptic seizure is a temporal behavioral alteration that can mediate objective, noticeable (e.g., muscular contractions) or subjective, covert manifestations (e.g., loss of consciousness). These alterations are presumably generated by hypersynchronous neural activities in various brain networks. The synchronized neural activity is evident in EEG or intracerebral LFP records during seizures (termed ictal periods) and will lead to specific behavioral manifestations, such as tonic and clonic convulsions among others. Time-targeted intervention of the abnormal neural oscillations characterizing preictal or ictal states can curtail their behavioral manifestation (Morrell, 2011) indicating a causal association between pathological oscillations and the symptoms of epilepsy
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