Objective.This study aims to characterize the time course of impedance, a crucial electrophysiological property of brain tissue, in the human thalamus (THL), amygdala-hippocampus, and posterior hippocampus over an extended period.Approach.Impedance was periodically sampled every 5-15 min over several months in five subjects with drug-resistant epilepsy using an investigational neuromodulation device. Initially, we employed descriptive piecewise and continuous mathematical models to characterize the impedance response for approximately three weeks post-electrode implantation. We then explored the temporal dynamics of impedance during periods when electrical stimulation was temporarily halted, observing a monotonic increase (rebound) in impedance before it stabilized at a higher value. Lastly, we assessed the stability of amplitude and phase over the 24 h impedance cycle throughout the multi-month recording.Main results.Immediately post-implantation, the impedance decreased, reaching a minimum value in all brain regions within approximately two days, and then increased monotonically over about 14 d to a stable value. The models accounted for the variance in short-term impedance changes. Notably, the minimum impedance of the THL in the most epileptogenic hemisphere was significantly lower than in other regions. During the gaps in electrical stimulation, the impedance rebound decreased over time and stabilized around 200 days post-implant, likely indicative of the foreign body response and fibrous tissue encapsulation around the electrodes. The amplitude and phase of the 24 h impedance oscillation remained stable throughout the multi-month recording, with circadian variation in impedance dominating the long-term measures.Significance.Our findings illustrate the complex temporal dynamics of impedance in implanted electrodes and the impact of electrical stimulation. We discuss these dynamics in the context of the known biological foreign body response of the brain to implanted electrodes. The data suggest that the temporal dynamics of impedance are dependent on the anatomical location and tissue epileptogenicity. These insights may offer additional guidance for the delivery of therapeutic stimulation at various time points post-implantation for neuromodulation therapy.

Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Czech Republic

Department of Biomedical Engineering Faculty of Electrical Engineering and Communication Brno University of Technology Brno Czech Republic

Department of Engineering Science University of Oxford; MRC Brain Network Dynamics Unit University of Oxford Oxford OX3 7DQ United Kingdom

Department of Neurologic Surgery Mayo Clinic Rochester MN United States of America

Department of Neurology Mayo Clinic Rochester MN United States of America

Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN United States of America

Faculty of Biomedical Engineering Czech Technical University Prague Kladno Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Mayo College of Medicine and Science Mayo Clinic Rochester MN United States of America

medRxiv. 2024 Jan 24:2024.01.23.24301672. doi: 10.1101/2024.01.23.24301672. PubMed

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