Abstract
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 (AMG-HPC), and posterior hippocampus (post-HPC) over an extended period.
Approach Impedance was periodically sampled every 5-15 minutes over several months in five subjects with drug-resistant epilepsy using an experimental 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-hour 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 days 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-hour 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.
Competing Interest Statement
G.A.W., B.H.B., J.V.G., and B.N.L. are inventors of intellectual property developed at Mayo Clinic and licensed to Cadence Neuroscience Inc. The intellectual property for impedance modulation and tracking was filed by G.A.W., V.K., V.S., and B.H.B. G.A.W. has also licensed intellectual property developed at Mayo Clinic to NeuroOne Inc. B.N.L., G.A.W., J.V.G., and N.G. are investigators in the Medtronic Deep Brain Stimulation Therapy for Epilepsy Post-Approval Study (EPAS). Mayo Clinic has received research support and consulting fees on behalf of G.A.W., B.N.L., J.V.G., and B.H.B. from UNEEG, NeuroOne Inc., Epiminder, Medtronic Plc., and Philips Neuro. J.V.G. is a stock owner of NeuroOne Inc and the site Primary Investigator in the Polyganics ENCASE II trial, the NXDC Gleolan Men301 trial, and the Insightec MRgUS EP001 trail. T.D. is a consultant for Synchron, a member of the advisory board of Cortec Neuro, and a shareholder-collaborator of Bioinduction Ltd and shareholder director of Amber Therapeutics Ltd. T.D. also has patents in the field of impedance measurement instrumentation and its application in epilepsy seizure prediction. B.N.L. declares intellectual property licensed to Cadence Neuroscience Inc (contractual rights waived; all funds to Mayo Clinic) and Seer Medical Inc (contractual rights waived; all funds to Mayo Clinic), is a site investigator for Medtronic EPAS and Neuroelectrics tDCS for Epilepsy, and an industry consultant for Epiminder, Medtronic, Neuropace, and Philips Neuro (all funds to Mayo Clinic). The other authors have no disclosures.
Funding Statement
This study was funded by National Institutes of Health (NIH) supported this study by grants UH3-NS095495, R01-NS092882 (to G.W.), and R01-NS112144 (to G.W., H.L.W., and L.J.W.). J.C. was also partially supported by the Epilepsy Foundation of America's My Seizure Gauge grant (to B.H.B), the National Institutes of Health grant UG3 NS123066 (to B.H.B.), and the Mayo Clinic RFA CCaTS-CBD Pilot Awards for Team Science UL1TR000135 (to J.C.).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All activities were approved by Mayo Clinic IRB:18-005483 'Human Safety and Feasibility Study of Neurophysiologically Based Brain State Tracking and Modulation in Focal Epilepsy,' and all subjects provided informed consent.
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Yes
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Footnotes
(E-mail: cui.jie{at}mayo.edu, ORCID: 0000-0003-1000-8869), (E-mail: Mivalt.Filip{at}mayo.edu, ORCID: 0000-0002-0693-9495), (E-mail: Sladky.Vladimir{at}mayo.edu, ORCID: 0000-0002-4712-7039), (E-mail: Kim.Jiwon{at}mayo.edu), (E-mail: Richner.Thomas{at}mayo.edu), (E-mail: Lundstrom.Brian{at}mayo.edu, ORCID: 0000-0002-5310-5549), (E-mail: VanGompel.Jamie{at}mayo.edu, ORCID: 0000-0001-8087-7870), (E-mail: hwang{at}mayo.edu, ORCID: 0000-0001-9013-3007), (E-mail: Miller.Kai{at}mayo.edu), (E-mail: Gregg.Nicholas{at}mayo.edu, ORCID: 0000-0002-6151-043X), (E-mail: wu.longjun{at}mayo.edu, ORCID: 0000-0001-8019-3380), (E-mail: timothy.denison{at}bndu.ox.ac.uk, ORCID:0000-0002-5404-4004), (E-mail: Winter.Bailey{at}mayo.edu, ORCID: 0000-0003-1157-2138), (E-mail: Brinkmann.Benjamin{at}mayo.edu, ORCID: 0000-0002-2392-8608), (E-mail: Kremen.Vaclav{at}mayo.edu, ORCID: 0000-0001-9844-7617), (E-mail: Worrell.Gregory{at}mayo.edu, ORCID: 0000-0003-2916-0553)
Data Availability
Data are available upon reasonable request to the authors.