Abstracts

Rationale:
Electrical impedance of cortical tissue plays an important role in a variety of phenomena, including coordinated neural activity at various scales and clinical applications for electrical neuromodulation. Despite reports of impedance changes after surgical electrode implantation, few chronic studies have investigated impedance changes adjacent to seizures in humans.  This study examines long-term impedance dynamics and seizure-related impedance in thalamus (THL), amygdala-hippocampus (AMG-HPC) and posterior hippocampus (post-HPC) structures of humans with temporal lobe epilepsy (TLE).

Methods:
Five patients with drug resistant left side TLE were implanted with bilateral electrodes. Electrical brain stimulation (EBS) was continuously delivered to the thalamus with intermittent gaps. Impedance was periodically sampled (5-15 minutes) with the investigational Medtronic Summit RC+S™ device over multiple months.  The initial implant effect and recovery behavior of impedance was modeled with a piecewise parabolic and exponential function. Long-term impedance changes were characterized by the impedance dynamics during therapeutic gaps and the stability of the amplitude and phase of the apparent 24-hour cycle. Seizure-related impedance change was analyzed using cross-correlation between impedance and seizures ± 12 hours onset and compared between true and surrogate seizures.

Results:
The descriptive model could explain the variance in short-term impedance changes. Interestingly, our results indicated that the temporal dynamics of the THL of the most epileptogenic hemisphere were remarkably slower than those of other regions. During stimulation gaps, the degree of rebound decreased with time and did not change significantly after ~200 days post-implant, indicating biological maturity of the foreign body response and fibrous tissue encapsulation around the electrodes. The amplitude and phase of 24-hour impedance oscillation were stable throughout the recording. Circadian variation dominated long-term impedance measures. Seizures and surrogate seizures show a peak in correlation in the hippocampus and a valley in the thalamus around seizure onsets. The cross-correlation of seizures was higher than surrogate seizures in the thalamus, indicating a potential pathological in this brain area.

Conclusions:
The results support the idea that the temporal dynamics of impedance after implantation depend on the anatomical location and epileptogenicity of the tissue. Our findings may provide additional guidance for delivering therapeutic stimulation at different time points after implantation for neuromodulation therapy.  Our preliminary results on seizure and impedance correlation suggest that seizure onsets may be phase locked to the 24-hour sleep/wake cycle of impedance, which is thought to be correlated to subject behavior, as being previously shown.  Further investigation is needed to determine the effect of process of fibrous tissue encapsulation on the seizure-related impedance changes in the long run.

Funding: National Institutes of Health grants UH3-NS095495, UG3 NS123066, R01-NS092882, and R01-NS112144. Medtronic Summit RC+S™ devices were donated by Medtronic LTD.