Chronic Evaluation of a Clinical System for Deep Brain Stimulation and Recording of Neural Network Activity

Abstract

Background/Aims: In conjunction with therapeutic stimulation, next-generation deep brain stimulation (DBS) devices may offer the ability to record and analyze neural signals, providing for unprecedented insight into DBS effects on neural networks. This work was conducted to evaluate an implantable, clinical-grade system that permits concurrent stimulation and recording using a large animal (ovine) model recently developed to study DBS for epilepsy. Methods: Following anesthesia and 1.5-tesla MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted (n = 3) using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and local field potentials were collected with the implanted device and analyzed off-line. Results: Hippocampal EPs were stable over long-term (>1 year) recording and consistent in morphology and latency with prior acute results. Thalamic and hippocampal DBS produced both excitatory and inhibitory network effects that were stimulation site and parameter dependent. Free roaming recordings illustrated periods of highly correlated activity between these two structures within the circuit of Papez. Conclusions: These results provide further insight into mechanisms of DBS therapy for epilepsy and an encouraging demonstration of the capabilities of this new technology, which in the future, may afford unique opportunities to study human brain function and neuromodulation mechanism of action.

Placement of Deep Brain Electrodes in the Dog Using the Brainsight Frameless Stereotactic System: A Pilot Feasibility Study

“…For this reason, large animal models such as the sheep and minipig are being developed that will allow better translation of DBS strategies into people. Recently, one such study has investigated the feasibility of implanting leads into the ANT and hippocampus of a sheep model as part of the evaluation of a novel device capable of both stimulating and recording from the brain 22, 23…”

Sensing-enabled hippocampal deep brain stimulation in idiopathic nonhuman primate epilepsy

“…The LFP signals were amplified, filtered from 0.5 Hz to 100 Hz, digitized at a sampling frequency of either 200 or 422 Hz, and recorded with the chronically implanted Activa PCϩS device (investigational device, Medtronic). Recording parameters were set, and data were saved to memory and subsequently uploaded for analysis periodically via a wireless Medtronic model 8180 sensing programmer, a modified tablet computer, and the Medtronic model 37642 patient programmer designed to noninvasively interface with the Activa PCϩS neurostimulator via radiotelemetry, as previously described (Ryapolova-Webb et al 2014;Stypulkowski et al 2013). During telemetry the monkey was anesthetized with ketamine (Ketaset, 5 mg/kg), as data download required ϳ30 min per session.…”

“…To elucidate the effect of electrical stimulation on the activity of neural substrates of TLE, we performed DBS concurrently with local field potential (LFP) recordings in the hippocampus of a nonhuman primate (NHP) with idiopathic epilepsy, using a novel platform for simultaneous stimulation and long-term recording of electrical brain activity (PCϩS, Medtronic) (Afshar et al 2012;Freestone et al 2013;Ryapolova-Webb et al 2014;Stypulkowski et al 2013Stypulkowski et al , 2014. Using this modified version of a standard clinical DBS device, Stypulkowski et al recently examined the acute effects of DBS on limbic neural networks in the normal ovine brain.…”

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

“…Conceivably, the RNS could be adapted to accomplish this. Alternatively, using a novel bidirectional stimulation and recording pulse generator unit approved for research in humans (Activa PC+S; Medtronic, Minneapolis, MN, USA), a closed loop state control algorithm was recently tested in a large animal (sheep) model [121]. One DBS electrode was implanted in the ANT and a second one in the hippocampus.…”