Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording.

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads. Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects. Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network. Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.

Industrial perspectives on brain-computer interface technology.

Neuromodulation therapies offer a unique opportunity for translating brain-computer interface (BCI) technologies into a clinical setting. Several diseases such as Parkinson's disease are effectively treated by invasive device stimulation therapies, and the addition of sensing and algorithm technology is an obvious evolutionary expansion of capabilities. In addition, this infrastructure might enable a roadmap of novel BCI technologies. While the initial applications are focused on epilepsy and movement disorders, the technology is potentially transferable to a broader base of disorders, including stroke and rehabilitation. The ultimate potential of BCI technology will be determined by forthcoming chronic evaluation in multiple neurologic disorders.

Modulation of hippocampal activity with fornix Deep Brain Stimulation.

BACKGROUND: Deep Brain Stimulation (DBS) within the Papez circuit is under investigation as a treatment for epilepsy and Alzheimer's disease. We previously reported the effects of stimulation at nodes within this network (anterior thalamic nucleus and hippocampus) on hippocampal activity in a large animal model, using a chronic implantable, clinical-grade system that permits concurrent stimulation and recording. OBJECTIVE: In this study we extended earlier work to compare the effects of fornix DBS on evoked potentials (EPs) and local field potential (LFP) activity within the hippocampus, and to assess closed-loop stimulation. METHODS: Unilateral fornix and hippocampal DBS leads were implanted in three ovine subjects using image-guided, frameless stereotaxy. Chronic, awake recordings of EPs and LFPs in response to fornix and hippocampal stimulation were collected with the implanted device and analyzed off-line. RESULTS: Stimulation of the fornix produced robust, short latency hippocampal EPs. High frequency fornix stimulation generated parameter-dependent effects. At low amplitudes, short lasting inhibition of LFP activity occurred. Above a specific amplitude threshold, DBS elicited pronounced bursts of theta activity, followed by a marked state shift in hippocampal activity. These effects persisted for minutes post-DBS and were reflected as changes in LFP spectral content and phase-amplitude coupling. Real-time modulation of hippocampal activity via the implanted device was demonstrated using LFPs as the control signal for closed-loop stimulation. CONCLUSIONS: The current results expand earlier findings and demonstrate target-specific effects produced by DBS within this neural circuit. These changes in network activity may provide insights into stimulation targets and parameter selection for clinical investigations.

Brain stimulation for epilepsy--local and remote modulation of network excitability.

BACKGROUND: The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy. OBJECTIVE: In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network. METHODS: Following anesthesia and 1.5T MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted in three subjects using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and LFPs in response to thalamic and hippocampal stimulation were collected with the implanted device and analyzed off-line. RESULTS: Consistent with earlier reports, thalamic DBS and direct stimulation of the hippocampus produced parameter-dependent effects on hippocampal activity. LFP suppression could be reliably induced with specific stimulation parameters, and was shown to reflect a state of reduced network excitability, as measured by effects on hippocampal EP amplitudes and after-discharge thresholds. Real-time modulation of network excitability via the implanted device was demonstrated using hippocampal theta-band power level as a control signal for closed-loop stimulation. CONCLUSIONS: The results presented provide evidence of network excitability changes induced by stimulation that could underlie the clinical effects that have been reported with both thalamic and direct cortical stimulation.

Chronic evaluation of a clinical system for deep brain stimulation and recording of neural network activity.

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.