Background: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. Objectives: Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. Methods: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. Results: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. Conclusions: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration.

Deep brain stimulation (DBS) for Parkinson’s disease, essential tremor and epilepsy is an established palliative treatment. DBS uses electrical neuromodulation to suppress symptoms. Most current systems provide a continuous pattern of fixed stimulation, with clinical follow-ups to refine settings constrained to normal office hours. An issue with this management strategy is that the impact of stimulation on circadian, i.e. sleep-wake, rhythms is not fully considered; either in the device design or in the clinical follow-up. Since devices can be implanted in brain targets that couple into the reticular activating network, impact on wakefulness and sleep can be significant. This issue will likely grow as new targets are explored, with the potential to create entraining signals that are uncoupled from environmental influences. To address this issue, we have designed a new brain-machine-interface for DBS that combines a slow-adaptive circadian-based stimulation pattern with a fast-acting pathway for responsive stimulation, demonstrated here for seizure management. In preparation for first-in-human research trials to explore the utility of multi-timescale automated adaptive algorithms, design and prototyping was carried out in line with ISO risk management standards, ensuring patient safety. The ultimate aim is to account for chronobiology within the algorithms embedded in brain-machine-interfaces and in neuromodulation technology more broadly.

Objective: To provide a design analysis and guidance framework for the implementation of concurrent stimulation and sensing during adaptive deep brain stimulation (aDBS) with particular emphasis on artifact mitigations. Approach: We defined a general architecture of feedback-enabled devices, identified key components in the signal chain which might result in unwanted artifacts and proposed methods that might ultimately enable improved aDBS therapies. We gathered data from research subjects chronically-implanted with an investigational aDBS system, Summit RC+S, to characterize and explore artifact mitigations arising from concurrent stimulation and sensing. We then used a prototype investigational implantable device, DyNeuMo, and a bench-setup that accounts for tissue-electrode properties, to confirm our observations and verify mitigations. The strategies to reduce transient stimulation artifacts and improve performance during aDBS were confirmed in a chronic implant using updated configuration settings. Main results: We derived and validated a “checklist” of configuration settings to improve system performance and areas for future device improvement. Key considerations for the configuration include 1) active instead of passive recharge, 2) sense-channel blanking in the amplifier, 3) high-pass filter settings, 4) tissue-electrode impedance mismatch management, 5) time-frequency trade-offs in the classifier, 6) algorithm blanking and transition rate limits. Without proper channel configuration, the aDBS algorithm was susceptible to limit-cycles of oscillating stimulation independent of physiological state. By applying the checklist, we could optimize each block’s performance characteristics within the overall system. With system-level optimization, a ‘fast’ aDBS prototype algorithm was demonstrated to be feasible without reentrant loops, and with noise performance suitable for subcortical brain circuits. Significance: We present a framework to study sources and propose mitigations of artifacts in devices that provide chronic aDBS. This work highlights the trade-offs in performance as novel sensing devices translate to the clinic. Finding the appropriate balance of constraints is imperative for successful translation of aDBS therapies.