Developing new tools to better understand disorders of the nervous system, with a goal to more effectively treat them, is an active area of bioelectronic medicine research. Future tools must be flexible and configurable, given the evolving understanding of both neuromodulation mechanisms and how to configure a system for optimal clinical outcomes. We describe a system, the Summit™ RC+S “neural coprocessor,” that attempts to bring the capability and flexibility of a microprocessor to a prosthesis embedded within the nervous system. The paper describes the updated system architecture for the Summit™ RC+S system, the five custom integrated circuits required for bidirectional neural interfacing, the supporting firmware/software ecosystem, and the verification and validation activities to prepare for human implantation. Emphasis is placed on design changes motivated by experience with the CE-marked Activa™ PC+S research tool; specifically, enhancement of sense-stim performance for improved bi-directional communication to the nervous system, implementation of rechargeable technology to extend device longevity, and application of MICS-band telemetry for algorithm development and data management. The technology was validated in a chronic treatment paradigm for canines with naturally-occurring epilepsy, including free ambulation in the home environment, which represents a typical use case for future human protocols.

Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal (6 months) within-subject crossover protocol (DBS OFF, OL-DBS, and CL-DBS). Most patients with ET experience involuntary limb tremor during goal-directed movements, but not during rest. Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulation amplitude based on patient-specific motor behavior, suppressing the pathological tremor on-demand based on a cortical electrode detecting upper limb motor activity. Here, we demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal and distal posture, water pouring, and writing) while having a consistent reduction in energy delivery. The proposed paradigm is an important step toward a behaviorally modulated fully embedded DBS system, capable of delivering stimulation only when needed, and potentially mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device replacement.

Humans are highly adept at processing speech. Recently, it has been shown that slow temporal information in speech (i.e., the envelope of speech) is critical for speech comprehension. Furthermore, it has been found that evoked electric potentials in human cortex are correlated with the speech envelope. However, it has been unclear whether this essential linguistic feature is encoded differentially in specific regions, or whether it is represented throughout the auditory system. To answer this question, we recorded neural data with high temporal resolution directly from the cortex while human subjects listened to a spoken story. We found that the gamma activity in human auditory cortex robustly tracks the speech envelope. The effect is so marked that it is observed during a single presentation of the spoken story to each subject. The effect is stronger in regions situated relatively early in the auditory pathway (belt areas) compared to other regions involved in speech processing, including the superior temporal gyrus (STG) and the posterior inferior frontal gyrus (Broca's region). To further distinguish whether speech envelope is encoded in the auditory system as a phonological (speech-related), or instead as a more general acoustic feature, we also probed the auditory system with a melodic stimulus. We found that belt areas track melody envelope weakly, and as the only region considered. Together, our data provide the first direct electrophysiological evidence that the envelope of speech is robustly tracked in non-primary auditory cortex (belt areas in particular), and suggest that the considered higher-order regions (STG and Broca's region) partake in a more abstract linguistic analysis.