A Translatable System for Bi-Directional Stimulation and Evoked Response Measurement to Enable Neuronal Network Exploration

Neural stimulation therapies continue to evolve as new technologies are introduced into clinical practice. It has been over a decade since the initial descriptions of fully implantable, bidirectional neural systems, which allowed for concurrent sensing and stimulation, have been published. A major confounding issue in these types of neural recordings is the contamination of the signal of interest with electrical stimulus artifact, which can obscure short latency evoked activity and corrupt spectral analysis of longer duration signals. Approach. Here we describe the design and early preclinical evaluation of a neurostimulator with improved capabilities for sensing, with particular emphasis on managing stimulus artifact. The system was tested in three ovine deep brain stimulation (DBS) subjects, one with a DBS lead targeting the hippocampus, and two with DBS leads targeting the subthalamic nucleus (STN). All leads were externalized with percutaneous lead extensions. Main results. Results demonstrate that it was possible to record evoked potentials with a latency of 1-2 ms following stimulation in all subjects with the new system. Recordings from the hippocampal target showed clear short-latency responses exhibiting behavior consistent with evoked compound action potentials (ECAPs). In contrast, recordings from the STN target demonstrated highly resonant activity, dependent upon stimulus frequency, which could persist for 20-30 ms following individual stimuli. Both directional stimulation and directional recordings were evaluated to determine their influence on this evoked resonant neural activity (ERNA). The system was also characterized for sensing in one spinal cord stimulation (SCS) ovine subject and one sacral nerve modulation ovine subject. Significance. The bidirectional stimulation and evoked-response sensing system presented here enables sensing evoked responses elicited from stimulation, empowering continued research to expand the understanding and optimization of DBS therapy. Additionally, the example recordings from other therapy spaces demonstrate the capability of the system across neural stimulation therapies.