Toward true closed-loop neuromodulation: artifact-free recording during stimulation

•Artifacts distort recorded neural signals and obscure reliable biomarker detection.•Stimulation artifact cancellation and artifact mitigation methods are reviewed.•A combination of mitigation and cancellation techniques produce the best results. Closed-loop and responsive neuromodulation systems improve open-loop neurostimulation by responding directly to measured neural activity and providing adaptive, on-demand therapy. To be effective, these systems must be able to simultaneously record and stimulate neural activity, a task made difficult by persistent stimulation artifacts that distort and obscure underlying biomarkers. To enable simultaneous stimulation and recording, several techniques have been proposed. These techniques involve artifact-preventing system configurations, resilient recording front-ends, and back-end signal processing for removing recorded artifacts. Co-designing and integrating these artifact cancellation techniques will be key to enabling neuromodulation systems to stimulate and record at the same time. Here, we review the state-of-the-art for these techniques and their role in achieving artifact-free neuromodulation.