PROJECT SUMMARY/ABSTRACT Empirical neuroethics studies of patient/user perspectives have demonstrated profound effects that novel neurotechnological therapies, such as implanted devices, can have on people’s understandings of themselves and their illnesses. However, to date the incorporation of such perspectives in the design of neurotechnologies is not a standard practice, and this gap presents risk for ethical harms and may negatively impact the usability and feasibility of interventions based on BRAIN Initiative-supported research. The long-term goal of this proposal is to facilitate the BRAIN Initiative’s success in discovering effective and ethically sound therapies for disorders of the nervous system. The central hypothesis is that human-centered design, an interdisciplinary approach that prioritizes user perspectives and has been successfully applied to implementation problems in fields such as digital technology and health systems design, can be applied to related problems in neurotechnology. The work will be conducted by pursuing three specific aims: 1) Examine adverse user experiences with non-human-centered design, highlighting pitfalls and needs for improvement; 2) Assess prevailing attitudes regarding human- centered design and barriers to adoption among neurotechnology developers; and 3) Convene neurotechnologists to identify needs and to develop strategies for integrating user perspectives in neurotechnology. Under the first aim, in-depth qualitative interviews will be conducted with blind people implanted with the Argus II retinal implant, a commercially non-viable technology no longer supported by its manufacturer, which may illustrate how failures to incorporate user perspectives in design can lead to ethical harm and to technology abandonment. For the second aim, professionals engaged in neurotechnology (including neuroscientists, engineers, businesspeople, and officials/regulators) will be interviewed about incorporating user perspectives generally and about human-centered design specifically. These interviews will offer insight into the lack of adoption of human-centered design in neurotechnology to date. In the third aim, two convenings of neurotechnologists will be organized to co- create plans for making the incorporation of user perspectives a standard practice in neurotechnology. The approach is innovative, shifting research paradigms in neuroethics and neurotechnology through new conceptual and methodological linkages with human-centered design. The proposed research is significant, because the ethical and effective provision of novel treatments depends on incorporating the priorities of patients and prospective users more directly in their design. Ultimately, we envision a mutually reinforcing relationship between neuroethics and human-centered design, two interdisciplinary fields that can bring needed new outlooks and methods to the practice of neuroscience.