Regenerative peripheral nerve interfaces (RPNIs) and implanted electrodes improve online control of prostheses for hand and wrist ^*

<i>Objective.</i>Upper limb amputation severely limits daily activities and independence. Current prosthetic control methods often rely on surface electromyography (sEMG), which suffers from low signal quality and limited functionality. This study investigates whether implanted electrodes in regenerative peripheral nerve interfaces (RPNIs) and residual innervated muscles can provide stable and high-quality control signals to improve dexterous prosthetic hand and wrist function.<i>Approach.</i>Two individuals with upper-limb amputation had RPNIs created by suturing free skeletal muscle grafts to peripheral nerves or nerve fascicles in the residual limb. Intramuscular EMG (iEMG) electrodes were implanted into the RPNIs and muscles in the residual limb. EMG signals were recorded from both sEMG and iEMG electrodes and used to control a virtual prosthetic hand + wrist in real time. Performance was assessed through multiple degrees-of-freedom (DoF) control tasks, comparing RPNIs and iEMG against conventional sEMG.<i>Main Results.</i>Implanted electrodes demonstrated high signal-to-noise ratios and long-term stability, enabling independent and simultaneous control of multiple hand + wrist DoFs. Participants achieved faster, more accurate, and more reliable control using RPNIs and iEMG-based control compared with sEMG-based systems, based on classification accuracy and trial success rate. Importantly, we find that the ability to control wrist rotation reduces total body compensations when performing a functional assessment (Coffee Task), and implanted electrodes greatly reduced task completion times compared to surface electrodes when wrist rotation was added as an additional control movement.<i>Significance.</i>In this study, we demonstrate that RPNIs and iEMG electrodes in combination enable significantly more accurate and stable prosthetic control of hand and wrist movements compared to surface electrodes, especially during dynamic arm movements. These findings suggest that RPNIs and iEMG electrodes offer meaningful advantages over sEMG for achieving more intuitive and reliable control of upper-limb prostheses in real-world conditions.