Reinnervation of Muscle Targets Enhances the Separability of Motor Unit Signals Following Peripheral Nerve Transfers

ABSTRACT After amputation, advanced prosthetic limbs offer a promising means of restoring motor function. However, state‐of‐the‐art prostheses often rely on aggregate electromyogram (EMG) signals to decode motor intention, which limits their ability to replicate natural limb movements. Decomposing EMG signals into individual motor unit components has shown potential for more natural control, but distinguishing between individual units can be challenging when nearby signals overlap. This study demonstrates that muscle target reinnervation surgeries can naturally increase physical separation between motor unit signals, thereby mitigating this overlap. Reinnervation of individual motor units is evaluated in a rodent hindlimb model after direct nerve‐to‐muscle implantation. Histological and electrophysiological analyses reveal that structural changes following reinnervation surgery result in beneficial motor unit signal changes, particularly improving spatial separation between motor unit signals compared to those in intact muscle. This spatial separation contributed to fewer instances of complex, overlapping signals in reinnervated muscle recordings. Motor unit signals were leveraged to provide a proof‐of‐concept of precise control of a virtual prosthesis for the first time after direct nerve‐to‐muscle implantation surgery. These findings highlight the potential of reinnervated muscle targets as key biological interfaces that facilitate motor unit separation, reducing the burden on decomposition algorithms and improving prosthetic control.