Resting state neurophysiology of agonist-antagonist myoneural interface in persons with transtibial amputation.

The agonist-antagonist myoneural interface (AMI) is a novel amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects (Srinivasan et al., Sci. Transl. Med. 2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this first study on resting state fMRI in AMI subjects, we compared resting state functional connectivity in patients with transtibial AMI (n=12) and traditional (n=7) amputations, as well as biologically intact control subjects (n=10). We hypothesized that the AMI surgery will induce functional network reorganization that significantly differs from the traditional amputation surgery and also more closely resembles the neural configuration of controls. We found AMI subjects to have lower connectivity with salience and motor seed regions compared to traditional amputees. Additionally, with connections affected in traditional amputees, AMI subjects exhibited a connectivity pattern more closely resembling controls. Lastly, sensorimotor connectivity in amputee cohorts was significantly associated with phantom sensation (R 2 =0.7, p =0.0008). These findings provide researchers and clinicians with a critical mechanistic understanding of the effects of the AMI surgery on the brain at rest, spearheading future research towards improved prosthetic control and embodiment.