Highlights
The agonist-antagonist myoneural interface (AMI) is designed to restore natural muscle-to-muscle communication after amputation, aiming to reproduce physiologic feedback loops that are absent in conventional limb loss surgery.
In a small human cohort of traumatic upper extremity amputations, AMI-based reconstruction was technically feasible in both transradial and transhumeral procedures.
At 12 months, patients showed preserved residual limb volume, measurable muscle excursion, correlation between antagonist strain and agonist activation, and frequent improvement in pain and phantom limb perception.
Clinical Background and Unmet Need
Upper extremity amputation creates profound functional and sensory disability. Beyond loss of grasp and dexterity, patients frequently experience residual limb pain, phantom limb pain, altered body schema, and difficulty using prosthetic devices effectively. Conventional amputation techniques focus on soft tissue coverage and durable closure, but they do not re-establish the neuromuscular relationships that normally allow muscles to communicate position, load, and movement to the nervous system.
The agonist-antagonist myoneural interface was developed to address this gap. In intact limbs, muscles work in paired opposition: when one contracts, its antagonist stretches, creating coordinated mechanical feedback that is sensed by muscle spindles and integrated into motor control. AMI surgically links an agonist muscle to its antagonist so that they move against each other even after amputation. The intent is not merely an anatomic reconstruction, but a mechanoneural one—an attempt to preserve the biological basis for proprioception, phantom limb embodiment, and more natural prosthetic control.
Before this report, most of the strongest evidence for AMI had come from lower extremity amputation, where earlier clinical studies suggested improved neuromuscular function, phantom sensation, and residual limb muscle preservation compared with standard amputation. The current report extends that concept to upper extremity amputation, where the stakes for sensory-motor integration are arguably even higher because prosthetic control demands fine coordination, and hand function relies heavily on feedback.
Study Design
This was a clinical experience report of modified upper extremity amputation procedures performed at Brigham & Women’s Hospital or Walter Reed National Military Medical Center. The cohort included seven patients undergoing trauma-related amputations: five transradial amputations (TRA) and two transhumeral amputations (THA). Most patients were men, and the median age at amputation was 42.0 ± 19.5 years.
The operative technique incorporated AMI construction during amputation. Prospectively collected outcomes included clinical, functional, and sensorial measures. Reported endpoints included operative time, residual limb volume preservation, reconstructed muscle excursion, the relationship between antagonist muscle strain and agonist muscle activation, and patient-reported pain and phantom limb perception at 12 months.
This was not a randomized comparison with standard amputation. Therefore, the findings should be interpreted as early feasibility and signal-generating data rather than definitive proof of superiority.
Key Findings
Feasibility and operative characteristics
All seven operations were successfully completed using modified upper extremity amputation techniques that incorporated AMI construction. The median operative time was 399 ± 23 minutes for TRA and 670 ± 85 minutes for THA, indicating that the approach is technically more complex and time-intensive than conventional amputation. This increase in operative time is not surprising given the need to create anatomically aligned agonist-antagonist muscle constructs and preserve viable tissue for reinnervation and mechanical coupling.
Although the report does not present a control arm, the ability to perform the procedure in both distal and more proximal upper limb levels suggests that the concept may be adaptable across a clinically relevant range of amputations.
Residual limb preservation and muscle mechanics
At 12 months postoperatively, patients had preserved nearly all of their residual limb volume, retaining a median of 97% of their preoperative limb size ±5%. For amputees, residual limb atrophy is more than a cosmetic issue; it can compromise prosthetic socket fit, reduce load tolerance, and worsen functional use. The observed preservation of limb volume therefore has practical importance, particularly for long-term prosthetic accommodation.
The reconstructed muscle units demonstrated a median excursion of 6 mm ±1 mm. Muscle excursion is a key mechanistic marker because it indicates that the paired muscles retained the ability to move relative to one another, which is fundamental to the AMI concept. In other words, the muscles were not simply sewn together for coverage; they were functionally arranged to generate biologically meaningful motion.
Antagonist muscle strain and agonist muscle activation were strongly correlated. This is a central mechanistic observation. In intact limbs, the nervous system depends on reciprocal muscle dynamics to infer joint position and movement. A strong correlation here suggests that the interface may be restoring a more natural proprioceptive signal pathway, which could help explain both improved phantom limb perception and the potential for more intuitive prosthetic control.
Pain and phantom limb perception
By 12 months, 83% of patients reported resolution of preoperative limb pain and experienced functional phantom limb perception. This finding is clinically notable because persistent pain after amputation is common and often difficult to manage. Phantom limb pain and residual limb pain can interfere with sleep, rehabilitation, prosthesis use, and quality of life. The report does not establish causality, but the magnitude of symptomatic improvement is encouraging and aligns with the mechanistic rationale for AMI.
Functional phantom limb perception is particularly interesting. Rather than purely painful or disordered phantom experiences, some patients reported a sensation pattern that appeared functionally useful. This may reflect a more coherent central representation of the missing limb, potentially mediated by preserved peripheral feedback from the reconstructed muscle pairs.
Comparison with prior lower extremity experience
The authors conclude that upper extremity AMI may provide benefits similar to those observed in lower extremity amputations. This is plausible because the biological principle is shared across limb types: paired muscles normally create reciprocal tension and proprioceptive signaling. If AMI can preserve this feedback loop in the arm as it appears to do in the leg, it may help support both pain reduction and better embodied control of prosthetic devices.
However, upper extremity function presents unique challenges. Hand and wrist tasks demand higher dexterity, greater fine motor control, and often a more stringent sensory-motor match than lower extremity mobility. As a result, the ultimate clinical value of AMI in upper limb amputation will likely depend not only on pain outcomes, but on whether it improves prosthetic dexterity, socket tolerance, daily function, and patient satisfaction over time.
Expert Commentary
This report is important because it moves AMI from an intriguing lower-limb innovation toward a broader reconstructive amputation strategy. The biologic premise is compelling: by preserving agonist-antagonist dynamics, surgeons may maintain peripheral signals that help the central nervous system interpret movement and limb state. That hypothesis is consistent with modern views of sensorimotor integration and with the growing recognition that amputations should be designed not just for wound closure, but for functional neuroprosthetic integration.
Still, caution is warranted. The study involved only seven patients, all with traumatic amputations, and it lacks a conventional control group. That makes it impossible to separate the effect of AMI from selection factors, surgical expertise, rehabilitation intensity, or natural recovery over time. The operative times were substantial, which raises questions about scalability, operative resource use, and adoption in trauma systems or civilian centers with limited reconstructive capacity.
Another important limitation is the absence of detailed comparative data on prosthetic use, standardized functional testing, and long-term durability beyond the first postoperative year. For clinicians, the most important unanswered question is whether AMI translates into measurable gains in daily activity, prosthesis retention, and quality of life relative to established amputation approaches.
Despite these limitations, the findings are hypothesis-generating and clinically meaningful. They support the view that amputation surgery can evolve from a purely ablative procedure into a biologically reconstructive one. If future studies confirm these early signals, AMI could become part of a broader strategy that includes targeted muscle reinnervation, osseointegration in selected patients, and advanced myoelectric prosthetics.
Clinical Implications
For reconstructive surgeons, trauma surgeons, and limb-loss specialists, this report suggests that AMI deserves consideration as an emerging option when planning upper extremity amputation. It may be particularly relevant in younger, trauma-related amputees who are likely to pursue long-term prosthetic use and rehabilitation. The technique may also be most valuable when performed by teams with expertise in peripheral nerve surgery, complex soft tissue reconstruction, and postoperative rehabilitation.
From a health systems perspective, implementation will require attention to operative complexity, rehabilitation infrastructure, and follow-up assessment. Future adoption should be paired with standardized outcomes, including objective prosthetic function, pain scales, patient-reported outcomes, and imaging or biomechanical markers of muscle viability.
Conclusion
Human upper extremity amputation with AMI construction appears feasible and biologically promising. In this small cohort, the approach was associated with preserved residual limb volume, measurable muscle excursion, strong agonist-antagonist coupling, and frequent improvement in pain and phantom limb perception. The study extends encouraging lower-extremity AMI data into the upper limb and supports the concept that amputation surgery can be designed to preserve physiologic feedback, not just anatomy. Larger comparative studies are now needed to determine whether these early benefits translate into superior long-term function and prosthetic integration.
Funding and ClinicalTrials.gov
The abstract does not report funding sources or a ClinicalTrials.gov registration number. These details should be confirmed in the full publication.
References
1. Carty MJ, Fernandez M, Sullivan CL, Chiao R, Berger L, Sparling TL, Souza JM, Potter BK, Beltran L, Herr HM. Human Implementation of Upper Extremity Amputation Incorporating Agonist-Antagonist Myoneural Interface Construction. Plast Reconstr Surg. 2025;157(6):874e-886e. PMID: 41396271.
2. Herr HM, et al. Agonist-antagonist myoneural interface: a mechanoneural construct for restoring muscle feedback after amputation. PubMed-indexed foundational literature on AMI and lower extremity application.
3. Targeted muscle reinnervation and related reconstructive strategies in limb amputation: peer-reviewed literature on pain reduction and prosthetic control.