A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees

Classified as probably not a substantial claim.

An RPNI consists of a transected peripheral nerve or nerve fascicle implanted into a free muscle graft.

“RPNI is composed of a transected peripheral nerve, or peripheral nerve fascicle, that is implanted into a free muscle graft (12, 13).”

• cites [12] sourceNot checked — no full text of the source
• cites [13] sourcePartly supported

  The Introduction and Methods describe an RPNI attached to the end of a divided peripheral nerve. But this study constructed it with cultured myoblasts in a scaffold—silicone mesh or acellular muscle—not by implanting the nerve or a fascicle into a free muscle graft. The cited passages also do not describe use of a nerve fascicle. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

This process creates a stable peripheral nerve bioamplifier that produces high-amplitude EMG signals that could be used to control a prosthetic device.

“This process creates a stable, peripheral nerve bioamplifier that produces high-amplitude EMG signals, which could be used to control a prosthetic device (14–17).”

• cites [14] sourceNot checked — no full text of the source
• cites [15] sourceNot checked — no full text of the source
• cites [16] sourceSupported
• cites [17] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

RPNIs have been shown to prevent and treat neuroma pain and phantom pain after amputation.

“In addition, RPNIs have been shown to prevent and treat neuroma pain and phantom pain after amputation (18–20).”

• cites [18] sourceNot checked — no full text of the source
• cites [19] sourceNot checked — no full text of the source
• cites [20] sourcePartly supported

  The Results and Discussion report reduced neuroma and phantom pain after RPNI surgery in 16 amputees treated for symptomatic neuromas. The Conclusions and Future Directions describe neuroma prevention at primary amputation as a potential use requiring further study; this pilot study does not show prevention of either neuroma or phantom pain. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Intraneural electrodes can record distinct efferent motor action potentials, but their signal amplitude tends to decline over time.

“Electrodes placed within a peripheral nerve can record distinct efferent motor action potentials but over time are susceptible to decline in signal amplitude (3, 4).”

• cites [3] sourceNot checked — no full text of the source
• cites [4] sourcePartly supported

  The Results section, “Decoding USEA recordings allowed intuitive control of many movements” (page unavailable), reports neuronal action potentials and distinct movement-related firing patterns from intraneural electrodes. It also reports fewer electrodes with movement-correlated activity over time in one subject, but does not report a decline in signal amplitude; the Discussion (“Decode,” page unavailable) likewise describes declining recording ability, not amplitude. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

That approach gave usable signal amplitude and allowed some prosthetic limb control in transradial amputees.

“This strategy has provided reasonable signal amplitude and some control of a prosthetic limb in patients undergoing transradial amputations (24–28).”

• cites [24] sourceNot checked — no full text of the source
• cites [25] sourceNot checked — no full text of the source
• cites [26] sourceNot checked — no full text of the source
• cites [27] sourcePartly supported

  The Introduction says powered transradial prostheses use forearm EMG signal amplitudes for limited control. The Abstract reports that five transradial amputees used residual-forearm signals to control a virtual arm, but the Discussion explicitly says they did not test a physical prosthesis. The paper does not establish a particular ‘reasonable’ signal amplitude. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [28] sourcePartly supported

  The Methods and amputee-subject Results report that two transradial amputees used EMG to control a cursor in a virtual task. The Discussion explicitly says physical-prosthesis testing remains to be done, and the paper does not establish that the strategy provided reasonable signal amplitude. Thus, it supports some myoelectric control in transradial amputees, but not the claimed signal amplitude or control of a physical prosthetic limb. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

RPNIs effectively reduce symptomatic neuroma pain and prevent neuroma formation.

“RPNIs have shown to be an effective technique to reduce symptomatic neuroma pain and also prevent neuroma formation (18–20).”

• cites [18] sourceNot checked — no full text of the source
• cites [19] sourceNot checked — no full text of the source
• cites [20] sourcePartly supported

  The Results report a 71% reduction in neuroma pain among 16 amputees treated with RPNIs. The Abstract Conclusions and Discussion state that RPNIs prevent neuroma formation through their proposed mechanism, but the Conclusions and Future Directions say prophylactic use still needs study. This pilot study therefore supports pain reduction, not a demonstrated clinical benefit in preventing new neuromas. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Prior work found that RPNI recordings yielded stable EMG for as long as 7.5 years.

“have been previously observed to record stable EMG for up to 7.5 years (23).”

• cites [23] sourcePartly supported

  The Results (Electrode performance; page not provided) report that nerve cuff electrodes continued to function for 7.5 years in one subject. The Methods describe separate implanted EMG recording electrodes, and the Discussion says subjects used them for control, but neither passage reports stable EMG recordings for 7.5 years or identifies the electrodes as RPNIs. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Intraneural probes such as the Utah slanted electrode array can provide large signals but currently have problems with signal stability over time.

“In addition, intraneural probes, such as the Utah slanted electrode array, can provide large signals but currently run into issues of signal stability over time (4).”

• cites [4] sourcePartly supported

  The Discussion (Study limitations and Decode; page unavailable) reports unstable USEA recording ability and a decline in neural recording from post-implant day 13 to 30. It does not establish that the probes provide large neural signals; its reference to higher-amplitude signals concerns EMG that masked neural activity. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

TMR necessarily cuts nerve branches to residual muscles and denervates existing muscle.

“as is necessary in TMR (29).”

• cites [29] sourcePartly supported

  The Introduction (page unavailable) says TMR transfers remaining arm nerves to residual muscles, and the Methods (page unavailable) identify muscles that received those transfers. Our copy does not say that TMR necessarily cuts the target muscles’ existing nerve branches or denervates existing muscle. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

TMR has shown comparable results, and a newer study found that TMR reduces phantom limb pain.

“Similar results have been demonstrated with TMR (37), with a more recent study providing evidence that TMR decreases phantom limb pain (38).”

• cites [37] sourceSupported
• cites [38] sourceNot checked — no full text of the source

May combine two claims.

EMG-driven musculoskeletal models exist for real-time, physiologically accurate prosthesis control in functional tasks, but they have controlled only two to three DOFs.

“EMG-driven musculoskeletal models have been developed for real-time, physiologically accurate prosthesis control during functional tasks (30) but have only shown control of two to three DOFs.”

• cites [30] sourceSupported

May combine two claims.

Independent efferent motor action potentials were recorded from RPNIs and provided real-time prosthetic finger control for up to 300 days without recalibrating the control algorithm.

“In addition, we successfully recorded independent efferent motor action potentials from RPNIs, which provided real-time prosthetic finger control up to 300 days without recalibration of the control algorithm.”

May combine two claims.

In P1, median RPNI 1 contracted for thumb flexion, while median RPNI 2 through RPNI 4 and part of RPNI 1 contracted for index finger flexion.

“Specifically, median RPNI 1 contracted for thumb flexion, whereas median RPNI 2 to RPNI 4 and a subsection of RPNI 1 contracted for index finger flexion (Fig. 2A).”

May combine two claims.

P4's median nerve RPNI had an average peak-to-peak amplitude of 579 ± 209 μV (SNR 19.1), ulnar RPNI 1 had 334 ± 80.9 μV (SNR 15.6), and ulnar RPNI 2 had 501 ± 164 μV (SNR 28.3).

“Likewise, P4’s median nerve RPNI had an average peak-to-peak amplitude of 579 ± 209 μV (SNR = 19.1), ulnar nerve RPNI 1 had an amplitude of 334 ± 80.9 μV (SNR = 15.6), and ulnar nerve RPNI 2 had an amplitude of 501 ± 164 μV (SNR = 28.3) (fig. S2, C and D).”

May combine two claims.

During index finger flexion, median RPNI 1 contracted more than surrounding tissue (P < 0.001), while median RPNI 2 to RPNI 4 showed smaller contractions and mixed pixel changes.

“For index finger flexion, median RPNI 1 contracted more than the surrounding tissue (P < 0.001), whereas observation of median RPNI 2 to RPNI 4 demonstrated smaller contractions and had mixed pixel changes (table S2).”

May combine two claims.

In P1, clear EMG spikes were associated with thumb movements in median RPNI 1 (SNR 4.62) and with small finger movements in ulnar RPNI 1 and RPNI 2 (mean SNR 3.80).

“Here, we observed clear EMG spikes associated with thumb movements in median RPNI 1, with a signal-to-noise ratio (SNR) of 4.62, and for small finger movements in ulnar RPNI 1 and RPNI 2 (mean SNR = 3.80) (Fig. 2C).”

May combine two claims.

RPNIs remained a stable peripheral nerve interface for 2 years in P1, 8 months in P2, 3 years in P3, and 1 year in P4.

“In comparison, RPNIs have remained a stable peripheral nerve interface for 2 years in P1, 8 months in P2, 3 years in P3, and 1 year in P4.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A small subsection of P1's ulnar RPNI showed small but visible contractions during volitional index finger movement.

“A small subsection of the ulnar RPNI did appear to undergo small but visible contractions during volitional index finger movement.”

May combine two claims.

Most movements were selected quickly, with the fastest motion selection times under 0.3 s.

“The majority of movements were selected quickly, with the fastest motion selection times, or the times between EMG onset and the classifier’s prediction, less than 0.3 s”

May combine two claims.

P1's median RPNI 1 and ulnar RPNI 1 and RPNI 2 showed a significant change in mean pixel intensity compared with surrounding tissue during thumb and small finger flexion, respectively, with P < 0.001 for both comparisons.

“Overall, P1’s median RPNI 1 and ulnar RPNI 1 and RPNI 2 had a significant change in mean pixel intensity than the surrounding tissue during thumb and small finger flexion, respectively (P < 0.001 for both comparisons).”

May combine two claims.

On day 0, P3 and P4 acquired virtual thumb targets with 100% and 96.3% accuracy, respectively.

“P3 and P4 acquired targets with 100 and 96.3% accuracy on day 0, respectively.”

May combine two claims.

The mean SNR of recorded EMG was 4.21 in P1, 68.9 in P3, and 21.0 in P4.

“The SNR of the recorded EMG had a mean of 4.21 in P1, 68.9 in P3, and 21.0 in P4.”

May combine two claims.

P3 and P4 performed a two-axis thumb target hitting task, hitting eight targets with 100% and 97.2% accuracy and average times to success of 0.987 ± 0.16 s and 2.83 ± 0.43 s, respectively.

“P3 and P4 performed the same target hitting task in these two axes, hitting eight targets with 100 and 97.2% accuracy with an average time to success of 0.987 ± 0.16 and 2.83 ± 0.43 s, respectively (Fig. 5, E and F, and movie S9).”

May combine two claims.

Single motor units extracted from P3 and P4's median RPNIs showed day-to-day signal amplitude variability of ±17.2% and ±6.63%, respectively, with no observable decreasing trend in amplitude.

“In addition, extraction of single motor units from P3 and P4’s median RPNIs showed signal amplitude variability from day to day, ±17.2 and ±6.63%, respectively, but no observable decreasing trend in amplitude (Fig. 5, C and D).”

May combine two claims.

For P3's most preferred movement, the median RPNI had an average peak-to-peak amplitude of 2.77 ± 0.660 mV with SNR 102, and the ulnar RPNI had 501 ± 145 μV with SNR 36.1.

“The averaged peak-to-peak amplitude for the most preferred movement on the RPNIs was 2.77 ± 0.660 mV with an SNR of 102 and 501 ± 145 μV with an SNR of 36.1 on P3’s median and ulnar RPNIs, respectively (fig. S2, A and B).”

May combine two claims.

In P1, most of ulnar RPNI 1 and RPNI 2 contracted during volitional small finger PIP/DIP joint flexion, while a subsection of both contracted for thumb movement.

“The bulk of RPNI 1 and RPNI 2 contracted during volitional small finger PIP/DIP joint flexion of the phantom hand, whereas a subsection of both RPNIs contracted for thumb movement (Fig. 2A and movie S2).”

May combine two claims.

P4 performed the same two-axis task using surface EMG, hitting targets with 78.4% accuracy and an average time to success of 4.40 ± 0.50 s.

“As a direct comparison, P4 performed the same task using surface EMG (see Materials and Methods), hitting targets with 78.4% accuracy with an average time to success of 4.40 ± 0.50 s (movie S10).”

May combine two claims.

Ulnar nerve RPNIs activated during phantom thumb flexion and showed minimal activation during index finger flexion.

“For the ulnar nerve RPNIs, RPNI activation appropriately occurred during flexion of the phantom thumb, whereas minimal activation occurred during index finger flexion.”

May combine two claims.

P3 and P4 had averaged motion selection times across all movements of 0.172 ± 0.105 s and 0.234 ± 0.0894 s, respectively.

“P3 and P4’s averaged motion selection time across all movements were 0.172 ± 0.105 and 0.234 ± 0.0894 s, respectively (means ± SD; table S3).”

May combine two claims.

The RPNI operation avoided cutting nerve branches to residual upper-arm muscles, so it did not denervate existing muscle.

“we did not need to transect any nerve branches to any of the residual muscles of the upper arm and, thus, did not denervate existing muscle”

May combine two claims.

Recording specific efferent motor action potentials is difficult because the signals are small, which limits how many independent control signals can be recorded.

“However, recording specific efferent motor action potentials is challenging because of the small amplitude of the signals, limiting the number of independent control signals that can be recorded (9).”

• cites [9] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In targeted muscle reinnervation, a normally innervated muscle must be partially denervated to create a new target for recording EMG signals from the implanted nerve.

“With TMR, a normally innervated muscle must be partially denervated to provide a new target for recording EMG signals from the implanted nerve.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Electrical stimulation of afferent sensory axons has shown promise for providing tactile feedback.

“Instead, electrical stimulation has shown promise in providing tactile feedback through stimulation of afferent sensory axons (3, 5–7).”

• cites [3] sourceNot checked — no full text of the source
• cites [5] sourceNot checked — no full text of the source
• cites [6] sourceNot checked — no full text of the source
• cites [7] sourceNot checked — no full text of the source

May combine two claims.

In upper limb amputees, the regenerative peripheral nerve interface acts as a biologically stable amplifier of efferent motor action potentials and remains stable over the long term.

“Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in upper limb amputees.”

May combine two claims.

In targeted muscle reinnervation, two or three nerves may be implanted into the same target muscle, which makes recording independent control signals from individual nerves or fascicles difficult.

“In addition, two or three nerves (median, radial, and ulnar) may be implanted into the same target muscle (for example, the pectoralis major muscle), making it difficult to record independent control signals from individual nerves or fascicles.”

May combine two claims.

Targeted muscle reinnervation can provide multiple control signals by transferring divided peripheral nerves in a residual limb to intact local or regional muscles, with surface EMG used to record efferent motor control signals.

“Targeted muscle reinnervation (TMR) can provide multiple control signals by transferring divided peripheral nerves in a residual limb to intact local or regional muscles. Surface electromyography (EMG) is then used to record the efferent motor control signals (10).”

• cites [10] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Surface EMG amplitude was lower than intramuscular EMG, which may have contributed to the lower performance.

“Surface EMG amplitude was lower than intramuscular EMG, which may have contributed to the decrease in performance.”

Probably not a substantial claim: may not pass S3 (load-bearing).

P3's nerves had an additional two years to reinnervate his muscle grafts before electrode implantation.

“P3’s nerves had an additional 2 years to reinnervate his muscle grafts before electrode implantation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The unexpected ulnar RPNI contraction during index finger movement may be explained by P1's 16 years without a hand, which could make some volitional movements hard to generate independently.

“This was anatomically unexpected but may be due to P1’s 16-year period without a hand, making certain volitional movements difficult to generate independently.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study design did not directly compare RPNIs with other surgical approaches such as TMR.

“Our study design did not include a direct comparison to other surgical approaches (for example, TMR).”

May combine two claims.

RPNI contractions in two participants lacking finger-related musculature suggest that nerves carrying efferent motor action potentials for finger function successfully reinnervated the RPNIs, giving P1 and P2 volitional control over their phantom hand.

“These RPNI contractions, seen in two participants missing finger-related musculature, suggest that nerves carrying efferent motor action potentials controlling finger functionality successfully reinnervated the RPNIs, allowing P1 and P2 to have volitional control over their phantom hand.”

• AssumptionRests on an assumption: The attempted phantom finger movements made by participants correspond to volitional motor commands in the residual nerves that can drive RPNI contractions.

May combine two claims.

The wide SNR gap between P1, P3, and P4 is likely due to the smaller bipolar electrode spacing in acute fine wires (1 mm) versus indwelling EMG electrodes (10 mm), while the difference between P3 and P4 may be due to the period of reinnervation.

“The wide SNR gap between P1, P3, and P4 is likely due to the smaller bipolar electrode spacing in acute fine wires (1 mm) versus indwelling EMG electrodes (10 mm), whereas the difference between P3 and P4’s measured SNR may be due to the period of reinnervation.”

May combine two claims.

These findings suggest that efferent motor action potentials can be recorded from individual nerve fascicles using RPNIs, and each fascicle may carry distinct motor control signals.

“These findings suggest that efferent motor action potentials can be recorded using RPNIs from individual nerve fascicles, each of which may have distinct and unique motor control signals.”

• AssumptionRests on an assumption: The signals recorded from RPNI electrodes are efferent motor action potentials generated by the RPNI grafts rather than by other sources.

Probably not a substantial claim: may not pass S3 (load-bearing).

More accurate surgical targeting of the bipolar indwelling electrode into the RPNI may explain the larger amplitude efferent motor action potential signals compared with P1.

“The more accurate surgical targeting of the bipolar indwelling electrode into the RPNI may account for the larger amplitude efferent motor action potential signals compared with P1.”

May combine two claims.

These findings suggest that RPNI grafts amplify efferent motor nerve action potentials, actively contract, and produce EMG signals similar to residual muscle.

“This suggests that these RPNI grafts amplify efferent motor nerve action potentials, actively contract, and generate EMG signals similar to residual muscle.”

• AssumptionRests on an assumption: The signals recorded from RPNI electrodes are efferent motor action potentials generated by the RPNI grafts rather than by other sources.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The University of Michigan Institutional Review Board approved the study, and each participant gave written informed consent.

“The Institutional Review Board at the University of Michigan approved this study, and each participant provided written and informed consent.”

Probably not a substantial claim: may not pass S3 (load-bearing).

No power analysis was performed before the study.

“No power analysis was calculated before the study.”

May combine two claims.

The study was a first-in-human, non-blinded, nonrandomized pilot.

“This was a first-in-human, non-blinded, nonrandomized pilot study.”

Classified as probably not a substantial claim.

That electrode limit required careful selection of which residual muscles to implant for best prosthesis control.

“This led to a careful decision on which residual muscles to implant to provide the best prosthesis control for the subjects.”