A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

May combine two claims.

The most frequent use of PNS interfaces is in FES, with clinical applications for controlling micturition and defecation by stimulating the sacral roots.

“Nowadays, the most frequent use of PNS interfaces resides in FES, which has clinical applications in various systems designed to control micturition and defecation by stimulating the sacral roots”

• cites Brindley et al., 1986 sourcePartly supported

  The Discussion reports that most patients used sacral anterior root stimulators mainly for micturition. Methods and Results also reports that a few used S3 or S4 stimulation to aid defaecation. The paper does not establish that FES is the most frequent use of PNS interfaces overall. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Creasey, 1993 sourceNot checked — no full text of the source
• cites Van Kerrebroeck et al., 1993 sourceNot checked — no full text of the source

May combine two claims.

Acoustic signals increase in parallel with surface EMG signals during voluntary and evoked contraction, but acoustic amplitude decays with fatigue whereas EMG amplitude does not.

“Acoustic signals increase in parallel with surface EMG signals during voluntary and evoked contraction, but acoustic amplitude decays with fatigue whereas EMG amplitude does not”

• cites Barry et al., 1985 sourcePartly supported

  The Abstract reports that acoustic amplitude decayed with fatigue while surface EMG amplitude did not, and the Figure 5 discussion describes both signals increasing together when voluntary effort increased. The copy does not establish that they increase in parallel during evoked contractions; the Discussion describes external nerve stimulation as a proposed future test. It also notes that surface EMG began to decay below 45% of maximal voluntary contraction, so the claim that EMG amplitude does not decay needs qualification. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Barry et al., 1992 sourcePartly supported

  The Results (page unavailable) report that vibration amplitude declines with fatigue, but also state that the evoked compound muscle action potential (CMAP) declines, though less rapidly. The discussion (page unavailable) says surface EMG amplitude typically does not decline during moderate voluntary contractions. The paper does not support the broader claim that acoustic and EMG signals increase in parallel during both types of contraction, or that electrical-signal amplitude does not decline with evoked fatigue. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

After more than 10 years of development, Brindley's group reported the first 50 cases of a radio frequency-controlled sacral anterior root stimulator implant in humans.

“After more than 10 years of development, Brindley's group reported the first 50 cases of a radio frequency-controlled implant from series production with medical approval called sacral anterior root stimulator (SARS) in humans (Brindley et al., 1986) .”

• cites Brindley et al., 1986 sourcePartly supported

  The Abstract reports the first 50 human recipients of sacral anterior root stimulators; Methods and Results describes external radio transmitters, and the References include development work dating to 1972. But the printed sentence goes further: Methods and Results says the first 11 implants were made in the Neurological Prostheses Unit, not series-produced, and our copy does not establish medical approval. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

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

The Finetech-Brindley stimulator was commercialized, and less than a decade later 500 patients had benefited from the system.

“The implant was commercialized as FinetechBrindley stimulator, and less than a decade later 500 patients benefited from the system (Brindley, 1994) .”

• cites Brindley, 1994 sourcePartly supported

  The Introduction says the 500th London-design stimulator was implanted in February 1992, and Sources of information identifies Finetech Medical Ltd as the manufacturer. The paper does not date commercialization, so it cannot establish the claimed interval of less than a decade. Its benefits discussion describes potential benefits but does not establish that all 500 patients benefited. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

In acute experiments, multiple-wire-microelectrode arrays were inserted into rat nerves to investigate selective stimulation of motor units.

“In acute experiments, multiple-wire-microelectrode arrays were inserted into rat nerves to investigate selective stimulation of motor units (Smit et al., 1999) .”

• cites Smit et al., 1999 sourceSupported

May combine two claims.

Histology of animal nerves with metal or polymer longitudinal intrafascicular electrodes implanted for six months showed the implants were biocompatible and caused no damage, although a slight increase in connective tissue around the implant site was evident long-term.

“The histology of animal nerves that had metal or polymer LIFEs implanted for a period of 6 months revealed that the implants are biocompatible and that no damage was caused by the presence of the electrode, although a slight increase in connective tissue surrounding the implant site was evident in the longterm (Lefurge et al., 1991; Lawrence et al., 2002) .”

• cites Lefurge et al., 1991 sourceNot checked — no full text of the source
• cites Lawrence et al., 2002 sourceSupported

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

Activity of embryonic mouse spinal cord cells has been recorded simultaneously over several months on a planar glass substrate with 64 iridium tin oxide electrodes.

“The activity of embryonic spinal cord cells of mice has been recorded simultaneously over a period of several months on a planar glass substrate with 64 iridium tin oxide electrodes (Droge et al., 1986)”

• cites Droge et al., 1986 sourcePartly supported

  The Cell culture section describes recordings from embryonic mouse spinal-cord cells, and the paper describes simultaneous multisite recording. But its recording matrix had 36 gold-conductor electrodes, not 64 iridium tin oxide electrodes; the Results describe cultures examined 3–5 weeks after seeding, not recordings over several months. No page numbers are available in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Different complex algorithms have been developed to extract force/torque information from sEMG signals to address these limitations, although in some cases good results have been achieved using a simple proportional control law.

“Different complex algorithms have been developed to extract force/torque information from sEMG signals that address these limitations, although in some cases good results have been achieved using a simple proportional control law (Gordon and Ferris, 2004)”

• cites Gordon and Ferris, 2004 sourcePartly supported

  The Virtual object interface section describes a simple proportional law: processed surface EMG amplitudes generated virtual forces, and the Discussion reports that subjects improved their control with practice. The Discussion also mentions signal-processing algorithms for myoelectric prostheses, but our copy does not say those algorithms extract force or torque from sEMG; the study's proportional forces were virtual, not measured force or torque estimates. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

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

Patients learned to open and close the hand reliably after a few minutes of practice.

“The patients learned to open and close the hand reliably after a few minutes of practice”

• cites Barry et al., 1986Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Attempts to develop material surfaces that may be recognized as biological and form truly biocompatible interfaces with tissue are under investigation, although they have yet to be integrated in functional neural interfaces.

“Attempts to develop material surfaces that may be recognized as biological and form truly biocompatible interfaces with the tissue are under investigation, although they have yet to be integrated in functional neural interfaces.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Extraneural electrodes such as cuff and epineurial electrodes provide simultaneous interface with many axons in the nerve.

“Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve”

May combine two claims.

Nerve electrodes have the potential to damage the nerves on which they are implanted, whereas muscle electrodes are generally considered safer.

“However, nerve electrodes also have the potential to damage the nerves on which they are implanted, whereas muscle electrodes are generally considered as safer”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Signals are transmitted by axons in series of impulses or action potentials, with intensity mainly coded in impulse frequency along the peripheral axon.

“Signals are transmitted by the corresponding axons in series of impulses or action potentials, with intensity of the signal mainly coded in impulse frequency along the peripheral axon.”

• AssumptionRests on an assumption: Signals are transmitted by axons in series of impulses or action potentials, with intensity mainly coded in impulse frequency along the peripheral axon.

May combine two claims.

Patients are able to use implantable neuroprostheses for activities of daily living and to enhance their quality of life and independence.

“Patients are able to use the system for activities of daily living and enhancing their quality of life and independency.”

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

Nerve fibers are grouped in fascicles surrounded by connective tissue in the peripheral nerve.

“Nerve fibers, both afferent and efferent, are grouped in fascicles surrounded by connective tissue in the peripheral nerve”

• cites Peters et al., 1991Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Most patients with nervous system injury suffer from an incomplete lesion, so modular, controllable systems for supporting functions are being developed.

“New technological developments are taking into account the fact that the most patients with nervous system injury suffer from an incomplete lesion, and thus modular, controllable systems for supporting these functions are being developed”

• cites Rupp and Gerner, 2004 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Recruitment of motor units follows an order of size, with slow fatigue-resistant motor units activated first and large fast-fatigue motor units activated only at high levels of tension.

“Recruitment of motor units follows an order of size, with slow fatigue-resistant motor units activated first and large fast-fatigue motor units activated only at high levels of tension.”

• AssumptionRests on an assumption: Recruitment of motor units follows an order of size, with slow fatigue-resistant motor units activated first and large fast-fatigue motor units activated only at high levels of tension.

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

The fascicular architecture changes throughout the length of the nerve, with an increasing number of fascicles of smaller size in distal compared with proximal segments.

“The fascicular architecture changes throughout the length of the nerve, with an increasing number of fascicles of smaller size in distal with respect to proximal segments.”

• AssumptionRests on an assumption: The fascicular architecture changes throughout the length of the nerve, with an increasing number of fascicles of smaller size in distal compared with proximal segments.

May combine two claims.

Nerve electrodes implanted adjacent to, around, or within a peripheral nerve trunk or spinal root reduce the stimulus intensity required for activation compared with muscular or surface electrodes, thereby decreasing hazardous electrochemical processes and power consumption.

“Due to the proximity to the nerve, the stimulus intensity required for activation is reduced in comparison with muscular or surface electrodes and, consequently, hazardous electrochemical processes and power consumption of the stimulator system can be decreased”

• cites Loeb and Peck, 1996 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

The perineurium is the main contributor to the tensile strength of the nerve, acts as a diffusion barrier, and maintains the endoneurial fluid pressure.

“The perineurium is the main contributor to the tensile strength of the nerve, acts as a diffusion barrier, and maintains the endoneurial fluid pressure.”

• AssumptionRests on an assumption: The perineurium is the main contributor to the tensile strength of the nerve, acts as a diffusion barrier, and maintains the endoneurial fluid pressure.

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

Intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle.

“intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle”

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

Compatibility between a technical and a biological system can be divided into structural biocompatibility and surface biocompatibility.

“In general, the compatibility between a technical and a biological system (Bronzino, 1995) can be divided into the structural biocompatibility and the surface biocompatibility”

• cites Bronzino, 1995Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Epimysial electrodes offer a good signal-to-noise ratio because of their position and large surface and provide exact selectivity, namely the implanted muscle.

“In general, they offer a good signal-to-noise ratio because of their position and large surface and provide exact selectivity, namely the implanted muscle.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

For recording purposes, electrodes made of silver/silver chloride in the form of bars (10-1 mm) have been found to give adequate signal-to-noise ratio.

“For recording purposes, electrodes made of silver/silver chloride in the form of bars (10 -1 mm) have been found to give adequate signal-to-noise ratio.”

May combine two claims.

Multichannel surface EMG electrodes have been developed that enable measurements of motor unit potentials size and number and provide topographical information beyond the capability of intramuscular needle electrodes.

“Multichannel (linear and high-density arrays) surface EMG electrodes have been developed that enable measurements of motor unit potentials size and number and provide topographical information that is beyond the capability of intramuscular needle electrodes”

• cites Zwarts and Stegeman, 2003 sourceNot checked — no full text of the source

May combine two claims.

Surface electrodes can also supply a perceivable sensation to the skin or excite nerve tracts or muscles underneath the skin.

“they can also be employed to supply a perceivable sensation to the skin or to excite nerve tracts or muscles underneath the skin”

• cites Patterson and Lockwood, 1993 sourceNot checked — no full text of the source
• cites Taylor et al., 1999 sourceNot checked — no full text of the source

May combine two claims.

Disadvantages of acoustic myography include susceptibility to interference by environmental noise and vibrations and limited experience with its use.

“Disadvantagesinclude the susceptibility to interference by environmental noise and vibrations and limited experience with its use.”

May combine two claims.

A final issue with percutaneous electrodes is that muscle contractions may result in eventual breakage, although these problems have become less frequent with the improvement of electrodes and lead wires.

“A final issue with percutaneous electrodes is that muscle contractions may result in eventual breakage, although these problems have become less frequent with the improvement of electrodes and lead wires”

• cites Onishi et al., 2000 sourceNot checked — no full text of the source

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

The active recording electrode should be located near but not on the motor point because at this point the stability of signals suffers from minor physical displacement of the electrode.

“The active recording electrode should be located near but not on the motor point because at this point the stability of signals suffers from minor physical displacement of the electrode”

• cites De Luca, 2002Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Further technical developments to increase sensitivity of measurements are needed before magnetic interfaces can be used for single-unit activity recordings.

“Further technical developments to increase sensitivity of measurements are needed before magnetic interfaces can be used for single-unit activity recordings.”

May combine two claims.

Although epimysial electrodes can be used for EMG recording, their main application area is for muscle stimulation.

“Although they can be used for EMG recording, the main application area is for muscle stimulation”

May combine two claims.

The number of electrodes to be used depends on the working application: a low number for robust use and limited functionality, or high numbers for good spatial resolution and selectivity.

“The number of electrodes to be used depends on the working application: low number of electrodes for robust use and limited functionality or high numbers for good spatial resolution and selectivity”

May combine two claims.

Muscle sounds have been used to measure twitch force, monitor fatigue, and in the diagnosis of muscle diseases.

“Muscle sounds have been used to measure twitch force, monitor fatigue and in the diagnosis of muscle diseases.”

May combine two claims.

As a control signal for externally powered prostheses, acoustic myography may present advantages over surface EMG because it is unaffected by changes in skin impedance, less sensitive to placement on the muscle, and requires less amplification and electrical shielding.

“As a control signal for externally powered prostheses, acoustic myography may present some advantages over surface EMG because it is unaffected by changes in skin impedance, less sensitive to placement on the muscle, and requires less amplification and electrical shielding.”

May combine two claims.

The impedance at the electrode-skin interface is largely variable between individuals at low frequencies, whereas at high frequencies the decline of impedance values with time depends on the electrode type.

“The impedance at the electrode-skin interface is largely variable between individuals at low frequencies, whereas at high frequencies the decline of impedance values with time depends on the electrode type”

• cites Hewson et al., 2003 sourceNot checked — no full text of the source

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

Cuff and intrafascicular electrodes can be applied to intact nerves in acute or chronic studies, whereas regenerative sieve electrodes are implanted in transected nerves that need to regenerate across the electrode sieve over several months.

“cuff and intrafascicular electrodes can be applied to intact nerves in acute or chronic studies, whereas, by definition, regenerative sieve electrodes are implanted in transected nerves that need to regenerate across the electrode sieve over several months.”

May combine two claims.

Intramuscular electrodes may damage many muscle fibers, but in most instances this loss will not represent a noticeable reduction in muscle force.

“These electrodes may damage many muscle fibers, but in most instances this loss will not represent a noticeable reduction in muscle force”

• cites Mortimer et al., 1980 sourceNot checked — no full text of the source

May combine two claims.

Measurements for magnetoneurography are usually performed inside a magnetically shielded room to minimize external contamination, limiting its application for control of neuroprostheses.

“To minimize external contamination, measurements are usually performed inside a magnetically shielded room, thus limiting its application for control of neuroprostheses.”

May combine two claims.

Compared with nerve cuff electrodes, intramuscular electrodes have been shown to produce more reliable, more graded, and less fatigable recruitment of motor units.

“Compared with nerve cuff electrodes, intramuscular electrodes have been shown to produce more reliable, more graded, and less fatigable recruitment of motor units”

• cites Singh et al., 2000Not checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

High energy consumption is required to activate the muscle with epimysial electrodes.

“In addition, high energy consumption is required to activate the muscle.”

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

To avoid problems derived from excess charge delivery, stimulation is given in cycles, and the system is explanted once regenerating axons reinnervate the muscles of interest.

“To avoid problems derived from excess charge delivery, stimulation is given in cycles, and the system is explanted once regenerating axons reinnervate the muscles of interest.”

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

The BION implantable microstimulator consists of a small cylindrical capsule (16-2 mm) whose internal components are connected to electrodes sealed hermetically into its ends.

“This device consists of a small cylindrical capsule (16 -2 mm) whose internal components are connected to electrodes sealed hermetically into its ends.”

• cites Loeb et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

Electrode and lead failures or infections have been found to be rare and the electrode response was stable over time in patients with intramuscular or epimysial electrodes during more than 3 years.

“Electrode and lead failures or infections have been found to be rare and the electrode response was stable over time in patients with intramuscular or epimysial electrodes during more than 3 years”

• cites Kilgore et al., 2003 sourceNot checked — no full text of the source

May combine two claims.

The currents required to produce contractions are high and may induce discomfort and tissue damage.

“In addition, the currents required to produce contractions are high and may induce discomfort and tissue damage”

• cites Chae and Hart, 1998 sourceNot checked — no full text of the source

May combine two claims.

Adequate EMG signals can be obtained with epimysial and intramuscular electrodes, but the fatigue of the muscle and the derived change of the recorded signal have to be taken into account for long-term use.

“Adequate EMG signals can be obtained with epimysial and intramuscular electrodes, but the fatigue of the muscle and the derived change of the recorded signal have to be taken into account for long-term use.”

May combine two claims.

The BION electrode was found to be stable, biocompatible, and effective in experimental animals when implanted passively or used for muscle stimulation over long-term implantation.

“Tests performed indicated that the BION is a stable, biocompatible, and effective electrode when implanted passively or used to stimulate muscles in experimental animals for long-term implantation (Cameron et al., 1998) .”

• cites Cameron et al., 1998 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Management may be difficult when many epimysial electrodes on different muscles are used because of the interconnection between them, providing additional risks and possible source of failure.

“Management may be difficult when many epimysial electrodes on different muscles are used because of the interconnection between them, providing additional risks and possible source of failure.”

May combine two claims.

The main advantage of surface electrodes being non-invasive and easily adaptable is counteracted by disadvantages such as the need for daily placement and frequent calibration, and low reproducibility and quality of acquired signals.

“Their main advantage of being non-invasive and easily adaptable is counteracted by several disadvantages, such as the need for daily placement and frequent calibration, and by the low reproducibility and quality of acquired signals.”

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

Recorded EMG signals are used to determine the activation time of a muscle, estimate the force produced during muscle contraction, and estimate the rate of muscle fatigue.

“Currently, recorded EMG signals are used to determine the activation time of a muscle, to estimate the force produced during muscle contraction and to estimate the rate of muscle fatigue.”

May combine two claims.

Capacitive electrodes such as titanium nitride might reduce the risk of corrosion under stimulation conditions, but their performance highly varies with the fabrication technology.

“Capacitive electrodes such as titanium nitride might reduce the risk of corrosion under stimulation conditions, but their performance highly varies with the fabrication technology”

• cites Janders et al., 1996Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Weiland et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

For large muscles, the EMG activity mainly reflects the action potentials of motor units located more superficial or closer to the electrode.

“For large muscles, the EMG activity mainly reflects the action potentials of motor units located more superficial or closer to the electrode.”

May combine two claims.

This requires the implantation and maintenance of many electrodes subjected to considerable mechanical stress caused by strong muscle contractions.

“This requires the implantation and maintenance of many electrodes subjected to considerable mechanical stress caused by strong muscle contractions”

• cites Devasahayam, 1992 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The choice of an adequate electrode size and material, in combination with a structurally compatible design, is always a compromise between electrode impedance, signal-to-noise ratio, and selectivity.

“The choice of an adequate electrode size and material, in combination with a 'structural compatible' design, is always a compromise between electrode impedance, signal-to-noise ratio, and selectivity.”

May combine two claims.

Direct muscle stimulation may be used to recover chronically denervated muscles, although activation requires long duration pulses and extremely high current that are usually not generated by common FES devices.

“Direct muscle stimulation may be also used to recover chronically denervated muscles, although activation requires long duration pulses and extremely high current that are usually not generated by common FES devices”

• cites Kern et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

There was no gross evidence of axonal damage one day after implantation of the slowly penetrating interfascicular nerve electrode, but chronic implants have not been reported.

“There was no gross evidence of axonal damage after 1 day, but chronic implants have not been reported.”

• cites Tyler and Durand, 1997 sourceNot checked — no full text of the source

May combine two claims.

Quasi-trapezoidal stimulation pulses induce more gradual contraction than rectangular pulses, an effect attributed to activation of fatigue-resistant motor units before large fast-fatigue units with cuff electrodes.

“For example, quasi-trapezoidal stimulation pulses have been shown to induce more gradual contraction than rectangular pulses, an effect that was attributed to activation of fatigue-resistant motor units before activation of large fast-fatigue units with cuff electrodes (Fang and Mortimer, 1991; Rozman et al., 1993) .”

• cites Fang and Mortimer, 1991 sourceNot checked — no full text of the source
• cites Rozman et al., 1993 sourceNot checked — no full text of the source

May combine two claims.

Using short pulsewidths and a subthreshold transverse current from a steering anode restricts the region of excitation of the nerve trunk and significantly improves stimulation selectivity.

“The use of short pulsewidths and the introduction of a subthreshold transverse current from a steering anode allows restriction of the region of excitation of the nerve trunk, significantly improving the selectivity of stimulation (Gorman and Mortimer, 1986; Sweeney et al., 1990; Grill and Mortimer, 1996b; Navarro et al., 2001) .”

• cites Gorman and Mortimer, 1986Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Sweeney et al., 1990 sourceNot checked — no full text of the source
• cites Grill and Mortimer, 1996bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Chronic implantation of snug cuffs modifies nerve shape and produces loss of large nerve fibers, which are the most sensitive to compression.

“Although snug-fitting nerve cuffs have been advocated to reduce the stimulus charge injection or to obtain a high signal-to-noise ratio for neural recordings (Naples et al., 1990) , different studies have shown that chronic implantation of snug cuffs modifies the nerve shape and produces a loss of large nerve fibers, which are the most sensitive to compression (Krarup et al., 1989; Grill and Mort”

• cites Krarup et al., 1989 sourceNot checked — no full text of the source
• cites Grill and Mortimer, 1998 sourceNot checked — no full text of the source
• cites Larsen et al., 1998 sourceNot checked — no full text of the source

May combine two claims.

A tripolar electrode configuration is preferred to reduce noise pickup and provides a biophysically ideal way to use a differential amplifier to reject large bioelectric signals arising outside the cuff.

“Tripolar (central active electrode vs. two reference electrodes near the ends of the cuff) electrode configuration is preferred to reduce noise pickup (Stein et al., 1977) ; it provides a biophysically ideal way to use a differential amplifier to reject almost completely the large bioelectric signals arising from outside the cuff (e.g., EMG).”

• cites Stein et al., 1977 sourceNot checked — no full text of the source

May combine two claims.

Histological cross-sections showed that the slowly penetrating interfascicular nerve electrode rearranges the epineurium and penetrates deep within a multifascicular nerve but does not disrupt the perineurium.

“Histological cross-sections showed that the SPINE rearranges the epineurium and penetrates deep within a multifascicular nerve but did not disrupt the perineurium (Tyler and Durand, 1997) .”

• cites Tyler and Durand, 1997 sourceNot checked — no full text of the source

May combine two claims.

Flattening a nerve into a more elliptical shape makes fascicles more accessible and moves central fibers closer to the stimulating electrode compared with cylindrical cuffs.

“By flattening the nerve into a more elliptical shape, fascicles become more accessible and central fibers are moved closer to the stimulating electrode in comparison with cylindrical cuffs.”

• cites Tyler and Durand, 2002 sourceNot checked — no full text of the source

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

The first micturition caused by electrical nerve root stimulation was reported in 1973.

“The first micturition because of electrical nerve root stimulation was reported in 1973 (Brindley, 1973) .”

• cites Brindley, 1973Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Postoperative infections after helicoidal electrode implants in vagus nerve patients occur in less than 3% of cases, and removal of the device is required in 1%.

“Postoperative infections after helicoidal electrode implants in vagus nerve patients occur in less than 3% of cases, requiring removal of the device in 1%.”

• cites McLachlan, 1997 sourceNot checked — no full text of the source

May combine two claims.

Helicoidal electrodes conform to the shape of the nerve and minimize mechanical trauma.

“Helicoidal electrodes, placed circumjacent to the nerve, are made of flexible platinum ribbon with an open helical design (Fig. 5), allowing the electrode to conform to the shape of the nerve and minimizing mechanical trauma (Naples et al., 1990) .”

• cites Naples et al., 1990Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Flat-interface nerve electrodes that moderately flattened the nerve demonstrated the best selectivity for limb motion measurements, and this selectivity was maintained throughout the implant time.

“Electrodes that moderately flattened the nerve demonstrated the best selectivity for limb motion measurements, which were maintained throughout the implant time (Tyler and Durand, 2003; Leventhal and Durand, 2004) .”

• cites Tyler and Durand, 2003 sourceNot checked — no full text of the source
• cites Leventhal and Durand, 2004 sourceNot checked — no full text of the source

May combine two claims.

Using epineurial electrodes for neuropathic pain has limited benefit because it should be applied only when pain involves one nerve territory in the head or limbs, and it has frequent morbidity from electrode approximation, electrode displacement, and lead failure.

“The latter application is of limited benefit because it should be applied only when pain involves one nerve territory in the head or the limbs and has frequent morbidity associated with electrode approximation, electrode displacement, and lead failure (Hassenbusch et al., 1996) .”

• cites Hassenbusch et al., 1996 sourceNot checked — no full text of the source

May combine two claims.

Acute experiments showed that individual fascicles of the cat sciatic nerve, and groups of fibers within fascicles, can be selectively activated with the flat-interface nerve electrode, and selectivity strongly depends on the relative locations of the fascicle and electrode contacts.

“Results on acute experiments showed that it is possible to selectively activate individual fascicles of the cat sciatic nerve with the FINE, as well as groups of fibers within the fascicles, and revealed the strong dependency of selectivity on the relative locations of the fascicle and the electrode contacts (Tyler and Durand, 2002; Leventhal and Durand, 2003) .”

• cites Tyler and Durand, 2002 sourceNot checked — no full text of the source
• cites Leventhal and Durand, 2003 sourceNot checked — no full text of the source

May combine two claims.

Ventral root stimulation causes simultaneous contraction of the sphincter and detrusor muscles, so voiding occurs in brief spurts at the end of stimulation when the striated sphincter relaxes faster than the smooth detrusor.

“Because ventral root stimulation produces simultaneous contraction of both sphincter and detrusor muscles, voiding is achieved in brief spurts at the end of the stimulation, when the striated sphincter muscle relaxes faster than the smooth detrusor muscle.”

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

Occasional fracture of the electrode wire has been reported for helicoidal electrodes.

“Occasional fracture of the electrode wire has been reported (McLachlan, 1997) .”

• cites McLachlan, 1997 sourceNot checked — no full text of the source

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

There are now 2,000 patients worldwide with a urinary bladder stimulator.

“Nowadays, there are 2,000 patients worldwide that carry a urinary bladder stimulator (Rijkhoff, 2004) .”

• cites Rijkhoff, 2004 sourceNot checked — no full text of the source

May combine two claims.

Epineurial electrodes have been used in biomedical functional electrical stimulation for breathing control by phrenic nerve stimulation, foot-drop improvement, and relief of neuropathic pain.

“Epineurial electrodes are used in biomedical FES applications for breathing control by phrenic nerve stimulation (Creasey et al., 1996) , foot-drop improvement (Liberson et al., 1961) , and relief of neuropathic pain (Strege et al., 1994) .”

• cites Creasey et al., 1996Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Liberson et al., 1961Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Strege et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

Chronic studies in laboratory animals with flat-interface nerve electrodes implanted for 1 to 3 months showed that high reshaping force induced nerve damage, whereas moderate and small forces caused no detectable change in nerve physiology and histology.

“Chronic studies in laboratory animals with FINE implanted over 1-3 months showed that electrodes applying high reshaping force induced nerve damage, whereas those with moderate and small forces did not cause any detectable change in nerve physiology and histology.”

• cites Tyler and Durand, 2003 sourceNot checked — no full text of the source
• cites Leventhal and Durand, 2004 sourceNot checked — no full text of the source

May combine two claims.

The applicability of regenerative electrodes depends on successful axonal regeneration through the perforations or holes, the possibility of nerve damage from mechanical load or constrictive forces within the holes, and the biocompatibility of the components.

“Applicability of regenerative electrodes is dependent on the success of axonal regeneration through the perforations or holes, the possibility of nerve damage from the mechanical load imposed by the electrode or from constrictive forces within the holes, and the biocompatibility of the components (Rosen et al., 1990; Navarro et al., 1996) .”

• cites Rosen et al., 1990 sourceNot checked — no full text of the source
• cites Navarro et al., 1996 sourceNot checked — no full text of the source

May combine two claims.

Recruitment curves for the Utah electrode array were broader, with twitch thresholds starting at much lower currents than usual for cuff electrodes.

“Recruitment curves for the electrode array were broader with twitch thresholds starting at much lower currents than usual for cuff electrodes.”

• cites Branner et al., 2001 sourceNot checked — no full text of the source

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

A study used a microelectrode to stimulate the sensory nerve of an operator to indicate contact with an object by a remote robotic hand.

“An interesting study used a microelectrode to stimulate the sensory nerve of an operator to indicate contact with an object by a remote robotic hand (Shimojo et al., 2003) .”

• cites Shimojo et al., 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

A negative aspect in the volunteer case was gradual degradation of the electrode wire bundle.

“One negative aspect was the gradual degradation of the electrode wire bundle.”

• cites Warwick et al., 2003 sourceNot checked — no full text of the source

May combine two claims.

A slanted array with electrodes of varying length from 0.5 to 1.5 mm and 0.1 mm difference between rows of neighboring electrodes was developed to decrease redundant electrodes and provide access to more fascicles within the nerve.

“To decrease the number of redundant electrodes and provide access to more fascicles within the nerve, a slanted array with electrodes of varying length, ranging from 0.5 to 1.5 mm with 0.1 mm difference in length between rows of neighboring electrodes, has been developed (Branner et al., 2001) .”

• cites Branner et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

Using multiple-hole silicon arrays, researchers demonstrated axonal regeneration and neural activity recording in peripheral nerves of rat, frog, and fish.

“Using multiple-hole silicon arrays, the researchers demonstrated axonal regeneration and even neural activity recording was demonstrated in peripheral nerves of rat, frog, and fish (Kovacs et al., 1994; Navarro et al., 1996; Bradley et al., 1997; Della Santina et al., 1997; Mensinger et al., 2000) .”

• cites Kovacs et al., 1994 sourceNot checked — no full text of the source
• cites Navarro et al., 1996 sourceNot checked — no full text of the source
• cites Bradley et al., 1997 sourceNot checked — no full text of the source

May combine two claims.

Activity from cutaneous receptors in response to stimuli has been recorded in several studies, but the activity was small and difficult to distinguish from background noise.

“Activity arising from cutaneous receptors in response to stimuli has been recorded in several studies, although activity was found to be small and difficult to distinguish from the background noise in the recording (Malmstrom et al., 1998; Yoshida et al., 2000) .”

• cites Malmstrom et al., 1998 sourceNot checked — no full text of the source
• cites Yoshida et al., 2000 sourceNot checked — no full text of the source

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

Rutten and colleagues concluded that an electrode separation of 120 μm was optimal for selective interfacing of peripheral nerves such as the rat peroneal nerve containing around 350 alphamotor fibers.

“In a series of experimental and modeling studies, Rutten and colleagues concluded that an electrode separation of 120 m m was optimal for selective interfacing peripheral nerves, such as the rat peroneal”

• cites Rutten, 2002 sourceNot checked — no full text of the source

May combine two claims.

A trade-off must be made between selectivity of stimulation and the total number of nerve fibers that can be activated, and optimal selectivity requires redundant electrodes in a 3D configuration.

“Thus, a trade-off must be made between selectivity of stimulation and the total number of nerve fibers that can be activated; optimal selectivity requires the use of redundant electrodes in the 3D configuration (Rutten et al., 1999) .”

• cites Rutten et al., 1999 sourceNot checked — no full text of the source

May combine two claims.

Microstimulation through a microneurography electrode can activate single axons, although in most cases it affects small groups of axons in the fascicle.

“Microstimulation through the electrode can be used to activate single axons, although in most cases stimulation affects small groups of axons in the fascicle (Ochoa and Torebjo ¨ rk, 1983; Torebjo ¨ rk et al., 1987) .”

• cites Ochoa and Torebjo ¨ rk, 1983 sourceNot checked — no full text of the source
• cites Torebjo ¨ rk et al., 1987Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Regenerating axons grow through the holes of regenerative electrodes, making it possible to record action potentials from and stimulate individual axons or small fascicles.

“Regenerating axons eventually grow through the holes (Fig. 12), making it possible to record action potentials from and to stimulate individual axons or small fascicles.”

• cites Llina ´ s et al., 1973Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Edell, 1986 sourceNot checked — no full text of the source
• cites Kovacs et al., 1992 sourceNot checked — no full text of the source

May combine two claims.

The volunteer received feedback from force and slip sensors in a prosthetic hand and used the array to control the hand for grasping an unseen object.

“The subject received feedback information from force and slip sensors in a prosthetic hand and subsequently used the array to control the hand for grasping an unseen object.”

• cites Warwick et al., 2003 sourceNot checked — no full text of the source

May combine two claims.

Stimulation properties stabilized in 80% of the Utah array electrodes over the course of the experiment, but the recorded sensory signals were not stable over time.

“The stimulation properties stabilized in 80% of the electrodes over the course of the experiment, but the recorded sensory signals were not stable over time.”

• cites Branner et al., 2004 sourceNot checked — no full text of the source

May combine two claims.

The Utah multielectrode array can record more effectively from more dorsal root ganglion neurons than conventional recording techniques, providing a more stable option for chronic implantation.

“The Utah MEA is also capable of recording more effectively from more dorsal root ganglion neurons than has been achieved by conventional recording techniques, providing a more stable option for chronic implantation (Aoyagi et al., 2003) .”

• cites Aoyagi et al., 2003 sourceNot checked — no full text of the source

May combine two claims.

A one-to-one design allowing access to each individual regenerated axon through one hole of 2-10 μm diameter has proved impossible, because nerve regeneration fails with holes of such small size.

“Ideally a one-to-one design would allow access to each individual regenerated axon grown through one hole (2-10 m m in diameter). However, this has been proved impossible; nerve regeneration fails with holes of such small size.”

• cites Edell, 1986 sourceNot checked — no full text of the source
• cites Rosen et al., 1990 sourceNot checked — no full text of the source
• cites Navarro et al., 1996 sourceNot checked — no full text of the source

May combine two claims.

Electrodes in the Utah array selectively recorded single-unit responses from mechanoreceptors, although only in 10-20% of the electrodes, and evoked graded recruitment of force in muscle groups in a highly selective fashion with current injections in the 1-20 μA range.

“Electrodes in the array were capable of selectively recording single-unit responses from mechanoreceptors, although only in 10-20% of the electrodes, and evoked graded recruitment of force in muscle groups in a highly selective fashion with current injections in the 1-20 m A range (Branner and Norman, 2000; Branner et al., 2001) .”

• cites Branner and Norman, 2000 sourceNot checked — no full text of the source
• cites Branner et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

Longitudinal intrafascicular electrodes offer good selectivity for stimulation and for multiunit extracellular recording, and their geometry makes them suitable for long-term implantation.

“The LIFEs offer good selectivity for stimulation (Nannini and Horch, 1991; Yoshida and Horch, 1993) and for multiunit extracellular recording (Goodall et al., 1991; McNaughton and Horch, 1994; Yoshida and Stein, 1999) , and their geometry, make them suitable for longterm implantations (Lefurge et al., 1991) .”

• cites Nannini and Horch, 1991 sourceNot checked — no full text of the source
• cites Yoshida and Horch, 1993 sourceNot checked — no full text of the source
• cites Lefurge et al., 1991 sourceNot checked — no full text of the source

May combine two claims.

The use of multistrand Kevlar longitudinal intrafascicular electrodes increases tensile strength and signal-to-noise ratio.

“The use of multistrand Kevlar LIFEs (m-polyLIFE) increases the tensile strength and signal-to-noise ratio (Lawrence et al., 2004) .”

• cites Lawrence et al., 2004 sourceNot checked — no full text of the source

May combine two claims.

Silicon regenerative interfaces cause frequent signs of axonopathy and constitute a physical barrier that limits elongation of regenerating axons depending on the size of the holes.

“However, such silicon interfaces cause frequent signs of axonopathy and constitute a physical barrier that limits the elongation of regenerating axons depending on the size of the holes (Edell, 1986; Rosen et al., 1990; Navarro et al., 1996; Zhao et al., 1997) .”

• cites Edell, 1986 sourceNot checked — no full text of the source
• cites Rosen et al., 1990 sourceNot checked — no full text of the source
• cites Navarro et al., 1996 sourceNot checked — no full text of the source

May combine two claims.

Both recording and stimulation with the Utah array were stable over the 36-hour-long period of the experiments.

“Both the recording and stimulation were stable over the 36-h-long period of the experiments.”

• cites Branner et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

Loss of neurons in the spiral ganglion and cochlear nucleus was found after cochlear nerve microelectrode implants, thought to be due to difficulty with electrode insertion and chronic motion of the implants.

“Nevertheless, the loss of neurons in spiral ganglion and cochlear nucleus was found, thought to be due to difficulty with electrode insertion and chronic motion of the implants.”

• cites Arts et al., 2003 sourceNot checked — no full text of the source

May combine two claims.

A silicon-based ribbon electrode with high flexibility functioned successfully after chronic implantation of up to one year, but its interconnect cable was not designed for the highly mobile somatic peripheral nerve and was too stiff and brittle for intrafascicular application.

“A silicon-based ribbon electrode with high flexibility demonstrated successful function after chronic implantation of up to 1 year (Hetke et al., 1994) , but this interconnect cable was not designed for implants in the highly mobile somatic peripheral nerve and was too stiff and brittle for intrafascicular application (Najafi and Hetke, 1990) .”

• cites Hetke et al., 1994 sourceNot checked — no full text of the source
• cites Najafi and Hetke, 1990 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

In the PNS, bioelectronic interfaces are in an early and experimental stage.

“In the PNS, bioelectronic interfaces are in an early and experimental stage.”

May combine two claims.

Pine et al. placed single rat hippocampus cells into a 3D silicon structure and demonstrated that the transplanted cells retained capacity for axonal outgrowth and that nerve action potentials could be recorded extracellularly from the soma.

“Pine et al . (1994) managed to place single hippocampus cells of the rat into a 3D silicon structure, which was termed 'cultured neuron probe.' They could demonstrate that the transplanted cells inside the microcompartments retained their capacity for axonal outgrowth and that nerve action potentials could be directly recorded extracellularly from the soma of the cells.”

• cites Pine et al., 1994Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Fromherz et al. obtained a current-free measurement of the membrane potential of a single leech neuron by direct coupling to the gate of a field effect transistor.

“they obtained a current-free measurement of the membrane potential of a single neuron of a leech by direct coupling to the gate of a field effect transistor (FET) (Fromherz et al., 1991a)”

• cites Fromherz et al., 1991aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Chronically implanted regenerative electrodes have allowed stimulation of different nerve bundles and recording of nerve action potentials in response to functional stimulation.

“been possible to stimulate different nerve bundles and to record nerve action potentials in response to functional stimulation (Navarro et al., 1998; Ceballos et al., 2002)”

• cites Navarro et al., 1998Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ceballos et al., 2002 sourceNot checked — no full text of the source

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

The formal scheme for EMG acquisition and analysis for prosthetic control includes signal conditioning, pre-processing, onset detection, feature extraction, dimensionality reduction, pattern recognition, and off-line and on-line learning.

“the formal scheme for the acquisition and analysis of EMG signals for the control of prosthetic devices is composed of several modules (Zecca et al., 2002) : (1) signal conditioning, pre-processing, and detection of onset movement (Micera et al., 1999) ; (2) feature extraction; (3) dimensionality reduction; (4) pattern recognition; and (5) off-line and on-line learning.”

• cites Zecca et al., 2002 sourceNot checked — no full text of the source
• cites Micera et al., 1999 sourceNot checked — no full text of the source

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

Fabrication of silicon-based interconnection cables is technologically feasible.

“The fabrication of silicon-based interconnection cables was shown to be technologically feasible (Hetke et al., 1990; 1994)”

• cites Hetke et al., 1990; 1994Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Interfacing regenerated axons with regenerative electrodes requires time, so acute experiments are not possible.

“some time is needed for interfacing the regenerated axons, thus precluding acute experiments”

May combine two claims.

The presence of a polyimide-based regenerative electrode showed no chronic foreign body response, and the immunohistochemically measured pattern of characteristic proteins was comparable with a healing reaction without any implant.

“The presence of a polyimide-based regenerative electrode showed no chronic foreign body response, and the immunohistochemically measured pattern of characteristic proteins was comparable with a healing reaction without any implant (Klinge et al., 2001a) .”

• cites Klinge et al., 2001a sourceNot checked — no full text of the source

May combine two claims.