Fascicle specific targeting for selective peripheral nerve stimulation
Open accessAbstract
OBJECTIVE: Electrical stimulation is a blunt tool for evoking neural activity. Neurons are naturally activated asynchronously and non-uniformly, whereas stimulation drives simultaneous activity within a population of cells. These differences in activation pattern can result in unintended side effects, including muddled sensory percepts and undesirable muscle contractions. These effects can be mitigated by the placement of electrodes in close approximation to nerve fibers and careful selection of the neural interface's location. This work describes the benefits of placing electrodes within specific fascicles of peripheral nerve to form selective neural interfaces for bidirectional neuroprosthetic devices. APPROACH: Chronic electrodes were targeted to individual fascicles of the ulnar and median nerves in the forearm of four human subjects. During the surgical implant procedure, fascicles were dissected from each nerve, and functional testing was used to identify the relative composition of sensory and motor fibers within each. FAST-LIFE arrays, composed of longitudinal intrafascicular arrays and fascicular cuff electrodes, were implanted in each fascicle. The location, quality, and stimulation parameters associated with sensations evoked by electrical stimulation on these electrodes were characterized throughout the 90-180 d implant period. MAIN RESULTS: FAST-LIFE arrays enable selective and chronic electrical stimulation of individual peripheral nerve fascicles. The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles. Stimulation thresholds and strength-duration time constants were typically higher within sensory fascicles. SIGNIFICANCE: Highly selective, stable neural interfaces can be created by placing electrodes within and around single fascicles of peripheral nerves. This method enables targeting electrodes to nerve fibers that innervate a specific body region or have specific functions. Fascicle-specific interfacing techniques have broad potential to maximize the therapeutic effects of electrical stimulation in many neuromodulation applications. (Clinical Trial ID NCT02994160.).
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Claims the paper makes
10 of 33 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured
- Premisecitation
The location and quality of sensations evoked by stimulation of implanted electrode arrays can change significantly.
“Additionally, the effects of stimulation can be difficult to predict; both the location and quality of sensations evoked by stimulation of implanted electrode arrays can change significantly [14,15].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [14] Charkhkar, 2018, High-density peripheral nerve cuffs restore natural sensation to individuals with lower-limb amputations, J. Neural Eng. source
- cites [15] Dhillon, 2005, Effects of short-term training on sensory and motor function in severed nerves of long-term human amputees, J. Neurophysiol. source
- Premisecitation
Some degree of functional separation (afferent versus efferent) is often present in peripheral nerve fascicles.
“Additionally, some degree of functional separation (afferent versus efferent) is often present [25,26].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [25] Delgado-Martínez, 2016, Fascicular topography of the human median nerve for neuroprosthetic surgery, Frontiers Neurosci. source
Results §3.3 reports that motor axons in the human median nerve were concentrated in patches rather than randomly mingled with other axons, supporting some degree of functional separation. It does not establish that afferent–efferent separation is often present across peripheral nerve fascicles; purely motor or sensory fascicles were described as exceptional. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [26] Chow, 1985, Surgical significance of the motor fascicular group of the ulnar nerve in the forearm, J. Hand Surg. source
- Premisecitation
Median nerve fascicles are less frequently unimodal.
“however, median nerve fascicles are less frequently unimodal [25].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [25] Delgado-Martínez, 2016, Fascicular topography of the human median nerve for neuroprosthetic surgery, Frontiers Neurosci. source
Results §3.3 reports that purely motor or purely sensory fascicles were exceptional at the sampled supraepicondylar levels, supporting the idea that unimodal fascicles were uncommon there. It does not establish a comparison with other nerves or show that this holds throughout the median nerve. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
Electrical stimulation of peripheral nerves can produce undesirable side effects, such as cocontraction of muscles or unnatural sensory percepts.
“Stimulation can produce undesirable side effects, such as cocontraction of muscles [11,12] or unnatural sensory percepts [8,13].”
Quote in the paperSubstantial claim1 of 4 sources checked- cites [11] McDonnall, 2004, Selective motor unit recruitment via intrafascicular multielectrode stimulation, Can. J. Physiol. Pharmacol. source
- cites [12] Polasek, 2007, Human nerve stimulation thresholds and selectivity using a multi-contact nerve cuff electrode, IEEE Trans. Neural Syst. Rehabil. Eng. source
- cites [8] Tan, 2014, A neural interface provides long-term stable natural touch perception, Sci. Transl. Med. source
- cites [13] Kiernan, 1997, Paraesthesiae induced by prolonged high frequency stimulation of human cutaneous afferents, J. Physiol. source
- Premisecitation
Fascicles contain groupings of nerve fibers organized somatotopically.
“Fascicles contain groupings of nerve fibers that are organized somatotopically [24].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [24] Hallin, 1990, Microneurography in relation to intraneural topography: somatotopic organisation of median nerve fascicles in humans, J. Neurol. Neurosurg. Psychiatry source
- Findingown data
In the median nerve of the transradial subject, the selected fascicles showed significant functional separation.
“In the median nerve, the separation of motor and sensory fibers is typically less discrete [25], however, the fascicles selected in the transradial subject did still show significant functional separation.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [25] Delgado-Martínez, 2016, Fascicular topography of the human median nerve for neuroprosthetic surgery, Frontiers Neurosci. source
- Rests on an assumption: A larger magnitude SSEP response to fascicle stimulation indicates a larger proportion of sensory fibers in that fascicle.
- Premisecitation
Proprioceptive sensations referred to the hand can clearly be evoked by stimulation that does not elicit contraction of the intrinsic and thenar muscles.
“Proprioceptive sensations referred to the hand can clearly be evoked by stimulation that does not elicit contraction of the intrinsic and thenar muscles [8,38,39].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [8] Tan, 2014, A neural interface provides long-term stable natural touch perception, Sci. Transl. Med. source
The Results report that stimulation produced sensations in the perceived hand before muscle activity that would interfere with prosthesis control. But the paper describes these sensations chiefly as touch or pressure; it does not establish that they were proprioceptive or specifically document the absence of intrinsic and thenar muscle contractions. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [38] Gandevia, 1985, Illusory movements produced by electrical stimulation of low-threshold muscle afferents from the hand, Brain source
- cites [39] Dhillon, 2004, Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs, J. Hand Surg. source
- Interpretationreasoning
A lack of specificity may contribute to the sensory adaptation reported by other groups during stimulation with cuff electrodes.
“This pattern suggests that a lack of specificity may contribute to the sensory adaptation which has been reported by other groups during stimulation with cuff electrodes [37].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [37] Graczyk, 2018, Sensory adaptation to electrical stimulation of the somatosensory nerves, J. Neural Eng. source
- Findingown data
Subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles.
“The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles.”
- Also stated in: § Stimulation induced sensory percept maps · plain
“Subjects described a variety of cutaneous sensations associated with stimulation on the ulnar sensory FAST-LIFE array.”
Quote in the paperSubstantial claim - Also stated in: § Stimulation induced sensory percept maps · plain
- Findingreasoning
The relative magnitude of the SSEPs evoked by broad stimulation of the ulnar fascicles was a reliable indicator of the quality of sensation evoked by intrafascicular stimulation.
“The relative magnitude of the SSEPs evoked by broad stimulation of the ulnar fascicles was a reliable indicator of the quality of sensation evoked by intrafascicular stimulation.”
Quote in the paperSubstantial claim - Findingown data
All participants reported sensations evoked by stimulation of multiple single electrodes throughout the duration of their participation.
“All participants reported sensations evoked by stimulation of multiple single electrodes throughout the duration of their participation in the study.”
Quote in the paperNot a substantial claim - Findingown data
Stimulation of ulnar sensory electrodes primarily resulted in sensations restricted to the ring finger, small finger, and hypothenar eminence.
“Stimulation of the ulnar sensory electrodes primarily resulted in sensations restricted to the ring finger, small finger, and hypothenar eminence (figure 3(b)).”
Quote in the paperSubstantial claim - Findingown data
FAST-LIFE arrays enable selective and chronic electrical stimulation of individual peripheral nerve fascicles.
“FAST-LIFE arrays enable selective and chronic electrical stimulation of individual peripheral nerve fascicles.”
Quote in the paperSubstantial claim - Findingown data
In the transradial amputee (S3), where no residual musculature of the hand was present, stimulation of the ulnar sensory fascicle produced significantly larger sensory percepts than stimulation of the ulnar motor fascicle (single-tailed t-test, p < 0.05).
“Notably, this pattern was reversed in the transradial amputee (S3), where no residual musculature of the hand was present-stimulation of the ulnar sensory fascicle produced significantly larger sensory percepts (single-tailed t-test, p < 0.05).”
Quote in the paperNot a substantial claim - Findingreasoning
Stronger SSEPs were generated in fascicles that produced cutaneous sensations.
“Stronger SSEPs were generated in fascicles that produced cutaneous sensations; these fascicles are expected to contain a high proportion of afferent sensory fibers.”
Quote in the paperSubstantial claim - Findingown data
The electrodes on the ulnar motor fascicle had a lower average time constant than the electrodes on the ulnar sensory fascicle.
“The electrodes on the ulnar motor fascicle had a lower average time constant than the electrodes on the ulnar sensory fascicle.”
Quote in the paperNot a substantial claim - Findingown data
In all participants, the distribution of sensations evoked by stimulation on FAST-LIFE arrays placed within the ulnar motor and ulnar sensory fascicles were distinct.
“In all participants, the distribution of sensations evoked by stimulation on FAST-LIFE arrays placed within the ulnar motor and ulnar sensory fascicles were distinct.”
Quote in the paperSubstantial claim - Findingcitation
The SSEP magnitude was less predictive of sensory modality in the median nerve of the transradial amputee than in the ulnar nerve.
“The SSEP magnitude was less predictive of sensory modality in the median nerve of our transradial amputee than in ulnar nerve; however, median nerve fascicles are less frequently unimodal [25].”
Quote in the paperNot a substantial claim - Findingown data
Subjects described a variety of cutaneous sensations associated with stimulation on the ulnar sensory FAST-LIFE array, including brushing, tapping, touch, pressure, stinging, buzzing, and tingling.
“Subjects described a variety of cutaneous sensations associated with stimulation on the ulnar sensory FAST-LIFE array.These included sensations with positive connotation such as brushing, tapping, touch, and pressure as well as those with more negative connotations, including stinging, buzzing, and tingling.”
Quote in the paperNot a substantial claim - Findingown data
Subjects reported deeper proprioceptive sensations during stimulation of motor fascicles.
“The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles.”
- Also stated in: § Stimulation induced sensory percept maps · plain
“Stimulation of the ulnar motor fascicle largely produced sensations with distinct proprioceptive qualities.”
Quote in the paperSubstantial claim - Also stated in: § Stimulation induced sensory percept maps · plain
- Findingown data
In two partial hand amputees (S1, S4), sensations evoked by stimulation of the ulnar motor fascicle were perceived to be significantly larger than those evoked by stimulation of the ulnar sensory fascicle (single-tailed t-test, p < 0.05).
“As shown in figure 4, sensations evoked by stimulation of the ulnar motor fascicle in two of the partial hand amputees (S1, S4) were perceived to be significantly larger than those evoked by stimulation of the ulnar sensory fascicle (single-tailed t-test, p < 0.05).”
Quote in the paperNot a substantial claim - Findingown data
The ulnar fascicles of partial hand amputees followed the same pattern of one fascicle producing a stronger SSEP than the other.
“The ulnar fascicles of partial hand amputees followed the same pattern, however differences in experimental conditions, anesthetic protocols, and each patient's response to anesthesia affected both the absolute and relative magnitudes of the SSEP responses.”
Quote in the paperNot a substantial claim- Rests on an assumption: A larger magnitude SSEP response to fascicle stimulation indicates a larger proportion of sensory fibers in that fascicle.
- Findingnone given
Stimulation thresholds and strength-duration time constants were typically higher within sensory fascicles.
“Stimulation thresholds and strength-duration time constants were typically higher within sensory fascicles.”
Quote in the paperNot a substantial claim - Findingown data
The modality of the sensory percept, cutaneous or proprioceptive, was reliably predicted by the fascicle to which the electrode was implanted.
“Additionally, the modality of the sensory percept, cutaneous or proprioceptive, was reliably predicted by the fascicle to which the electrode was implanted.”
Quote in the paperSubstantial claim - Findingown data
Stimulation of the ulnar motor fascicle largely produced sensations with distinct proprioceptive qualities.
“Stimulation of the ulnar motor fascicle largely produced sensations with distinct proprioceptive qualities.”
Quote in the paperSubstantial claim - Findingown data
The charge required to elicit a sensory percept was significantly higher in sensory fascicles than in motor fascicles (single-tailed t-test, p < 0.05).
“The charge required to elicit a sensory percept was significantly higher in sensory fascicles than in motor fascicles (single-tailed t-test, p < 0.05).”
Quote in the paperSubstantial claim - Findingown data
The quality of sensations evoked by stimulation in each fascicle is predictable and distinct.
“The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles.”
Quote in the paperSubstantial claim - Findingown data
The pattern of sensations reported during stimulation of the ulnar sensory array was largely consistent between subjects.
“The pattern of sensations reported during stimulation of the ulnar sensory array were largely consistent between subjects.”
Quote in the paperNot a substantial claim - Findingown data
The pattern of localization of sensations evoked by stimulation of each fascicle was stable for the duration of the implant period.
“The pattern of localization of sensations evoked by stimulation of each fascicle were stable for the duration of the implant period (supplemental figure 1).”
Quote in the paperSubstantial claim - Findingreasoning
The locations of sensations evoked by stimulation of the ulnar motor FAST-LIFE array varied significantly between subjects.
“The locations of sensations evoked by stimulation of the ulnar motor FAST-LIFE array varied significantly between subjects.”
Quote in the paperNot a substantial claim - Findingown data
Proprioception-related sensations from ulnar motor fascicle stimulation often coalesced around joints or in muscles of the hand.
“These proprioception-related sensations often coalesced around joints or in the muscles of the hand.”
Quote in the paperNot a substantial claim - Findingown data
Similar size sensory percepts could be evoked by stimulation of either motor or sensory fascicles in every subject.
“Similar size sensory percepts could be evoked by stimulation of either motor or sensory fascicles in every subject.”
Quote in the paperNot a substantial claim - Findingown data
Subjects described sensations of movement, joint pressure, and muscle contraction or tension during ulnar motor fascicle stimulation.
“Subjects described sensations of movement, joint pressure, and muscle contraction or tension.”
Quote in the paperSubstantial claim - Findingown data
Stimulation of ulnar motor fascicles produced sensations distributed widely across the hand.
“Stimulation of ulnar motor fascicles produced sensations that were distributed widely across the hand (figure 3(a)).”
Quote in the paperSubstantial claim - Findingown data
The size difference between motor and sensory fascicle stimulation was less pronounced during stimulation of the median FAST-LIFE arrays.
“This size difference was less pronounced during stimulation of the median FAST-LIFE arrays.”
Quote in the paperNot a substantial claim - Findingnone given
Multiple distinct sensory percepts were induced by stimulation of different electrode contacts within the array.
“Multiple distinct sensory percepts were induced by stimulation of different electrode contacts within the array.”
Quote in the paperSubstantial claim - Findingreasoning
In the transradial amputee, one ulnar fascicle produced a much stronger SSEP than the other, as predicted by the function of axonal groups distal to the implant location.
“As predicted by the function of the axonal groups distal to the implant location, one ulnar fascicle produced a much stronger SSEP than the other.”
Quote in the paperSubstantial claim- Rests on an assumption: A larger magnitude SSEP response to fascicle stimulation indicates a larger proportion of sensory fibers in that fascicle.
- Findingown data
Stimulation trains with shorter pulse durations (0.15-0.3 ms) were typically reported as feeling 'sharper' and less natural.
“Stimulation trains with shorter pulse durations (0.15-0.3 ms) were typically reported as feeling 'sharper' and less natural.”
Quote in the paperSubstantial claim - Findingnone given
These sensations typically faded or became uncomfortable during prolonged stimulation trains (30 s to 3 min).
“These sensations typically faded or became uncomfortable during prolonged stimulation trains (30 s to 3 min).”
Quote in the paperSubstantial claim - Findingnone given
Our subjects strongly preferred the quality of sensations achieved by stimulation with longer pulse durations (0.4 ms).
“Our subjects strongly preferred the quality of sensations achieved by stimulation with longer pulse durations (0.4 ms).”
Quote in the paperNot a substantial claim - Findingown data
In the transradial amputee, the relationship was reversed, and the sensations evoked by stimulation of the motor fascicles were over a smaller area.
“In the transradial amputee, this relationship was reversed, and the sensations evoked by stimulation of the motor fascicles were over a smaller area.”
Quote in the paperSubstantial claim - Findingown data
The sizes of the sensory percepts evoked by stimulation were affected by the fascicle to which electrodes were implanted.
“The sizes of the sensory percepts evoked by stimulation were also affected by the fascicle to which electrodes were implanted.”
Quote in the paperSubstantial claim - Findingown data
Consistent lower frequency neural activity (0-200 Hz) could be detected and decoded for the duration of the 3-6 month implant periods.
“Further, consistent lower frequency neural activity (0-200 Hz) could be detected and decoded for the duration of the 3-6 month implant periods.”
Quote in the paperSubstantial claim - Findingcitation
The strength-duration time constant for motor fibers was shorter than for sensory fibers.
“Additionally, the strength-duration time constant for motor fibers was shorter than for sensory fibers, matching expectations [40,41].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Findingown data
The threshold for evoking sensory percepts in motor fascicles was significantly lower than the threshold for sensory fascicles.
“The threshold for evoking sensory percepts in motor fascicles was significantly lower than the threshold for sensory fascicles.”
- Also stated in: § Neural interfacing applications · plain
“Stimulation thresholds for the sensory fascicle were greater than those for the motor fascicle (single-tailed t-test, p < 0.05).”
Quote in the paperSubstantial claim - Also stated in: § Neural interfacing applications · plain
- Findingcitation
Sensations evoked by stimulation of ulnar sensory fascicles were well-localized to the expected cutaneous innervation region of the hand, the ring and small fingers and the hypothenar eminence.
“Sensations evoked by stimulation of ulnar sensory fascicles were well-localized to the expected cutaneous innervation region of the hand, the ring and small fingers and the hypothenar eminence [36].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Mannerfelt, 1966, Studies on the hand in ulnar nerve paralysis: a clinical-experimental investigation in normal and anomalous innervation, Acta Orthop. Scand. source
- Findingnone given
This subject also reported fewer vivid proprioceptive sensations during stimulation of the motor fascicles.
“This subject also reported fewer vivid proprioceptive sensations during stimulation of the motor fascicles.”
Quote in the paperNot a substantial claim - Findingown data
Single unit spike activity was observed.
“FAST-LIFE arrays can also be utilized for neural recording applications; single unit spike activity was observed (supplemental figure 2).”
Quote in the paperSubstantial claim - Findingown data
Tactile sensations were reliably produced by stimulation of the fascicles containing a high proportion of sensory nerve fibers.
“Tactile sensations were reliably produced by stimulation of the fascicles containing a high proportion of sensory nerve fibers.”
Quote in the paperSubstantial claim - Findingnone given
Implanting FAST-LIFE arrays within individual fascicles increases the specificity of recruitment due to electrical stimulation.
“Although implanting FAST-LIFE arrays within individual fascicles does increase the specificity of recruitment due to electrical stimulation, this approach may not be desirable in all neural interfacing applications.”
Quote in the paperSubstantial claim - Findingown data
In partial hand amputees, stimulation of motor fascicles generally evoked sensations over a larger portion of the hand than sensory fascicles.
“In partial hand amputees, stimulation of motor fascicles generally evoked sensations over a larger portion of the hand than sensory fascicles.”
Quote in the paperSubstantial claim - Findingown data
Stimulation of ulnar motor fascicles produced sensations within the intrinsic muscles of the hand in addition to regions of the fingers and palm outside the typical region of cutaneous innervation.
“Stimulation of ulnar motor fascicles produced sensations within the intrinsic muscles of the hand in addition to regions of the fingers and palm outside the typical region of cutaneous innervation.”
Quote in the paperSubstantial claim - Findingown data
Stimulation of FAST-LIFE arrays within individual peripheral nerve fascicles produces sensations with predictable location and percept quality.
“In this study, we demonstrated that stimulation of FAST-LIFE arrays within individual peripheral nerve fascicles produces sensations with predictable location and percept quality.”
Quote in the paperSubstantial claim - Interpretationreasoning
This method enables targeting electrodes to nerve fibers that innervate a specific body region or have specific functions.
“This method enables targeting electrodes to nerve fibers that innervate a specific body region or have specific functions.”
Quote in the paperSubstantial claim - Interpretationreasoning
Stimulation of electrodes placed directly within individual nerve fascicles can be used to preferentially recruit nerve fibers with predictable function or that innervate specific body regions.
“Stimulation of electrodes placed directly within individual nerve fascicles can therefore be used to preferentially recruit nerve fibers with predictable function or that innervate specific body regions.”
Quote in the paperSubstantial claim - Study design and conductnone given
No adverse events occurred during this study.
“No adverse events occurred during this study.”
Quote in the paperSubstantial claim - Interpretationown data
This finding suggests that FAST-LIFE arrays recruit substantially discrete populations of motor and sensory nerve fibers.
“This finding suggests that the FAST-LIFE arrays do recruit substantially discrete populations of motor and sensory nerve fibers.”
Quote in the paperSubstantial claim - Interpretationreasoning
Highly selective, stable neural interfaces can be created by placing electrodes within and around single fascicles of peripheral nerves.
“Highly selective, stable neural interfaces can be created by placing electrodes within and around single fascicles of peripheral nerves.”
Quote in the paperSubstantial claim - Interpretationown data
The strength-duration relationship provides further evidence that discrete populations of nerve fibers are recruited by stimulation of individual fascicles of peripheral nerve with FAST-LIFE arrays.
“The strength-duration relationship provides further evidence that discrete populations of nerve fibers are recruited by stimulation of individual fascicles of peripheral nerve with FAST-LIFE arrays.”
Quote in the paperSubstantial claim - Premisecitation
Despite customized insertion techniques, there is no guarantee that penetrating electrode designs will punch through both the tough perineurium and epineurium to enter a fascicle.
“Despite customized insertion techniques, there is no guarantee that these electrodes will punch through both the tough perineurium and epineurium to enter a fascicle [18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Branner, 2001, Selective stimulation of cat sciatic nerve using an array of varying-length microelectrodes, J. Neurophysiol. source
- Premisecitation
Intrafascicular electrodes have not been demonstrated to cause significant nerve damage.
“Despite their invasiveness, intrafascicular electrodes have not been demonstrated to cause significant nerve damage [31].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Lago, 2007, Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes, IEEE Trans. Biomed. Eng. source
- Study design and conductown data
The surgical procedure was well-tolerated by the subjects.
“The surgical procedure was well-tolerated by the subjects, and there were no sensory or motor deficits reported upon removal of the arrays at the end of the study period.”
Quote in the paperNot a substantial claim - Interpretationown data
The region of sensations from ulnar sensory stimulation closely matches the expected cutaneous receptive field of the ulnar nerve carried within the sensory fascicle.
“This region closely matches the region expected to represent the cutaneous receptive field of the ulnar nerve, carried within the sensory fascicle.”
Quote in the paperSubstantial claim- Rests on an assumption: The expected cutaneous receptive field of the ulnar nerve is carried within the sensory fascicle.
- Study design and conductreasoning
Inserting FAST-LIFE arrays through the epineurium and perineurium under direct visual observation and microsurgical guidance ensures that the electrode contacts are placed directly adjacent to nerve fibers.
“Inserting FAST-LIFE arrays through the epineurium and perineurium under direct visual observation and microsurgical guidance ensures that the electrode contacts are placed directly adjacent to nerve fibers.”
Quote in the paperSubstantial claim - Study design and conductown data
There were no sensory or motor deficits reported upon removal of the arrays at the end of the study period.
“The surgical procedure was well-tolerated by the subjects, and there were no sensory or motor deficits reported upon removal of the arrays at the end of the study period.”
Quote in the paperSubstantial claim - Premisecitation
Multicontact cuff electrodes can activate several distinct populations of nerve fibers.
“Multicontact cuff electrodes remain outside the nerve, but close approximation to the epineurium and methods such as current steering allow stimulation from these electrodes to activate several distinct populations of nerve fibers [16,17].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [16] Leventhal, 2003, Subfascicle stimulation selectivity with the flat interface nerve electrode, Ann. Biomed. Eng. source
- cites [17] Tarler, 2004, Selective and independent activation of four motor fascicles using a four contact nerve-cuff electrode, IEEE Trans. Neural Syst. Rehabil. Eng. source
- Premisecitation
Stimulation trains with longer pulse durations are expected to recruit nerve fibers with a wider distribution of diameters.
“Stimulation trains with longer pulse durations are expected to recruit nerve fibers with a wider distribution of diameters [42].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] Grill, 1996, The effect of stimulus pulse duration on selectivity of neural stimulation, IEEE Trans. Biomed. Eng. source
- Interpretationown data
This study demonstrates the suitability of the FAST-LIFE design and targeting strategy for stimulation of peripheral nerve.
“This study demonstrates the suitability of the FAST-LIFE design and targeting strategy for stimulation of peripheral nerve.”
Quote in the paperSubstantial claim - Premisecitation
Peripheral nerve in the forearm can demonstrate longitudinal excursion of 2 cm or more during natural movements.
“This is a significant concern, because peripheral nerve in the forearm can demonstrate longitudinal excursion of 2 cm or more during natural movements [32].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] McLellan, 1976, Longitudinal sliding of the median nerve during movements of the upper limb, J. Neurol. Neurosurg. Psychiatry source
- Interpretationcitation
Specificity comes at the cost of reduced sampling of the nerve.
“In particular, specificity comes at the cost of reduced sampling of the nerve; other electrode designs used within peripheral nerve are less specific but allow access to a greater proportion of the nerve via electrical stimulation [33].”
Quote in the paperSubstantial claim - Interpretationreasoning
Decreasing the specificity of stimulation among fibers with similar function may be advantageous in evoking naturalistic sensations.
“Decreasing the specificity of stimulation among fibers with similar function may be advantageous in evoking naturalistic sensations.”
Quote in the paperSubstantial claim - Interpretationcitation
This method is also suited to applications like vagal nerve stimulation where a lack of specificity can produce significant systemic side effects.
“This method is also suited to applications like vagal nerve stimulation where a lack of specificity can produce significant systemic side effects [43].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] Ben-Menachem, 2001, Vagus nerve stimulation, side effects, and long-term safety, J. Clin. Neurophysiol. source
- Interpretationown data
FAST-LIFE arrays can also be utilized for neural recording applications.
“FAST-LIFE arrays can also be utilized for neural recording applications; single unit spike activity was observed (supplemental figure 2).”
Quote in the paperSubstantial claim - Interpretationown data
The FAST-LIFE approach is suited for use in bidirectional, closed-loop neural interfaces.
“This is encouraging evidence that the FAST-LIFE approach is suited for use in bidirectional, closed-loop neural interfaces.”
Quote in the paperSubstantial claim - Interpretationreasoning
The differences in sensations reported by partial hand and transradial amputees suggest that the probability of evoking proprioceptive sensations may be higher when some functional muscle remains within the residual hand.
“The differences in the sensations reported by our partial hand and transradial amputees suggest that the probability of evoking proprioceptive sensations may be higher when some functional muscle remains within the residual hand.”
Quote in the paperSubstantial claim - Interpretationreasoning
Implanting FAST-LIFE arrays within individual fascicles may not be desirable in all neural interfacing applications.
“Although implanting FAST-LIFE arrays within individual fascicles does increase the specificity of recruitment due to electrical stimulation, this approach may not be desirable in all neural interfacing applications.”
Quote in the paperSubstantial claim - Interpretationown data
Stimulation of nerve fibers with different function via electrodes with high specificity demonstrates differences in recruitment profiles for these fiber types.
“In addition to evoking sensations of different quality and size, stimulation of nerve fibers with different function via electrodes with high specificity also demonstrates the differences in recruitment profiles for these fiber types.”
Quote in the paperSubstantial claim
- May combine two claims. 14
- Classified as probably not a substantial claim. 8
May combine two claims.
PremisecitationOther electrode designs used within peripheral nerve are less specific but allow access to a greater proportion of the nerve via electrical stimulation.
“other electrode designs used within peripheral nerve are less specific but allow access to a greater proportion of the nerve via electrical stimulation [33].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [33] Badia, 2011, Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles, J. Neural Eng. source
The Introduction (p. 3) says intrafascicular positioning enhances selectivity, while TIME’s distributed sites let it access several fascicles. The Selectivity of stimulation section (p. 12) reports that TIME had higher selectivity than both LIFE and cuff electrodes. Thus, the intraneural design with broader access was not less selective in this comparison; the less-selective cuffs are placed around, not within, the nerve. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIntrafascicular stimulation has been used for many years to study the function and organization of fibers within peripheral nerve.
“Intrafascicular stimulation has been used for many years to study the function and organization of fibers within peripheral nerve [24,34].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [24] Hallin, 1990, Microneurography in relation to intraneural topography: somatotopic organisation of median nerve fascicles in humans, J. Neurol. Neurosurg. Psychiatry source
- cites [34] Johansson, 1978, Tactile sensibility in the human hand: receptive field characteristics of mechanoreceptive units in the glabrous skin area, J. Physiol. source
May combine two claims.
Findingown dataSome sensations were occasionally reported outside the expected region; these oddball sensations were often highly repeatable within a single session.
“Some sensations were occasionally reported outside this region; these oddball sensations were often highly repeatable within a single session and should not be discarded as false positive reports.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn partial hand amputees, stimulation of fascicles with lower SSEP activity produced stronger contractions of residual thenar and intrinsic muscles, confirming these fascicles contained a larger proportion of motor fibers.
“In partial hand amputees, where the distal hand muscles are still present, stimulation of the fascicles with lower SSEP activity produced stronger contractions of the residual thenar and intrinsic muscles of the hand, confirming the hypothesis that these fascicles contained a larger proportion of motor fibers.”
Quote in the paperSubstantial claim- Rests on an assumption: Stronger contraction of residual thenar and intrinsic muscles during fascicle stimulation indicates a larger proportion of motor fibers in that fascicle.
May combine two claims.
Findingnone givenAlthough muscle contraction sometimes accompanied the sensation, the sensory descriptions persisted even when no surface EMG was detectable.
“Although muscle contraction sometimes accompanied the sensation, these sensory descriptions persisted even when no surface EMG was detectable.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataStimulation of both motor and sensory fascicles in the median nerve of the transradial amputee predominantly produced cutaneous sensations; weaker deep proprioceptive sensations were occasionally evoked.
“Stimulation of both the motor and sensory fascicles in the median nerve of the transradial amputee predominantly produced cutaneous sensations; weaker, deep proprioceptive sensations were occasionally evoked.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataStimulation of median nerve FAST-LIFE arrays produced smaller sensory maps than the ulnar fascicles, but there was not a significant difference in the area of sensations evoked by the two median nerve arrays.
“Stimulation of these fascicles produced smaller sensory maps than the ulnar fascicles, but there was not a significant difference in the area of the sensations evoked by stimulation of the two median nerve FAST-LIFE arrays.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBoth the sensory and motor fascicles of median nerve produced sensations in the thenar eminence, thumb, and index finger as expected.
“Both the sensory and motor fascicles of median nerve produced sensations in the thenar eminence, thumb, and index finger as expected.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Findingnone givenA variety of sensations could also be evoked by stimulation of these electrodes over the same duration.
“Analysis of longitudinal stimulation data was not included in this work, however a variety of sensations could also be evoked by stimulation of these electrodes over the same duration.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataStimulation of motor fascicles often evoked proprioceptive sensations, but some nonspecific cutaneous sensations were also evoked by stimulation of these fascicles.
“Stimulation of motor fascicles often evoked proprioceptive sensations, but some nonspecific cutaneous sensations were also evoked by stimulation of these fascicles.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThese sensations were reported to be vivid, easy to localize, and did not fade appreciably during prolonged stimulation.
“These sensations were reported to be vivid, easy to localize, and did not fade appreciably during prolonged stimulation.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPeripheral nerve contains both afferent and efferent fibers, and multiple types of sensory fibers whose activation produces sensations with distinct qualities.
“Peripheral nerve contains both afferent and efferent fibers; additionally, multiple types of sensory fibers are present, and activation of these fibers produce sensations with distinct qualities [21,22].”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationIntrafascicular electrodes penetrate the perineurium of individual fascicles and enable highly selective recruitment.
“Intrafascicular electrodes penetrate the perineurium of individual fascicles and are thus positioned immediately adjacent to the target nerve fibers, enabling highly selective recruitment [20].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Yoshida, 1993, Selective stimulation of peripheral nerve fibers using dual intrafascicular electrodes, IEEE Trans. Biomed. Eng. source
May combine two claims.
Interpretationown dataThe FAST-LIFE design and fascicle-targeting strategy used in this study enables electrical stimulation of peripheral nerve that is both selective and specific.
“The FAST-LIFE design and fascicle-targeting strategy utilized in this study enables electrical stimulation of peripheral nerve which is both selective and specific.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe variation in locations of ulnar motor sensations between subjects is likely due, in part, to effects of partial hand amputation and revision procedures on palm musculature.
“This is likely due, in part, to effects of partial hand amputation and revision procedures which affect the musculature in the palm.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe curve fits for the sensory electrodes are approximations (R2 ≅ 0.85), as the subject reported that no pulse durations at or below 0.1 ms produced sensations of comparable quality or intensity on those electrodes.
“The curve fits for the sensory electrodes are approximations (R 2 ≅ 0.85), as the subject reported that no pulse durations at or below 0.1 ms produced sensations of comparable quality or intensity on those electrodes.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
InterpretationreasoningThe ability to address individual nerve fascicles makes FAST-LIFE an attractive method for interfaces with even larger nerves, such as the sciatic and tibial nerves of the lower limb.
“The ability to address individual nerve fascicles makes it an attractive method for interfaces with even larger nerves, such as the sciatic and tibial nerves of the lower limb.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
InterpretationreasoningFAST-LIFE arrays represent a platform technology which holds great promise for enabling neuromodulation therapies, with high efficacy and low morbidity, based on the ability to sense and stimulate neural activity throughout the body.
“Due to their favorable selectivity and specificity, FAST-LIFE arrays represent a platform technology which holds great promise for enabling neuromodulation therapies, with high efficacy and low morbidity, based on the ability to sense and stimulate neural activity throughout the body.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Premisenone givenPrior reports have not clearly addressed the specificity of stimulation within single fascicles of peripheral nerve.
“However, these reports have not clearly addressed the specificity of stimulation within single fascicles of peripheral nerve.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIntrafascicular electrode arrays have been implanted in the arms of amputees to evaluate feasibility of sensory and motor neuroprosthetic applications.
“Additionally, intrafascicular electrode arrays have been implanted in the arms of amputees to evaluate feasibility of sensory and motor neuroprosthetic applications [15,35].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [15] Dhillon, 2005, Effects of short-term training on sensory and motor function in severed nerves of long-term human amputees, J. Neurophysiol. source
- cites [35] Horch, 2011, Object discrimination with an artificial hand using electrical stimulation of peripheral tactile and proprioceptive pathways with intrafascicular electrodes, IEEE Trans. Neural Syst. Rehabil. Eng. source
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationreasoningThe selective and specific stimulation of neural tissue enabled by the FAST-LIFE approach is well-suited to a wide variety of neural interfacing applications beyond upper extremity neuroprosthetics.
“The selective and specific stimulation of neural tissue enabled by the FAST-LIFE approach is also well-suited to a wide variety of neural interfacing applications beyond upper extremity neuroprosthetics.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The motor and sensory fascicular groups of the ulnar and median nerves can be identified and dissected based on predictable intraneural topography.
“the motor and sensory fascicular groups of each nerve were identified and dissected microsurgically based on predictable intraneural topography.”
The paper relies on this without support.
A larger magnitude SSEP response to fascicle stimulation indicates a larger proportion of sensory fibers in that fascicle.
“The sensory fascicles were positively identified as those that elicited a larger magnitude SSEP response.”
The paper relies on this without support.
Stronger contraction of residual thenar and intrinsic muscles during fascicle stimulation indicates a larger proportion of motor fibers in that fascicle.
“stimulation of the fascicles with lower SSEP activity produced stronger contractions of the residual thenar and intrinsic muscles of the hand, confirming the hypothesis that these fascicles contained a larger proportion of motor fibers.”
The paper relies on this without support.
The expected cutaneous receptive field of the ulnar nerve is carried within the sensory fascicle.
“This region closely matches the region expected to represent the cutaneous receptive field of the ulnar nerve, carried within the sensory fascicle.”
The paper relies on this without support.
The sample size of four patients in this study is sufficient to characterize the effects of stimulation of single fascicles within peripheral nerve.
“The sample size of four patients in this study, though small, is sufficient to characterize the effects of stimulation of single fascicles within peripheral nerve.”
The paper relies on this without support.
Fascicles that produced cutaneous sensations contain a high proportion of afferent sensory fibers.
“these fascicles are expected to contain a high proportion of afferent sensory fibers.”
The paper relies on this without support.
Fascicles containing efferent motor fibers often contain sensory fibers, particularly muscle spindles and Golgi tendon organs.
“Fascicles containing efferent motor fibers still produce SSEPs because they often contain sensory fibers, particularly muscle spindles and Golgi tendon organs.”
The paper relies on this without support.
Transverse penetrating electrodes are more likely to move within the fascicle or to displace from the fascicle by nerve motion than longitudinal intrafascicular arrays.
“Transverse penetrating electrodes are also more likely to move within the fascicle or to displace from the fascicle by nerve motion than longitudinal intrafascicular arrays.”
Cites
PEST: Efficient Estimates on Probability Functions
Taylor, M. M., & Creelman, C. D. (1967) · The Journal of the Acoustical Society of America · doi:10.1121/1.1910407 · Cited by 1,173 · see citing works
Restoring natural sensory feedback in real-time bidirectional hand prostheses
Raspopovic, S., Capogrosso, M., Petrini, F. M., Bonizzato, M., Rigosa, J., Di Pino, G., Carpaneto, J., Controzzi, M., Boretius, T., Fernandez, E., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3006820 · Cited by 1,001 · see citing works
A neural interface provides long-term stable natural touch perception
Tan, D. W., Schiefer, M. A., Keith, M. W., Anderson, J. R., Tyler, J., & Tyler, D. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008669 · Cited by 751 · see citing works
Tactile sensory coding in the glabrous skin of the human hand
Johansson, R. S., & Vallbo, Å. B. (1983) · Trends in Neurosciences · doi:10.1016/0166-2236(83)90011-5 · Cited by 680 · see citing works
Direct neural sensory feedback and control of a prosthetic arm
Dhillon, G. S., & Horch, K. W. (2005) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2005.856072 · Cited by 573 · see citing works
Johansson, R. S. (1978) · The Journal of Physiology · doi:10.1113/jphysiol.1978.sp012411 · Cited by 430 · see citing works
Vagus nerve stimulation, side effects, and long-term safety
Ben-Menachem, E. (2001) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-200109000-00005 · Cited by 400 · see citing works
Selective Stimulation of Cat Sciatic Nerve Using an Array of Varying-Length Microelectrodes
Branner, A., Stein, R. B., & Normann, R. A. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.85.4.1585 · Cited by 358 · cited 2× · see citing works
“Penetrating electrode arrays cross the epineurium and may enter fascicles, however some proportion of the electrodes are likely to reside in the endoneurium [18, 19].”
BackgroundStrength-duration properties of human peripheral nerve
Mogyoros, I., Kiernan, M. C., & Burke, D. (1996) · Brain · doi:10.1093/brain/119.2.439 · Cited by 358 · see citing works
Dhillon, G. S., Lawrence, S. M., Hutchinson, D. T., & Horch, K. W. (2004) · The Journal of Hand Surgery · doi:10.1016/j.jhsa.2004.02.006 · Cited by 354 · cited 1× · see citing works
“Proprioceptive sensations referred to the hand can clearly be evoked by stimulation that does not elicit contraction of the intrinsic and thenar muscles [8, 38, 39].”
BackgroundDavis, T. S., Wark, H. A. C., Hutchinson, D. T., Warren, D. J., O’Neill, K., Scheinblum, T., Clark, G. A., Normann, R. A., & Greger, B. (2016) · Journal of Neural Engineering · doi:10.1088/1741-2560/13/3/036001 · Cited by 314 · see citing works
Badia, J., Boretius, T., Andreu, D., Azevedo-Coste, C., Stieglitz, T., & Navarro, X. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/3/036023 · Cited by 227 · see citing works
Lago, N., Yoshida, K., Koch, K. P., & Navarro, X. (2007) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2006.886617 · Cited by 227 · see citing works
The effect of stimulus pulse duration on selectivity of neural stimulation
Grill, W. M., & Mortimer, J. T. (1996) · IEEE Transactions on Biomedical Engineering · doi:10.1109/10.481985 · Cited by 215 · see citing works
Specific sensations evoked by activity in single identified sensory units in man
TOREBJÖRK, H. E., & OCHOA, J. L. (1980) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1980.tb06695.x · Cited by 212 · see citing works
Selective stimulation of peripheral nerve fibers using dual intrafascicular electrodes
Yoshida, K., & Horch, K. (1993) · IEEE Transactions on Biomedical Engineering · doi:10.1109/10.243412 · Cited by 208 · see citing works
Horch, K., Meek, S., Taylor, T. G., & Hutchinson, D. T. (2011) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2011.2162635 · Cited by 194 · see citing works
Longitudinal sliding of the median nerve during movements of the upper limb
McLellan, D. L., & Swash, M. (1976) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.39.6.566 · Cited by 190 · see citing works
Dhillon, G. S., Krüger, T. B., Sandhu, J. S., & Horch, K. W. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00937.2004 · Cited by 183 · see citing works
GANDEVIA, S. C. (1985) · Brain · doi:10.1093/brain/108.4.965 · Cited by 165 · see citing works
Mannerfelt, L. (1966) · Acta Orthopaedica Scandinavica · doi:10.3109/ort.1966.37.suppl-87.01 · Cited by 157 · see citing works
Hebert, J. S., Olson, J. L., Morhart, M. J., Dawson, M. R. W., Marasco, P. D., Kuiken, T., & Chan, K. M. (2014) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2013.2294907 · Cited by 146 · see citing works
Review of recent advances in peripheral nerve stimulation (PNS)
Chakravarthy, K., Nava, A., Christo, P. J., & Williams, K. (2016) · Current Pain and Headache Reports · doi:10.1007/s11916-016-0590-8 · Cited by 136 · see citing works
Charkhkar, H., Shell, C. E., Marasco, P. D., Pinault, G. J., Tyler, D. J., & Triolo, R. J. (2018) · Journal of Neural Engineering · doi:10.1088/1741-2552/aac964 · Cited by 131 · see citing works
Sensory adaptation to electrical stimulation of the somatosensory nerves
Graczyk, E. L., Delhaye, B. P., Schiefer, M. A., Bensmaia, S. J., & Tyler, D. J. (2018) · Journal of Neural Engineering · doi:10.1088/1741-2552/aab790 · Cited by 124 · see citing works
Human nerve stimulation thresholds and selectivity using a multi-contact nerve cuff electrode
Polasek, K. H., Hoyen, H. A., Keith, M. W., & Tyler, D. J. (2007) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2007.891383 · Cited by 111 · see citing works
Tarler, M. D., & Mortimer, J. T. (2004) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2004.828415 · Cited by 110 · see citing works
Control of urinary bladder function with devices: successes and failures
Gaunt, R. A., & Prochazka, A. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(05)52011-9 · Cited by 105 · see citing works
Interfaces with the Peripheral Nerve for the Control of Neuroprostheses
del Valle, J., & Navarro, X. (2013) · International Review of Neurobiology · doi:10.1016/b978-0-12-420045-6.00002-x · Cited by 105 · see citing works
Electrical Stimulation Research Techniques
(1981) · Elsevier eBooks · doi:10.1016/b978-0-12-547440-5.x5001-3 · Cited by 99 · see citing works
Panizza, M., Nilsson, J., Roth, B. J., Rothwell, J., & Hallett, M. (1994) · Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section · doi:10.1016/0168-5597(94)90078-7 · Cited by 83 · see citing works
Subfascicle stimulation selectivity with the flat interface nerve electrode
Leventhal, D. K., & Durand, D. M. (2003) · Annals of Biomedical Engineering · doi:10.1114/1.1569266 · Cited by 81 · see citing works
Peripheral nerve stimulation for restoration of motor function
Bhadra, N., & Peckham, P. H. (1997) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-199709000-00004 · Cited by 80 · see citing works
Fascicular topography of the human median nerve for neuroprosthetic surgery
Delgado-Martínez, I., Badia, J., Pascual-Font, A., Rodríguez-Baeza, A., & Navarro, X. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00286 · Cited by 77 · see citing works
Hallin, R. G. (1990) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.53.9.736 · Cited by 62 · see citing works
Posterior tibial nerve stimulation and faecal incontinence: a review
Findlay, J. M., & Maxwell-Armstrong, C. (2011) · International Journal of Colorectal Disease · doi:10.1007/s00384-010-1085-4 · Cited by 61 · see citing works
Nerve Transfers to Restore upper Extremity Function: A Paradigm Shift
Moore, A. M. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00040 · Cited by 57 · see citing works
Selective motor unit recruitment via intrafascicular multielectrode stimulation
McDonnall, D., Clark, G. A., & Normann, R. A. (2004) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y04-047 · Cited by 53 · see citing works
Surgical significance of the motor fascicular group of the ulnar nerve in the forearm
Chow, J. A., Van Beek, A. L., Meyer, D. L., & Johnson, M. C. (1985) · The Journal of Hand Surgery · doi:10.1016/s0363-5023(85)80164-7 · Cited by 50 · see citing works
Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment
Petersen, B. A., Nanivadekar, A. C., Chandrasekaran, S., & Fisher, L. E. (2019) · Muscle & Nerve · doi:10.1002/mus.26294 · Cited by 39 · see citing works
Electrical stimulation of peripheral nerve
Swett, J. E., & Bourassa, C. M. (1981) · Electrical Stimulation Research Techniques · doi:10.1016/b978-0-12-547440-5.50016-4 · Cited by 39 · see citing works
Paraesthesiae induced by prolonged high frequency stimulation of human cutaneous afferents
Kiernan, M. C., Hales, J. P., Gracies, J., Mogyoros, I., & Burke, D. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.461bn.x · Cited by 32 · see citing works
Diaphragm pacing by electrical stimulation of the phrenic nerve
Glenn, W. W., & Phelps, M. L. (1985) · Neurosurgery · doi:10.1097/00006123-198512000-00021 · Cited by 15 · see citing works
Nerve transfers of the forearm and hand: a review of current indications
Sassu, P., Libberecht, K., & Nilsson, A. (2015) · Plastic and Aesthetic Research · doi:10.4103/2347-9264.160887 · Cited by 13 · see citing works
Posterior tibial nerve stimulation for faecal incontinence
Findlay, J., & Maxwell-Armstrong, C. (2010) · British Journal of Nursing · doi:10.12968/bjon.2010.19.12.48652
Flagged first, then by citations
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Sorted by citations
Sensory feedback for limb prostheses in amputees
Raspopovic, S., Valle, G., & Petrini, F. M. (2021) · Nature Materials · doi:10.1038/s41563-021-00966-9 · Cited by 308 · see citing works
Neuromorphic hardware for somatosensory neuroprostheses
Donati, E., & Valle, G. (2024) · Nature Communications · doi:10.1038/s41467-024-44723-3 · Cited by 115 · see citing works
Neural Decoding for Intracortical Brain–Computer Interfaces
Dong, Y., Wang, S., Huang, Q., Berg, R. W., Li, G., & He, J. (2023) · Cyborg and Bionic Systems · doi:10.34133/cbsystems.0044 · Cited by 81 · see citing works
“The specific fascicles can be selectively sim ulated, and it is beneficial to create highly selective peripheral nerve interfaces [70].”
BackgroundGeorge, J. A., Page, D. M., Davis, T. S., Duncan, C. C., Hutchinson, D. T., Rieth, L. W., & Clark, G. A. (2020) · Journal of Neural Engineering · doi:10.1088/1741-2552/abc025 · Cited by 75 · see citing works
“longitudinal intrafascicular arrays [26].”
Compliant peripheral nerve interfaces.
Paggi, V., Akouissi, O., Micera, S., & Lacour, S. P. (2021) · Journal of Neural Engineering · doi:10.1088/1741-2552/abcdbe · Cited by 60 · see citing works
“However, the implantation procedure appears to be more complicated with respect to other standard devices, requiring careful excision of the epineurium and clipping of the cuff around smaller and more fragile individual fascicles [130].”
BackgroundAnodal block permits directional vagus nerve stimulation
Ahmed, U., Chang, Y.-C., Cracchiolo, M., Lopez, M. F., Tomaio, J. N., Datta, T., Zanos, T. P., Rieth, L. W., Al‐Abed, Y., & Zanos, S. P. (2020) · Scientific Reports · doi:10.1038/s41598-020-66332-y · Cited by 59 · see citing works
A bioelectric neural interface towards intuitive prosthetic control for amputees
Nguyen, A. T., Xu, J., Jiang, M., Luu, D. K., Wu, T., Tam, W.-K., Zhao, W., Drealan, M. W., Overstreet, C. K., Zhao, Q., et al. (2020) · Journal of Neural Engineering · doi:10.1088/1741-2552/abc3d3 · Cited by 52 · see citing works
Self-citationDecoding of grasping tasks from intraneural recordings in trans-radial amputee
Cracchiolo, M., Valle, G., Petrini, F. M., Strauss, I., Granata, G., Stieglitz, T., Rossini, P. M., Raspopović, S., Mazzoni, A., & Micera, S. (2020) · Journal of Neural Engineering · doi:10.1088/1741-2552/ab8277 · Cited by 45 · see citing works
A portable, self-contained neuroprosthetic hand with deep learning-based finger control
Nguyen, A. T., Drealan, M. W., Luu, D. K., Jiang, M. X., Xu, J., Cheng, J., Zhao, Q., Keefer, E. W., & Yang, Z. (2021) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac2a8d · Cited by 46 · see citing works
“The first innovation lies in the development of the intrafascicular microelectrode array that connects nerve fibers and bioelectronics, as presented in Overstreet et al [ 26].”
Self-citationArtificial Intelligence Enables Real-Time and Intuitive Control of Prostheses via Nerve Interface
Luu, D. K., Nguyen, A. T., Jiang, M. X., Drealan, M. W., Xu, J., Wu, T., Tam, W.-K., Zhao, W., Lim, B. Z. H., Overstreet, C. K., et al. (2022) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2022.3160618 · Cited by 51 · see citing works
“The AI neural decoder reported in this manuscript complements our previous works [16], [40], [41], in which we develop a neural stimulator and create distinct and reliable sensory feedback for amputees by neural stimulators.”
BackgroundSelf-citationDARPA investment in peripheral nerve interfaces for prosthetics, prescriptions, and plasticity
Naufel, S. N., Knaack, G. L., Miranda, R. A., Best, T. K., Fitzpatrick, K., Emondi, A. A., Gieson, E. J. V., & McClure‐Begley, T. D. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.108539 · Cited by 30 · see citing works
“, 2019), penetrating (e.g., Davis et al., 2016; Jung et al., 2018; Overstreet et al., 2019; Raspopovic et al., 2014) and non-penetrating (e.”
Upper limb prostheses: bridging the sensory gap
Roche, A. D., Bailey, Z., Gonzalez, M. A., Vu, P. P., Chestek, C. A., Gates, D. H., Kemp, S. W. P., Cederna, P. S., Ortiz-Catalan, M., & Aszmann, O. C. (2023) · Journal of Hand Surgery (European Volume) · doi:10.1177/17531934221131756 · Cited by 30 · see citing works
“A more flexible version made from polyimide with an increased number of electrodes has been developed called the thin-film LIFE (tf-LIFE) (Overstreet et al., 2019).”
MethodEvolution, biomechanics, and neurobiology converge to explain selective finger motor control
Xu, J., Mawase, F., & Schieber, M. H. (2024) · Physiological Reviews · doi:10.1152/physrev.00030.2023 · Cited by 28 · see citing works
A Psychometric Platform to Collect Somatosensory Sensations for Neuroprosthetic Use
Valle, G., Iberite, F., Strauss, I., D’Anna, E., Granata, G., Iorio, R. D., Stieglitz, T., Raspopović, S., Petrini, F. M., Rossini, P. M., et al. (2021) · Frontiers in Medical Technology · doi:10.3389/fmedt.2021.619280 · Cited by 23 · see citing works
Deep Learning-Based Approaches for Decoding Motor Intent From Peripheral Nerve Signals
Luu, D. K., Nguyen, A. T., Jiang, M. X., Xu, J., Drealan, M. W., Cheng, J., Keefer, E. W., Zhao, Q., & Yang, Z. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.667907 · Cited by 23 · see citing works
Self-citationPeripheral Nerve Stimulation for Lower Extremity Pain
Busch, C., Smith, O., Weaver, T. E., Vallabh, J. C., & Abd-Elsayed, A. A. (2022) · Biomedicines · doi:10.3390/biomedicines10071666 · Cited by 21 · see citing works
“Other areas of growth could include new targets such as nerve ganglia, targeting specific nerve fascicles to avoid unwanted motor stimulation, and incorporating PNS as an additional arm in multimodal pain control [33,58,59].”
BackgroundTessellation of artificial touch via microstimulation of human somatosensory cortexPreprint
Greenspon, C. M., Shelchkova, N. D., Valle, G., Hobbs, T. G., Berger-Wolf, E. I., Hutchison, B. C., Dogruoz, E., Verbaarschot, C., Callier, T., Sobinov, A. R., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.23.545425 · Cited by 21 · see citing works
“Indeed, electrical activation of tactile nerve fibers evokes sensations experienced at a specific location on the skin, known as the projected field (PF) (Ochoa and Torebjörk, 1983; Ortiz-Catalan et al., 2020b; Overstreet et al., 2019; Petrini et al., 2019; Tan et al., 2014; Wendelken et al., 2017).”
Nguyen, A. T., Xu, J., Luu, D. K., Overstreet, C. K., Cheng, J., Keefer, E. W., & Yang, Z. (2021) · IEEE Journal of Solid-State Circuits · doi:10.1109/jssc.2021.3057041 · Cited by 18 · see citing works
Self-citationCheng, J., Yang, Z., Overstreet, C. K., et al. (2021) · Hand Clinics · doi:10.1016/j.hcl.2021.04.004 · Cited by 15 · see citing works
Self-citationClinical Applications and Future Translation of Somatosensory Neuroprostheses
Graczyk, E. L., Hutchison, B. C., Valle, G., Bjånes, D. A., Gates, D. H., Raspopović, S., & Gaunt, R. A. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1237-24.2024 · Cited by 17 · see citing works
Peripheral neurostimulation for encoding artificial somatosensations
Valle, G. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15822 · Cited by 16 · see citing works
“…limb eliciting multiple sensation locations referred directly on the phantom limb (i.e., somatotopic sensations) (Charkhkar et al., 2018; Davis et al., 2016; Dhillon & Horch, 2005; Overstreet et al., 2019; Petrini, Valle, Bumbasirevic, et al., 2019; Strauss et al., 2019; Tan et al., 2015).”
BackgroundPellot-Cestero, J. E., Herring, E. Z., Graczyk, E. L., Memberg, W. D., Kirsch, R. F., Ajiboye, A. B., & Miller, J. P. (2023) · Neurosurgery · doi:10.1227/neu.0000000000002561 · Cited by 11 · see citing works
Taghlabi, K. M., Cruz-Garza, J. G., Hassan, T., Potnis, O., Bhenderu, L. S. S., Guerrero, J. R., Whitehead, R. E., Wu, Y. C., Luan, L., Xie, C., et al. (2024) · Journal of Neural Engineering · doi:10.1088/1741-2552/ad200f · Cited by 8 · see citing works
“Six cuff electrodes are incorporated into the larger body of the array, while eight platinum intrafascicular electrodes are positioned on the thin extension of the array, separated by 0.5 mm [73].”
BackgroundInfluentialIn vivo closed-loop control of a locust’s leg using nerve stimulation
Zurita, F., Duca, F. D., Teshima, T., Hiendlmeier, L., Gebhardt, M., Luksch, H., & Wolfrum, B. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-13679-z · Cited by 8 · see citing works
Abiri, A., Chau, S., James, N. R., Goshtasbi, K., Birkenbeuel, J. L., Sahyouni, R., Edwards, R. A., Djalilian, H. R., & Lin, H. W. (2022) · Brain Sciences · doi:10.3390/brainsci12111457 · Cited by 7 · see citing works
“In recent years, advancements in intraneural electrodes have even enabled selective activation at the level of single fascicles [12].”
BackgroundConnecting residual nervous system and prosthetic legs for sensorimotor and cognitive rehabilitation
Valle, G., Preatoni, G., & Raspopović, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822828-9.00007-1 · Cited by 7 · see citing works
EEG Features of Evoked Tactile Sensation: Two Cases Study
Qin, C., Liang, W., Xie, D., et al. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.904216 · Cited by 6 · see citing works
“Therefore, a commonly used stimulus paradigm called steady-state somatosensory evoked potentials (SSEPs; Hebert et al., 2014; Overstreet et al., 2019) evoked by stable and high-frequency ( > 5 Hz) stimulation, is often used as a diagnostic method for neurological diseases due to rarely affected by cognition.”
MethodPhosphotungstic Acid Staining to Visualize the Vagus Nerve Perineurium Using Micro‐CT
Upadhye, A. R., Cintron, E., Zhang, J., Coleman, J., Kolluru, C., Jenkins, M. W., Wilson, D. L., Pelot, N. A., & Shoffstall, A. J. (2025) · Journal of Neuroimaging · doi:10.1111/jon.70040 · Cited by 5 · see citing works
Accelerating neurotechnology development using an Agile methodology
Thota, A. K., & Jung, R. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1328540 · Cited by 5 · see citing works
“The specificity (Overstreet et al., 2019; Verma et al., 2023) is defined as the ability to activate a specific targeted group of nerve fibers to elicit a desired neural function.”
BackgroundMulti-Channel Microscale Nerve Cuffs for Spatially Selective Neuromodulation
Riley, M., Tala, F., Johnson, K. J., & Johnson, B. C. (2024) · Micromachines · doi:10.3390/mi15081036 · Cited by 5 · see citing works
“…intensity varies with distance, where fascicles deeper in the nerve receive less stimulation than fascicles closer to the electrode interface [9,10]; and (3) the stimulation threshold varies with fiber diameter, where larger-diameter fibers have a lower threshold than smaller-diameter fibers…”
BackgroundElectrical nerve stimulation for sensory-neural pathway reconstruction in upper-limb amputees
Wang, Y., Liu, H., Zeng, P., Ji, L., Zhou, Y., Zhou, L., & Tao, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1114962 · Cited by 4 · see citing works
“, 2016, 2017) or the peripheral nerves (Overstreet et al., 2019; Zollo et al., 2019), evoking haptic sensations that are perceived as originating from different locations on the hand.”
BackgroundLópez-de–Celis, C., Fernández‐de‐las‐Peñas, C., Malo-Urriés, M., Albarova‐Corral, I., Arias‐Buría, J. L., Pérez‐Bellmunt, A., Rodríguez‐Sanz, J., González-Rueda, V., & Borrella-Andrés, S. (2023) · Healthcare · doi:10.3390/healthcare11111603 · Cited by 4 · see citing works
“To optimize the therapeutic effects, highly targeted applications can be achieved by placing neuromodulation on specific nerve fascicles [15].”
BackgroundShu, Y., Yang, S., Li, P., Gou, S., Cheng, Y., Jia, Q., & Du, Z. J. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1476447 · Cited by 3 · see citing works
Tanner, J., Keefer, E. W., Cheng, J., & Tillery, S. H. (2023) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2023.1083307 · Cited by 2 · see citing works
“This design and strategy has seen success in human subjects, with respect to stability, recruitment, and sensation (Overstreet et al., 2019).”
BackgroundSelf-citationSelective Wireless Stimulation of Rat Sciatic Nerve
Frederick, R. A., Troyk, P. R., & Cogan, S. F. (2020) · Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society · doi:10.1109/embc44109.2020.9175335 · Cited by 2 · see citing works
“[4-7] Intrafascicular MEAs can allow customization of several design parameters to make devices more application specific.”
BackgroundDisruption of Proprioceptive Information During Electrical Stimulation of the Cutaneous AfferentsPreprint
Katic, N., Balaguer, J.-M., Gorskii, O., Pavlova, N., Карал-оглы, Д. Д., Bulgin, D. V., Orlov, S., Евгеньевич, М. П., Raspopović, S., & Capogrosso, M. (2021) · Research Square · doi:10.21203/rs.3.rs-1104392/v1 · Cited by 2 · see citing works
Mogharrabi, B., Cheng, J., Ratakonda, R., Keefer, E. W., & Chhabra, A. B. (2022) · Skeletal Radiology · doi:10.1007/s00256-022-04079-5 · Cited by 1 · see citing works
Self-citationValle, G., Carpaneto, J., & Micera, S. (2023) · Handbook of Neuroengineering · doi:10.1007/978-981-16-5540-1_27 · Cited by 3 · see citing works
Katic, N., Balaguer, J.-M., Gorskii, O., Pavlova, N., Liang, L., Ho, J. C., Grigsby, E. M., Gerszten, P. C., Карал-оглы, Д. Д., Bulgin, D. V., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.19.469209
Features of the spatial orientation of the thoracodorsal nerve bundles
Gorbunov, N. S., Kober, K. V., Каспаров, Э. В., et al. (2024) · Kazan medical journal · doi:10.17816/kmj516489
Compression-Based Feature Reduction for Upper Limb Motor Decoding from Peripheral Neural Signal
Jeong, B., Wu, T., Nguyễn, A. T., Xu, J., Cheng, J., Keefer, E. W., & Yang, Z. (2024) · Wearable and Implantable Body Sensor Networks · doi:10.1109/bsn63547.2024.10780574 · Cited by 1 · see citing works
Self-citationBioengineered Interfaces for Peripheral Nerve Sensory Restoration
Swedick, S., Hadwe, S. E., Liang, K., Malliaras, G. G., & Barone, D. G. (2026) · Advanced Materials · doi:10.1002/adma.74815
Technological Innovations in the Restoration of Upper Limb Amputees
Cheng, J., & Jao, B. C. (2026) · Hand Clinics · doi:10.1016/j.hcl.2026.08.010
Self-citation
- Authors
- Overstreet, C. K., Cheng, J., & Keefer, E. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Overstreet, Cynthia K
- Venue
- Journal of Neural Engineering
- Publisher
- IOP Publishing
- Published
- 2019-11-11
- Volume
- 16
- Issue
- 6
- Pages
- 066040
- ISSN
- 1741-2552 (ISSN-L)
- 1741-2560
- OpenAlex
- W2972675070
- Semantic Scholar
- 66917415aefadc52861fdf307fac2f87c0376c21
- Cited by
- 46
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 5 · 2019: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Neural Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Defense Advanced Research Projects Agency (N66001-15-C-4016)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Physical Sciences › Engineering › Biomedical Engineering › Muscle activation and electromyography studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
- Keywords
- peripheral nerve stimulation, neural interfaces, intrafascicular electrodes, ulnar nerve, median nerve, stimulation threshold, strength-duration time constant, proprioception
- MeSH terms
- Adult, Transcutaneous Electric Nerve Stimulation, Electrodes, Implanted, Evoked Potentials, Somatosensory, Female, Humans
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