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Microneurography and Intraneural Microstimulation for Upper Limb Sensory Investigation in Healthy and Amputee Subjects (MICROAMP)

7. juli 2026 oppdatert av: Stefano Taddei, Azienda Ospedaliero, Universitaria Pisana

Experimental Study to Investigate Sensory Control of the Upper Limb Through Microneurography and to Restore Near-natural Tactile Sensations Through Intraneural Microstimulation in Healthy and Amputee Subjects

The goal of this experimental study is to investigate the somatosensory system through intraneural recording and stimulation of the median nerve in healthy volunteers and participants with upper-limb amputation. The main questions it aims to answer are:

  • How does median nerve activity encode tactile perception during different types of mechanical tactile stimulation in healthy subjects?
  • How can tactile information be artificially encoded and restored through intraneural microstimulation in both healthy subjects and upper-limb amputee participants? How rich and functionally meaningful is the restored sensory information?
  • What are the neurophysiological mechanisms underlying tactile stimulus processing and the associated patterns of brain activation during tactile stimulation?

Participants will undergo median nerve recordings using microneurography during controlled mechanical tactile stimulation, as well as intraneural microstimulation with specific patterns to evoke near-natural tactile sensations. They will perform perceptual reporting tasks related to stimulus type, intensity, and localization, as well as psychophysical tests under different stimulation conditions. When possible, they will also undergo non-invasive recordings of brain activity using electroencephalography during sensory stimulation.

Studieoversikt

Detaljert beskrivelse

Participants will attend the laboratory where the entire research protocol will be conducted in a single visit lasting up to 4 hours.

Medical history and a physical examination will be collected. In participants with amputation, additional clinical information from previous neurological assessments will be reviewed (including medical records, nerve conduction velocity data, and ultrasound or MRI examinations required to verify inclusion/exclusion criteria). Psychometric tests will also be administered to assess language abilities, visuospatial skills, and general intelligence, ensuring that participants are able to understand and perform the experimental tasks. If inclusion and exclusion criteria are met, participants will undergo microneurography and/or intraneural microstimulation procedures. Participants will be seated comfortably, with the dominant arm (healthy volunteers) or the residual limb (participants with amputation) supported. A trained medical operator will identify the median nerve using external stimulation and/or ultrasound guidance to assist electrode insertion. The active electrode will be inserted into the nerve, while a reference electrode will be placed in the subcutaneous tissue a few centimeters away. Correct electrode placement will then be refined using intraneural stimulation. Once the nerve fascicle is reached, tactile stimulation of the hand will be used to identify single mechanoreceptive units. Final electrode placement will be confirmed by visual and auditory inspection of the neural signal. The median nerve activity must be clearly distinguishable from background activity when mechanical stimuli are applied to the skin. During electrode insertion, participants will be instructed to remain still until the procedure is completed. The intraneural microstimulation session, performed in both healthy volunteers and participants with upper-limb amputation, is preceded by peripheral neural recordings using microneurography during the presentation of tactile stimuli (e.g., Von Frey filaments). This step is used for accurate nerve localization and preliminary assessment of the receptors and their receptive fields. Once the neural target is identified, participants undergo intraneural stimulation involving the perception and recognition of artificially generated tactile stimuli. These stimuli are delivered via intraneural microstimulation and are derived from mechanoneural transduction, using a sensorized artificial finger interacting with different surfaces to encode surface-dependent tactile information. Participants will be asked to recognize different properties of the presented stimuli. During the tests, electroencephalographic (EEG) activity may be recorded using a 128-channel EEG system, synchronized with the onset of stimulation.

Studietype

Intervensjonell

Registrering (Antatt)

100

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

    • Pisa
      • Pisa, Pisa, Italia, 56127
        • Rekruttering
        • Laboratorio Congiunto di Microneurografia e Microneurostimolazione
        • Ta kontakt med:
        • Hovedetterforsker:
          • Calogero Maria Oddo, PhD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen

Tar imot friske frivillige

Ja

Beskrivelse

Inclusion Criteria:

Healthy participants

  • Age between 18-60 years, of any sex
  • Signed informed consent
  • No neurological diseases
  • Presence of both intact upper limbs
  • Normal language, visuospatial, and general intellectual abilities, assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Appendix 1)

Amputee participants

  • Age between 18-60 years, of any sex
  • Signed informed consent
  • Upper-limb amputation (transradial or hand amputation)
  • Stable amputation for at least one year
  • Normal language, visuospatial, and general intellectual abilities, assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Appendix 1)
  • Evidence of residual peripheral nerve function in the stump, based on nerve conduction studies as documented in clinical records

Exclusion Criteria:

Healthy participants

  • Conditions affecting perceptual abilities
  • Inability to provide informed consent
  • Pregnancy or breastfeeding (self-reported)
  • Clinical conditions that, in the judgment of the investigator responsible for recruitment, may interfere with microneurography, microstimulation, and EEG procedures
  • Current or past substance abuse
  • Brain injury with residual motor impairment
  • Depression
  • Presence of neurological or musculoskeletal disorders
  • Diabetes mellitus
  • Current or previous dermatological conditions
  • Morphological nerve abnormalities, as indicated by ultrasound or MRI findings in clinical records
  • Upper-limb amputation

Amputee participants

  • Psychological and/or cognitive disorders
  • Inability to provide informed consent
  • Pregnancy or breastfeeding (self-reported)
  • Clinical conditions that, in the judgment of the investigator responsible for recruitment, may interfere with microneurography, microstimulation, and EEG procedures
  • Current or past substance abuse
  • Brain injury with residual motor impairment
  • Depression
  • Presence of neurological or musculoskeletal disorders
  • Diabetes mellitus
  • Current or previous dermatological conditions
  • Morphological nerve abnormalities, as indicated by ultrasound or MRI findings in clinical records
  • Bilateral upper-limb amputation

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Microneurographic Session
During MNG session, microneurographic signals are recorded while mechanical tactile stimuli (e.g., Von Frey filaments) are applied. This recording-only task is used to characterize the mechanoreceptor properties, including receptive field mapping, response type, and firing behavior.
Microneurography is a minimally invasive neurophysiological technique that allows direct recording of the electrical activity of single peripheral nerve fibers using specific microelectrodes inserted into the nerve.
Eksperimentell: Intraneural Microstimulation Session
During INMS session, intraneural microstimulation is delivered via the microelectrode to evoke tactile sensations. Stimulation patterns are generated from sensor-based interactions with different surfaces and are used to assess tactile perception, including stimulus recognition, intensity, and localization in both healthy and amputee participants.
Intraneural microstimulation is a minimally invasive neurophysiological technique in which small electrical currents are delivered through a microelectrode inserted into a peripheral nerve to selectively activate nerve fibers and evoke sensory perceptions.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Mechanoreceptor identification success rate
Tidsramme: During the experimental protocol (up to 3 hours)
The proportion of experimental sessions in which a single mechanoreceptive afferent is successfully isolated and identified using MNG during controlled mechanical tactile stimulation, expressed as the percentage of successful recordings (%).
During the experimental protocol (up to 3 hours)
Mechanoreceptor classification accuracy
Tidsramme: During the experimental session (up to 3 hours)
The accuracy of mechanoreceptor type classification (e.g., SA1, SA2, RA, PC) based on MNG recordings during mechanical tactile stimulation, expressed as the percentage of correctly classified receptors (%).
During the experimental session (up to 3 hours)
Peripheral afferent firing rate during tactile stimulation
Tidsramme: During the experimental session (up to 3 hours)
The mean firing rate (spikes/s) of mechanoreceptive afferents recorded by MNG during controlled mechanical tactile stimulation.
During the experimental session (up to 3 hours)
Tactile mechanical detection threshold
Tidsramme: During the experimental session (up to 3 hours)
The minimum stimulus intensity (expressed in grams of calibrated Von Frey Hairs) required to evoke a consistent neural response during mechanical tactile stimulation.
During the experimental session (up to 3 hours)
Receptive field size of mechanoreceptive afferents
Tidsramme: During the experimental session (up to 3 hours)
The spatial extent of skin area (mm²) eliciting neural responses during mechanical tactile stimulation mapped via MNG.
During the experimental session (up to 3 hours)
Perceived sensory perception during intraneural microstimulation
Tidsramme: During the experimental protocol (up to 3 hours)
Participant-reported sensory percepts will be classified into predefined categories (e.g., pressure, vibration, tingling, tapping) and summarized as the frequency and percentage of each sensory class across stimulation conditions.
During the experimental protocol (up to 3 hours)
Perceived intensity of tactile sensations elicited during intraneural microstimulation
Tidsramme: During the experimental protocol (up to 3 hours)
Participants will rate the perceived intensity of each evoked sensation using a numerical rating scale from 0 (no sensation) to 10 (maximum imaginable intensity). Mean and standard deviation (or median and interquartile range) will be reported for each stimulation condition.
During the experimental protocol (up to 3 hours)
Perceived location of tactile sensations elicited during intraneural microstimulation
Tidsramme: During the experimental protocol (up to 3 hours)
Participants will indicate the anatomical location of each evoked sensation on a standardized hand map. Responses will be summarized as frequencies and percentages for each anatomical region.
During the experimental protocol (up to 3 hours)
Tactile discrimination performance
Tidsramme: During the experimental session (up to 3 hours)
Discrimination performance will be assessed using a two-alternative forced-choice (2AFC) psychophysical paradigm during intraneural microstimulation. Performance will be quantified using the Elo rating system, a continuous score derived from pairwise stimulus comparisons. The Elo rating has no predefined minimum or maximum value. Higher Elo scores indicate greater discrimination performance.
During the experimental session (up to 3 hours)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Event-related potential amplitude during intraneural microstimulation
Tidsramme: During the experimental protocol (up to 3 hours)
Event-related potentials (ERPs) elicited by intraneural microstimulation and recorded using 128-channel EEG will be quantified by peak amplitude (µV) of stimulus-locked cortical responses.
During the experimental protocol (up to 3 hours)
Event-related potential latency during intraneural microstimulation
Tidsramme: During the experimental protocol (up to 3 hours)
Event-related potentials (ERPs) elicited by intraneural microstimulation and recorded using 128-channel EEG will be quantified by peak latency (ms) of stimulus-locked cortical responses.
During the experimental protocol (up to 3 hours)
EEG spectral power modulation during intraneural microstimulation
Tidsramme: During the experimental session (up to 3 hours)
Changes in EEG spectral power recorded using 128-channel EEG during intraneural microstimulation expressed as spectral power (µV²) or percentage change from baseline (%)
During the experimental session (up to 3 hours)
Decoding accuracy of tactile stimulation conditions from EEG signals
Tidsramme: During the experimental session (up to 3 hours)
Machine learning-based classification of tactile stimulation conditions using EEG-derived features (classification accuracy %)
During the experimental session (up to 3 hours)

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Publikasjoner og nyttige lenker

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Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

4. mars 2024

Primær fullføring (Antatt)

31. desember 2026

Studiet fullført (Antatt)

31. desember 2026

Datoer for studieregistrering

Først innsendt

21. mai 2026

Først innsendt som oppfylte QC-kriteriene

7. juli 2026

Først lagt ut (Faktiske)

9. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

9. juli 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. juli 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Andre studie-ID-numre

  • 18385_TADDEI
  • TUNEBEAM_MICROAMP (Annen identifikator: Tuscany Region)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Upon publication of results, anonymized data and analysis code will be shared to ensure reproducibility.

IPD-delingstidsramme

Upon publication of results

Tilgangskriterier for IPD-deling

Data and code will be available for research purposes upon request to authors.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • ANALYTIC_CODE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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