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

NCT07691957 | Recruiting

• 2 other identifiers: 18385_TADDEITUNEBEAM_MICROAMP
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Upper Limb Amputation; Healthy Subjects

Keywords

Microneurography; Intraneural Microstimulation; Somatosensory System; Upper limb amputation

Outcome Measures

Primary Outcomes (9)

• Mechanoreceptor identification success rate

  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

  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

  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

  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

  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

  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

  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

  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

  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)

Secondary Outcomes (4)

• Event-related potential amplitude during intraneural microstimulation

  During the experimental protocol (up to 3 hours)

• Event-related potential latency during intraneural microstimulation

  During the experimental protocol (up to 3 hours)

• EEG spectral power modulation during intraneural microstimulation

  During the experimental session (up to 3 hours)

• Decoding accuracy of tactile stimulation conditions from EEG signals

  During the experimental session (up to 3 hours)

Study Arms (2)

Microneurographic Session

EXPERIMENTAL

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.

Procedure: Microneurography

Intraneural Microstimulation Session

EXPERIMENTAL

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.

Procedure: Intraneural Microstimulation

Interventions

Microneurography PROCEDURE

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.

Microneurographic Session

Intraneural Microstimulation PROCEDURE

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.

Intraneural Microstimulation Session

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Ospedaliero, Universitaria Pisana: lead
• Scuola Superiore di Studi Universitari e di Perfezionamento Sant'Anna: collaborator

Study Sites (1)

Laboratorio Congiunto di Microneurografia e Microneurostimolazione

Pisa, Pisa, 56127, Italy

RECRUITING

Related Publications (4)

• Ackerley R, Watkins RH. Microneurography as a tool to study the function of individual C-fiber afferents in humans: responses from nociceptors, thermoreceptors, and mechanoreceptors. J Neurophysiol. 2018 Dec 1;120(6):2834-2846. doi: 10.1152/jn.00109.2018. Epub 2018 Sep 26.

  PMID: 30256737 BACKGROUND

• Oddo CM, Raspopovic S, Artoni F, Mazzoni A, Spigler G, Petrini F, Giambattistelli F, Vecchio F, Miraglia F, Zollo L, Di Pino G, Camboni D, Carrozza MC, Guglielmelli E, Rossini PM, Faraguna U, Micera S. Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans. Elife. 2016 Mar 8;5:e09148. doi: 10.7554/eLife.09148.

  PMID: 26952132 BACKGROUND

• Vallbo AB. Microneurography: how it started and how it works. J Neurophysiol. 2018 Sep 1;120(3):1415-1427. doi: 10.1152/jn.00933.2017. Epub 2018 Jun 20.

  PMID: 29924706 BACKGROUND

• Statache M, Filosa M, Ballanti S, D'Alesio G, Di Salvo G, Camboni D, Oddo CM. Neuromorphic Touch Sensors for Pleasantness Encoding via Spike Patterns: A Bio-Inspired Artifical Fingertip for Restoring Affective Sensations. IEEE Sensors, 2024, Kobe, Japan. doi: 10.1109/SENSORS60989.2024.10784624.

  RESULT

Central Study Contacts

Stefano Taddei

CONTACT

+39 050993699; stefano.taddei@unipi.it

Calogero Maria Oddo

CONTACT

+39 050 883111; calogero.oddo@santannapisa.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: July 9, 2026
• Study Start: March 4, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Upon publication of results
• Access Criteria: Data and code will be available for research purposes upon request to authors.

Locations

IT (1)