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

7 de julho de 2026 atualizado por: 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.

Visão geral do estudo

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

100

Estágio

  • Não aplicável

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

Locais de estudo

    • Pisa
      • Pisa, Pisa, Itália, 56127
        • Recrutamento
        • Laboratorio Congiunto di Microneurografia e Microneurostimolazione
        • Contato:
        • Investigador principal:
          • Calogero Maria Oddo, PhD

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto

Aceita Voluntários Saudáveis

Sim

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Ciência básica
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Experimental: 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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Mechanoreceptor identification success rate
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Event-related potential amplitude during intraneural microstimulation
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Publicações e links úteis

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Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

4 de março de 2024

Conclusão Primária (Estimado)

31 de dezembro de 2026

Conclusão do estudo (Estimado)

31 de dezembro de 2026

Datas de inscrição no estudo

Enviado pela primeira vez

21 de maio de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

7 de julho de 2026

Primeira postagem (Real)

9 de julho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

9 de julho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de julho de 2026

Última verificação

1 de julho de 2026

Mais Informações

Termos relacionados a este estudo

Outros números de identificação do estudo

  • 18385_TADDEI
  • TUNEBEAM_MICROAMP (Outro identificador: Tuscany Region)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

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

Prazo de Compartilhamento de IPD

Upon publication of results

Critérios de acesso de compartilhamento IPD

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

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • ANALYTIC_CODE

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

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