Proprioceptive Sensorimotor Integration With Neural Interfaces for Hand Prostheses (PSI)

The purpose of this study is to characterize proprioceptive sensations in the missing limb of upper limb amputees using nerve stimulation, and to develop advanced controllers for moving a prosthesis. Proprioceptive sensations are the sensations that tell individuals where their hand is in space, and if it is moving. The research team uses Functional Electrical Stimulation (FES), which involves applying small electric currents to the nerves. These signals are then transferred to the brain just like the information about the individual's intact hand used to be transferred to their brain. This study will test different placements for stimulation and determine which one(s) provide the individual with proprioceptive sensations. The investigators want to know what the participants feel and if the investigators can use proprioceptive sensation to give the participants information about limb movement and position.

Study Overview

• Status: Recruiting
• Conditions: Upper Limb Amputees
• Intervention / Treatment: Device: Chronically Implanted Neural and Muscular Interface

Detailed Description

Hands are the primary means of interacting with the world, and Veterans who have lost a hand must cope with diminished functional and sensory capabilities. While myoelectric prostheses can restore the basic grasping function of the lost hand, many amputees abandon use of prostheses because current prosthetic options do not meet their needs. In addition, many amputees struggle with phantom pain and psychosocial deficits following limb loss that are not fully mitigated by current treatments.

In the normal sensorimotor system, proprioception, which is the sense of limb position and movement, is critical for informing motor plans and correcting errors in movement. In addition, proprioception plays a key role in body ownership, agency, and phantom pain. Despite its importance, proprioception is absent in current prosthetic options.

The goal of the proposed project is to make upper limb prosthetic devices more natural and useful for Veterans who have lost a hand by providing proprioceptive feedback about prosthesis postures and movements. The central hypothesis is that effectively closing the loop between a prosthesis user and their device requires that the sensory inputs and control outputs closely mimic the underlying sensorimotor neural processes of the body schema. The investigators will examine integration of artificial proprioception with prosthesis control in eight trans-radial or four trans-humeral amputees using the investigators' implanted neural-interfacing system and intramuscular EMG.

Aim 1. Characterize proprioceptive sensations elicited by peripheral nerve stimulation. The investigators will test time-varying Peripheral Nerve Stimulation (PNS) patterns and examine the impact on the kinematics of the evoked proprioceptive percept using position matching with the contralateral intact limb and multivariate regression analyses. The investigators will investigate paired agonist-antagonist stimulation strategies and compare the discriminability between agonist-only and paired agonist-antagonist strategies using psychometric tests. As well as assess the psychometric properties of PNS-evoked proprioceptive percepts and examine the interaction of proprioception with concurrent touch feedback and voluntary muscle contraction.

Aim 2. Investigate the mechanisms of stimulation-evoked proprioception. The neurophysiological basis of proprioception from PNS is unknown. To investigate whether proprioceptive percepts originate from direct afferent activation or indirect recruitment via direct muscle activation, the investigators will perform a motor block of the residual forearm of trans-radial participants and examine changes to the proprioceptive percepts. In trans-humeral participants, Targeted Muscle Reinnervation will be performed at the time of system implant, and percepts will be compared before and after muscle ingrowth.

Aim 3. Determine the integration of proprioceptive stimulation with motor control during posture matching. To restore proprioception to Veterans during active prosthesis use, PNS-evoked percepts must be integrated with voluntary limb control. The investigators will determine the impact of proprioception on motor control through a virtual reality posture matching task and compare performance with velocity and position-based prosthetic hand controllers with and without proprioceptive PNS. The investigators will determine the impact of voluntary control on the perception of PNS-evoked proprioception through a psychometric dissimilarity rating task. The investigators will assess the impact of artificial proprioception on embodiment via surveys. The investigators will also explore how control of multi-DOF movements with intramuscular EMG signals can be decoded via machine learning (ML)-based controllers by comparing the integration of proprioception with machine learning-based velocity control vs machine learning-based position control in virtual hand posture matching tasks. Investigators will access this impact by having the participants perform functional tasks in the laboratory with the best performing controller and a multi-DOF prosthetic hand with joint position sensors.

The project will be the first to investigate the sensorimotor integration of proprioception from PNS in a broad population of upper-limb amputees and with both position and velocity controllers. The study will provide important information about the kinematics of artificial proprioception and the role of direct muscle activation in forming proprioceptive percepts. The investigators expect that knowledge gained in this proposal will improve prosthesis utility and acceptance for Veterans with limb loss and will advance prosthetic hand technology and standard of care in the neurorehabilitation field.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emily L Graczyk, PhD; Phone Number: 63571 (216) 791-3800; Email: Emily.Graczyk@va.gov
• Study Contact Backup: Name: Jessica R Jarvela, MS BS; Phone Number: 63801 (216) 791-3800; Email: Jessica.Jarvela@va.gov

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-1702
      • Recruiting
      • Louis Stokes VA Medical Center, Cleveland, OH
      • Principal Investigator: Emily L Graczyk, PhD
      • Contact: Melissa S Schmitt; Phone Number: 63801 (216) 791-3800; Email: Melissa.Schmitt@va.gov
      • Contact: Jessica R Jarvela, MS BS; Phone Number: 63801 (216) 791-3800; Email: Jessica.Jarvela@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Unilateral upper limb amputation above or below the elbow with fully healed and healthy surgical sites
• Viable peripheral nerve function in the residual nerves serving the limb
• Volitional activity of the residual muscles in the amputated limb or actuating movement of the limb
• Medically fit to undergo general anesthesia
• Fitted with a prosthesis by a certified prosthetic and orthotic specialist (CPO) and at least one month of experience using a prosthesis
• Willingness and availability to follow the study protocol
• Willingness to undergo psychological evaluation, if recommended by study surgeons or investigators, to determine that the participant is mentally competent and capable of completing the study-related activities

Exclusion Criteria:

• Bilateral upper limb amputation, unless the amputation on the contralateral side only involves missing digits but does not qualify as a partial hand amputation
• Inability to speak English
• Medically unfit to undergo surgery
• Pregnancy, or those who are of childbearing potential, unwilling to prevent pregnancy during the trial
• Uncontrolled diabetes (HgbA1c>8.0%)
• History of neuropathy and/or radiculopathy in the target limb
• Active infection or open sores on the residual limb
• History of frequent infection or sores with unknown cause
• Inability to provide informed consent or follow experimental protocols
• Severe pain that would prevent the participant from completing study-related activities
• Poor surgical candidate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronically Implanted Neural and Muscular Interface; 8 eligible participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES).	Device: Chronically Implanted Neural and Muscular Interface; Participants will be chronically implanted with neural and muscular interfaces to characterize proprioceptive sensations using Functional Electrical Stimulation (FES).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of change in perceived joint position	Magnitude of change in perceived joint position, as measured by joint angle transducers in the Cyberglove. As well as just noticeable difference (JND) of perceived magnitude, JND of perceived frequency, temporal detection threshold (TDT), and adaptation time constants for proprioceptive percepts	This metric will be measured approximately each month for two years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multi-Dof posture matching	Participants will perform a multi-DOF posture matching task in virtual reality, where they will be asked to control multiple DOF simultaneously to achieve a multi-DOF target posture. Each controlled DOF will have a matched proprioceptive percept, and the number of DOF controlled in this task will be 2-4. Trial time will be the primary metric measure.	This metric will be measured approximately each month for two years.
Object Discrimination	The participant will complete object discrimination tasks and simulated activities of daily living both with and without proprioceptive feedback. Identification accuracy will be the primary metric measure	This metric will be measured approximately each month for two years.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Emily L Graczyk, PhD, Louis Stokes VA Medical Center, Cleveland, OH

Publications and helpful links

General Publications

• Wright JD, Charkhkar H, Graczyk EL. Mind the gap: the temporal discrimination threshold of tactile sensation from implanted peripheral nerve stimulation. J Neuroeng Rehabil. 2026 Apr 18. doi: 10.1186/s12984-026-01986-9. Online ahead of print. No abstract available.

Helpful Links

• E. Gardner, J. Martin, in Principles of neural science (2000;

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Prosthesis; Peripheral Nerve Stimulation; Proprioception; Embodiment; Upper Extremity Limb Loss; Sensorimotor; Neuroprostheses
• Other Study ID Numbers: A3699-R; RX003699-01 (Other Grant/Funding Number: VA RR&D); 1624763 (Other Identifier: IRBNET); 1I01RD000699-01A2 (Other Grant/Funding Number: VA RR&D)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes