A neural interface provides long-term stable natural touch perception

Abstract

Touch perception on the fingers and hand is essential for fine motor control, contributes to our sense of self, allows for effective communication, and aids in our fundamental perception of the world. Despite increasingly sophisticated mechatronics, prosthetic devices still do not directly convey sensation back to their wearers. We show that implanted peripheral nerve interfaces in two human subjects with upper limb amputation provided stable, natural touch sensation in their hands for more than 1 year. Electrical stimulation using implanted peripheral nerve cuff electrodes that did not penetrate the nerve produced touch perceptions at many locations on the phantom hand with repeatable, stable responses in the two subjects for 16 and 24 months. Patterned stimulation intensity produced a sensation that the subjects described as natural and without "tingling," or paresthesia. Different patterns produced different types of sensory perception at the same location on the phantom hand. The two subjects reported tactile perceptions they described as natural tapping, constant pressure, light moving touch, and vibration. Changing average stimulation intensity controlled the size of the percept area; changing stimulation frequency controlled sensation strength. Artificial touch sensation improved the subjects' ability to control grasping strength of the prosthesis and enabled them to better manipulate delicate objects. Thus, electrical stimulation through peripheral nerve electrodes produced long-term sensory restoration after limb loss.

Conflict of interest statement

Competing interests: D.J.T. is Founder and President of Bear Software, LLC. D.J.T. is an inventor on the patent entitled “The flat interface nerve electrode and a method for use” (US6456866 B1); Case Western Reserve University holds the patents on this technology. D.W.T., M.A.S., and D.J.T. are named inventors on a provisional patent on the stimulation paradigm described in the paper, which is jointly held by Case Western Reserve University and the Louis-Stokes Cleveland VA Medical Center.

Copyright © 2014, American Association for the Advancement of Science.

Figures

Fig. 1. Stability and selectivity of implanted cuff electrodes

(A) We implanted three cuffs with a total of 20 channels in the forearm of subject 1: a four-contact spiral cuff on the radial nerve of the forearm and an eight-contact FINE on the median and ulnar nerves. The electrode leads ran subcutaneously to the upper arm and connected to open-helix percutaneous leads via spring-and-pin connectors (–29). A Universal External Control Unit (UECU, Ardiem Medical) supplied single-channel, charge-balanced, monopolar nerve stimulation. (B) Sensation locations after threshold stimulation at week 3 post-op. Cuff electrodes were highly selective, with each contact producing either a unique location or unique sensation. Here, the letter represents the nerve and the number represents the stimulus channel within the nerve cuff around that nerve. Thus, M3 is the third stimulus channel within the median nerve cuff. Ulnar (U) locations presented the most overlap at threshold, but differentiated in area expansion at suprathreshold responses. The subjects drew the borders around areas of perception. Areas outside the template, for example, M3, represent a small wrap-around of sensation on the digit. (C) Repeated weekly overlapping threshold locations of channels M2, M3, M4, M5, and M8 for weeks 3 through 10 post-op indicated consistent location perception. Locations remained stable for all stimulation waveforms used. (D) Mean normalized threshold charge density for all channels on the median (blue), ulnar (green), and radial (red) cuffs of subject 1 shown as a solid line. Shaded areas indicate the 95% confidence interval. An unbiased, stepwise search determined the threshold. Frequency was a constant 20 Hz. During weeks 2 to 8, percept thresholds for subject 1 were 95.5 ± 42.5 nC (n = 59), 70.7 ± 59.2 nC (n = 50), and 40.7 ± 12.4 nC (n = 24) for the median, ulnar, and radial nerves, respectively. Linear regression of the threshold stimulation intensity for perception over 8 weeks for every channel was unchanging [18/19, analysis of variance (ANOVA) test, P ≥ 0.067] or decreasing (1/19, ANOVA, P = 0.044). Subject 2 was also stable (P ≥ 0.087) with thresholds of 141 ± 46 nC and 95 ± 47 nC for the median and radial nerves, respectively. (E) Threshold tracking of median channels M3, M4, and M5 to 68 weeks and thereafter showed no significant change in threshold over time (P = 0.053, 0.587, and 0.773, respectively).

Fig. 2. Waveform patterns

(A) Square, charge-balanced, cathodic-first stimulation pulsing pattern. Prior neural stimulation maintained constant parameters, such as pulse amplitude (PA), pulse width (PW), and interpulse interval (IPI) or frequency (f). (B) In general, constant PA and PW modulate the area of perception. M5 showed a channel-specific recruitment pattern as PW was increased from 24 to 60 μs. M3 showed that the percept area increases as PA increases from 1.1 to 2.0 mA. These recruitment patterns matched the sensory nerve innervation patterns of the digital nerve. (C) An example of full-scale modulation, using a sinusoidal (1 Hz) PW envelope that produced a natural sensation of pulsing pressure (top plot). The schematic resulting stimulation waveform where the IPI is 0.1 s (10 Hz) is shown in the bottom plot. Our stimulation trials typically used an IPI of 0.01 s (100 Hz).

Fig. 3. Full-scale modulation sinusoidal PW envelope

(A) At threshold (Bth), a pulsing pressure was felt at the bold circle area (M3, M4, M8; blue). Increasing the PW to a secondary threshold (Btingle) introduced an additional pulsing paresthesia, which typically covered a larger area that overlapped the pressure location. Increasing the PW further caused the area of par-esthesia to increase but the area of constant pressure did not increase. Light moving touch was described as someone lightly brushing the skin with a finger. It consistently moved in the same direction for a given stimulus (R1, R4; pink). (B) Psychometric rating of sensation intensity as a function of PWmax showing a relationship between PW and the strength of the perceived intensity. The subject was provided five PWmax stimuli (100, 114, 131, 150, and 167 μs), and each level was presented three to six times in random order. (C) Threshold windows for natural sensation were measured on every channel of the median cuff. Pressure occurred at Bth (green), was accompanied by paresthesia at Btingle (black line, yellow), and was overwhelmed by paresthesia at BMask (red). The largest PW windows for a particular channel were found when PA was lowest. Higher levels of stimulation were avoided for M6 because of pain response.

Fig. 4. Small-scale, offset modulation

(A) Typical example of a small-scale, offset (SSO) modulation using sinusoidal (1 Hz) PW with offset stimulation on M4 (solid, red line). PWpk-pk = 90 to 95 μs was the lowest stimulation level that produced constant pressure sensation. For comparison, the threshold for pulsing pressure from full-scale modulation is shown (dotted blue line). (B) Contralateral pressure matching indicated that frequency can control the intensity of constant pressure sensation. The subject was provided SSO modulation with the IPI set to 50, 20, 10, 5, or 2 ms (20, 50, 100, 200, or 500 Hz) on channel M4 and asked to match the perceived pressure with the contralateral hand. Pressure intensity was proportional to the stimulus frequency. (C) The PWmin-max window that produced a sensation of constant pressure was influenced by the PA (left figure: 0.6 mA, right figure: 0.7 mA), which altered both the size and the location of the window. We found that frequency had a weaker effect on the window but affected the intensity. At PA of 0.5 mA, there was no response. For PA 0.8 mA and above, the data suggested that the window for continuous pressure sensation decreased.

Fig. 5. Functional tasks with sensory feedback

(A) Without the sensory feedback system enabled, the subject was often unable to adequately control the grip force in a delicate task such as holding a cherry while removing the stem. (B) With the sensory feedback enabled, the subject felt contact with the cherry and the force applied. He successfully gripped the cherry and removed the stem without damaging the fruit. (C) Total force from thumb and index tip sensors when subject 1 had audiovisual feedback (sighted) but not sensory feedback (feedback off). Peak force during the trial is denoted with a red asterisk. (D) Total force from thumb and index tip sensors when subject 1 had both audiovisual feedback (sighted) and sensory feedback (feedback on). Peak forces (red asterisks) were significantly reduced. (E) Sighted and blinded performance with the sensory feedback on or off during the cherry task showed an improvement in success rate (test of proportions, P < 0.005, n = 15 per condition). (F) Peak forces were significantly lower in the feedback enabled condition under both blinded and sighted conditions (Welch’s t test, P < 0.001, n = 15 per condition).