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Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

Open AccessPublished:March 20, 2019DOI:https://doi.org/10.1016/j.apmr.2018.07.445

      Highlights

      • A man with paralysis regained hand grasp through BCI-controlled arm muscle stimulation.
      • The device enabled the patient to twist and pour using lateral, palmar, and tip-to-tip grips.
      • Grips for training objects carried over successfully to novel objects and tasks.
      • The patient’s functional motor level improved when using the BCI from C5-6 to C7-T1.
      • Translation to home use could decrease dependence for activities of daily living.

      Abstract

      Objective

      To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic.

      Design

      Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478.

      Setting

      Tertiary care outpatient rehabilitation center.

      Participant

      A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury

      Interventions

      After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements.

      Main Outcome Measures

      Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES.

      Results

      With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects.

      Conclusions

      Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics.

      Graphical Abstract

      Keywords

      List of abbreviations:

      ARAT (Action Research Arm Test), BBT (Box and Block Test), BCI (brain-computer interface), CUE-T (Capabilities of Upper Extremity Test), FES (functional electrical stimulation), GAIN (Generalizability, Ability, Independence, Neurologic Level), GRASSP (Graded Redefined Assessment of Strength, Sensibility, and Prehension), GRT (Grasp and Release Test), MEA (microelectrode array), MMT (manual muscle training), QIF-SF (Quadriplegia Index of Function-Short Form), SCI (spinal cord injury), SCIM-SR (Spinal Cord Independence Measure–Self-Report), SRD (smallest real difference)
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      or transcutaneous
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      BCI and FES training of a spinal cord injured end-user to control a neuroprosthesis.
      • Rupp R.
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      Think2grasp - bci-controlled neuroprosthesis for the upper extremity.
      • Grimm F.
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      • Rosenstiel W.
      • Gharabaghi A.
      Hybrid neuroprosthesis for the upper limb: combining brain-controlled neuromuscular stimulation with a multi-joint arm exoskeleton.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
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      Restoring cortical control of functional movement in a human with quadriplegia.
      • Sharma G.
      • Friedenberg D.A.
      • Annetta N.
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      Using an artificial neural bypass to restore cortical control of rhythmic movements in a human with quadriplegia.
      • Friedenberg D.A.
      • Schwemmer M.A.
      • Landgraf A.J.
      • et al.
      Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human.
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      functional electrical stimulation (FES).
      • Pfurtscheller G.
      • Müller G.R.
      • Pfurtscheller J.
      • Gerner H.J.
      • Rupp R.
      ‘Thought’–control of functional electrical stimulation to restore hand grasp in a patient with tetraplegia.
      • Kreilinger A.
      • Kaiser V.
      • Rohm M.
      • Rupp R.
      • Müller-Putz G.R.
      BCI and FES training of a spinal cord injured end-user to control a neuroprosthesis.
      • Rupp R.
      • Rohm M.
      • Schneiders M.
      • et al.
      Think2grasp - bci-controlled neuroprosthesis for the upper extremity.
      • Grimm F.
      • Walter A.
      • Spüler M.
      • Naros G.
      • Rosenstiel W.
      • Gharabaghi A.
      Hybrid neuroprosthesis for the upper limb: combining brain-controlled neuromuscular stimulation with a multi-joint arm exoskeleton.
      • Ajiboye A.B.
      • Willett F.R.
      • Young D.R.
      • et al.
      Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      However, clinically significant gains on tests of upper limb function have not been demonstrated using BCI-FES. The critical translational path for BCI neuroprosthetics requires demonstration of clinically meaningful gains in speed, dexterity, and smooth integration of grip with other arm movements to perform complex tasks.
      Our goal was to evaluate whether an individual with tetraplegia could make clinically significant gains in skillful grasp coordination
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      High-performance neuroprosthetic control by an individual with tetraplegia.
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      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      using an investigational MEA-BCI-FES. We formulated a framework

      Bockbrader M, Eipel K, Friedenberg DA, Sharma G. Clinical performance evaluation for a take-home brain computer interface for grasp. Paper presented at: the 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. July 17-21, 2018; Honolulu, HI.

      called Generalizability, Ability, Independence, Neurologic Level (GAIN) that reflects design goals for BCI neuroprosthetics to assist in this assessment. GAIN was inspired by end-user perspectives,
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      We anticipate it being useful for comparing performance across neuroprosthetic technologies and justifying (eg, to regulatory or payer sources) that a device measurably improves function on the International Classification of Functioning, Disability, and Health domains recognized by the World Health Organization.
      World Health Organization
      The International Classification of Functioning, Disability and Health (ICF).
      Devices meeting the GAIN standard include the following: (1) demonstrate generalizability, defined as performing well without retraining for objects with similar grip features (e.g., lateral, tip-to-tip, palmar, pincer grasps); (2) confer clinically significant gains in motor ability on standardized, psychometrically validated, and expert-endorsed
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      tests of upper limb function; (3) affect daily life by facilitating functional independence for activities of daily living (ADLs) on psychometrically validated assessments
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      • Post M.W.
      Measurement outcomes of upper limb reconstructive surgery for tetraplegia.
      • van Tuijl J.H.
      • Janssen-Potten Y.J.M.
      • Seelen H.A.M.
      Evaluation of upper extremity motor function tests in tetraplegics.
      • Mulcahey M.J.
      • Hutchinson D.
      • Kozin S.
      Assessment of upper limb in tetraplegia: considerations in evaluation and outcomes research.
      • Alexander M.S.
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      • et al.
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      Rick Hansen Institute Spinal Cord Injury Research Evidence (SCIRE) Project. Outcome measures toolkit: implementation steps. Available at: https://scireproject.com/wp-content/uploads/om_toolkit_implementation_guide.pdf. Accessed June 27, 2018.

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      ; and (4) improve the user’s neurologic level of function on validated measures normed to the International Standards for the Neurological Classification of Spinal Cord Injury standards.
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      • Verrier M.C.
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      Development of the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific to the upper limb in tetraplegia.

      Methods

      This was a Phase I trial of a MEA-BCI interfaced with the Neurolifea transcutaneous, forearm FES. Like similar intracortical BCI studies,
      • Ajiboye A.B.
      • Willett F.R.
      • Young D.R.
      • et al.
      Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      • Sharma G.
      • Friedenberg D.A.
      • Annetta N.
      • et al.
      Using an artificial neural bypass to restore cortical control of rhythmic movements in a human with quadriplegia.
      • Friedenberg D.A.
      • Schwemmer M.A.
      • Landgraf A.J.
      • et al.
      Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human.
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
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      • et al.
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      Intracortical microstimulation of human somatosensory cortex.
      this report was limited to 1 participant, the first to use the system, due to the invasive nature of the investigational brain implant and time required for training and assessment. Technical BCI-FES features
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      • Friedenberg D.A.
      • Bouton C.E.
      • Annetta N.V.
      • et al.
      Big data challenges in decoding cortical activity in a human with quadriplegia to inform a brain computer interface.
      (fig 1), the Utah Arrayb MEA implantation procedures, and machine learning algorithms used to generate decoders were described previously. The participant provided written informed consent as approved by our local institutional review board.
      Figure thumbnail gr1
      Fig 1Cortical implant and NeuroLife BCI-FES system. (At left) A. 96-channel Utah MEA. B. Close-up view of array orientation (yellow) on the left motor cortex. C. Head computerized tomography image showing the implant location. D. Rendering of the location of the array (yellow) on the precentral gyrus. (At right) BCI-FES Operation: (1) Neurons fire when the user thinks about grasping. (2) Neural data is sampled at 30,000Hz with a Neuroport system, converted into 100-ms blocks of MWP, and analyzed with nonlinear, SVM-movement decoders trained in MATLAB. Each decoder is trained iteratively over 5 blocks (3 to 4 trials/block) using MWP in multiunit activity frequency bands as described previously.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      • Friedenberg D.A.
      • Bouton C.E.
      • Annetta N.V.
      • et al.
      Big data challenges in decoding cortical activity in a human with quadriplegia to inform a brain computer interface.
      (3) Continuous decoder outputs, updated every 100 ms, animate a computer-generated hand and (4) Stimulate transcutaneous, forearm, cathode and anode electrode sites calibrated to finger and wrist flexors and extensors. (5) FES-evoked movements allow the user to manipulate objects. NOTE. Figures and photographs by M. Bockbrader and N. Austin. Abbreviations: MWP, mean wavelength power; SVM, support vector machine.

      Participant

      The participant was a 27-year-old man with chronic, traumatic, C5 American Spinal Injury Association Impairment Scale A tetraplegia. He had 5 out of 5 strength for shoulder and elbow flexion; 1 out of 5 wrist extension; and flaccid paralysis with lack of sensation below C6.

      Procedures

      The participant began practicing BCI-FES-evoked movements of his right forearm and hand 1 month postimplant (3.5h/session, 2 to 3 sessions/wk) and started standardized testing 3 months later (fig 2). Only portions of standardized tests were given in any session due to time constraints, with the full battery of tests extending over months. Data reported here were collected between postimplant days 137 through 1478, with simpler standardized test items (eg, manual muscle training [MMT]) occurring earlier than more complex tasks (eg, pouring).
      Figure thumbnail gr2
      Fig 2Standardized tests. A. Upper limb motor ability measures. I. GRASSP
      • Kalsi-Ryan S.
      • Curt A.
      • Verrier M.C.
      • Fehlings M.G.
      Development of the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific to the upper limb in tetraplegia.
      objects II. Black mechanical pinch gauge (0 kg to 13.6 kg) III. Electronic handgrip digital dynamometer (0 kg to 90 kg) IV. ARAT
      • Yozbatiran N.
      • Der-Yeghiaian L.
      • Cramer S.C.
      A standardized approach to performing the action research arm test.
      objects V. GRT
      • Wuolle K.S.
      • Van Doren C.L.
      • Thrope G.B.
      • Keith M.W.
      • Peckham P.H.
      Development of a quantitative hand grasp and release test for patients with tetraplegia using a hand neuroprosthesis.
      objects VI. BBT
      • Mathiowetz V.
      • Volland G.
      • Kashman N.
      • Weber K.
      Adult norms for the Box and Block Test of manual dexterity.
      box with blocks B. Examples of grip types in each upper limb motor ability measure. The GRASSP and ARAT assess the ability to form palmar and precision grips independently from other upper limb movements. The GRASSP, ARAT, GRT, and BBT assess integration of palmar or precision grasps with upper limb movements required to transfer objects (shoulder internal and external rotation) or transfer and lift objects (shoulder internal and external rotation and flexion and extension). The GRASSP and ARAT also assess integration of palmar or precision grasps with forearm pronation and supination (as in pouring or turning a doorknob) or radial and ulnar deviation (as in twisting a lid). NOTE. Figures and photographs by M. Bockbrader and N. Austin.

      FES Calibration

      Anode-cathode calibrations were developed for each object and grasp using knowledge of forearm anatomy. Initial calibrations took 30 to 60 minutes, while recalibration in subsequent sessions typically took 2 to 3 minutes to verify consistent electrode placement and adjust stimulation intensity. Figure 3 depicts representative stimulation patterns, target muscle groups, and FES-evoked movements.
      Figure thumbnail gr3
      Fig 3BCI-FES activation for GRT can grasp sequences. A representative example of neural modulation, decoder outputs, electrode calibration, target muscles, and evoked movements is shown for one 30-second trial of GRT can manipulation. The spike raster plots threshold-crossing events (per 100 ms) across channels. The heatmap depicts normalized MWP (“db4” wavelet scales 3 to 6; 234 Hz to 3750 Hz) across channels. Decoder outputs for “hand open” (blue) and “hand closed” (gray) palmar grips were modulated with activity changes in the spike raster and the MWP heatmap. “Rest” states occurred when all decoder outputs were less than zero. Five paired “hand open”–”hand closed” decoder peaks are shown in 30 seconds, corresponding to 5 successful transfers. The inset depicts electrode stimulation patterns, target muscle groups, and FES-evoked movements during “hand open” (left) and “hand closed” (right) states. Cathodes are shown in black and anodes are shown in red. NOTE. See for a demonstration of object manipulation with BCI-FES. Figures by M. Bockbrader and N. Austin, photographs by M. Bockbrader and S. Colachis. Abbreviations: APL, abductor pollicis longus; EDC, extensor digitorum communis; FDS/P, flexor digitorum superficialis/profundus; FPL, flexor pollicis longus; MWP, mean wavelength power.

      Decoder training

      For standardized testing, each decoder was trained with the number of grip classes needed to complete 1 subtest item (1 to 2 movements plus rest). We chose this for simplicity, minimizing training time, and facilitating subtest comparison across days. In some cases, 1 grasp type or decoder was used to test several similarly shaped objects (eg, day 833: Grasp and Release Test (GRT) fork decoder was used to “eat” polystyrene foam “food” with a metal dinner fork and to transfer Action Research Arm Test [ARAT] cylinders). Multiple, sequentially-trained decoders were often built on the same day to allow testing for multiple items per session. To demonstrate that performance obtained during standardized testing was reproducible with multiclass decoders, we compared single-class GRT performance to previously published results
      • Colachis IV, S.C.
      Optimizing the brain-computer interface for spinal cord injury rehabilitation.
      for a decoder with classes for all GRT objects or grips.
      Decoder training took 10 to 15 minutes, with 3 to 4 repetitions of each movement across 4 to 6 blocks. Decoders appeared to be sensitive to grasp context
      • Downey J.E.
      • Brane L.
      • Gaunt R.A.
      • Tyler-Kabara E.C.
      • Boninger M.L.
      • Collinger J.L.
      Motor cortical activity changes during neuroprosthetic-controlled object interaction.
      ; thus, they were trained with objects and any voluntary shoulder or elbow movements required for performing the task. Figures 3 and 4 describe representative examples of decoder activation (line graphs) and evoked movements (pictures) for items from each outcome measure.
      Figure thumbnail gr4
      Fig 4BCI-FES evoked grips in upper limb motor tasks. Representative examples of decoder activation (line graphs) and evoked movements (pictures) are shown for single trials from each outcome measure. GRASSP Pour (A), GRASSP Jar (A), and ARAT Ball (B) required sustained decoder activation to maintain grip during reaching, pronating, or twisting, respectively. Timed tests like the GRASSP 9-Hole Peg (A), GRT (C), and BBT (D) required rapid initiation and termination of decoder activity to optimize performance. Tasks that required a series of movements are labeled with stages of task completion (or failed attempts) along the decoder timeline to correlate decoder activity with behavioral performance. For example, the GRASSP Jar (A) task consisted of a series of integrated hand, wrist, forearm, and shoulder movements to twist lids off of 2 jars. The first jar’s lid was removed after 5 sequential pairs of hand-open and shoulder flexion (gray peaks) and hand-close and shoulder extension with radial deviation (blue peaks). In the BBT (D) trial, the participant dropped a block coincident with a short duration peak in decoder activity (at approximately 11 s). Drops could be explained as user control failures (ie, inability to sustain decoder activation above threshold as [D]) or due to FES calibration difficulty (sustained, correct, suprathreshold decoders in GRASSP 9-hole peg [A]) associated with muscle fatigue or surface electrode displacement. NOTE. See also for performance on these tasks. Figures by M. Bockbrader and N. Austin, photographs by M. Bockbrader, S. Colachis, and M. Zhang.

      Standardized testing

      Measures of motor ability (see fig 2), functional independence, and neurologic level of function
      • Sinnott K.A.
      • Dunn J.A.
      • Wangdell J.
      • Johanson M.E.
      • Hall A.S.
      • Post M.W.
      Measurement outcomes of upper limb reconstructive surgery for tetraplegia.
      • van Tuijl J.H.
      • Janssen-Potten Y.J.M.
      • Seelen H.A.M.
      Evaluation of upper extremity motor function tests in tetraplegics.
      • Mulcahey M.J.
      • Hutchinson D.
      • Kozin S.
      Assessment of upper limb in tetraplegia: considerations in evaluation and outcomes research.
      • Alexander M.S.
      • Anderson K.D.
      • Biering-Sorensen F.
      • et al.
      Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.

      Rick Hansen Institute Spinal Cord Injury Research Evidence (SCIRE) Project. Outcome measures toolkit: implementation steps. Available at: https://scireproject.com/wp-content/uploads/om_toolkit_implementation_guide.pdf. Accessed June 27, 2018.

      • Boakye M.
      • Harkema S.
      • Ellaway P.H.
      • Skelly A.C.
      Quantitative testing in spinal cord injury: overview of reliability and predictive validity.

      Academy of Neurologic Physical Therapy. Spinal Cord Injury EDGE Task Force Outcome Measure Recommendations. Available at: http://www.neuropt.org/docs/sci-edge-/sci-edge-complete-recommendations.pdf?sfvrsn=2. Accessed June 27, 2018

      • Miller W.C.
      • Chan W.L.
      • Noonan V.N.
      • et al.
      Outcome measures.
      • Carlozzi N.E.
      • Goodnight S.
      • Casaletto K.B.
      • et al.
      Validation of the NIH toolbox in individuals with neurologic disorders.
      were obtained with and without BCI-FES. Functional independence without BCI-FES was rated as the participant’s home level of function. Functional independence with BCI-FES was his expected level of function if he was able to use BCI-FES at home. Generalization of upper limb motor ability was evaluated by training decoders with standardized test objects and testing with household objects.

      Instruments

      Graded and Redefined Assessment of Sensibility, Strength, and Prehension (GRASSP
      • Kalsi-Ryan S.
      • Curt A.
      • Verrier M.C.
      • Fehlings M.G.
      Development of the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific to the upper limb in tetraplegia.
      • Kalsi-Ryan S.
      • Beaton D.
      • Ahn H.
      • et al.
      Responsiveness, sensitivity, and minimally detectable difference of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension, version 1.0.
      • Kalsi-Ryan S.
      • Beaton D.
      • Curt A.
      • et al.
      The Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity.
      • Kalsi-Ryan S.
      • Curt A.
      • Fehlings M.
      • Verrier M.
      Assessment of the hand in tetraplegia using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) impairment versus function.
      )

      Dorsal and palmar sensation on digits I, III, and V were scored from 0 (unable) to 4 (0.4 kg) using Semmes-Weinstein Monofilamentc testing. Strength was graded from 0 (flaccid) to 5 (full) using MMT. Prehension ability was scored for lateral, palmar, and tip-to-tip grips from 0 to 4 (unable; moves wrist; moves wrist and fingers, no force; moves wrist and fingers, some force; moves wrist and fingers, full force). Prehension performance included: pouring, unscrewing lids, turning keys, 9-Hole Peg, inserting coins into slots, and fastening nuts onto bolts. Scores were rated (0 to 5) reflecting best performance within 75 seconds (unable; object grasped, <50% complete; object grasped, >50% complete; task completed, incorrect grip; task completed slowly, correct grip; task completed normally).

      Myometry
      • Mathiowetz V.
      • Kashman N.
      • Volland G.
      • Weber K.
      • Dowe M.
      • Rogers S.
      Grip and pinch strength: normative data for adults.
      • Lang C.E.
      • Edwards D.F.
      • Birkenmeier R.L.
      • Dromerick A.W.
      Estimating minimal clinically important differences of upper-extremity measures early after stroke.
      • Chen H.M.
      • Chen C.C.
      • Hsueh I.P.
      • Huang S.L.
      • Hsieh C.L.
      Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke.

      Pinch force (tip-to-tip, lateral) and palmar grip were measured with a Black Mechanical Pinch Gauged (range: 0 to 13.6 kg, accuracy: ±0.05 kg) and the Camry Electronic Digital Dynamometere (range: 0 to 90 kg, accuracy: ±0.1 kg).

      Action Research Arm Test
      • Yozbatiran N.
      • Der-Yeghiaian L.
      • Cramer S.C.
      A standardized approach to performing the action research arm test.
      • Chen H.M.
      • Chen C.C.
      • Hsueh I.P.
      • Huang S.L.
      • Hsieh C.L.
      Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke.
      • Van der Lee J.H.
      • De Groot V.
      • Beckerman H.
      • Wagenaar R.C.
      • Lankhorst G.J.
      • Bouter L.M.
      The intra-and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke.
      • Lin K.C.
      • Chuang L.L.
      • Wu C.Y.
      • Hsieh Y.W.
      • Chang W.Y.
      Responsiveness and validity of three dexterous function measures in stroke rehabilitation.
      • Connell L.A.
      • Tyson S.F.
      Clinical reality of measuring upper-limb ability in neurologic conditions: a systematic review.

      Objects included blocks (2.5 cm3, 5 cm3, 7.5 cm3, 10 cm3), balls (6-mm, 16-mm, 7.1-cm diameter), bar (10 cm × 2.5 cm × 1 cm), cup (7-cm diameter), cylinders (1-cm, 2.5-cm diameter), and 3.5-cm ring. Scoring ranged from 0 to 3 based ability to grasp and transfer objects (unable in 60 s, partially performed in 60 s, performed >5 s, performed <5 s).

      Grasp and Release Test
      • Wuolle K.S.
      • Van Doren C.L.
      • Thrope G.B.
      • Keith M.W.
      • Peckham P.H.
      Development of a quantitative hand grasp and release test for patients with tetraplegia using a hand neuroprosthesis.
      • Mulcahey M.
      • Smith B.
      • Betz R.
      Psychometric rigor of the Grasp and Release Test for measuring functional limitation of persons with tetraplegia: a preliminary analysis.

      Objects included peg (0.6 cm × 7.6 cm), weight (5 cm × 1.4 cm), block (2.5 cm3), can (5.4 cm × 9.1 cm), video tape (20.4 cm × 12 cm × 3 cm), and fork (1.2 cm × 14.5 cm). Most objects were grasped, transferred lateral-to-medially, and released. The fork was grasped, depressed 2 cm against a 4.4-N spring, and released. Item scores were median successes across 3, 30-second trials.

      Box and Block Test (BBT)
      • Mathiowetz V.
      • Volland G.
      • Kashman N.
      • Weber K.
      Adult norms for the Box and Block Test of manual dexterity.
      • Chen H.M.
      • Chen C.C.
      • Hsueh I.P.
      • Huang S.L.
      • Hsieh C.L.
      Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke.

      Scoring reflected the number of successful (2.5 cm3) block transfers in a 2-compartment box over 3, 60-second trials.

      Capabilities of Upper Extremity Test (CUE-T)
      • Marino R.J.
      • Shea J.A.
      • Stineman M.G.
      The capabilities of upper extremity instrument: reliability and validity of a measure of functional limitation in tetraplegia.
      • Oleson C.V.
      • Marino R.J.
      Responsiveness and concurrent validity of the revised Capabilities of Upper Extremity-Questionnaire (CUE-Q) in patients with acute tetraplegia.

      Thirty-two activities in 4 domains (reaching and lifting, pushing and pulling, wrist actions, hand and finger actions) were scored from 0 to 4 (unable, severe difficulty, moderate difficulty, mild difficulty, no difficulty) based on participant self-report and physiatrist observation.

      Quadriplegic Index of Function-Short Form (QIF-SF)
      • Marino R.J.
      • Goin J.E.
      Development of a short-form Quadriplegia Index of Function scale.

      Scores (0 to 4) reflected participant self-ratings (dependent, physical assistance, supervision, independent with device, independent without device) on 6 self-care tasks.

      Spinal Cord Injury Independence Measure-Self-Report (SCIM-SR)
      • Prodinger B.
      • Ballert C.S.
      • Brinkhof M.W.
      • Tennant A.
      • Post M.W.
      Metric properties of the Spinal Cord Independence Measure - Self Report in a community survey.

      Scores reflected participant self-ratings on 17 activities in 3 domains (self-care, respiration and sphincter management, mobility).

      Analyses

      Best performance with and without BCI-FES were reported. Nonparametric statistics were used due to small sample size and nonnormal distributions. Smallest real difference (SRD) and minimum clinically important difference were used to interpret scores (fig 5). Calculations were performed using MATLABf software.
      Figure thumbnail gr5
      Fig 5Motor function with and without BCI-FES. All open squares and white bars represent performance without BCI-FES; all filled squares and colored bars represent performance with BCI-FES. A. Timeline for standardized testing, ADL measures, and generalization tasks (household objects, adapted “Battleship” game). The shaded region to the right of day 875 indicates when training sessions focused on multiclass decoders that allowed for switching between grips. B. Scores on GRASSP subscales improved beyond the test’s SRD for strength, prehension ability and prehension performance. The inset shows items that improved with BCI-FES on MMT (top) and prehension performance (bottom). C. Overall ARAT score improved by 12 points, which exceeds the minimum clinically important difference for the test subscales showing improvement were Grasp and Grip. The inset shows items that improved on the Grasp (top) and Grip (bottom) subscales. D. BBT and GRT scores only improved for objects the user could not manipulate at baseline Figure at left displays BBT (days 137, 835) and GRT (days 703, 833 to 835) boxplots for median number of successes across 3 trials. The inset (right) contrasts transfer performance at baseline (day 137, without BCI-FES), using the single grip decoders trained for standardized test items (days 833 to 835 and 1473 to 1476), and a multiclass decoder trained to switch between all grips needed for GRT objects (days 855, 857, 869, 897). When the participant used the multiclass decoder to perform the GRT, he appropriately switched between grip types to use the optimal grip for the object he was manipulating. The decoder had 7 classes: hand open, peg (index-thumb pinch), fork (tight palmar grip), block (tripod grip), can (cylindrical palmar grip), weight (lateral grip), and video tape (palmar power grip with extended fingers). Data represent mean GRT scores (each of which was calculated per test instructions as the median of 3 trials for each test day). Scores that were obtained on more than 1 day have SD depicted as error bars. E. Generalization of grips from GRT peg and 9-Hole Peg to video game pieces transfer of horizontal and vertical peg grip skills enabled the participant to play “Battleship” (day 1466). NOTE. See for BBT task performance with and without the BCI-FES. Figures by M. Bockbrader and N. Austin.

      Results

      The participant improved qualitatively over time in his ability to use BCI-FES to evoke movements of his dominant arm and hand. We observed hypertrophy of right forearm and hand muscles over the first 2 months, resulting in a relative reversal of his SCI-related atrophy, but no change in his International Standards for the Neurological Classification of Spinal Cord Injury exam or electromyogram and nerve conduction study findings.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      Initially, the participant reported concentrating intensely “like taking a calculus test” when imagining gross motor movements. He experienced mental fatigue and found fine motor control and individual finger movements onerous. After 8 to 12 months, however, he began to require fewer training blocks and less intense focus to master new movements. Figure 5A shows the progression of testing, beginning with GRASSP and ARAT (supplemental video S1), progressing to BBT and GRT (supplemental video S2), then addressing ADLs and ability to transfer skills to household objects (toothbrush, fork, book, beverage can; supplemental video S3, available online only at http://www.archives-pmr.org/) and leisure activities (adapted “Battleship” supplemental video S4) (see fig 5E).

      Graded Redefined Assessment of Strength, Sensibility, and Prehension

      GRASSP strength improved from 12 to 40 (24% to 80% normal), achieving normal strength for 5 forearm muscle groups (see fig 5B, table 1). Force increased on myometry for all grips (table 2). However, maximal palmar, lateral, and tip-to-tip grip force could not be accurately quantified. High compressive force altered the participant’s ability to apply force directly to the pinch gauge and dynamometer transducers. Prehension ability scores were therefore based on ability to grip objects against resistance. BCI-FES improved prehension ability scores from 5 to 11 (42% to 92% normal), with submaximal tip-to-tip grip noted from inadequate thenar muscle stimulation. Prehension performance improved with BCI-FES from 9 to 15 (30% to 50% normal), due to better ability to pour a bottle (supplemental video S5), unscrew lids, and perform 9-Hole Peg. No gains were noted for key, coins, or fastener items (no FES-evoked pinch grips could be calibrated for these objects). Dorsal and palmar sensation did not change.
      Table 1GRASSP performance across subscales for the right upper limb with and without the BCI-FES
      ItemBaseline Adaptive Grip (Day 260)BCI-FES Controlled Grip
      ScoreDescriptionTest DaysBest ScoreDescriptionn
      Dorsal Sensation: Semmes-Weinstein Monofilament Testing
       Hand, Digit I (C6)1300-kg force was detected on 2/3 trials260, 1357, 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      24-kg force was detected3
       Hand, Digit III (C7)0No force was detected260, 1357, 14760No force was detected3
       Hand, Digit V (C8)0No force was detected260, 1357, 14760No force was detected3
      TOTAL (Max 12)1 (8% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C6
      Dates (postimplant day) for best performance beyond baseline scores.
      2 (17% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C6
      Dates (postimplant day) for best performance beyond baseline scores.
      Palmar Sensation: Semmes-Weinstein Monofilament Testing
       Hand, Digit I (C6)40.4-kg force was detected260, 1357, 147640.4 kg-force was detected3
       Hand, Digit III (C7)0No force was detected260, 1357, 14760No force was detected3
       Hand, Digit V (C8)0No force was detected260, 1357, 14760No force was detected3
      TOTAL (Max 12)4 (33% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C6
      Dates (postimplant day) for best performance beyond baseline scores.
      4 (33% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C6
      Dates (postimplant day) for best performance beyond baseline scores.
      Strength: MMT
       MMT: Shoulder flexion (C5)5Full ROM against gravity, maximum resistance260, 14765
      Items could not be performed with FES.
      --
       MMT: Elbow flexion (C5)5Full ROM against gravity, maximum resistance260, 14765
      Items could not be performed with FES.
      --
       MMT: Elbow extension (C7)0No visible or palpable contraction260, 14760
      Items could not be performed with FES.
      --
       MMT: Wrist extension (C6)1Visible or palpable contraction265
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      5Full ROM against gravity, maximum resistance2
       MMT: Hand, Digit III extension (C7)0No visible or palpable contraction265
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      5Full ROM against gravity, maximum resistance2
       MMT: Hand, Digit I opposition (T1)1Visible or palpable contraction (likely fasciculations)265, 14765Full ROM against gravity, maximum resistance2
       MMT: Hand, Digit I flexion (C8)0No visible or palpable contraction265
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      5Full ROM against gravity, maximum resistance2
       MMT: Hand, Digit III flexion (C8)0No visible or palpable contraction272
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      5Full ROM against gravity, maximum resistance2
       MMT: Hand, Digit V abduction (T1)0No visible or palpable contraction272
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      3Full ROM against gravity2
       MMT: Hand, Digit II abduction (T1)0No visible or palpable contraction275, 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      2Full ROM gravity eliminated2
      TOTAL (Max 50)12 (24% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C6
      Dates (postimplant day) for best performance beyond baseline scores.
      40
      Change exceeds smallest real difference.30
      (80% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C8
      Dates (postimplant day) for best performance beyond baseline scores.
      Prehension Ability
       Cylindrical grasp2Moves fingers into the prehension pattern; fails to generate force143
      Dates (postimplant day) for best performance beyond baseline scores.
      , 153
      Dates (postimplant day) for best performance beyond baseline scores.
      ,275
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      4Able to keep the wrist in neutral & generate the grasp with full thumb & finger movement2
       Lateral key pinch1Moves wrist actively and fingers passively into the prehension pattern275
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      4Able to keep the wrist in neutral & generate the grasp with full thumb & finger movement2
       Tip-to-tip pinch2Moves fingers into the prehension pattern; fails to generate force278
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      3Positions fingers and thumb into the prehension pattern with some force2
      TOTAL (Max 12)5 (42% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C5-6
      Dates (postimplant day) for best performance beyond baseline scores.
      11
      Change exceeds smallest real difference.30
      (92% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C7-T1
      Dates (postimplant day) for best performance beyond baseline scores.
      Prehension Performance
       Pour bottle (cylindrical grasp; 242 g)1<50% complete

      >75 s (0 drops)
      286, 1476
      Dates (postimplant day) for best performance beyond baseline scores.
      5Completed in 8 s without difficulty 0 drops4
       Unscrew lids (spherical grasp; small 13.6 g, large 19.0 g)3Completed in 47 s

      Alternate grasp (0 drops)
      300
      Dates (postimplant day) for best performance beyond baseline scores.
      4Completed in 51 s with difficulty 0 drops4
       9-hole peg (tip-to-tip pinch; 0.7 g each)1<50% complete

      >75 s (2 drops)
      288
      Dates (postimplant day) for best performance beyond baseline scores.
      , 1073, 1434, 1438, 1476, 1478
      Dates (postimplant day) for best performance beyond baseline scores.
      2>50% complete

      >75 s

      0 drops (5 of 9 pegs)
      11
       Turn key in lock (lateral grip; 6.9 g)2>50% complete

      >75 s (Multiple drops)
      2902
      Items could not be performed with FES.
      --
       Transfer coins (tip-to-tip pinch; largest to smallest: 6.3 g, 4.5 g, 3.9 g, 1.8 g)1<50% complete

      >75 s (Multiple drops)
      290, 2971
      Items could not be performed with FES.
      --
       Screw nuts (tip-to-tip pinch; largest to smallest: 10.3 g, 4.6 g, 1.0 g, 0.7 g)1<50% complete

      >75 s (1 drop)
      3021
      Items could not be performed with FES.
      --
      TOTAL (Max 30)9 (30% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C5-7
      Dates (postimplant day) for best performance beyond baseline scores.
      15
      Items could not be performed with FES.
      (50% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      ; C5-7
      Dates (postimplant day) for best performance beyond baseline scores.
      Total GRASSP (Max 115)31 (27% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      72 (63% of normal)
      Dates (postimplant day) for best performance beyond baseline scores.
      NOTE. International Standards for the Neurological Classification of Spinal Cord Injury sensory and motor level interpretations for subset scores are listed with item totals. Completion times and number of drops are given for prehension performance tasks.
      Abbreviations: ROM, range of motion.
      Dates (postimplant day) for best performance beyond baseline scores.
      Items could not be performed with FES.
      Change exceeds smallest real difference.
      • Boakye M.
      • Harkema S.
      • Ellaway P.H.
      • Skelly A.C.
      Quantitative testing in spinal cord injury: overview of reliability and predictive validity.
      Table 2Maximum grip measured by hand-held myometry
      GripBaseline Adaptive GripBCI-FES Controlled GripHealthy NormsImplanted FES
      Lateral pinch0 kg (day 279)1.15 kg (day 279)11.8 kg0.82-2.8 kg
      • van Tuijl J.H.
      • Janssen-Potten Y.J.M.
      • Seelen H.A.M.
      Evaluation of upper extremity motor function tests in tetraplegics.
      • Mulcahey M.J.
      • Hutchinson D.
      • Kozin S.
      Assessment of upper limb in tetraplegia: considerations in evaluation and outcomes research.
      • Alexander M.S.
      • Anderson K.D.
      • Biering-Sorensen F.
      • et al.
      Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.
      Tip-to-tip pinch0 kg (day 276)1.35 kg
      Change exceeds smallest real difference,35 but not minimum clinically important difference.34
      (day 276)
      8.2 kg
      Palmar grasp0 kg (day 153)2.9 kg
      Change exceeds smallest real difference,35 but not minimum clinically important difference.34
      (day 153)
      54 kg0.21-2.8 kg
      • van Tuijl J.H.
      • Janssen-Potten Y.J.M.
      • Seelen H.A.M.
      Evaluation of upper extremity motor function tests in tetraplegics.
      • Mulcahey M.J.
      • Hutchinson D.
      • Kozin S.
      Assessment of upper limb in tetraplegia: considerations in evaluation and outcomes research.
      • Alexander M.S.
      • Anderson K.D.
      • Biering-Sorensen F.
      • et al.
      Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.
      Change exceeds smallest real difference,
      • Hochberg L.R.
      • Serruya M.D.
      • Friehs G.M.
      • et al.
      Neuronal ensemble control of prosthetic devices by a human with tetraplegia.
      but not minimum clinically important difference.
      • Kalsi-Ryan S.
      • Curt A.
      • Verrier M.C.
      • Fehlings M.G.
      Development of the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific to the upper limb in tetraplegia.

      Action Research Arm Test

      BCI-FES improved manual dexterity on total ARAT, grasp, and grip scores (see fig 5C, table 3), increasing from 18 to 30 (32% to 53% normal), 8 to 15 (44% to 83% normal), and 4 to 9 (33% to 75% normal), respectively. Performance improved with BCI-FES for the 7.1-cm ball, bar, both cylinders, cup (pouring) and 2.5-cm3, 5-cm3, and 7.5-cm3 blocks. No change was observed for gross movement, pincer items, the 10-cm3 block, and ring.
      Table 3ARAT performance for the right upper limb with and without the BCI-FES
      ItemBaseline Adaptive Grip (Day 148)BCI-FES Controlled Grip
      ScoreTimeTest DaysBest ScoreTime (s)n
      MinimumAverage Mean ± SDMaximum
      Grasp Subscale
       Transfer Block 2.5 cm3
      Included in modified ARAT.11,12
      (9.1 g)
      25.6707
      Dates with best item performance beyond baseline scores.
      34.56.9±2.712.922
       Transfer Block 5 cm3
      Included in modified ARAT.11,12
      (91.2 g)
      29.4223, 227, 1274
      Dates with best item performance beyond baseline scores.
      32.710.7±3.9>6010
       Transfer Block 7.5 cm3
      Included in modified ARAT.11,12
      (287.6 g)
      217.6209, 227, 241, 258, 1274
      Dates with best item performance beyond baseline scores.
      33.69.6±3.6>6010
       Transfer Block 10 cm3
      Included in modified ARAT.11,12
      (>500 g)
      1>60-1----
       Transfer Ball 7.1 cm
      Included in modified ARAT.11,12
      (142.8 g)
      1>60209
      Dates with best item performance beyond baseline scores.
      , 234
      Dates with best item performance beyond baseline scores.
      , 237, 1274
      Dates with best item performance beyond baseline scores.
      24.612.7±16.5>6012
       Transfer Bar 10 × 2.5 × 1 cm
      Included in modified ARAT.11,12
      (151.8 g)
      0>60155, 202
      Dates with best item performance beyond baseline scores.
      32.94.6±2.68.54
      TOTAL (Max 18)8
      Dates with best item performance beyond baseline scores.
      15
      Dates with best item performance beyond baseline scores.
      ,
      Change exceeds smallest real difference and minimum clinically important difference for ARAT.
      Grip Subscale
       Pour 7-cm cup
      Included in modified ARAT.11,12
      (146.2 g)
      0>60840

      842
      Dates with best item performance beyond baseline scores.
      36.411.4±4.519.919
       Transfer Cylinder 2.5 cm
      Included in modified ARAT.11,12
      (32.4 g)
      237.3833
      Dates with best item performance beyond baseline scores.
      34.11
       Transfer Cylinder 1.0 cm
      Included in modified ARAT.11,12
      (6.5 g)
      215.2833
      Dates with best item performance beyond baseline scores.
      34.01
       Transfer Ring 3.5 cm (9.2 g)0>60-0----
      TOTAL (Max 12)4
      Dates with best item performance beyond baseline scores.
      9
      Dates with best item performance beyond baseline scores.
      ,
      Change exceeds smallest real difference and minimum clinically important difference for ARAT.
      Gross Arm Movement Subscale
       Hand to back of head25.0-2----
       Hand to mouth21.9-2----
       Hand on top of head22.6-2----
      TOTAL (Max 9)6
      Dates with best item performance beyond baseline scores.
      6
      Dates with best item performance beyond baseline scores.
      Pinch Subscale
       6-mm ball, Dig I-IV (0.9 g)0>60-0----
       16-mm ball, Dig I-II (13.6 g)0>60-0----
       16-mm ball, Dig I-III (13.6 g)0>60-0----
       16-mm ball, Dig I-IV (13.6 g)0>60-0----
       6-mm ball, Dig I-II (0.9 g)0>60-0----
       6-mm ball, Dig I-III (0.9 g)0>60-0----
      TOTAL (Max 18)0
      Dates with best item performance beyond baseline scores.
      0
      Dates with best item performance beyond baseline scores.
      Total ARAT (Max 57)18
      Dates with best item performance beyond baseline scores.
      30
      Dates with best item performance beyond baseline scores.
      ,
      Change exceeds smallest real difference and minimum clinically important difference for ARAT.
      Modified ARAT Total
      Included in modified ARAT.11,12
      (Max 27)
      12
      Dates with best item performance beyond baseline scores.
      24
      Dates with best item performance beyond baseline scores.
      NOTE. All baseline scores were obtained on postimplant day 148. Minimum, maximum and average (SD) time to task completion and number of trials are listed for items that could be completed with FES grips. All other items are marked with dashes (-).
      Abbreviations: n, number of trials.
      Included in modified ARAT.
      • Müller-Putz G.R.
      • Scherer R.
      • Pfurtscheller G.
      • Rupp R.
      EEG-based neuroprosthesis control: a step towards clinical practice.
      • Ajiboye A.B.
      • Willett F.R.
      • Young D.R.
      • et al.
      Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.
      Dates with best item performance beyond baseline scores.
      Change exceeds smallest real difference and minimum clinically important difference for ARAT.

      Grasp and Release Test

      BCI-FES improved median success rates for peg, weight, fork, can, and tape, but not block (see fig 5D, table 4). This pattern of results was also found when the GRT was performed using a multiclass decoder that included grips for all GRT objects
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      (see fig 5D).
      Table 4GRT median number and interquartile range (IQR) of successful transfers and drops with and without BCI-FES
      Item (Weight or Force)Baseline Adaptive GripBCI-FES Controlled Grip
      SuccessDropPostimplant DaySuccessDrops Median (IQR)Postimplant Day
      Median (IQR)MaximumMedian (IQR)Maximum
      Peg (1.6 g)5.0 (0.5)61.0 (0.5)7036.0 (1.0)71.0 (0.5)833
      4.0 (1.5)60.0 (0.0)1473
       Toothbrush: 10.5 g
      Weight (264 g)0.0 (0)07.0 (1.5)7026.0 (0.5)60.0 (0.5)833
      Fork (4 N)0.0 (0)01.0 (0.0)7025.0 (0.5)60.0 (0.5)833
      6.0 (1.0)70.0 (0.0)1473
       Dinner fork: 70 g
      Can (214 g)0.0 (0.5)11.0 (1.0)7025.0 (0.5)50.0 (0.0)835
      2.0 (1.5)30.0 (0.5)1476
       Espresso can: 169 g
      Video tape (356 g)1.0 (0.5)11.0 (1.5)7022.0 (1.0)30.0 (1.0)835
       Hardbound book: 500 g
      Block (10.6 g)11.0 (0.25)120.0 (0.0)7029.0 (0.5)90.0 (0.0)835
      NOTE. One run for each GRT object consisted of 3 trials of 30 seconds. In each trial, the participant was asked to transfer the object as many times as possible within the time limit. The score for that object was the median across the 3 trials.
      • Van der Lee J.H.
      • De Groot V.
      • Beckerman H.
      • Wagenaar R.C.
      • Lankhorst G.J.
      • Bouter L.M.
      The intra-and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke.
      To quantify variability in performance across the 3 trials in each run, we calculated the interquartile range for the run. To describe the upper limit of function observed on any one trial within the run, we report the within-run maximum. Novel items manipulated with GRT decoders are listed below GRT items with their weights.

      Box and Block Test

      Transfer rates did not improve with BCI-FES (9 blocks/min) compared to baseline (12 blocks/min) (table 5, fig 5D, fig 6A, supplemental video S4).
      Table 5BBT median (interquartile range; IQR) values of successful transfers with and without BCI-FES were equivalent
      Change does not exceed smallest real difference (5.5).35
      Baseline Adaptive Grip

      Postimplant Day 137
      BCI-FES Controlled Grip

      Postimplant Day 835
      Median (IQR)MaximumMedian (IQR)Maximum
      2.5-cm3 blocks (10 g) any grip13.0 (1.5)139.0
      Change does not exceed smallest real difference (5.5).35
      (2.5)
      11
      Transfer times:5.3-9.9 s/block3.0-7.5 s/block
      Transfer time measurement started at grasp initiation, included the transfer period, and stopped when the object was released.
      NOTE. One run of the BBT consisted of 3 trials of 60 s. In each trial, the participant was asked to transfer as many blocks as possible within the time limit. The score for that day was the median across the 3 trials.
      • Van der Lee J.H.
      • De Groot V.
      • Beckerman H.
      • Wagenaar R.C.
      • Lankhorst G.J.
      • Bouter L.M.
      The intra-and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke.
      To quantify variability in performance across the 3 trials in each run, we calculated the interquartile range for the run. To describe the upper limit of function observed on any one trial within the run, we report the within-run maximum.
      Change does not exceed smallest real difference (5.5).
      • Hochberg L.R.
      • Serruya M.D.
      • Friehs G.M.
      • et al.
      Neuronal ensemble control of prosthetic devices by a human with tetraplegia.
      Transfer time measurement started at grasp initiation, included the transfer period, and stopped when the object was released.
      Figure thumbnail gr6
      Fig 6Comparison of BCI-FES performance with BCI control of robotic limbs. A. Mean BBT speed for BCI-FES was significantly faster than BCI control of a robotic limb on a modified BBT task using a 7.5-cm3 block,
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      t5=6.06, P<.01. However, our participant’s performance with and without BCI-FES was equivalent, with difference between scores within the SRD (5.5) for the test. B. Median transfer speeds of BCI-FES on ARAT items fell within general population norms (red line) for many objects
      • Yozbatiran N.
      • Der-Yeghiaian L.
      • Cramer S.C.
      A standardized approach to performing the action research arm test.
      and were significantly faster than speeds reported for BCI control of a robotic limb
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      for the bar and 2.5-cm3, 5-cm3, and 7.5-cm3 blocks, all P<.01 by Mann-Whitney U tests. (Median transfer speed for the ball did not differ significantly between BCI-FES and the robotic limb, P>.05. Statistical tests were not conducted for the 10-cm3 block, cup, and cylinders due to inadequate sample sizes.) C. Faster transfer speed resulted in a higher maximum modified ARAT score for BCI-FES than reported for BCI control of a robotic limb.
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      Performance differences between BCI-FES and our participant’s baseline as well as differences between BCI-FES and the BCI-robotic limb were real and clinically significant; they were greater than the SRD and minimum clinically important difference for the ARAT.
      • Van der Lee J.H.
      • De Groot V.
      • Beckerman H.
      • Wagenaar R.C.
      • Lankhorst G.J.
      • Bouter L.M.
      The intra-and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke.
      NOTE. Figures and photographs by M. Bockbrader and N. Austin.

      Capabilities of Upper Extremity Test

      BCI-FES improved unilateral arm and hand function on the CUE-T (table 6, fig 7C). Total score increased from 27 to 49 (45% to 82% normal) due to gains for wrist actions (from 4 to 8 points; 50% to 100% normal) and hand actions (4 to 22 points; 17% to 92% normal). BCI-FES did not change reaching and lifting or pushing and pulling scores.
      Table 6Observational ratings on the CUE-T and subjective ratings on the QIF-SF and SCIM-SR
      Baseline Adaptive GripBCI-FES Controlled Grip
      CUE-T (Day 532): Unilateral Items
       Reach out33
       Reach overhead00
       Reach down00
      Reaching and Lifting (Maximum 12)3 (25% of normal)3 (25% of normal)
       Pull light object44
       Pull heavy object44
       Push light object44
       Push heavy object44
      Pushing and Pulling (Maximum 16)16 (100% of normal)16 (100% of normal)
       Wrist up04
       Palm down44
      Wrist Actions (Maximum 8)4 (50% of normal)8 (100% of normal)
       Grasp hammer04
       Small pinch14
       Key pinch04
       Wide grasp04
       Manipulate coin02
       Push with finger34
      Hand and Finger Actions (Maximum 24)4 (17% of normal)22 (92% of normal)
      CUE-T unilateral Total score (Maximum 60)27 (45% of normal)49
      Change exceeds minimum clinically important difference calculated as 10% of test range.
      (82% of normal)
      QIF-SF (Day 821)
       Wash/dry hair13
       Supine to side01
       Lower body dressing00
       Open carton/jar03
       Bed to chair03
       Lock wheelchair33
      QIF-SF Total score (Maximum 24; Maximum using any device 18)4 (13% of normal; 22% of independent with device)13
      Change exceeds minimum clinically important difference calculated as 10% of test range.
      (54% of normal; 72% of independent with device)
      SCIM-SR (Day 532)
       Feeding23
       Bathing
      Upper body11
      Lower body00
       Dressing
      Upper body11
      Lower body00
       Grooming23
      Self-care (Maximum 20)6 (30% of normal)8 (40% of normal)
       Respiration55
       Bladder03
       Bowel12
       Toileting02
      Respiration and Sphincter Management (Maximum 17)6 (30% of normal)12 (71% of normal)
       Bed mobility01
       Bed transfer00
       Bath transfer00
       Indoor mobility11
       Mobility 10-100 m11
       Outdoor mobility11
       Stairs00
       Car transfer00
       Ground transfer00
      Mobility (Maximum 37)3 (8% of normal)4 (11% of normal)
      SCIM-SR Total score (Maximum 74)15 (20% of normal)24
      Change exceeds minimum clinically important difference calculated as 10% of test range.
      (32% of normal)
      NOTE. CUE-T ratings were jointly made by the participant and the research physiatrist based on observed performance in the lab of arm actions without using the BCI-FES (baseline) and with the BCI-FES. The participant provided QIF-SF and SCIM-SR ratings for his actual baseline level of function at home and his expected ability if he could use the BCI-FES at home. Higher scores indicate greater level of independence.
      Change exceeds minimum clinically important difference calculated as 10% of test range.
      Figure thumbnail gr7
      Fig 7The GAIN model: implications for neuroprosthetic use in daily life. A. Generalization to everyday objects. Our participant practiced with BCI decoders and FES grips for standardized GRT objects (peg, video tape, can, “fork”) and successfully transferred these skills to grasp and manipulate a toothbrush, hardcover book, metal dinner fork (stabbing a piece of polystyrene foam “food”), and full beverage container B. Ability on activity measures. BCI-FES enabled our participant to form palmar, lateral, and tip-to-tip grips, but not fine pincer grips due to lack of thenar muscle stimulation. Use of the device enabled successful object manipulation activities, like pouring and twisting, which required integration of palmar grip with shoulder and forearm movements. Tip-to-tip grip integrated with shoulder movements was also successful, but not always faster than the participant’s baseline performance with adaptive grips. Some tip-to-tip grips with forearm and wrist pronation and all dynamic pincer grips were a challenge, due to lack of thenar muscle stimulation. C. Independence on functional participation measures. Our participant reported that he expected to make gains in SCIM-SR and QIF-SF self-care, toileting, and upper limb-related mobility tasks if he could use the BCI-FES at home. He did not expect BCI-FES to affect lower limb-related mobility tasks. Expectations for increased independence for self-care were attributed to observed normalization of CUE-T Hand and Wrist domain abilities with BCI-FES. Overall, he reported BCI-FES in the home would allow him to require fewer hours of home care assistance for his ADLs. D. Neurologic level of performance. Based on GRASSP norms for the International Standards for Neurological Classification of Spinal Cord Injury neurologic levels, our participant started at C5-6 and improved to C7-T1 with BCI-FES. This is a clinically significant improvement of upper limb motor control that confers increased independence for activities of daily living. NOTE. See . Figures by M. Bockbrader, photographs by M. Bockbrader and N. Austin, N. Annetta, and M. Zhang.

      Quadriplegia Index of Function-Short Form

      BCI-FES raised the participant’s expected level of independence for ADLs (see table 6, fig 7C) beyond his home function (QIF-SFactual=4, QIF-SFexpected=13). At baseline, the participant was “dependent” for bed mobility, lower body dressing, opening jars, and transferring from bed to chair; required (minimum to moderate); “physical assistance” for grooming; and was “independent with assistive device” to lock his powerchair. Using BCI-FES, he expected to gain “independence with assistive device” for grooming, feeding, and patient-lift transfers.

      Spinal Cord Independence Measure–Self-Report

      BCI-FES raised the participant’s expected level of independence for self-care and toileting but not mobility (see table 6, fig 7C). At baseline (SCIM-SR=15), he had normal function for respiration; moderate impairments (25% to 70% normal) for upper body dressing, bowel management, grooming, and feeding; and severe impairments (0% to 10% normal) for mobility and transfers, toileting, bladder management, and lower body dressing. Using BCI-FES (SCIM-SR=24), he anticipated becoming independent from others (100% normal) for feeding and grooming; increasing his independence for bladder management, bowel management, toileting, and bed mobility (30% to 60% normal).

      Discussion

      Our objective was to evaluate, using GAIN criteria, whether an individual with tetraplegia could make clinically significant gains in grasp coordination with an investigational MEA-BCI-FES (fig 7). GAIN is a framework for evaluating clinical utility of a device, based on measured recovery of motor function, improved neurologic level, and independence for ADLs. Use of this metric can facilitate reproducibility across studies; identify design and performance strengths and challenges for research and development; enable objective comparison of features and limitations across devices; and aid decision making—for both clinicians and end-users—to balance expected costs and benefits.

      Generalizability

      Generalizability, the ability to transfer skills from trained objects or grips to untrained but similar objects or grips, is an important practical step toward clinical translation. We suspected it could be achieved with MEA-BCI-FES given overlap in neural representations for GRT objects handled with similar grips
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      and other evidence that motor cortex encodes grip shape.
      • Downey J.E.
      • Brane L.
      • Gaunt R.A.
      • Tyler-Kabara E.C.
      • Boninger M.L.
      • Collinger J.L.
      Motor cortical activity changes during neuroprosthetic-controlled object interaction.
      • Schaffelhofer S.
      • Agudelo-Toro A.
      • Scherberger H.
      Decoding a wide range of hand configurations from macaque motor, premotor, and parietal cortices.
      We demonstrated generalizability by performing ADL-like activities with household objects using palmar, lateral, and tip-to-tip grip decoders trained on GRT objects (fig 7A, supplemental video S3): the participant mimicked brushing with a toothbrush using peg decoder-calibrations. Similarly, the fork grip carried over to successful use of a dinner fork to “eat” polystyrene foam “food,” the video tape grip enabled manipulation of a book, and the can grip enabled simulated drinking. The participant also played a 20-minute adapted “Battleship” game using decoder-calibrations built on GRASSP, 9-Hole-Peg, and GRT peg, dividing his focus to strategize and win while also switching between grips for the vertical and horizontal game boards.
      Generalizability can also refer to the number of grip types that a user can switch between using the same decoder. A limitation of training minimal-class decoders for individual test items is that additional setup time is needed to switch grips, resulting in standardized testing that stretches across days. This can confound effects specific to objects (eg, weight, shape) with time effects (eg, learning) and limit opportunities for reassessing performance over time. It also fails to address user priorities of spontaneity, decreased setup times, and number of functions available per decoder. For this reason, multiclass GRT decoders were implemented
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      that allowed assessment of all objects without retraining. Performance with the multiclass decoder (see fig 5D) was similar to the single-class decoder for some objects (peg, weight, fork, video tape) but not others (can, block). For block and can, the participant required more time to select the appropriate grip decoder-calibration, reducing transfer rate in multiclass conditions compared to simpler 1 to 2 class decoders. The additional selection time for block was likely related to observed overlap in cortical representation with other GRT object or grips, and subsequent decreased separability of decoders.
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      For can, incremental multiclass decoder delays were likely compounded when performing 2 hand states (hand open, palmar grip) in sequence.

      Motor ability

      BCI-FES yielded clinically significant improvements in our participant’s ability to manipulate objects with speed, dexterity, and coordination (see fig 5 and 7B). This was evidenced by ARAT change (score=12), exceeding the test’s SRD
      • Chen H.M.
      • Chen C.C.
      • Hsueh I.P.
      • Huang S.L.
      • Hsieh C.L.
      Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke.
      (score=5.5) and theoretically-derived
      • Van der Lee J.H.
      • De Groot V.
      • Beckerman H.
      • Wagenaar R.C.
      • Lankhorst G.J.
      • Bouter L.M.
      The intra-and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke.
      or experimentally-estimated
      • Lang C.E.
      • Edwards D.F.
      • Birkenmeier R.L.
      • Dromerick A.W.
      Estimating minimal clinically important differences of upper-extremity measures early after stroke.
      minimum clinically important difference (scores of 5.7 or 12, respectively). BCI-FES improved palmar, lateral, and tip-to-tip grip force and dexterity for objects across sizes and weights (GRASSP, ARAT). No improvement was observed for pincer grips or fine grips with forearm pronation and supination, due to absence of thenar electrodes. BCI-FES facilitated dynamic grips (eg, palmar, lateral, tip-to-tip grasps with transfer or reaching, and complex movements; and palmar grip with pronation or radial deviation [GRASSP jar, GRASSP pour, ARAT pour]); dynamic grips are essential for ADLs and desired by end-users,
      • Kilgore K.L.
      • Scherer M.
      • Bobblitt R.
      • et al.
      Neuroprosthesis consumers’ forum: consumer priorities for research directions.
      but difficult to perform with rigid exoskeletons, tendon transfers,
      • Sinnott K.A.
      • Dunn J.A.
      • Wangdell J.
      • Johanson M.E.
      • Hall A.S.
      • Post M.W.
      Measurement outcomes of upper limb reconstructive surgery for tetraplegia.
      or BCI-controlled robotic arms.
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      Motor strength on grip myometry could not be accurately measured with the pinch gauge and hand dynamometer, necessitating an alternate measurement method in the future. Values obtained were consistent with individuals with tetraplegia using implanted FES
      • Smith B.
      • Mulcahey M.
      • Betz R.
      Quantitative comparison of grasp and release abilities with and without functional neuromuscular stimulation in adolescents with tetraplegia.
      • Peckham P.H.
      • Keith M.W.
      • Kilgore K.L.
      • et al.
      Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: a multicenter study.
      and below age and gender norms
      • Mathiowetz V.
      • Kashman N.
      • Volland G.
      • Weber K.
      • Dowe M.
      • Rogers S.
      Grip and pinch strength: normative data for adults.
      (see table 2), which was expected as SCI alters muscle fibers, causing early fatigability and decreased maximal contractile force.
      • Bhadra N.
      • Peckham P.H.
      Peripheral nerve stimulation for restoration of motor function.
      BCI-FES evoked greater wrist extension strength (5 out of 5) than has been found for individuals with C5 SCI
      • Smith B.
      • Mulcahey M.
      • Betz R.
      Quantitative comparison of grasp and release abilities with and without functional neuromuscular stimulation in adolescents with tetraplegia.
      (0 out of 5 to 3 out of 5), potentially due to the participant’s partially preserved (1 out of 5) wrist extension strength. Consequently, evoked FES stabilized his wrist against gravity without splinting, facilitating naturalistic forearm range of motion. However, wrist stabilization through FES risks prosthetic failure from muscle fatigue. This can be mitigated by optimizing FES parameters
      • Mangold S.
      • Keller T.
      • Curt A.
      • Dietz V.
      Transcutaneous functional electrical stimulation for grasping in subjects with cervical spinal cord injury.
      • Sayenko D.G.
      • Nguyen R.
      • Popovic M.R.
      • Masani K.
      Reducing muscle fatigue during transcutaneous neuromuscular electrical stimulation by spatially and sequentially distributing electrical stimulation sources.
      • Ibitoye M.O.
      • Hamzaid N.A.
      • Hasnan N.
      • Wahab A.K.A.
      • Davis G.M.
      Strategies for rapid muscle fatigue reduction during FES exercise in individuals with spinal cord injury: a systematic review.
      • Koutsou A.D.
      • Moreno J.C.
      • del Ama A.J.
      • Rocon E.
      • Pons J.L.
      Advances in selective activation of muscles for non-invasive motor neuroprostheses.
      and employing spatially distributed sequential stimulation.
      • Sayenko D.G.
      • Nguyen R.
      • Popovic M.R.
      • Masani K.
      Reducing muscle fatigue during transcutaneous neuromuscular electrical stimulation by spatially and sequentially distributing electrical stimulation sources.
      We encountered fatigue-induced weakness only when stimulating for long periods without breaks.
      BCI-enabled manual dexterity and skilled object manipulation have been reported for robotic limbs using 7 to 10 degrees of freedom to control translation, orientation, and hand shape.
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      BCI-robot performance on a modified BBT (<1 block/min) was significantly slower than BCI-FES BBT performance (8.7 blocks/min) (see fig 6). Similarly, BCI-robot transfer speed for a cylindrical object by 2 participants (mean transfers per min ± SD: 1.09±1.09 and 5.28±1.21) was slower than GRT can rate (7 transfers/min) with BCI-FES. In addition, BCI-FES enabled comparatively higher modified ARAT scores (score=24) than the BCI-robotic limb
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      • Wodlinger B.
      • Downey J.E.
      • Tyler-Kabara E.C.
      • Schwartz A.B.
      • Boninger M.L.
      • Collinger J.L.
      Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.
      (score=17). Higher scores were due to significantly faster grip and transfer speed, which met general population norms for many ARAT objects (see fig 6B: metal bar, cylinders, and blocks). Speed was achieved by leveraging our participant’s preserved shoulder strength and simplifying neural decoding into FES-calibrated grip states.
      The critical advance reported here for BCI-FES is intuitive control
      • Ajiboye A.B.
      • Willett F.R.
      • Young D.R.
      • et al.
      Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.
      of high-performance grasp
      • Collinger J.L.
      • Wodlinger B.
      • Downey J.E.
      • et al.
      High-performance neuroprosthetic control by an individual with tetraplegia.
      at naturalistic speed. BCI-FES had previously only demonstrated rudimentary grasping
      • Pfurtscheller G.
      • Müller G.R.
      • Pfurtscheller J.
      • Gerner H.J.
      • Rupp R.
      ‘Thought’–control of functional electrical stimulation to restore hand grasp in a patient with tetraplegia.
      • Lauer R.T.
      • Peckham P.H.
      • Kilgore K.L.
      EEG-based control of a hand grasp neuroprosthesis.
      • Müller-Putz G.R.
      • Scherer R.
      • Pfurtscheller G.
      • Rupp R.
      EEG-based neuroprosthesis control: a step towards clinical practice.
      • Ajiboye A.B.
      • Willett F.R.
      • Young D.R.
      • et al.
      Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration.
      • Bouton C.E.
      • Shaikhouni A.
      • Annetta N.V.
      • et al.
      Restoring cortical control of functional movement in a human with quadriplegia.
      or slow performance
      • Müller-Putz G.R.
      • Scherer R.
      • Pfurtscheller G.
      • Rupp R.
      EEG-based neuroprosthesis control: a step towards clinical practice.
      (GRT weight rate=1.7 transfers/min). However, observation of BBT performance with BCI-FES on a task the participant could do at baseline (supplemental video S4) reveals an opportunity to further improve system speed: though grasp strength and time to transfer each block improved with BCI-FES, total transfers within 60 seconds remained below baseline rates due to delays for decoder processing and neuromuscular stimulation. These were visible as delayed initiation and release of block grasps when using BCI-FES.

      Independence

      Our participant expected home use of BCI-FES to increase independence for self-care, toileting, and food preparation (QIF-SF, SCIM-SR) (see fig 7C). The magnitude of his expected functional gain was greater than those reported for myoelectrically-controlled, implanted FES
      • Mulcahey M.J.
      • Betz R.R.
      • Kozin S.
      • Smith B.T.
      • Hutchinson D.
      • Lutz C.
      Implantaton of the freehand system during initial rehabilitation using minimally invasive techniques.
      (CUE-T: 2.75 to 17.25) and FES-mediated exercise in chronic SCI
      • Ptasinski J.
      • Sharif H.
      • Ditor D.
      The effects of functional electrically stimulated (FES)-arm ergometry on upper limb function and resting cardiovascular outcomes in individuals with tetraplegia: a pilot study.
      (bilateral CUE-T hand: 31.6 to 38.0; QIF-SF: 1.4 to 9.2) but similar to SCIM-SR self-care change seen after FES-therapy in incomplete tetraplegia
      • Popovic M.R.
      • Kapadia N.M.
      • Zivanovic V.
      • Furlan J.C.
      • Craven B.C.
      • McGillivray C.
      Functional electrical stimulation therapy of voluntary grasping versus only conventional rehabilitation for patients with subacute incomplete tetraplegia: a randomized clinical trial.
      (1.9 to 12.1).

      Neurologic level

      Over time, the participant gained skill and coordination on GRASSP tasks with BCI-FES. This change likely correlated with use-dependent cortical plasticity under the implant, retuning neurons to the distal limb movements he wished to evoke. By 4 years postimplant, GRASSP strength, prehension ability, and prehension performance improvements exceeded subscale SRDs
      • Kalsi-Ryan S.
      • Beaton D.
      • Ahn H.
      • et al.
      Responsiveness, sensitivity, and minimally detectable difference of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension, version 1.0.
      (see fig 5B), consistent with International Standards for the Neurological Classification of Spinal Cord levels of C8, C7-T1, and C5-7, respectively. Thus, BCI-FES improved the user’s neurologic level from C5-6 to C7-T1 (see fig 7D), a clinically important change conferring potential to live independently.

      Study limitations

      Findings are limited to 1 participant with a C5 American Spinal Injury Association Impairment Scale class A SCI, and may not generalize across tetraplegia: maximal benefit for grasp requires some residual ability to reach and not all end-users are successful with BCI or transcutaneous FES components.
      • Kreilinger A.
      • Kaiser V.
      • Rohm M.
      • Rupp R.
      • Müller-Putz G.R.
      BCI and FES training of a spinal cord injured end-user to control a neuroprosthesis.
      Clinical implications of standardized test performance should be interpreted cautiously, because most are not normed for SCI. In addition, clinical gains were demonstrated with test item-specific decoders which lack multifunctionality and translational practicality, though results appear replicable with multiclass decoders for the GRT
      • Colachis I.V. S.C.
      • Bockbrader M.A.
      • Zhang M.
      • et al.
      Dexterous control of seven functional hand movements using cortically-controlled transcutaneous muscle stimulation in a person with tetraplegia.
      (see fig 5D). Furthermore, implications for independence were extrapolated, rather than observed.
      Multiple design challenges were revealed by functional testing, including: suboptimal thenar stimulation; need for sensors to self-calibrate FES based on pronation state; barriers to portability and independent setup by end users; and requirements for daily decoder retraining. Future work should also optimize multiclass decoders to facilitate demonstrations of GAIN that can be evaluated in a single day.

      Conclusions

      Implanted BCI is a viable FES control mechanism for chronic tetraplegia, performing well >4 years after MEA implantation. With home use, BCI-FES-evoked grips are expected to confer greater independence for self-care. Next steps will address translational barriers: (1) developing accurate, faster, performance sustaining decoders and (2) developing wireless, portable, and wearable components.

      Suppliers

      • a.
        NeuroLife brain-computer interface functional electrical stimulation; Battelle.
      • b.
        Utah Array; Blackrock Microsystems.
      • c.
        Semmes-Weinstein monofilaments; Fabrication Enterprises.
      • d.
        Black Mechanical Pinch Gauge; B&L Engineering.
      • e.
        Electronic Handgrip Digital Dynamometer; Camry Scale Store.
      • f.
        MATLAB; The MathWorks, Inc.

      Acknowledgments

      We thank the donors to the Ohio State University Neurological Institute for making this work possible and the leadership of The Ohio State University and the Battelle Memorial Institute. We additionally thank Neil Austin, BA for his time and talents with image design, video production, and fabrication of standardized objects.

      Supplementary Data

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