DExterous Hand Control Through Fascicular Targeting (DEFT) - (Human Subjects)

Study Procedures:

Subjects will be consented during a pre-operative visit in the Plastic Surgery Clinic and
screened for participation.

Subject pre-operative task training

The study team will train subjects to complete the standardized task-based assessment
protocol using the patient's existing myoelectric hand prosthesis. These tests will include:

- Disabilities of the Arm, Shoulder and Hand

- Orthotics and Prosthetics User Survey Upper Extremity Functional Status

- Trinity Amputation Prosthesis Experience Scale

- Southampton Hand Assessment Procedure

- Box and Blocks

Screening history and physical Potential human subjects will receive a full medical
assessment by the PI. The screening interview will focus on details of the patient's upper
extremity condition and comprehensive details of the patient's overall health status. The
screening examination will include general examination of the subject.

Pre-operative imaging and diagnostic studies MRI, x-ray, EMG/Nerve conduction studies (NCS) -
Each subject who passes the screening H&P will receive the following for their residual limb:
magnetic resonance neurogram (MRN), plain x-rays, and EMG/nerve conduction studies. Other
studies will be performed in accordance with the UT (University of Texas) Southwestern
pre-operative testing protocol, and will depend on the age/gender/medical history of the
subject.

MR neurogram will provide information regarding the location and health of amputated
peripheral nerve stumps in the residual limb.

Plain x-rays will allow assessment of the bony anatomy of the amputation stump, and
suitability for nerve/muscle implants.

Electromyogram/Nerve conduction studies will include motor and sensory nerve conduction of
the median and ulnar nerves, and needle exam (voluntary activation EMG) of the residual
forearm and hand muscles.

Other studies Based on UT Southwestern pre-operative testing protocol, other studies may be
required prior to surgery. CBC (complete blood count) with type and screen will be performed
, and HCG (pregnancy test) in females age 15-50. EKG will be performed in males > 40, and
females > 50. Chest x-ray will be performed in subjects with a prior history of smoking or
lung/chest injury. If surgery is scheduled for more than 90 days after this testing is
completed, another set of tests will be needed.

Patient treatment, week of surgery Subjects who have passed all screening measures and who
have completed the consent process will be seen for a routine pre-operative H&P up to 30 days
before surgery.

Prophylaxis for Methicillin-Resistant Staph Aureus (MRSA) The subject will receive mupirocin
ointment to place intranasal, to both nares, twice a day for 5 days prior to surgery.

Implantation surgery Surgery will be performed by Jonathan Cheng, MD, at Clements University
Hospital at UT Southwestern Medical Center in Dallas. General anesthesia will be provided by
the Department of Anesthesiology at UT Southwestern. Procedures will require placement of a
standard catheter for intravenous (IV) access and a urethral (Foley) catheter. Long-lasting
neuromuscular blockade will be avoided in the anesthetic regimen. Preoperative IV antibiotic
will be administered for infection prophylaxis. One 4-6 inch-long incision will be needed for
implantation of nerve (volar forearm) electrodes. In hand-level amputees, two 0.5-1.0cm long
dorsal hand incisions will be needed for placement of bipolar fine wire muscle electrodes
into the intrinsic hand muscles. In hand-level and forearm-level amputees, two 6-10cm long
forearm incisions will be used to place bipolar fine wire muscle electrodes into the residual
forearm muscles. The implant lead wires will be tunneled under the skin for a distance, and
then placed through the skin. In the forearm-level amputees the wire exit sites may be below
or above the elbow depending on the subject's prosthesis configuration. Small counter
incisions may be needed along the paths of the lead wires to facilitate placement. The point
where the lead wires exit the skin will be dressed with a sterile/antimicrobial dressing used
commonly for indwelling vascular access devices (VAD). The implants will be surgically placed
under tourniquet control in order to limit bleeding. Following implantation, incisions will
be infiltrated with bupivacaine for postoperative analgesia and closed with sutures and skin
glue. The hand and forearm will be placed in a protective splint for the first 3 weeks after
surgery.

Motor and somatosensory evoked potentials Nerve dissection will be performed under the
operating microscope or surgical loupes. The motor and sensory fascicular groups of the ulnar
and median nerves will be identified microsurgically as needed for the planned electrode
implantations (ulnar only, or ulnar+median) based on their predictable intraneural
topography.

Nerve electrode implantation The ulnar and median nerves will be accessed as needed (ulnar
only, or ulnar+median) through a volar forearm incision (4-6 inches long). One FAST-LIFE
array will be inserted within each of the main motor and sensory fascicular groups of the
ulnar nerve. The median nerve will be microdissected to identify the thenar motor fascicle
and the 3-4 sensory fascicles that terminate in the hand. One FAST-LIFE array will be
inserted within the motor and one or more sensory fascicles of the median nerve.

Muscle electrode implantation The hand intrinsic muscles (hand-level amputations) will be
accessed through small dorsal hand incisions (0.5-1cm long). Up to 4 bipolar fine wire
electrodes will be placed into the intrinsic muscles and tunneled to a common exit point at
the forearm skin.

The forearm muscles (hand-level and forearm-level amputations) will be accessed through two
6-10cm long forearm incisions. Up to 15 bipolar fine wire electrodes will be placed into the
residual forearm muscles and tunneled to a common exit point at the forearm skin. In the
forearm-level amputees the wire exit sites may be below or above the elbow depending on the
subject's prosthesis configuration.

Post-operative care in the hospital Immediately following surgery, subjects will receive
routine postoperative care. Overnight hospital stay for up to 2 nights will be optional
depending on the level of pain control in the PACU (Post-Anesthesia Care Unit) following
surgery. Analgesia will consist of acetaminophen and parenteral and oral narcotics, and
pregabalin or gabapentin and/or nortriptyline as needed for neuropathic pain. The operated
hand will be elevated at all times. The Foley catheter will be removed as soon as possible
following surgery. The IV fluids will be capped as soon as the patient demonstrates adequate
oral intake and normal fluid balance. The patient will wear sequential devices on the legs
and will walk on a scheduled basis for venous thromboembolism prophylaxis. Prophylactic
antibiotics will be administered during the hospital stay up to 24 hours after surgery.
Discharge criteria will be met when the patient demonstrates pain controlled adequately by
oral analgesics, independent ambulation, and tolerance of oral intake.

X-rays After implantation surgery, plain film x-rays will be obtained of the subject's
forearm in order to establish a baseline for the position of implanted electrodes and leads.

Outpatient care The subject will be seen in clinic on a weekly basis following implantation
surgery for 3 weeks and then as needed until explantation if there is evidence of local
redness, inflammation, serous drainage or skin irritation near the incisions.

Percutaneous leads The electrode leads will be inspected at each weekly visit, and the
dressings will be changed using sterile technique based on VAD protocols. If any dressing
ever becomes wet, soiled, or leaking, the subject will be instructed to change it. After the
first 3 clinic visits wire site dressing changes will be performed by research personnel who
have been trained by the principal investigator.

Experimental data collection in implanted subjects (2 - 180 +/- 30 days)

Timing: Human physiology experiments will begin after 2 days following implantation, to allow
tissue-electrode interactions to stabilize.

Location: Most of the human physiology experiments will take place at UT Southwestern. Some
participants may be asked to travel to the University of Minnesota Bioengineering Lab up to 3
times during the study participation period for the human physiology experiments.

Motor assessment: We will ask subjects to attempt to perform hand movements and positions.
The movement trials will consist of simultaneous volitional movements and positioning of both
the uninjured/sound limb and the injured/amputated "phantom" limb. We will record nerve and
muscle electrode activity during all of the movement trials.

Sensory assessment: We will also perform sensory detection and discrimination trials. Here,
the subject will be asked to report if he/she detects any sensation during microstimulation
via LIFE electrodes. If they do have a sensory perception, they will be asked to describe the
quality and strength of the perception, e.g. location, touch, vibration, temperature.
Subjects may also be asked to fill out standardized sensory/pain assessments during
microstimulation and after microstimulation is turned off. Other stimulation trials that may
be done will include single or multiple electrode stimulation to see if subjects can perceive
multiple sensory percepts simultaneously.

Sensory-motor integration: After determining the subject's sensory detection and
discrimination parameters, we will ask them to repeat the standardized assessments listed in
(4.1.3.2) using the existing myoelectric hand prosthesis.

Explantation surgery - Will be planned for 180 +/- 30 days after implantation. If
explantation surgery is scheduled for less than 90 days from the implantation pre-operative
testing then the pre-operative testing requirement will be waived. Surgery will be performed
by the PI. General anesthesia will be provided by the Department of Anesthesiology at UT
Southwestern. Procedures are estimated to last 2-3 hours, and will require placement of a
standard catheter for IV access. Preoperative IV antibiotic will be administered for
infection prophylaxis. The previous incisions used to place nerve and muscle electrodes will
be redeveloped for access to the implanted systems. The implants will be surgically removed
under tourniquet control in order to limit bleeding. Following explantation, incisions will
be infiltrated with bupivacaine for postoperative analgesia and closed with sutures and skin
glue. Postoperative analgesia will be performed as listed above. Jonathan Cheng, MD, will see
the subject in clinic once the week following surgery and then as needed. The dressing will
be removed and replaced at the first postoperative visit. The incisions will be visually
inspected at each visit. The subject will be instructed to contact the research team by phone
on week 2 and week 3 to determine if they need to come to the clinic.

Post-participation interview - Subjects may be asked to participate in a recorded video
interview conducted by the research team to record their subjective experiences with the
study.

Criteria for Inclusion of Subjects:

Hand and forearm amputees:

1. Male or female, age 18 and older, of any race or ethnicity

2. Able and willing to sign Consent

3. Able and willing to participate in all study activities including implantation,
testing and explantation of the study device.

4. Able to communicate effectively in English without an interpreter

After preliminary screening subjects will be assessed for the following inclusion criteria:

1. Patient has an existing myoelectric hand prosthesis and demonstrates proficiency
during daily use

2. Overall and phantom pain are well-controlled and not incapacitating

Criteria for Exclusion of Subjects:

1. If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher
level than anticipated based on the appearance of the physical amputation stump, the
subject may be excluded from the study due to adverse neuromuscular anatomy which
would preclude use of the proposed experimental electrode implants. The radiographs
will be used to confirm suitability of the amputation stump configuration. If the bony
anatomy of the amputation stump is found to be unsuitable, the patient may be excluded
from the study.

2. Subjects who have a history of cardiac arrhythmia will be excluded from the study.