Investigation on the Bidirectional Cortical Neuroprosthetic System

This proposed early feasibility, investigator-initiated study is led by Dr. Pablo A. Celnik,
M.D. at Johns Hopkins Medicine (JHM). The Bidirectional Cortical Neuroprosthetic System
(BiCNS) consists of modified versions of 510(k) cleared NeuroPort Electrode Array Systems
(Blackrock Microsystems, Inc., Salt Lake City, UT) as well as a neurostimulator module
(CereStim R96) for long term neural recording and intracortical microstimulation (ICMS) of
the brain. The BiCNS is termed bidirectional because it permits both the recording of
information from the brain for controlling an end effector device, as well as enabling
information regarding that end effector to be returned to the brain in the form of ICMS. "End
effector" in this sense is used to mean a physical or virtual device designed to interact
with its (physical or virtual) environment. Electrode arrays will be implanted in the brain
in pairs, with a pair comprising a recording array and a stimulating array. A total of six
NeuroPort arrays, consisting of three array pairs, will be implanted in each study
participant. Each pair will consist of an array implanted in primary motor cortex (M1) for
recording and an array implanted in primary sensory cortex (S1) for stimulation and/or
recording; both arrays in each pair will be connected to a single percutaneous pedestal as an
external interface. In each participant, two such array pairs will be implanted in the
hand/arm area of M1 and S1 in the dominant brain hemisphere (e.g., the left hemisphere for a
right-handed individual). A third pair will be implanted in the hand/arm area of M1 and S1 in
non-dominant hemisphere (e.g. right hemisphere for a right handed-individual). The recording
arrays implanted in M1 are the NeuroPort microelectrode arrays with platinum (Pt) tips
(K070272), whereas the ICMS arrays implanted in S1 are NeuroPort microelectrode arrays with
Sputtered Iridium-Oxide Film (SIROF) tips (K110010). The study has Investigational Device
Exemption (IDE) approval from FDA to implant these devices for 52 weeks (plus/minus 2 weeks).

Inclusion Criteria:

Participants must meet all inclusion criteria, verified by medical evaluation,
psychological evaluation, and review of medical history. Inclusion criteria include:

- Participants with C4-C6 tetraplegia from any etiology except neurodegenerative disease
(e.g. amyotrophic lateral sclerosis) or active cancer.

- Complete or incomplete spinal cord injury classified by the American Spinal Injury
Association (ASIA) as A or B or C if fewer than three muscle groups in the leg and
foot (as identified in the ASIA Impairment Scale) can be contracted

- Injury more than one year prior to enrollment

- Participant has a life expectancy of greater than 5 years

- Meeting surgical safety criteria, including surgical clearance by the participant's
primary healthcare provider, study physicians, and any necessary consultants

- Willingness and ability to provide informed consent

- Screened by rehabilitation psychologist with a result showing that the participant has
a stable psychosocial support system with caregiver capable of monitoring participant
throughout the study

- Ability and willingness to travel to up to fifty miles to study location up to three
days per week for the duration of the study

- Ability to understand and comply with study session instructions

- Pain well controlled without narcotic medications

- No other neurological, orthopedic conditions beyond the spinal cord injury

- Participant consents to the study and still wishes to participate at the time of the
study

Exclusion Criteria:

All interested participants will be reviewed for the presence of exclusion criteria by
medical evaluation, review of medical history, self (or assistant) report and evaluation by
a psychologist. Presence of any of the following criteria will exclude participants from
eligibility to participate. In addition, the medical team has the right to withdraw the
participant at any time if any of the exclusion criteria emerge and participants can
withdraw at any time for any reason. Withdrawal details are outlined below exclusion
criteria. Exclusion criteria include:

- Neurological conditions: Impaired receptive and/or expressive verbal communication
skills

- Presence of memory impairment on the Rey Auditory Verbal Learning Test

- Intellectual impairment: score of 26 or less on the Mini-Mental State Examination or
history of Intelligence Quotient < 80

- Chronic psychiatric illness, including psychosis and treatment-resistant major
depression, as indicated by a diagnosis of Axis I or Axis II on the Symptom
Checklist-90-Revised Test

- Ventilator dependent

- Implanted devices such as: pacemakers, cardiac defibrillators, spinal cord or vagal
nerve stimulators, deep brain stimulators, cochlear implants or any other implantable
device incompatible with MRI.

- History of drug or alcohol dependence in past 24 months

- Cerebral lesions affecting frontal and parietal lobes

- Medical conditions contraindicating surgery of a chronically implanted device (e.g.
osteomyelitis, diabetes, hepatitis, any autoimmune disease/disorder, epilepsy, skin
disorders causing excessive skin sloughing or poor wound healing, blood or cardiac
disorder requiring chronic anti-coagulation)

- Other chronic, unstable medical conditions that could make control unsuitable (such as
tremor or spasticity)

- Presence of pre-surgical findings in anatomical, functional, and/or vascular
neuroimaging that makes achieving implant locations within desired risk levels too
challenging (to be decided by neurological and neurosurgical team)

- Prior cranioplasty

- Inability to undergo MRI or anticipated need for an MRI during the study period

- Participants with active infections or unexplained fever

- Participants with other morbid conditions making the implantation of the recording
elements unsafe; not limited to: significant pulmonary, cardiovascular, or renal
impairments making the surgical procedure unsafe

- Pregnancy (confirmation through blood test)

- Nursing an infant, planning to become pregnant, or not using adequate birth control

- Corrected vision no worse than 20/30

- HIV or AIDS infection

- Existing scalp lesions or skin breakdown

- Chronic oral or intravenous use of steroids or immunosuppressive therapy

- Active cancer within the past year or requires chemotherapy

- Uncontrolled autonomic dysreflexia within the past 3 months

- An implanted ventricular shunt

- Suicidal ideation within the past 12 months

- Medications that affect neuroplasticity: neuroleptics, Benzodiazepines (BDZ),
Tricyclic Antidepressants (TCA).