An Early Feasibility Study of a Robotically Implanted Brain-Computer Interface for Neural Control of External Devices in Spinal Cord Injury, Amyotrophic Lateral Sclerosis, and Chronic Ischemic Stroke (PRIME2)

Inclusion Criteria:

● A diagnosis of: (A) Spinal cord injury (SCI) for at least 12 months with a muscle power grade of ≤ 3/5 in all muscles of the arms and hands principally innervated by C6-T1 nerve roots at the time of screening AND the Investigator confirms that bilateral upper-limb weakness prevents reliable, independent use of standard digital-access devices. OR (B) Amyotrophic lateral sclerosis (ALS) with

1. Muscle power grade ≤4/5 at C5 in both arms; AND

2. Muscle power grade ≤3/5 in all muscles of both arms and hands principally innervated by C6-T1 nerve roots, except that strength above 3/5 in individual C6-T1 muscle groups is permitted if both of the following are met:

   1. ALSFRS-R Item 4 (Handwriting) score ≤2; AND

   2. The Investigator confirms that bilateral upper-limb weakness prevents reliable, independent use of standard digital-access devices. OR (C) Chronic ischemic stroke, with the event occurring at least 12 months before screening, resulting in residual hemiparesis of the pre-morbid dominant upper extremity, with a completion time on the Nine-Hole Peg Test (9-HPT), per standardized protocol, that exceeds 3 standard deviations above the respective established age- and hand-specific normative mean completion times for both hands.

      • Age ≥ 18 years.
      • Stable medical, physical, and psychological condition as considered by the investigators.
      • Ability to communicate verbally or with the use of a computer or communication aid.
      • Willingness to comply with all study procedures and availability for the duration of the study.
      • If the participant requires daily continuous support from a personal caregiver, the presence of a caregiver throughout the study is mandatory.
      • Willingness and ability of a caregiver to monitor the participant for medical complications and behavioral changes, and respond to alerts regarding device function.
      • Presence of or willingness to acquire reliable internet.*
      • Willing and able to provide informed consent. *Sponsor will reimburse participants for the cost of reasonable high-speed internet as needed during participation in the study

      Exclusion Criteria:

      • ● History of poorly controlled seizures or epilepsy.

        • History of poorly controlled autonomic dysreflexia.

        • Morbid obesity (Body Mass Index > 40).

        • Current deep venous thrombosis or pulmonary embolism.

        • Diagnosis of acute myocardial infarction or cardiac arrest within the last 12 months.

        • Requires magnetic resonance imaging (MRI) for any ongoing medical conditions within the next year

        • Any implanted, or previously explanted, intracranial device, except where:

          1. the device is a marketed intracranial stent or other endovascular implant that is labeled MR Conditional, and the Neurosurgeon confirms during preoperative surgical planning that its location is compatible with the planned craniectomy and thread insertion trajectory; or
          2. the explanted device was not previously implanted in the same hemisphere as the hemisphere of interest for the implantation of the N1 Implant

        • Any active implanted devices including but not limited to cardiac pacemakers, cardiac defibrillators, diaphragmatic pacemakers, peripheral or central nerve stimulators*.

        • Currently receiving or may receive transcranial magnetic stimulation therapy, diathermy, electroconvulsive therapy, or transcranial ultrasound within the next year.

        • Pregnant or of child-bearing potential and not using or planning to use contraception during the period of study participation.

        • Presence of mild or greater cognitive impairment per neuropsychological assessments.

        • Psychotic illness or chronic psychiatric disorder, or major depression if untreated (Diagnosis of Axis I or Axis II).

        • Contraindication for preoperative MRI.

        • Preoperative brain MRI demonstrating hemorrhage, tumor, distorted or adverse anatomy.

        • History of gadolinium contrast allergy.

        • Any type of destruction and/or damage to the primary motor cortex region as determined by MRI.

        • Are blind.

        • Ongoing use of anticoagulant or antiplatelet medication that cannot be suspended perioperatively.

        • Receiving invasive mechanical ventilation without a tracheostomy that has been in place for at least 3 months, or without stable ventilator settings for at least 1 month prior to enrollment.

        • May require invasive mechanical ventilation within the next year, and does not intend to undergo tracheostomy or placement of a percutaneous endoscopic gastrostomy (PEG) tube if invasive ventilation becomes necessary.

        • Currently participating in an investigational study (device and/or pharmaceutical) within 30 days prior to entering this study, or such investigational treatment planned during the 24 months following enrollment, unless approved by Sponsor.

        • Anatomical or functional characteristics of the skull, meninges, and brain incompatible with the surgical approach and N1 Implant, as assessed by

      MRI or CT, specifically:

      • Outer skull-to-pia distance < 5.4 mm over region of interest.
      • Scalp thickness < 3 or > 20 mm over region of interest.
      • Imaging evidence of stroke in the planned implant cortical target (for stroke patient population).
      • Any condition, including serious co-morbidities such as major organ failure, which in the opinion of the Investigator, would compromise the participant's ability to safely participate in the study or undergo the implantation procedure. *Intrathecal baclofen pumps are exempt from this criterion.