Brain-Computer Interface Implant for Severe Communication Disability

Inclusion Criteria:

1. Age between 22-75 years.
2. Clinical diagnosis of chronic Locked-In Syndrome (LIS) certified by an independentboard-certified neurologist, defined here as impairments of voluntary motor controlthat are widespread and severe enough to prevent independent initiation andmaintenance of communication, spoken or otherwise, without the assistance of acaregiver. Diagnosis of LIS requires exclusion of cognitive impairments as a cause forimpaired communication (see Exclusion Criteria). For inclusion in this study,participants may have one of the following clinical variants of LIS: a. "Classic" Locked-In Syndrome, with the following signs documented on neurologicalexamination i. Quadriplegia ii. Bulbar palsy iii. Anarthria iv. Partial or completepreservation of vertical eye movements and upper eyelid movements, or b. "Incomplete"Locked-In Syndrome, with the aforementioned signs of "Classic" LIS, documented onneurological examination, except that voluntary movements other than upper eyelid andvertical eye movement may be preserved, albeit still severe enough to preventindependent initiation and maintenance of communication, without the assistance of acaregiver. Preserved voluntary movements may include: i. Horizontal eye movements ii.Facial movements iii. Movements of the extremities not sufficient to reliably operatea joystick or mouse
3. Clinical diagnosis of, and confirmatory/exclusionary testing consistent with, one ofthe following irreversible or progressive neurological disorders as the cause forchronic Locked-In Syndrome, as defined above: a. Permanent lesion of corticospinal and corticobulbar tracts in the ventral pons (basis pontis) due to ischemic stroke, hemorrhage, or trauma, based on the following:i. Documented history of acute ischemic or hemorrhagic brainstem stroke or traumaticbrainstem injury at onset of LIS ii. Ancillary testing including the following:
4. Brain MRI confirming a chronic lesion of the ventral pons, with no change on serialimages at least 1 month apart, consistent with findings on neurological examination,involving at least 50% of the cross-sectional area on both sides of the basis pontis on atleast one axial section 2. Absence of lesions on brain MRI that could contribute tocommunication impairment, including lesions of Broca's or Wernicke's areas, or sensorimotorcortex 3. EEG demonstrating posterior basic rhythm reactive to eye opening and closing iii.No clinical evidence of improving communication ability for at least 1 year prior torecruitment, confirming chronic LIS b. Diagnosis of Amyotrophic Lateral Sclerosis (ALS),certified by an independent board-certified neurologist with expertise in neuromusculardisorders, satisfying the following El Escorial World Federation of Neurology diagnosticcriteria for probable, laboratory supported, or definite ALS: i. Signs of lower motorneuron (LMN) degeneration by neurological examination (weakness, atrophy, andfasciculations), electrophysiological (electromyographic findings of denervation), orneuropathological determination (muscle biopsy) in bulbar and at least two of three spinalregions (cervical, thoracic, lumbosacral), or in all three spinal regions ii. Signs ofupper motor neuron (UMN) degeneration by clinical examination (spasticity, hyperreflexia,pseudobulbar affect, pathological reflexes) in bulbar and at least two of three spinalregions (cervical, thoracic, lumbosacral), or in all three spinal regions iii. Progressivespread of signs within a region or to other regions, together with the absence ofelectrophysiological or neuroimaging evidence of other disease processes that might explainclinical and electrophysiological signs of LMN and/or UMN degeneration (see below) iv.Confirmatory testing including:
5. Electrophysiological Studies
6. Electromyographic findings of denervation (reduced recruitment, large motor unitaction potentials, and fibrillation potentials) in clinically involved regions,including 3 of the following 4 muscle regions: bulbar, cervical, thoracic, andlumbosacral
7. Nerve conduction studies confirming absence of demyelination as an explanationfor aforementioned LMN signs
8. Neuroimaging, including brain and spine MRI, ruling out brain or spinal lesions (spinal cord or root compression) that could explain aforementioned LMN or UMN signs
9. Clinical laboratory examinations, determined by clinical judgment, to ascertainpossible ALS-related syndromes v. History, physical, and laboratory examinationsruling out alternative diagnoses as cause of aforementioned clinical syndrome,including monoclonal gammopathy, autoimmune motor system degeneration,hyperthyroidism, hyperparathyroidism, paraneoplastic syndrome, infections of thecentral nervous system, toxic-metabolic disorders, or spinal cord injury due totrauma, electric shock, radiation therapy, vasculitis, ischemia, hemorrhage, orspondylotic myelopathy vi. No clinical evidence for improving communication abilityfor at least 6 months, confirming chronic LIS
10. Reliable means of communicating with caregiver(s) before entering the study, forexample using vertical eye movements or eye blinking. Assessment of communicationcapabilities may be made by a physiatrist, a speech therapist, and/or an occupationaltherapist.
11. Residence within a reasonable driving distance from the JHU research team
12. Medically stable, including stable respiratory function, with or without artificialventilation (see Section 12.2.3, Section 12.2.6, and Section 12.2.11).
13. Surgical clearance by the participant's primary healthcare provider, study physicians,and any necessary consultants
14. Stable psychosocial support system with caregiver(s) capable of monitoring theparticipant throughout the study. Caregivers must be willing and able to be presentand provide routine care during all study activities except during hospitalization fordevice implantation.
15. Ability to understand and comply with study session instructions determined throughthe regular administration of simple study questionnaires.

Exclusion Criteria:

1. Strong and frequent muscle spasms not controlled by medication
2. Recent or remote history of brain tumor or tumor resection in any location
3. Cognitive impairments, according to neurological examination and neuropsychologicaltesting, that contribute to impaired communication, or that could interfere withinformed consent or participation in study activities
4. "Complete" Locked-In Syndrome without any voluntary movement, including vertical eyemovements or blinking, without any reliable means of communicating with caregivers orothers.
5. Known allergy to implanted materials
6. Contraindications to MRI prior to implantation (inability to lie flat in the scanner,MRI-incompatible metal objects in or attached to the body, claustrophobia)
7. Brain lesions that involve potential targets for implantation of BCI electrodes insensorimotor cortical areas
8. No clearly identifiable targets for implantation of BCI electrodes after twopre-implantation functional magnetic resonance imaging (fMRI) localizer scans. Targetsare identified as cortical areas of activation during attempted movements and/orspeech.
9. Severe psychiatric illness that could interfere with informed consent or participationin study activities
10. Persistent suicidal ideation within the past 12 months or prior suicide attempt
11. Medical conditions contraindicating surgery or chronic device implantation
12. Treatment with immunosuppressive drugs
13. Chronic or acute medical condition that is anticipated to require surgery,radiotherapy, chemotherapy, immunosuppression, and/or MRI
14. Pregnant (confirmation through blood test), planning to become pregnant (sexuallyactive without using effective birth control), or nursing an infant.
15. Visual impairment that would prevent use of computer monitor
16. Active cancer within the past year