GoKawiilExperimental procedures
Study participants
This study includes data from eight participants who each gave informed consent before any experimental procedures. Participants T5, T11, T12, T15, T16 and T17 were enrolled in the BrainGate2 Neural Interface System clinical trial (ClinicalTrials.gov Identifier: NCT00912041, registered 3 June 2009), and represent all BrainGate2 participants who were enrolled at the time the data were collected and analysed. This pilot clinical trial was approved under an Investigational Device Exemption (IDE) by the US Food and Drug Administration (FDA; Investigational Device Exemption #G090003). Permission was also granted by the Stanford University Institutional Review Board (IRB; protocol #20804), the Mass General Brigham IRB (protocol #2009P000505), the University of California, Davis IRB (protocol #1843264), the Emory University IRB (protocol #00003070) and the Providence VA Healthcare IRB. Participants C1 and C2 were enrolled under a separate multi-site clinical trial (ClinicalTrials.gov Identifier: NCT01894802, registered 10 July 2013), which was also conducted under an IDE from the US FDA and approved by the IRBs at the University of Pittsburgh and the University of Chicago. C1 and C2 represent all participants enrolled under NCT01894802 who were available at the time of data collection to participate in this study, given competing demands on participant time for other research goals. All research was performed in accordance with relevant guidelines and regulations.
Recognizing that cortical mapping and neural activity recording in humans introduces distinctive ethical and philosophical considerations, ethics oversight was embedded from the outset. All risks (including surgical risks) arise solely from the parent safety and feasibility trials (and not the present study), each approved and monitored by local IRBs. Additional safeguards were provided by multiple and in part redundant additional layers of protection, including continuous oversight from local Clinical Oversight Committees including an independent medical monitor, a Data Safety and Monitoring Board, strict adherence to FDA guidance on conduct and safety under our IDE, clinical trial offices from the US National Institutes of Health (NIH), and engagement with the Neuroethics Working Group (NEWG) of the NIH BRAIN Initiative, to ensure adherence to the highest standards of safety and ethical rigour. All study procedures complied with the Declaration of Helsinki, the Belmont Report, CIOMS guidance and the NIH BRAIN Neuroethics Principles. In the parent clinical trials, a months-long, dialogue-driven consent process safeguards participant autonomy and adapts to evolving communication needs, protecting participant privacy. During this process, we explained that there would be no direct benefits from the implanted device. Within the trials, proactively embedded neuroethics expertise encourages continual reflection on risk–benefit balance, participant welfare and societal impact.
T5 is a right-handed man, 69 years of age at the time of this study, with tetraplegia due to cervical spinal cord injury (classified as C4 AIS-C), which occurred approximately 9 years before enrolment in the clinical trial. T5 has two 96-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in the hand-knob area of the left PCG. The hand-knob area was identified anatomically by preoperative MRI. T5 has full movement of the face and head and the ability to shrug his shoulders. Below the level of the spinal cord injury, T5 has very limited voluntary motion of the legs and arms.
T11 is a right-handed man, 38 years of age at the time of this study, with tetraplegia due to a cervical spinal cord injury (classified as C4 AIS-B), which occurred approximately 14 years before. T11 has two 96-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in the left dorsal PCG, targeting the hand-knob area as identified anatomically by preoperative MRI. T11 has full movement of the face and head with very limited voluntary motion of the arms.
T12 is a left-handed woman, 67 years of age at the time of this study, with slowly progressive bulbar-onset ALS. T12 was diagnosed at age 59 with an ALS-Functional Rating Scale score of 26 at the time of study enrolment. T12 has four 64-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in the left (language dominant, motor non-dominant) hemisphere, based on preoperative anatomical MRI, fMRI and cortical parcellation using the Human Connectome Project (HCP)32 multi-modal parcellation pipeline (see Extended Data Fig. 5 for cortical parcellation results). Two arrays were placed in the inferior frontal gyrus (not included in this study), and two arrays were placed in the ventral PCG, targeting area 6v; see Willett et al. for more details56. T12 remains functionally independent with 3–4 out of 5 strength (assessed using the Medical Research Council (MRC) scale) in all limbs, but is anarthric (able to vocalize, but unable to produce intelligible speech).
T15 is a left-handed man, 45 years of age at the time of this study, with ALS (ALS-Functional Rating Scale score of 23 at the time of study enrolment). T15 has four 64-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in the left (language dominant, motor non-dominant) PCG, based on preoperative anatomical MRI and HCP cortical parcellation (see Extended Data Fig. 5 for cortical parcellation results). One array was placed targeting area 55b, two arrays targeting area 6v and one array targeting area 4; see Card et al. for more details61. T15 has limited orofacial movement with the capacity for vocalization, but is unable to produce intelligible speech. T15 has very limited voluntary motion of the rest of the body.
T16 is a right-handed woman, 52 years of age at the time of this study, with tetraplegia and dysarthria due to a pontine stroke approximately 19 years before enrolment in the BrainGate2 clinical trial. T16 has four 64-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in her left PCG: two in the hand-knob area (targeting area 6d), one in the speech-related ventral premotor cortex (targeting ventral area 6v) and one in the middle PCG (targeting area 55b). Implant area targets were identified by the HCP multimodal cortical parcellation procedure (see Extended Data Fig. 5 for the cortical parcellation results). Examination of post-implant array locations indicated that the middle PCG array appears to be on the border between area PEF and 55b. T16 is able to speak slowly and quietly, but speech cadence is reduced due to poor diaphragm voluntary control. She has limited voluntary control of her upper extremities, with some shoulder motion and some slow and contractured wrist and finger movements. She has limited-to-no voluntary control of her lower extremities. Sensation for T16 is fully intact.
T17 is a right-handed man, 33 years of age with a history of rapidly progressive ALS. T17 has six 64-channel intracortical microelectrode arrays (Blackrock Microsystems; 1.5-mm electrode length) placed in the left hemisphere, based on preoperative anatomical MRI, task-based fMRI and cortical parcellation using the HCP multimodal parcellation pipeline. Two arrays were placed in the dorsal PCG (targeting area 6d), two arrays were placed in the ventral PCG (targeting area 6v) and two arrays were placed in area 55b. At the time of this study, T17 is quadriplegic, anarthric and ventilator dependent. His only remaining volitional motor control is over his extra-ocular movements.
... continue reading