Spine and Brain Stimulation for Movement Recovery After Cervical Spinal Cord Injury

To assess safety of spinal cord stimulation and paired spine and brain stimulation for movement recovery after spinal cord injury, the investigators will record the number of serious adverse events related to the study device.

To assess tolerability of spinal cord and brain stimulation for movement recovery after spinal cord injury, the investigators will record the number of instances a participant requests permanent cessation of stimulation.

Efficacy of stimulation is calculated as 1/threshold for provoking an motor evoked potentials. The threshold will be calculated from the spine-only and brain-recruitment curves. It is measured in units of 1/mA.

Selectivity of stimulation is calculated from the recruitment curves of the target muscle compared to non-targeted muscles. Selectivity is unitless.

Immediate effect of volitional motor activation combined with spinal stimulation will be defined as the area under the curve (AUC) of the motor evoked potential (MEP) generated by attempted volitional activation optimally integrated with SCS divided by the sum of MEPs generated by attempted volitional activation at 10%-20% maximum effort alone and SCS alone. The immediate effect is unitless.

Immediate pairing effect of spine and brain stimulation will be defined as the area under the curve (AUC) of the motor evoked potential (MEP) generated by optimally paired spine and brain stimulation divided by the sum of MEPs generated by SCS and TMS alone. Immediate pairing effect is unitless.

To analyze the effects of sustained pairing (facilitation of muscle responses to spine and/or brain stimulation following sustained pairing), the AUC of target muscle MEPs generated from spine-only and brain-only stimulation will be compared before sustained pairing, immediately after, and every 15 minutes for up to an hour. AUC of the MEP is measured in microVolt-seconds.

Magnitude of motor evoked potentials (MEPs) are calculated as the area under the curve of the MEP. The unit of the AUC of the MEP is microVolt-seconds. These values are then weighted across the area of responsive cortex. The final unit of measure is microVolt-seconds-cm^2.

The size of the responsive cortex will be measured as an area of responsive cortex. The unit of measure is cm^2.

Power of cortical field potentials will be calculated from EEG using the Hilbert transform. The units of power are micro-Volts-squared per Hz.

The COPM is a standard subjective assessment in occupational therapy. In this assessment, participants identify a list of daily tasks (including in areas of self-care, leisure, etc) that are important to them, rank the importance of that task to them (1-10, 10 being most important).

The COPM is a standard subjective assessment in occupational therapy. In this assessment, participants identify a list of daily tasks (including in areas of self-care, leisure, etc) that are important to them, rank their self-perception of their performance of that task (1-10, 10 being best performance).

The COPM is a standard subjective assessment in occupational therapy. In this assessment, participants identify a list of daily tasks (including in areas of self-care, leisure, etc) that are important to them, then rank their self-perception of their satisfaction with their performance of that task (1-10, 10 being highest satisfaction).

The Patient Global Impression of Change provides a broad assessment of the patient or clinician's response to a therapy. Using a 7-point Likert scale ranging from (1) very much improved to (7) very much worse, patients are asked to rate their overall status with respect to their spinal cord injury since starting the therapy in the trial. The investigators will record the numerical value of the participant's answer to the 7-point Likert scale questionnaire.

The Clinician Global Impression of Change provides a broad assessment by the clinician of the patient's response to a therapy. Using a 7-point Likert scale ranging from (1) very much improved to (7) very much worse, clinicians are asked to rate the patient's overall status with respect to their spinal cord injury since starting the therapy in the trial. The investigators will record the numerical value of the participant's answer to the 7-point Likert scale questionnaire.

The Off Target Effects Questionnaire asks the participant simple yes/no questions about the impact of cervical stimulation on a number of other functions outside of arm and hand function including spasticity, bowel/bladder function, sexual function, balance, and cognition). The questionnaire also invites the participant to describe any changes in each of these functions in free text form. Participants will record the yes/no and narrative answers to the questionnaire. The investigators will record and report the number of participants who complete the questionnaire.

The Patient-specific Daily Activity Assessment is an outcome measure that will be developed individually for each participant based on their specific goals for recovery. Despite the variability across participants in specific content of this outcome measure, each one will be a quantitative metric of patient performance (e.g. for a participant who wishes to improve their time required to transfer out of a wheelchair, this assessment may be "time required to transfer from wheelchair to chair"). Percentage change in this outcome measure will be reported for each participant for the sake of comparison across individuals.

Grasp force will be measured with a manual dynamometer and reported in Newtons.

Pinch force will be measured with a manual dynamometer and reported in Newtons.

In the box and block assessment, a subject is provided with one hundred and fifty 2.5 cm-sided blocks and asked to move as many of them as possible from one compartment (i.e. box) to another within 60 seconds. The box and block test provides an assessment of reach, grasp, transport, and release as well as fine motor control, coordination, and dexterity. The investigators will report the number of blocks moved successfully from one compartment to the other in 60 seconds.

International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Scale (ISNCSCI-UESS) includes an assessment of motor and sensory function used to assess the severity of spinal cord injury. Motor scores characterize motor power in the bilateral upper and lower extremities (10 myotomes on each side) using the Medical Research Council (MRC) scale from grade 0 (no contraction) to grade 5 (normal). The maximum ISNCSCI motor score is 100. For motor scores, a higher score indicates better function.

International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Scale (ISNCSCI-UESS) includes an assessment of motor and sensory function used to assess the severity of spinal cord injury. Sensory scores include an assessment of light touch and pinprick for each of 28 dermatome bilaterally. For both light touch and pinprick, each bilateral dermatome is scored as follows: 0 for absent sensation, 1 for altered, and 2 for normal. The maximum sensory score is 224. For sensory scores, a higher score indicates better function.

The ISNCSCI-UEMS is a subscore of the broader ISNCSCI assessment. The ISNCSCI-UEMS characterizes motor power in the bilateral upper extremities (5 myotomes on each side) using the Medical Research Council (MRC) scale from grade 0 (no contraction) to grade 5 (normal). The maximum ISNCSCI-UEMS score is 50. A higher score indicates better motor function.

Proprioceptive function with and without continuous stimulation will be assessed using the threshold to detect passive motion (TTDPM) assessment at the metacarpophalangeal joint of the index fingers and at the joint located in a dermatome that corresponds to the primary site of stimulation. This outcome measure will be reported as the angle of motion (degrees) required to detect passive motion.

The Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) is a validated assessment of sensorimotor function in patients with cervical spinal cord injury. The GRASSP (version 2) will be administered by an occupational therapist certified in GRASSP assessment. The GRASSP is reported as a series of subscores: strength (0-100, with 100 representing normal function).

The Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) is a validated assessment of sensorimotor function in patients with cervical spinal cord injury. The GRASSP (version 2) will be administered by an occupational therapist certified in GRASSP assessment. The GRASSP is reported as a series of subscores: sensation (0-24, with 24 representing normal sensation).

The Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) is a validated assessment of sensorimotor function in patients with cervical spinal cord injury. The GRASSP (version 2) will be administered by an occupational therapist certified in GRASSP assessment. The GRASSP is reported as a series of subscores: prehension ability (0-24, with 24 representing normal function).

The Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) is a validated assessment of sensorimotor function in patients with cervical spinal cord injury. The GRASSP (version 2) will be administered by an occupational therapist certified in GRASSP assessment. The GRASSP is reported as a series of subscores: prehension performance (0-40, with 40 representing normal prehension performance).

The Capabilities of Upper Extremity Test (CUE-T) is a validated assessment of sensorimotor function in patients with cervical spinal cord injury. The CUE-T will be administered by an occupational therapist certified in CUE-T assessment. The maximum CUE-T score is 124, with a higher score representing greater upper extremity function and a lower score representing greater limitations in upper extremity function.

The investigators will record the portion of study visits completed and report this value as a percentage of total planned visits.