Real-time Personalized Brain State-dependent TMS After Stroke

Transcranial magnetic stimulation (TMS) interventions could feasibly strengthen residual corticospinal tract (CST) connections and enhance recovery of paretic hand function after stroke. This project will test whether personalized brain state-dependent TMS can activate the residual corticospinal tract better than standard TMS, and evaluate the relationship between this activation and hand motor impairment.

Transcranial magnetic stimulation (TMS) interventions could feasibly strengthen residual corticospinal connections and enhance recovery of paretic hand function after stroke. To maximize the therapeutic effects of such interventions, they must be delivered during poststroke brain activity patterns during which TMS best activates the residual corticospinal tract and enhances neural transmission within it (i.e., brain state-dependent TMS). In this study, the investigators will test the feasibility of real-time, personalized brain state-dependent TMS in chronic stroke survivors. The investigators will also quantify the relationship between personalized poststroke brain state-dependent activation of the residual corticospinal tract and hand motor impairment; results will inform future clinical trial inclusion criteria.

Participants will visit the laboratory for two days of testing that are separated by at least one night of sleep. On Day 1, participants will provide their informed consent. The MacArthur Competence Assessment Tool and the Frenchay Aphasia Screening Test will be used to evaluate consent capacity and confirm the presence of expressive aphasia as needed. Afterwards, the investigators will complete eligibility screening and clinical assessment of upper extremity motor impairment using the Upper Extremity Fugl-Meyer Assessment, measurements of grip and pinch strength, and a dexterity measurement that requires participants to place small pegs into round holes using their affected hand. Participants will then be screened for the presence of residual corticospinal connections from the lesioned hemisphere to an affected hand muscle at rest. Recording electrodes will be attached to the affected first dorsal interosseous, abductor pollicis brevis, opponens pollicis, and extensor digitorum communis muscles in order to record TMS-evoked twitches in these muscles. During this screening procedure, single-pulse TMS will be applied to each point of a 1 cm resolution grid covering primary and secondary motor areas of the lesioned hemisphere at maximum stimulator output. If TMS reliably elicits a muscle twitch in any of these muscles, that participant will be considered to have residual corticospinal connections and will be eligible for the full study. If no muscle twitch can be elicited in any of these muscles, that participant will not be eligible for the full study. Afterwards, all recording electrodes will be removed and the participant will leave the laboratory.

On Day 2, participants will return to the laboratory. The investigators will place recording electrodes on the scalp using a swim-type cap. The investigators will also place recording electrodes on the affected hand muscle in which a twitch was most reliably observed during Day 1 as well as four additional muscles of the affected hand and wrist. After determining the location at which TMS best elicits muscle twitches, the investigators will determine the lowest possible intensity at which TMS elicits muscle twitches at least half of the time. Then, they will deliver 6 blocks of 100 single TMS pulses while the participant rests quietly with their eyes open; stimulation will be delivered at an intensity that is 20% greater than the lowest possible intensity at which TMS elicits muscle twitches at least half of the time. Afterwards, the investigators will use the muscle and brain activity recordings acquired during these 6 blocks to build a personalized mathematical model that identifies which patterns of brain activity correspond to the largest TMS-evoked muscle twitches. The investigators will then use this model to detect the occurrence of these brain activity patterns in real-time; when these patterns are detected, single TMS pulses will be delivered. For comparison, the investigators will also deliver single TMS pulses during random brain activity patterns. Afterwards, all recording electrodes will be removed, participation will be complete, and the participant will leave the laboratory.

The investigators will recruit a total of 37 chronic stroke survivors for this study. The number of participants needed for this study was determined from their preliminary studies and previous studies that explored the relationship between variability in corticospinal tract activation (a necessary component of building robust personalized classifiers) and corticospinal tract integrity (a correlate of motor impairment and recovery potential).

Eligibility Criteria:
Inclusion Criteria:

* History of stroke \>6 months ago
* Presence of residual upper extremity hemiparesis
* Willingness to participate
* Ability to provide informed consent
* Upper extremity Fugl-Meyer score \< 66
* Mini Mental State Exam score \> 24
* Discernable and reliable motor-evoked potential (MEP) following single-pulse transcranial magnetic stimulation to the lesioned hemisphere

Exclusion Criteria:

* History of neurological disease and/or neurological injury other than stroke
* Presence of contraindications to transcranial magnetic stimulation (TMS) or peripheral nerve stimulation (PNS) including: cardiac pacemaker, cochlear implant, cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine epidural stimulator, and/or ventriculoperitoneal shunt, ferromagnetic metallic implants above the level of the seventh cervical vertebrae, seizure in the last 12 months while taking anti-epilepsy medication, history of adverse reactions to TMS or PNS
* current, suspected, or planned pregnancy
* recent changes (within the last month) to medication use
* Upper extremity Fugl-Meyer score = 66
* Mini Mental State Exam score \<= 24
* No discernible or reliable MEP elicited following single-pulse TMS to the lesioned hemisphere