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Identifying Personalized Brain States Predicting Residual Corticospinal Tract Output After Stroke

Recruiting
18 years of age
Both
Phase 1

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Overview

Transcranial magnetic stimulation (TMS) interventions could feasibly strengthen residual corticospinal tract (CST) connections and promote poststroke hand motor recovery. To maximize the effects of such interventions, they must be delivered during brain activity patterns during which TMS best activates the residual CST and enhances its neural transmission. This approach is termed brain state-dependent TMS. The investigators have recently developed a machine learning framework that identifies personalized brain activity patterns reflecting strong CST activation in neurotypical adults. In this study, the investigators will apply this framework to the poststroke brain for the first time. They will also evaluate relationships between this framework's ability to detect strong and weak CST activation states and measures of CST pathway integrity.

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, participants will complete eligibility screening and clinical assessment of upper extremity motor impairment, motor function, and disability using the Upper Extremity Fugl-Meyer Assessment, the Wolf Motor Function Test, and the Modified Rankin Scale. Participants will then be screened for the presence of residual CST connections from the lesioned hemisphere to the affected first dorsal interosseous muscle. Recording electrodes will be attached to this muscle in order to record TMS-evoked twitches in these muscles. During this 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 the affected first dorsal interosseous, that participant will be considered to have residual CST connections and will be eligible for the full study. If no muscle twitch is observed, the participant will not be eligible for the full study. Afterwards, recording electrodes will be removed and the participant will leave the laboratory.

On Day 2, participants will return to the laboratory. The investigators will confirm continued eligibility and place recording electrodes on the scalp using a swim-type cap. The investigators will also place recording electrodes on the affected first dorsal interosseous as well as the affected abductor pollicis brevis and extensor digitorum communis muscles. After identifying the scalp location at which TMS best elicits muscle twitches in the affected first dorsal interosseous muscle, the investigators will determine the lowest possible TMS intensity that such evokes muscle twitches at least half of the time. Then, the investigators will deliver 6 blocks of 100 single TMS pulses while participants rest quietly with their eyes open. Stimulation will be delivered at an intensity that is 20% greater than the lowest possible TMS intensity that evokes muscle twitches at least half the time. Afterwards, all electrodes will be removed, participation will be complete, and participants will leave the laboratory.

The investigators will recruit a total of 20 chronic stroke survivors for this study.

Eligibility

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

Study details

Stroke

NCT06365099

University of Texas at Austin

29 April 2024

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