Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity

Recruiting

Phase Early 1 Results N/A

Trial Description

The investigators ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Several groups including the investigators have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. The investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.

Detailed Description

AIMS: The ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Even though stimulation is one of the most well studied methods to augment plasticity and boost recovery, it is still not approved for outpatient therapy. Benefits of stimulation are weak and variable especially in patients who suffer from greater damage and disability. The key limitation of the standard approach is its generic assumptions about plasticity. The current standard assumes that ipsilesional primary motor cortex (iM1) can impact recovery for patients in all ranges of severity, and intact, contralesional cortices always compete with iM1 to inhibit recovery. But, these long-standing assumptions fail to consider that iM1 or its pathways are damaged in a majority (58-83%) of patients. As such, the potential of iM1 would be weak and variable, and patients will have little option but to rely on plasticity of intact, contralesional cortices that are more likely to survive. Of all surviving cortices, contralesional dorsal premotor cortex (cPMd) expresses plasticity most consistently. cPMd is activated in movement of the paretic limb when activating iM1 is less likely. cPMd even reduces its competition with iM1 and offers its ipsilateral pathways instead to support recovery of the proximal paretic limb when pathways from iM1 are largely damaged.
Several groups including the investigator have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. These theoretical claims, however, remain untested since several gaps exist. For instance, what is the cut-off level of severity that stratifies those who respond to stimulation of iM1 from those who respond to stimulation of cPMd? Even then, are substrates for 'personalized' stimulation same as the substrates that express plasticity in recovery, i.e. if patients benefit from stimulation of cPMd, do they express contralesional plasticity in recovery? Here, the investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.

Conditions

Interventions

  • RTMS Contralesional M1 Device
    Intervention Desc: 1Hz Contalesional M1 repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 90% AMT
    ARM 1: Kind: Experimental
    Label: rTMS Contralesional M1 Inhibition
  • RTMS Contralesional PMC Device
    Intervention Desc: 5Hz Contralesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
    ARM 1: Kind: Experimental
    Label: rTMS Contralesional PMC facilitation
  • RTMS Ipsilesional PMC Device
    Intervention Desc: 5HZ Ipsilesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
    ARM 1: Kind: Experimental
    Label: rTMS Ipsilesional PMC facilitation
  • RTMS sham at Ipsilesional M1 Device
    Intervention Desc: 1Hz Ipsilesional M1 sham repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 50% MSO)
    ARM 1: Kind: Experimental
    Label: rTMS Sham at Ipsilesional M1

Outcomes

Type Measure Time Frame Safety Issue
Primary Aim 1: Change in time (seconds) to perform functional reaching Change in functional reaching from baseline to post rTMS, assessed for approximately 4-6 hours.
Secondary Aim 2:Change in plasticity evoked with rTMS. Change in neurophysiology from baseline to post rTMS assessed for approximately 4-6 hours.

Sponsors