Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity

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.

Inclusion criteria

• greater than 21 years old
• more than 6 months from first, unilateral index stroke
• unilateral paresis of the upper limb indexed as greater than or equal to 20% slowness in functional reaching compared to non-paretic limb
• UEFM less than or equal to 61 out of 66.

Exclusion criteria

• subjects who cannot perform reaching with shoulder
• severe cognitive deficit (less than or equal to 24 on Mini-Mental State examination.
• contraindication to TMS or MRI including: seizures, ongoing use of certain neuro- or psycho-active medications, implants, or pacemaker.
• currently receiving outpatient therapy.