Mechanisms of Open and Hidden Placebo in Stroke Recovery

Placebo effect leads to significant effects on brain excitability and connectivity, ultimately influencing clinical outcomes, including motor learning in stroke. This trial will provide critical mechanistic data to improve the understanding of placebo in stroke clinical trials, as to solve methodological and ethical dilemma in research designs, and to improve its clinical outcomes. It aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects. For this purpose, the investigators plan to recruit 56 chronic stroke participants, that will be randomized using blocked randomization in a 2:2:2:1 proportion to one of the following groups, respectively: 1) open placebo (OP) alone (16 subjects); 2) sham rTMS alone (16 subjects); 3) no intervention (16 subjects); or 4) active rTMS alone (8 subjects). All four groups will undergo 2 weeks of daily intervention visits (10 sessions).

Inclusion criteria

• Adults with hemiparesis due to chronic stroke
• Stroke duration of 6 months or more
• Fugl-Meyer scale upper extremity motor assessment score of > 11 and ≤ 56
• Pre-stroke disability (defined as a score of < 3 on the Modified Rankin Scale)
• Age 18 or older

Exclusion criteria

• Stroke of anterior cerebral artery territory with prefrontal lesion and stroke-related decreased EEG power in the prefrontal cortex
• Unable to understand instructions
• TMS contraindications: electronic hardware in close contact to the discharging coil such as cochlear implant, internal pulse generator or medical pump
• Concurrent unstable medical conditions
• A score of 24 or higher on the Hamilton Depression Rating Scale (HDRS)
• Joint or paretic extremity pain likely to interfere with assessments
• Pregnancy