Optimization of Time Parameters of Priming iTBS for Poststroke Motor Rehabilitation

Delivering Intermittent theta burst stimulation (iTBS) primed with continuous theta burst stimulation (cTBS) to the primary motor cortex (M1) may enhance the facilitatory effect of iTBS on the stimulated M1 through metaplasticity. Previous studies have verified the effectiveness of priming iTBS on improving motor rehabilitation in patients with stroke. However, the optimal time interval between cTBS and iTBS remains unknown. The aim of this clinical trial is to identify the effect of different time intervals between cTBS and iTBS, followed with a standard robot-assisted training (RAT) for sensorimotor rehabilitation in patients with chronic stroke. Using electroencephalography (EEG) to explore potential sensorimotor neuroplasticity. A three-arm randomized controlled trial (RCT) will be performed with an estimated total of 30 patients with chronic stroke. All participants will be randomly allocated to receive 10-session intervention of different TBS protocols (i.e., cTBS-3min interval-iTBS, cTBS-10min interval-iTBS and cTBS-20min interval-iTBS), delivered for 2-4 sessions per week, lasting for 3-4 weeks. All participants will receive a 20-minute standard RAT after each stimulation session. Primary outcome will be Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE). Secondary outcomes will be Action Research Arm Test (ARAT), kinematic outcomes generated during RAT as well as EEG.

Inclusion criteria

• diagnosis of hemorrhagic or ischemic stroke using computed tomography (CT) or magnetic resonance imaging (MRI).
• the first-ever stroke with unilateral hemiplegia.
• 18-75 years old.
• chronic stroke ( ≥ 6 months).
• residual hemiparetic upper limb functional level in the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) ≥ 2.
• can understand and read Chinese.
• signed informed consent.

Exclusion criteria

• diagnosis of any clinically significant or unstable medical disorder.
• any contraindications to TMS based on the TMS safety guidelines (Rossi, Hallett, Rossini, & Pascual-Leone, 2011).
• inability to follow treatment instructions due to severe cognitive (using the Hong Kong version of the Montreal Cognitive Assessment (MoCA-HK) < 22/30) and communication deficiency.
• extreme spasticity over the hemiparetic upper limb (Modified Ashworth Score>2) or severe pain that hindered movement.
• a history of neurological or psychiatric disease excluding stroke, or current use of psychoactive medication (sedatives, antipsychotics, antidepressants, etc.).