Multifocal Theta-Burst Stimulation to Enhance Upper Limb Motor Recovery After Stroke (INSPIRE)

Summary

Stroke is one of the leading causes of long-term disability worldwide. Many individuals who survive a stroke continue to experience weakness and reduced control of one arm, even months or years after the event. These motor impairments significantly affect independence, daily activities, and quality of life. Despite rehabilitation efforts, recovery of upper limb function remains incomplete for many patients.

Motor recovery after stroke depends on the brain's ability to reorganize itself, a process known as neuroplasticity. Recent research suggests that motor learning and brain recovery are influenced not only by activity in the primary motor cortex (M1), but also by its functional connectivity with other brain regions, particularly the parietal cortex (PC). Strengthening communication between these regions may enhance motor recovery.

This study aims to investigate a novel, non-invasive brain stimulation approach called intermittent theta-burst stimulation (iTBS). Unlike traditional stimulation methods that target a single brain region, this study uses a multifocal stimulation protocol targeting both the primary motor cortex and the parietal cortex. The stimulation is combined with structured motor training using an interactive tablet-based rehabilitation device (REAtouch®Lite 2), designed to improve arm movement through goal-directed reaching tasks.

The study is a single-center, randomized, sham-controlled, triple-blind clinical trial with parallel groups. Thirty-six individuals with chronic stroke-related upper limb impairment will be randomly assigned to receive either active multifocal iTBS or sham (placebo) stimulation. Both groups will complete identical motor training sessions. In addition, ten healthy participants will complete the same motor training protocol (without brain stimulation) to provide reference data.

Participants will attend six visits over approximately 10 days. Assessments will include motor performance tests using the interactive tablet, a standardized clinical motor scale (Fugl-Meyer Assessment for Upper Extremity), and resting-state electroencephalography (EEG) to measure brain connectivity changes.

The primary outcome is improvement in motor performance between baseline and one week after the intervention. Secondary outcomes include short-term motor improvements, retention of learning, changes in movement quality, and changes in brain functional connectivity.

This study seeks to determine whether combining multifocal brain stimulation with targeted motor training can enhance motor learning and promote better recovery of arm function after stroke. If effective, this approach could contribute to the development of more precise, network-based neurorehabilitation strategies.

Conditions

• Chronic Stroke Patient
• Motor Impairment
• Neurorehabilitation
• Theta Burst Stimulation

Interventions

DEVICE

Active iTBS

Standard 600-pulse intermittent theta burst stimulation (iTBS) can increase corticomotor excitability. The iTBS will be delivered with an intensity of 70% of the individual resting motor threshold (RMT) over the ipsilesional primary motor cortex (M1) and superior parietal lobule using a Magstim Rapid2 stimulator equipped with a figure-of-eight coil. Stimulation will follow the standard iTBS pattern consisting of bursts of 3 pulses at 50 Hz repeated at 5 Hz.

DEVICE

Tablet-based upper limb training

REAtouch® Lite 2 interactive rehabilitation device will be used for upper limb motor training. REAtouch® Lite 2 is a touchscreen-based, task-oriented rehabilitation device designed to train upper limb movements through interactive exercises. The device targets (1) goal-directed reaching movements, (2) hand transport toward visual targets, (3) grasp and release coordination in a two-dimensional workspace, and (4) movement accuracy and speed. Training is supported by customizable visual feedback and task-specific interactive exercises integrated into the device.

DEVICE

Sham iTBS

Sham intermittent theta burst stimulation (iTBS) mimics the auditory and somatosensory characteristics of active stimulation without inducing a biologically effective cortical electric field. Sham stimulation will be delivered over the ipsilesional primary motor cortex (M1) and superior parietal lobule using a placebo coil identical in appearance, sound, and positioning to the active coil. Stimulation procedures, session duration, neuronavigation, and device setup are identical to the active iTBS condition to ensure participant and assessor blinding.

Sponsors & Collaborators

• University Hospital, Geneva

  collaborator OTHER

• School of Health Sciences Geneva

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-09-05

Primary Completion

2026-08-31

Completion

2026-08-31

Countries

• Switzerland

Study Locations