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

The primary outcome is the change in the Global Motor Performance Index score between baseline (Day 0) and post-intervention follow-up (Day 10).

The Global Motor Performance Index is a composite performance score derived from a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index integrates movement accuracy (number of errors) and movement time into a single continuous score.

The score ranges from -100 to +100, with lower (more negative) values indicating better motor performance and improvement over time, and higher values indicating worse performance.

This outcome evaluates short-term motor learning effects by measuring the change in the Short-Term Motor Performance Index score between Baseline (Day 0) and immediate post-intervention (Day 3).

The Short-Term Motor Performance Index is a composite continuous score derived from a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index integrates movement accuracy (number of errors) and movement time into a single performance metric.

The score ranges from -100 (best motor performance) to +100 (worst motor performance). Lower (more negative) scores indicate better motor performance, and a decrease in the score over time reflects motor improvement.

This outcome assesses motor memory consolidation by measuring the change in the Offline Motor Consolidation Index score between immediate post-intervention (Day 3) and follow-up (Day 10).

The Offline Motor Consolidation Index is a continuous composite score derived from the same standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device. The index reflects performance retention or change after completion of the stimulation and training sessions.

The score ranges from -100 (best motor performance) to +100 (worst motor performance). Lower (more negative) scores indicate better motor performance. A decrease in the score between Day 3 and Day 10 reflects performance improvement, whereas stable scores indicate retention and an increase indicates performance deterioration.

Upper limb motor impairment will be assessed using the Fugl-Meyer Assessment - Upper Extremity (FMA-UE), a validated clinical scale measuring motor function of the upper limb after stroke.

The FMA-UE total score ranges from 0 to 66, where 0 indicates severe motor impairment and 66 indicates normal motor function. Higher scores represent better motor function.

Change in FMA-UE scores over time will be analyzed to evaluate clinical motor recovery.

The mean number of reaching errors will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

An error is defined as failure to reach or stabilize within the predefined target area during a trial.

The outcome is a continuous variable representing the average number of errors per session. The minimum possible value is 0 (no errors), with no predefined upper limit. Higher values indicate worse motor performance.

Changes in the mean number of errors over time will be analyzed.

Mean movement speed will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

Movement speed (cm/s) is calculated as the displacement divided by the time between movement initiation (defined as >5 mm displacement from the starting position) and movement stabilization within the target area.

This is a continuous variable with a minimum possible value of 0 cm/s and no predefined upper limit. Higher values indicate faster movement performance.

Changes in mean movement speed over time will be analyzed.

Mean movement smoothness will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

Movement smoothness is quantified using a jerk-based metric (third derivative of position with respect to time), expressed in centimeters per second cubed (cm/s³). The metric reflects the magnitude of trajectory corrections during movement execution.

This is a continuous variable with a minimum possible value of 0 cm/s³ and no predefined upper limit. Lower values indicate smoother movements and better motor control, whereas higher values indicate greater movement irregularity.

Changes in mean movement smoothness over time will be analyzed.

Mean maximum lateral deviation will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

Maximum lateral deviation (cm) is defined as the greatest perpendicular distance between the participant's actual movement trajectory and the optimal straight-line trajectory from the start position to the target.

This is a continuous variable with a minimum possible value of 0 cm (perfectly straight trajectory) and no predefined upper limit. Lower values indicate better trajectory control and movement accuracy, whereas higher values indicate greater deviation from the optimal path.

Changes in mean maximum lateral deviation over time will be analyzed.

Mean directional error at 100 milliseconds will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

Directional error (degrees) is defined as the angular deviation between the initial movement direction and the straight-line direction to the target, calculated 100 milliseconds after movement onset. Movement onset is defined as displacement exceeding 5 mm from the starting position.

This is a continuous variable expressed in degrees, with a minimum possible value of 0° (perfect alignment with the target direction) and no predefined upper limit. Lower values indicate greater motor planning accuracy, whereas higher values indicate greater deviation from the intended direction.

Changes in mean directional error over time will be analyzed.

Mean reaction time will be measured during a standardized two-dimensional reaching task performed using the REAtouch® Lite 2 interactive rehabilitation device.

Reaction time (seconds) is defined as the time elapsed between target appearance and movement initiation in the correct direction, defined as an initial movement trajectory within ≤15° of the straight-line direction to the target. Movement initiation is defined as displacement exceeding 5 mm from the starting position.

This is a continuous variable expressed in seconds, with a minimum possible value of 0 seconds and no predefined upper limit. Lower values indicate faster response initiation and better motor preparation, whereas higher values indicate slower response initiation.

Changes in mean reaction time over time will be analyzed.

Resting-state electroencephalography (EEG) will be used to assess functional connectivity between parietal and motor cortical regions.

Functional connectivity will be quantified using frequency-specific coherence values and graph-theoretical network metrics derived from EEG signals. Coherence values range from 0 to 1, with higher values indicating stronger functional connectivity between cortical regions. Graph-based metrics (e.g., global efficiency, clustering coefficient) are continuous measures without fixed theoretical minimum or maximum values; higher values indicate greater network integration or segregation depending on the specific metric analyzed.

Change in these connectivity measures between Baseline (Day 0) and Day 3 will be analyzed to evaluate neurophysiological effects of stimulation.

Upper limb activity during motor training sessions will be quantified using a wrist-worn ActiGraph® device.

Active duration (minutes) is defined as the total time during each training session in which wrist acceleration exceeds the predefined activity threshold.

This is a continuous variable expressed in minutes, with a minimum possible value of 0 minutes and a maximum corresponding to the total session duration. Higher values indicate greater active training time.

These values will be used to verify equivalence of training dose across study groups.

Upper limb movement intensity during motor training sessions will be quantified using a wrist-worn ActiGraph® device.

Mean movement intensity is calculated as the average vector magnitude of triaxial acceleration signals recorded during each training session.

This is a continuous variable expressed in activity counts (vector magnitude units) with no predefined theoretical maximum. Higher values indicate greater movement intensity.

These values will be used to verify equivalence of training intensity across study groups.

Upper limb activity during motor training sessions will be quantified using a wrist-worn ActiGraph® device.

Percentage of active time (%) is defined as the proportion of total session time during which wrist acceleration exceeds the predefined activity threshold.

This is a continuous variable expressed as a percentage ranging from 0% to 100%. Higher values indicate greater proportion of active training time.

These values will be used to verify equivalence of training exposure across study groups.