"Experimental Study on Stroke Rehabilitation Based on Dual-Task Exercises"

1. BACKGROUND AND CURRENT STATUS OF THE TOPIC In the context of physical and cognitive rehabilitation, the Dual-Task (DT) paradigm is defined as the simultaneous execution of two tasks that have independent goals. Generally, these tasks consist of a primary motor task (such as walking or maintaining balance) performed concurrently with a secondary task, which can be cognitive (mental arithmetic, verbal fluency) or motor (carrying an object). Stroke survivors often lose the "automaticity" of movement. Consequently, tasks that were once subconscious now require high levels of executive function and attention. When these patients encounter real-world environments-which are inherently "dual-task" in nature-they experience Dual-Task Interference (DTI). This interference manifests as a decrease in performance in one or both tasks, significantly increasing the risk of falls and limiting social reintegration. Recent evidence suggests that dual-task interventions may improve balance, gait performance, and functional recovery beyond traditional rehabilitation approaches. However, further evidence is required regarding the effectiveness of combining perturbation-based balance training with computerized cognitive stimulation in individuals with early subacute stroke.
2. HYPOTHESIS Participants receiving dual-task cognitive-motor rehabilitation combining perturbation-based balance training and computerized cognitive stimulation will demonstrate superior improvements in balance performance compared with participants receiving perturbation-based balance training alone.
3. OBJETIVES The principal objective of the study is to evaluate the effectiveness of a dual-task cognitive-motor rehabilitation programme combining Perturbation-Based Balance Training (PBT) and computerized cognitive stimulation delivered through NeuronUP on balance performance, as measured by the Berg Balance Scale (BBS), in individuals with early subacute stroke (<2 months post-onset). The secundary objectives are:

• SO1. To evaluate the effect of the program on motor and functional recovery.
• SO2. To determine the impact of the intervention on cognitive performance.
• SO3. To analyze the impact of the intervention on quality of life, emotional state, and functional independence.
• SO4. To assess the feasibility of the program through participant adherence, satisfaction, and safety of the intervention.

1. METHODOLOGY The study will be conducted at the Neurorehabilitation Unit of Bermingham Hospital (Matia). Participants will include individuals who have experienced a stroke within the past two months, reside in the Donostialdea catchment area, and are referred to our outpatient neurorehabilitation unit by the Basque Health Service (Servicio Vasco de Salud).
2. TYPE OF STUDY This information is described in detail in the corresponding section.
3. STUDY SUBJECTS This information is described in detail in the corresponding section.
4. SAMPLE SIZE The sample size calculation was based on the study primary outcome, the Berg Balance Scale (BBS). A minimum clinically important difference of 6 points on the Berg Balance Scale was considered clinically relevant between study groups. Published dual-task rehabilitation studies reported post-intervention BBS values of 45.5 ± 6.3 and 45.9 ± 7.2 (Song GB, Park EC. Effect of dual tasks on balance ability in stroke patients. J Phys Ther Sci. 2015 Aug;27(8):2457-60. doi: 10.1589/jpts.27.2457). Based on these data, a pooled standard deviation of 6.76 points was estimated. Assuming a clinically relevant difference of 6 points between groups, the corresponding standardized effect size was Cohen's d = 0.88. Using a two-sided alpha level of 0.05 and a statistical power of 90%, the minimum required sample size was estimated to be 33 participants per group. To account for an anticipated attrition rate of 20%, the sample size was increased to 40 participants per group. Therefore, the final planned sample size is 80 participants, with 40 participants allocated to the intervention group and 40 participants allocated to the control group. Sample size calculations were performed using G*Power software (version 3.1).
5. DESCRIPTION OF THE INTERVENTION The rehabilitation programme consists of two sequential phases. All participants receive the same initial rehabilitation programme, while the intervention differs during the perturbation-based balance training phase. Phase 1. Conventional Neurorehabilitation (Pre-Intervention Phase) Following enrolment, all participants undergo individualized conventional neurorehabilitation delivered by physiotherapists and occupational therapists. This initial phase focuses on the recovery of mobility, muscle strength, proprioception, postural control, balance, and functional performance. Rehabilitation begins with seated exercises and progressively advances to standing activities according to each participant's functional recovery. The duration of this phase varies between participants and depends on their ability to achieve sufficient postural control, standing balance, and physical capacity to safely participate in perturbation-based balance training. Phase 2. Perturbation-Based Balance Training (Intervention Phase) Once participants demonstrate the ability to maintain an upright posture and safely tolerate standing activities, they enter the intervention phase. Both study groups perform perturbation-based balance training (PBT) using the Balance Tutor system. The system consists of a treadmill mounted on a moveable platform capable of generating controlled multidirectional perturbations while participants are standing or walking. PBT aims to improve reactive postural control, dynamic balance, and gait performance by exposing participants to unexpected external perturbations that require rapid balance corrections. The system includes a safety harness and emergency stop mechanisms to ensure participant safety. Training progression, perturbation intensity, and exercise difficulty are individualized according to participant performance and rehabilitation needs. Training duration gradually increases during the first sessions, starting with short exposure periods and progressing up to a maximum of 30 minutes of active training per session. Treatment Schedule The intervention programme lasts approximately 16 weeks. Participants attend two treatment sessions per week. Each session lasts approximately 40 minutes and consists of:

• 5 minutes of preparation and familiarization.
• Up to 30 minutes of active training.
• 5 minutes of recovery and session closure. The physiotherapy and occupational therapy teams individualize exercise progression, intensity, and difficulty throughout the programme. Participant adherence, session attendance, progression parameters, and adverse events are recorded prospectively during the intervention period. Study Timeline and Assessment Schedule All participants undergo repeated assessments at five predefined time points: T0 - Baseline Assessment Before randomization and before the start of the intervention programme. Demographic, clinical, cognitive, functional, mobility, balance, and quality-of-life assessments are completed at this time point. T1 - Mid-Intervention Assessment Twelve weeks after initiation of the intervention programme. This assessment is designed to evaluate intermediate treatment effects on balance, cognition, mobility, and functional status. T2 - Post-Intervention Assessment At completion of the intervention programme. This represents the primary post-treatment evaluation and will be used to determine the immediate effectiveness of the intervention. T3 - Six-Month Follow-Up Six months after completion of the intervention programme. This assessment evaluates the maintenance of treatment effects over time. T4 - Twelve-Month Follow-Up Twelve months after completion of the intervention programme. This final assessment evaluates the long-term sustainability of treatment benefits on balance, cognitive performance, mobility, functional independence, and quality of life. All primary and secondary outcome measures will be collected at T0, T1, T2, T3, and T4 unless otherwise specified. Participant satisfaction will be assessed exclusively at T2 following completion of the intervention programme.

1. VARIABLES AND EVALUATION TOOLS The following variables will be collected at baseline to characterize the study population and evaluate potential confounding factors. Sociodemographic Variables

• Age
• Sex
• Marital status
• Educational level
• Living arrangement
• Occupational history
• Place of residence Clinical Variables
• Type of stroke (ischemic or hemorrhagic)
• Time since stroke onset
• Presence of recognized disability
• Weight
• Height
• Body Mass Index (BMI) Pharmacological Variables
• Number of medications
• Medication classes
• Psychotropic Burden Index (PBI) Comorbidity and Health Status
• Charlson Comorbidity Index (CCI)
• Visual impairment
• Hearing impairment
• Urinary incontinence
• Fecal incontinence
• Constipation
• Pressure ulcers
• Physical immobility
• Dysphagia
• Delirium
• Affective disorders Neuropsychiatric Symptoms The Neuropsychiatric Inventory (NPI) will be used to assess:
• Delusions
• Hallucinations
• Agitation
• Depression
• Anxiety
• Apathy
• Irritability
• Sleep disturbances
• Abnormal motor behaviour The outcome measures are described in a separate section

1. STATISTICAL ANALYSIS For data entry and management, REDCap (Research Electronic Data Capture) will be utilized. Statistical analyses will be performed using STATA and R (version 4.2.3 or higher).

Primary Analysis: Linear Mixed-Effects Models. To evaluate the effect of the intervention over time (T0 vs. T1) and differences between study arms (Intervention Group vs. Control Group), Linear Mixed-Effects Models (LMM) for repeated measures will be fitted.

Fixed Effects: The model will include "Group" (Intervention/Control), "Time" (T0/T1), and, critically, the Group and Time interaction term. The primary interest of the study lies in the statistical significance of this interaction term, which will test whether the trajectory of cognitive, functional, and clinical variables over time differs between groups.

Random Effects: A random intercept for "Participant" will be included to account for inter-individual variability and the intrinsic correlation of repeated measures within the same subject.

Secondary and Complementary Analyses. To complement the primary model and facilitate the clinical interpretation of changes, the following analyses will be conducted:

Intragroup Comparison (Pre-Post Evolution): To assess net changes within each study arm between T0 and T1, paired t-tests will be applied for normally distributed variables. If normality assumptions are violated, the non-parametric Wilcoxon signed-rank test will be used.

Intergroup Comparison (Magnitude of Change): Change scores (Δ=T1-T0) will be calculated for each variable. Differences in the magnitude of change between the control and intervention groups will be analyzed using independent-samples $t$-tests or Mann-Whitney $U$ tests, as appropriate.

Effect Size: To quantify the clinical relevance of the findings, effect sizes will be calculated using Cohen's d (for parametric contrasts) or Rosenthal's r (for non-parametric contrasts), interpreted as small (0.2), medium (0.5), or large (0.8).