Neurophysiological Markers for Prediction of Rehabilitation Outcomes After Ischemic Stroke

Neurophysiological Markers for Developing an Integrative Model of Rehabilitation Prognosis in Patients With Ischemic Stroke

The goal of this randomized controlled study is to develop and validate an integrated neurophysiological model for predicting rehabilitation potential in patients with ischemic stroke. The study focuses on identifying objective markers of brain activity associated with motor preparation and recovery.

The project includes two stages. First, healthy volunteers will participate in experimental motor and mental tasks to establish reference patterns of brain activity using electroencephalography and transcranial magnetic stimulation. These data will be used to define stable neurophysiological markers of motor network function.

In the second stage, patients in the acute and early recovery phases after ischemic stroke will be randomly assigned to receive either active intermittent theta-burst stimulation of the motor cortex or a sham procedure, in addition to standard rehabilitation. Brain activity and clinical motor function will be assessed before and after the intervention.

The study aims to determine which neurophysiological measures are sensitive to neuromodulation and are associated with clinical improvement, in order to construct a predictive model of rehabilitation outcome.

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Study Overview

• Status: Not yet recruiting
• Conditions: Ischemic Stroke; Upper Limb Motor Impairment
• Intervention / Treatment: Device: Intermittent Theta Burst Stimulation; Device: Sham Intermittent Theta Burst Stimulation

Detailed Description

Stroke remains a leading cause of long-term disability worldwide. Motor recovery after ischemic stroke is highly variable, and currently available clinical scales provide limited ability to predict rehabilitation potential at the individual level. There is a need for objective, neurophysiologically grounded biomarkers that reflect motor network integrity, cortical excitability, and adaptive neuroplasticity.

The present study aims to develop and validate an integrated neurophysiological model for predicting rehabilitation outcomes in patients with ischemic stroke. The model is based on a multimodal assessment combining electroencephalography (EEG), performed during standardized ecologically valid motor and mental paradigms, and diagnostic transcranial magnetic stimulation (TMS).

The project consists of two interconnected stages.

Stage 1 (Experimental Reference Phase in Healthy Volunteers):

Healthy adult participants will perform standardized motor execution and motor imagery paradigms under EEG and surface electromyography monitoring. Cortical excitability will be assessed using diagnostic TMS. This phase is designed to identify stable neurophysiological patterns associated with motor preparation and execution, including movement-related cortical potentials, sensorimotor rhythm modulation, and measures of functional connectivity. These data will serve as reference patterns to define candidate biomarkers for subsequent clinical testing.

Stage 2 (Randomized Controlled Clinical Phase):

Patients in the acute and early recovery stages following first-ever ischemic stroke will be randomly assigned to receive either active intermittent theta-burst stimulation (iTBS) of the ipsilesional primary motor cortex or sham stimulation, in addition to standard rehabilitation therapy. The intervention course will consist of multiple stimulation sessions delivered over a two-week period.

Neurophysiological assessments (EEG and diagnostic TMS) will be conducted before and after the intervention. Clinical motor and cognitive function will be evaluated using standardized scales at baseline and post-intervention time points.

The randomized design allows evaluation of the sensitivity of candidate neurophysiological markers to neuromodulatory intervention and their association with clinical recovery dynamics. By integrating electrophysiological measures of cortical excitability, motor network synchronization, and interregional connectivity with clinical outcomes, the study seeks to identify a minimal set of objective markers capable of predicting rehabilitation response.

The ultimate objective is to construct and statistically validate a predictive model of rehabilitation potential that may support individualized planning of post-stroke neurorehabilitation strategies.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paul D. Egorov; Phone Number: +7-977-878-11-60; Email: egorovpd@vk.com

Study Locations

• Russia
  • Moscow, Russia
    • Moscow Scientific and Practical Center of Medical Rehabilitation, Restorative and Sports Medicine
    • Contact: Paul D. Egorov; Phone Number: +7-977-878-11-60; Email: egorovpd@vk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Experimental phase:

will include healthy volunteers without contradictions to TMS

Clinical phase:

Inclusion Criteria:

• First-ever ischemic stroke confirmed by CT/MRI
• 5 days - 6 months post-stroke
• Age 40-65
• MoCA ≥20
• HADS <11 for anxiety and depression
• MRC 2-4 in upper limb
• Modified Ashworth Scale ≤3
• Signed informed consent

Exclusion Criteria:

• Implanted electronic devices
• Epilepsy
• Severe cardiac arrhythmias
• Intracranial aneurysm
• Decompensated somatic disease
• Pregnancy/lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham-iTBS	Device: Sham Intermittent Theta Burst Stimulation; Once a day, 10 days of Sham Theta-Burst Stimulation using placebo coil
Experimental: iTBS	Device: Intermittent Theta Burst Stimulation; Once a day, 10 days of Intermittent Theta-Burst Stimulation (iTBS) applied to ipsilesional primary motor cortex (M1).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle Strength Assessed by the Medical Research Council Scale (MRC)	Muscle strength of the affected upper limb assessed using the Medical Research Council (MRC) scale, ranging from 0 (no muscle contraction) to 5 (normal muscle strength). Higher scores indicate better motor function.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Muscle Tone Assessed by the Modified Ashworth Scale (MAS)	Muscle tone of the affected upper limb assessed using the Modified Ashworth Scale (MAS), which ranges from 0 (no increase in muscle tone) to 4 (Affected part(s) rigid in flexion or extension). Higher scores indicate greater spasticity.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Upper Limb Motor Function (Fugl-Meyer Assessment - Upper Extremity)	Upper limb motor impairment assessed using the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE). Scores range from 0 to 66, with higher scores indicating better upper limb motor function.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Cognitive Function Assessed by Montreal Cognitive Assessment (MoCA)	Global cognitive function assessed using the Montreal Cognitive Assessment (MoCA), a 30-point cognitive screening tool. Scores range from 0 to 30, with higher scores indicating better cognitive function.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Modified Rankin Scale (mRS) score	Global disability assessed using the modified Rankin Scale (mRS). Scores range from 0 to 6, higher scores indicate greater disability.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Action Research Arm Test (ARAT) score	Upper limb functional capacity assessed using the Action Research Arm Test (ARAT). Scores range from 0 to 57, with higher scores indicating better upper limb function.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Nine-Hole Peg Test (NHPT) completion time	Manual dexterity assessed using the Nine-Hole Peg Test (NHPT), a timed test of fine hand dexterity. Completion time is recorded in seconds; lower times indicate better manual dexterity.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Frenchay Arm Test (FAT) score	Upper limb functional performance in daily activities assessed using the Frenchay Arm Test (FAT), a 5-item test of arm and hand function after stroke. Scores range from 0 to 5, with higher scores indicating better upper limb function.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Event-Related Desynchronization (ERD) of Sensorimotor Rhythm	Event-related desynchronization (ERD) of sensorimotor rhythm in the 8-30 Hz frequency range measured using scalp electroencephalography during motor execution and motor imagery tasks. ERD is expressed as percentage decrease in band power relative to a pre-movement baseline, reflecting cortical activation.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Event-Related Synchronization (ERS) of Sensorimotor Rhythm	Event-related synchronization (ERS) of sensorimotor rhythm in the 8-30 Hz frequency range measured using scalp electroencephalography during motor execution and motor imagery tasks. ERS is expressed as percentage increase in band power relative to a pre-movement baseline, reflecting post-movement cortical synchronization.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Movement-Related Cortical Potential (MRCP) Amplitude	Amplitude of movement-related cortical potential (MRCP) recorded using scalp electroencephalography during motor execution and motor imagery tasks. MRCP amplitude is measured in microvolts (µV) relative to a pre-movement baseline and reflects cortical activity associated with motor preparation.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Movement-Related Cortical Potential (MRCP) Latency	Latency of movement-related cortical potentials (MRCPs) recorded using scalp electroencephalography during motor execution and motor imagery tasks. MRCP latency is defined as the time interval in milliseconds (ms) between MRCP onset and movement onset.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Motor Evoked Potential (MEP) Amplitude	Peak-to-peak amplitude of motor evoked potentials (MEPs) recorded at rest from the target upper limb muscle using surface electromyography following single-pulse transcranial magnetic stimulation of the primary motor cortex. MEP amplitude is measured in millivolts (mV) and reflects corticospinal excitability.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Resting Motor Threshold (RMT)	Resting motor threshold (RMT) defined as the minimum stimulator intensity required to evoke motor evoked potentials (MEPs) in the target muscle in at least 50% of trials with the muscle at rest. The threshold is expressed as a percentage of maximal stimulator output (% MSO).	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)
Change in Weighted Phase Lag Index (wPLI) in the Sensorimotor Network	Functional connectivity within the sensorimotor network assessed using the weighted phase lag index (wPLI), a phase-based connectivity measure derived from electroencephalography signals during motor execution and motor imagery tasks. wPLI values range from 0 to 1, with higher values indicating stronger phase synchronization between cortical regions.	Baseline and Week 2 (end of intervention, after 10 sessions of iTBS/Sham)

Collaborators and Investigators

• Sponsor: Moscow Scientific and Practical Center of Medical Rehabilitation, Restorative and Sports Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: NMIRP-IS-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No