Neurophysiological Markers for Prediction of Rehabilitation Outcomes After Ischemic Stroke

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.

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