Transcranial direct current stimulation for rehabilitation in stroke sufferers with upper limb deficit

Stroke is a leading cause of disability worldwide, often resulting in significant motor impairments, particularly affecting the upper limbs. These impairments severely impact the quality of life for stroke survivors. Recovery of motor function is highly variable, and traditional rehabilitation approaches often provide limited improvements. Therefore, there is a growing interest in the use of advanced neurorehabilitation techniques to promote neuroplasticity. One of the key tools used to study and understand brain function during stroke recovery is electroencephalography (EEG). EEG is a non-invasive technique that records the brain's activity, providing insights into the neurophysiological changes that occur after a stroke. Further to this, Transcranial Direct Current Stimulation (tDCS) is a novel non-invasive brain stimulation approach which has received significant notice in stroke rehabilitation. For tDCS, a low electric current is applied in order to modulate cortical excitability and has been shown to lead to functional improvement. Bihemispheric tDCS, where one electrode is placed over the affected hemisphere to facilitate activity and another on unaffected side to decrease its dominance, have shown a potential for restoring disturbed interhemipsheric balance in stroke patients. This dual modulation can improve motor function by facilitating neuroplastic changes in the brain. This PhD thesis, titled "Transcranial Direct Current Stimulation for Rehabilitation in Stroke Sufferers with Upper Limb Deficit," is divided into two main parts. The first part provides an overview of stroke, the underlying neurophysiological mechanisms and an in-depth exploration of EEG and tDCS as tools for neurorehabilitation for stroke. The second part of the thesis focuses on the experimental works developed over the three years of this PhD. It includes a detailed presentation of four preliminary studies that laid the basis for the core project. The first study focused on the changes of single hemisphere network connectivity in subacute stroke patients, emphasizing their role as predictive markers for functional recovery after stroke. Building on this, the second study explores the potential of EEG-based functional connectivity measures in combination with Artificial Intelligence algorithms. This approach aims to classify stroke patients, identify the affected hemisphere and predict functional recovery outcomes. The third study provides an innovative approach by investigating entropy as a measure of brain complexity. The study of hemispheric asymmetries in entropy adds a new dimension to the understanding of stroke-related brain changes. The fourth study represents the important transition to an experimental stroke model using mice treated with bihemispheric tDCS, where a preliminary investigation was conducted to validate the procedure explored in human subjects in the core project of the PhD thesis. These four preliminary studies were essential in shaping the core PhD project, which focuses on evaluating the effects of bihemispheric tDCS in a clinical context of subacute stroke patients. The knowledge gained from analyzing hemispheric dynamics, in terms of functional connectivity and entropy measures in both human and animal model guided the trajectory of the core project. The goal of this core project is to assess how bihemispheric tDCS influences neural recovery, specifically by targeting hemispheric imbalance and promoting reorganization of brain networks.