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In the last few years, stroke ranked as the second most common cause of death and is the third most significant condition affecting disability-adjusted life years (DALYs) worldwide. Being the most prevalent and quality of life impacting post-stroke symptoms, rehabilitation of motor deficits, such as paresis or speech impairments, have concentrated most of the stroke rehabilitation research. Nonetheless, approximatively 1 stroke survivor out of 4 will have to deal with permanent Homonimous Hemianopia (HH), the loss of half of the visual field due to postchiasmatic lesions. This Thesis uses non-invasive brain stimulation techniques to unveil the electrophysiological mechanisms underlying healthy human visual motion perception, and applies these new insights for the development of a novel functional plasticity index and a new biologically-inspired visual rehabilitation protocol. One of the clinically relevant pathways to study and promote in this context, is the neural pathway connecting the ipsilesional middle temporal area (MT) to the primary the visual cortex V1 that mediates motion perception and awareness. First, to measure plasticity induction along this pathway, we tested the potential of cortico-cortical paired associative stimulation (ccPAS) in enhancing spike-timing-dependent plasticity (STDP) between MT and V1. By triggering one TMS pulse first on MT followed 20ms after by a second TMS pulse over V1, we observed a significant connectivity increase in the MT-to-V1 inputs, correlated with motion discrimination improvement. A similar relationship was reported in HH stroke patients, but only in patients with sufficient structural or functional integrity between V1 and MT. Next, we focused on the idea that exogenously modulating the well-reported oscillatory interactions between the two areas would boost visual learning. We developed a cross-frequency (Alpha and Gamma) dual-site transcranial alternate current stimulation (tACS) protocol. We observed an increase in motion perception in the blind field after one tACS session associated with an increase in V1-MT coupling in both healthy and HH stroke patients, when tACS delivered Alpha oscillations over V1 and Gamma oscillations over MT. Furthermore, applied repeatedly during 10 daily training sessions in HH patients, this tACS condition enhanced motion discrimination in the blind field to similar extends to long-term training studies. In line with the previous approach, patients who better responded to the intervention were the ones with preserved structural integrity of the cortical motion pathway. Importantly, improvement in motion discrimination was accompanied by an enlargement of visual field borders assessed with kinetic perimetry, paving the way to a novel intervention for visual field recovery.In conclusion, this work deepens our understanding of MT-V1 motion discrimination pathway properties and highlights a multimodal marker to index visual system structural and functional integrity potentially predictive of treatment efficacy. Finally, it introduces the first steps towards a promising approach for rehabilitating visual impairments in stroke patients. Further improvements include a novel state-dependent version based on inter-areal coupling, aiming at reducing the variability and increasing the efficacy.
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Silvestro Micera, Daniela De Luca