Facilitating Vision Restoration: Brain Plasticity After Monocular Vision Loss and Multidisciplinary Interventions

Monocular vision loss induces a profound reorganisation of the primary visual cortex (V1), yet it remains unclear to what extent such plasticity can be modulated with minimally invasive clinical interventions. This thesis evaluates whether transcranial direct current stimulation (tDCS), cholinergic enhancement with donepezil, and a structured visual stimulation protocol modify V1 plasticity after monocular enucleation in rodents. The work is articulated in a sequence of objectives that include (i) the multimodal physiological characterisation of V1 under normal conditions, (ii) systematic comparison with the post-enucleation state, and (iii) testing each intervention separately and in combination, using local field potential (LFP) and unit activity recordings in awake animals, with spectral analysis (power and phase coherence) using the maxima of ERSP (Event-Related Spectral Perturbation) and ITC (Inter-Trial Coherence) as mesoscopic biomarkers of plasticity. Electrode placement in the binocular and monocular zones
of V1 was validated; standardised visual, auditory, and somatosensory stimulations were applied in control animals, enucleated animals without treatment, and animals treated with epicranial tDCS, donepezil, and the combination for 15 days synchronised with visual training.
In the reference physiology, V1 acted as a multisensory node with brief latencies and an oscillatory profile dominated by beta, accompanied by robust inter-trial phase coherence.
Following enucleation, event-related potential components did not change markedly, but a spectral reconfiguration was observed: power and phase coherence to visual stimuli decreased, and increased selectively to auditory and somatosensory stimuli, with beta (and, to a lesser extent, delta) as a sensitive axis of the intermodal readjustment.
Each treatment generated a distinct neurophysiological profile. tDCS selectively increased alpha power during auditory stimulation and attenuated the somatosensory response across the spectrum, although by itself it did not restore the lost visual organisation. Donepezil showed an overall depressant effect on power and coherence in V1 with the protocol applied. The tDCS + donepezil combination did not act as a non-specific amplifier: it tended to “focus” plasticity, with indications of power/coherence increase in theta during visual stimulation and of a reduction in auditory-somatosensory interference, suggesting a bias from cross-modal plasticity towards visual intramodality for the residual visual information.
Taken together, plasticity after monocular vision loss is not epiphenomenal but steerable. Spectral biomarkers (beta for non-visual inputs and theta for visual inputs), together with temporal metrics of coherence, offer operational principles for designing and monitoring rehabilitation and visual restoration strategies that combine electrical neuromodulation and cholinergic potentiation.