Plasticity and neuromodulation of the extended recurrent visual network

The extended visual network, which includes occipital, temporal and parietal posterior cortices, is a system characterized by an intrinsic connectivity consisting of bidirectional projections. This network is composed of feedforward and feedback projections, some hierarchically arranged and others bypassing intermediate areas, allowing direct communication across early and late stages of processing. Notably, the early visual cortex (EVC) receives considerably more feedback and lateral inputs than feedforward thalamic afferents, placing it at the receiving end of a complex cortical processing cascade, rather than just being the entrance stage of cortical processing of retinal input. The critical role of back-projections to visual cortices has been related to perceptual awareness, amplification of neural activity in lower order areas and improvement of stimulus processing. Recently, significant results have shown behavioural evidence suggesting the importance of reentrant projections in the human visual system, and demonstrated the feasibility of inducing their reversible modulation through a transcranial magnetic stimulation (TMS) paradigm named cortico-cortical paired associative stimulation (ccPAS). Here, a novel research line for the study of recurrent connectivity and its plasticity in the perceptual domain was put forward. In the present thesis, we used ccPAS with the aim of empowering the synaptic efficacy, and thus the connectivity, between the nodes of the visuocognitive system to evaluate the impact on behaviour. We focused on driving plasticity in specific networks entailing the elaboration of relevant social features of human faces (Chapters I & II), alongside the investigation of targeted pathways of sensory decisions (Chapter III). This allowed us to characterize perceptual outcomes which endorse the prominent role of the EVC in visual awareness, fulfilled by the activity of back-projections originating from distributed functional nodes.

Hypofractionated stereotactic radiotherapy after hyperbaric oxygenation for recurrent high-grade glioma: a pilot study

Purpose The presence of hypoxic cells in high-grade glioma (HGG) is one of the main reasons of local failure after radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of hypoxia in poorly oxygenated regions of the tumor. We performed a pilot study to evaluate the efficacy of hypofractionated image-guided helical TomoTherapy (HT) after HBO in the treatment of recurrent HGG (rHGG). Methods We enrolled 15 patients (aged >18 years) with diagnosis of rHGG. A total dose of 15-25 Gy was administered in daily 5-Gy fractions for 3-5 consecutive days after daily HBO. Each fraction was delivered up to maximum of 60 minutes after HBO. Results Median follow-up from HBO-RT was 28.6 (range: 5.3-56.8). No patient was lost to follow-up. Median progression-free survival (mPFS) for all patients was 3.2 months (95% CI: 1.34- 6.4 ), while 3-month, 6-month and 12 month PFS was 60% (95%CI: 31.8.4-79.7), 40% (95%CI: 16.5- 62.8) and10.0 (0.8-33.5) , respectively. Median overall survival (mOS) of HBO-RT was 11.7 months (95% CI: 7.3-29.3), while 3-month, 6-month and 12 month OS was 100% , 93.3% (61.3-99.0) and 46.7 % (21.2-68.8). No acute or late neurologic toxicity >grade 2 (CTCAE version 4.3) was observed in 86.66% of patients. Two patients developed G3 Radionecrosis. Conclusion HSRT combined to HBO seems effective and safe in the treatment of rHGG. One of advantages of HBO-RT is the reduced overall treatment time (3-5 consecutive days).