Visual awareness without visual cortex: from monkey neurophysiology to human patients

PRIN 2022 Avenanti

Abstract

Abstract Visual awareness – the online access to the content of our visual experience – enables flexibility and experiential richness. Its loss following brain injury can be profoundly disabling. However, patients with blindness resulting from primary visual cortex (V1) damage may retain non-conscious visual functions, even in the absence of awareness. In the VIVA project, we aim to promote the recovery of visual abilities after V1 damage. Achieving this goal requires a paradigm shift: from investigating the neural correlates of visual awareness to identifying its neural causes. To this end, we integrate three main branches of research into a coherent framework: multimodal brain activity measures, behavioral assessments, and cross-species comparisons. We investigate visual awareness by characterizing the local and global brain dynamics associated with conscious and non-conscious vision, across multiple spatial and temporal scales. This involves combining computational neuroimaging in humans with neurophysiological recordings in animal models with V1 lesions. At the micro-scale, we estimate population receptive fields using fMRI, in a way that parallels tuning property analysis in animal physiology. At the macro-scale, we examine interactions across distant brain regions by applying dynamic functional connectivity analyses to fMRI and EEG data. In parallel, we study cortical-subcortical networks in lesioned animal models through chronically implanted multielectrode arrays, focusing on the superior colliculus, pulvinar, and higher-order visual areas. Through this multi-scale approach, we are elucidating with unprecedented spatiotemporal resolution: 1) how specific brain structures translate visual inputs into signals associated with awareness; 2) how damage reshapes response properties in intact areas; 3) how multiplex functional dynamics emerge at the level of large-scale networks. Building on these insights, we are developing pre-clinical interventions aimed at supporting the (re)emergence of visual awareness after V1 damage. We apply novel non-invasive stimulation protocols that target complex cortical circuits and enhance directional connectivity to promote Hebbian plasticity and boost visual perception. Once refined in healthy individuals, these interventions will be adapted for use in patients. In parallel, in implanted monkeys, we apply deep-brain stimulation techniques with high temporal precision to modulate subcortical structures such as the pulvinar involved in non-conscious vision. We expect that these integrated efforts will lead to new therapeutic strategies for restoring visual functions, grounded in solid neuroscientific evidence.

Results achieved

: The VIVA project, coordinated by the University of Bologna and conducted in collaboration with research units at the Universities of Turin and Parma, achieved its planned objectives through an integrated program of studies involving patients with primary visual cortex (V1) lesions, healthy participants, and non-human primates. In patients with unilateral V1 lesions, the combined use of functional and structural magnetic resonance imaging, EEG, and TMS-EEG enabled characterization of the mechanisms underlying residual vision. The results showed that these abilities do not depend on the activity of a single brain area, but on the reorganization of distributed cortical and subcortical networks, in which the superior colliculus, pulvinar, and extrastriate visual areas play relevant roles. The project also identified specific connectivity profiles associated with the presence or absence of non-conscious visual abilities, commonly referred to as blindsight. Neurostimulation studies using transcranial magnetic stimulation (TMS) provided causal evidence that these networks can be modified by activating mechanisms of Hebbian plasticity. In healthy participants, a cortico-cortical paired associative stimulation (ccPAS) protocol was applied to strengthen feedback connections between the superior temporal sulcus and early visual cortex. This manipulation improved the recognition of emotional facial expressions and modulated electrophysiological markers of visual processing. In patients with V1 damage, personalized protocols were also developed that proved to be feasible and safe, producing short-term modulation of residual visual function. Studies conducted in non-human primates made it possible to directly investigate the neurophysiological changes occurring after V1 lesions. Longitudinal recordings documented compensatory changes in response timing and functional connectivity within the superior colliculus–pulvinar circuit, consistent with a reorganization of the pathways supporting residual vision. In addition, targeted stimulation of the pulvinar produced small but consistent and transient improvements in visual performance within the blind field, providing preliminary evidence of a possible causal role of subcortical structures in the recovery of visual functions. Overall, VIVA generated an integrated, multiscale, and cross-species model of the mechanisms underlying V1-independent vision and established a robust methodological foundation for developing neuromodulation interventions to rehabilitate cortical blindness. The findings were disseminated through seven peer-reviewed publications in international scientific journals and numerous presentations at national and international conferences, seminars, and scientific meetings.

Dettagli del progetto

Responsabile scientifico: Alessio Avenanti

Strutture Unibo coinvolte:
Dipartimento di Psicologia "Renzo Canestrari"

Coordinatore:
ALMA MATER STUDIORUM - Università di Bologna(Italy)

Contributo totale di progetto: Euro (EUR) 212.500,00
Contributo totale Unibo: Euro (EUR) 85.000,00
Durata del progetto in mesi: 24
Data di inizio 05/10/2023
Data di fine: 31/12/2025

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