Periodic Reporting for period 4 - LIGHTUP (Turning the cortically blind brain to see: from neural computations to system dynamicsgenerating visual awareness in humans and monkeys)
Période du rapport: 2023-02-01 au 2024-07-31
Visual awareness - the online access to the content of our visual experience - affords flexibility and experiential richness, and its loss following brain damage has devastating effects on quality of life and functional recovery. However, patients with blindness following cortical damage may retain visual functions, despite visual awareness is lacking - a phenomenon known as ‘blindsight’-. LIGHTUP starts exploring a neglected fundamental issue: how can we translate non-conscious visual abilities into conscious ones after damage to the visual cortex? LIGHTUP proposes to integrate into a coherent experimental framework human and non-human primate neuroscience. LIGHTUP will apply computational neuroimaging methods to the micro-scale level of each neural unit to understand how single brain structures translate visual properties into responses associated with awareness, and how the lesion to the visual cortex alters response properties in intact areas. LIGHTUP leverages a behavioral paradigm that can dissociate non-conscious visual abilities from visual awareness in human as well as non-human primates, thus offering a refined animal model of visual awareness that can be exploited for rehabilitation. By departing from current mainstream, LIGHTUP proposes to focus on new questions, bring our understanding of visual awareness to the next level, and inspire a new wave of empirical studies in human and non-human neuroscience.
The project initially focused on investigating the properties that characterize neural responses with and without visual awareness using computational neuroimaging and task-free paradigms. We defined and validated stimulus parameters best suited to drive maximal activity in the affected portions of the visual field. Key findings include the identification of cross-species emotional signals and their relationship to consciousness, which led to significant empirical and theoretical advancements published in prestigious international journals. We discovered that low spatial frequency sensitivity in response to emotional stimuli is preserved in patients with brain injuries. We developed a visual stimulation protocol to derive population receptive field (pRF) estimates, applicable to both human participants and non-human primates (NHPs), whether healthy or with visual cortex damage. We turned our attention to assessing brain responses at rest through longitudinal tests, examining synchrony of activity across brain areas, long-range anatomical connections, and neurochemical changes using SPECT. To investigate temporal-dependent functional changes, we adopted a novel dynamic functional connectivity method for resting-state data, which was successfully applied to healthy participants and patients. This revealed significant changes in GABA and Glutamate concentrations in spared associative visual areas, correlating with behavioural performance in detecting stimuli in the blind field. We conducted the first meta-analytic activation likelihood estimation of fMRI-responsive areas in patients with V1 damage and blindsight, identifying regions with preserved responses and the potential to compensate for V1 damage. Both group and individual analyses uncovered previously undescribed cortical thickness changes in the peri-calcarine cortex, indicative of structural plasticity.A new approach to analysing resting-state fMRI data in humans and NHPs focused on studying cortical gradients and decomposing redundant and synergistic interactions between brain areas. This method revealed that V1-damaged participants with non-conscious visual functions maintain preserved cortical organisation along the unimodal-transmodal axis, while those without blindsight exhibit disrupted organisation.We developed a behavioural training protocol for visual field rehabilitation in patients with V1 damage, which was accepted as a registered report in Brain Communications. Our non-invasive brain stimulation protocol using ccPAS was applied for the first time to volunteers undergoing visual masking of emotional faces. Interdisciplinary progress was underscored by several review papers in leading journals, contributing to the theoretical understanding of consciousness and its neural correlates, and paving the way for future advancements in neuroscience, ethology, psychology, and philosophy. All major project objectives have been successfully achieved. We have laid a strong foundation for future research and clinical applications, particularly in rehabilitating patients with cortical blindness through the combined use of non-invasive brain stimulation and visual training. The project’s outcomes are set to have both significant scientific impact and practical clinical applications, maintaining a robust parallel between human and NHP research, and bridging fundamental and applied studies in visual awareness and consciousness.
The project is distinguished by its novel methodologies and interdisciplinary integration, making significant progress beyond the state of the art. By analysing fMRI signals in a manner similar to how neuronal tuning properties are studied in neurophysiology, we have assessed how response properties shift when the same stimulus is processed with or without visual awareness in both intact and damaged brains. We have characterised multiple dimensions of brain plasticity, including the formation and strengthening of long-range anatomical connections between distant brain regions, as well as the coherence and synchrony of functional activity between these areas. This work has revealed that the brain exhibits a previously underappreciated capacity for post-lesional flexibility, particularly in the visual system. Our findings indicate that these plastic changes occur not only in higher-order areas traditionally associated with compensatory activity but also in primary sensory regions, where we observe subtle functional recovery. By the end of the project, we aim to steer these compensatory changes toward enabling partial but genuine restitution of conscious visual function in previously blind fields, potentially paving the way for innovative rehabilitation protocols.We have developed a convolutional neural network (CNN) model of the superior colliculus, a critical structure involved in non-conscious perception after V1 damage. This is the first biologically plausible deep learning model of a subcortical visual structure, tailored to reproduce its connectional and functional properties accurately. Our CNN captures the intricate interplay between subcortical pathways and cortical networks, offering insights into how non-conscious visual processing occurs without V1. The intersection of fundamental and applied research has led to the successful proposal of a Proof of Concept project, funded as of August 1st, 2024. We expect to fully exploit the potential of an animal model of visual awareness to establish a comprehensive understanding of the neural mechanisms that sustain vision with and without damage to the visual cortex. This knowledge will be leveraged to devise and test active interventions to enhance compensatory mechanisms in patients, potentially leading to the restoration of credible visual functions after brain damage. We aim to not only contribute to the scientific understanding of vision and awareness but also develop therapeutic strategies that could transform patient care for individuals suffering from cortical blindness and related disorders.