Periodic Reporting for period 3 - LIGHTUP (Turning the cortically blind brain to see: from neural computations to system dynamicsgenerating visual awareness in humans and monkeys)
Reporting period: 2021-08-01 to 2023-01-31
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?
To answer this question, LIGHTUP proposes to integrate into a coherent experimental framework human and non-human primate neuroscience. This will place our understanding of visual awareness on firm neurobiological and mechanistic bases. Next, the project will translate this wisdom into pre-clinical intervention.
First, 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.
Second, we will place this knowledge in the macro-scale context of dynamic system interactions across distant brain 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.
The next wave of progress consists in integrating this behavioral paradigm with neuroimaging methods. This will enable us to build up a generative model that specifies the directionality of information flow in the interactions across brain areas, and their causal role in generating visual awareness.
The third and final part of the project will devise a rehabilitation protocol to promote the (re)emergence of lost visual awareness following visual cortex damage. Here we will combine in a multimodal approach the two major inducers of neural plasticity: brain stimulation and visual training. LIGHTUP will exploit non-invasive brain stimulation protocol that target complex cortical circuits, rather than a single area, and then selects the direction of connectivity that is enhanced.
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.
To answer this question, LIGHTUP proposes to integrate into a coherent experimental framework human and non-human primate neuroscience. This will place our understanding of visual awareness on firm neurobiological and mechanistic bases. Next, the project will translate this wisdom into pre-clinical intervention.
First, 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.
Second, we will place this knowledge in the macro-scale context of dynamic system interactions across distant brain 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.
The next wave of progress consists in integrating this behavioral paradigm with neuroimaging methods. This will enable us to build up a generative model that specifies the directionality of information flow in the interactions across brain areas, and their causal role in generating visual awareness.
The third and final part of the project will devise a rehabilitation protocol to promote the (re)emergence of lost visual awareness following visual cortex damage. Here we will combine in a multimodal approach the two major inducers of neural plasticity: brain stimulation and visual training. LIGHTUP will exploit non-invasive brain stimulation protocol that target complex cortical circuits, rather than a single area, and then selects the direction of connectivity that is enhanced.
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.
According to the original timetable, the first 30 months have been dedicated essentially to investigating with computational neuroimaging and task-free paradigms the properties that characterize the neural responses with vs. without visual awareness.
The first stage involved definition and validation of the individual images and stimulus parameters best suited to drive maximal activity in the affected portions of the visual field. We have identified cross-species emotional signals and their relations to consciousness; an effort that has already fostered empirical and theoretical developments published in prestigious international journals. We have also directly tested spatial frequency responsivity, discovering that low spatial frequency sensitivity in response to emotional stimuli is preserved in patients with brain injury.
Based on this knowledge, we moved to the next stage aimed at devising the visual stimulation protocol to derive population receptive field estimation (pRF) applicable to both human participants and non-human primates, either healthy or with damage to the visual cortex. We have piloted and validated the protocol on healthy volunteers. In parallel, we have started the recruitment procedures for neuropsychological patients, including clinical and behavioral assessment. Results on one such patients with hemispherectomy have been already published and we have been able to document for the first time a selective expansion of pRF size at specific eccentricities, which are indicative of cerebral plasticity.
Another line of activity was devoted to assess brain response at rest in a series of longitudinal tests, analyzing synchrony of activity across areas as well as long-range anatomical connections. To investigate temporal-dependent functional changes, we have adopted a novel method to analyze resting-state data: dynamic functional connectivity. We have therefore applied the method to healthy participants. We have also performed the first meta-analytic activation likelihood estimation of fMRI responsive areas in patients with V1 damage and blindsight that enabled us to identify for the first time the most promising regions in terms of preserved response without V1 and highest potential to take over its functions. In addition to group analyses, we proceeded to in-depth analyses of individual subjects. We advanced in this direction, reporting that one informative case of blindsight has previously undescribed changes of cortical thickness in peri-calcarine cortex, an anatomical hallmark of structural plasticity.
Capitalizing of previous knowledge and initial animal evidence, we have defined a behavioural training protocol for rehabilitation of visual field defect due to V1 damage, combined with analysis of white matter changes. The protocol has been finally accepted as registered report. Interdisciplinary developments are also testified by a number of review papers in top interdisciplinary journals that have contributed to the theoretical definition of consciousness and its neural correlates, thus paving the way to future empirical developments and identification of major achievements and challenges in fields such as neuroscience, ethology, psychology and philosophy.
In sum, the most of the goals envisaged for the initial stages of the project have been fully achieved, and we have created the conditions to progress smoothly to the next stages in the coming months.
The first stage involved definition and validation of the individual images and stimulus parameters best suited to drive maximal activity in the affected portions of the visual field. We have identified cross-species emotional signals and their relations to consciousness; an effort that has already fostered empirical and theoretical developments published in prestigious international journals. We have also directly tested spatial frequency responsivity, discovering that low spatial frequency sensitivity in response to emotional stimuli is preserved in patients with brain injury.
Based on this knowledge, we moved to the next stage aimed at devising the visual stimulation protocol to derive population receptive field estimation (pRF) applicable to both human participants and non-human primates, either healthy or with damage to the visual cortex. We have piloted and validated the protocol on healthy volunteers. In parallel, we have started the recruitment procedures for neuropsychological patients, including clinical and behavioral assessment. Results on one such patients with hemispherectomy have been already published and we have been able to document for the first time a selective expansion of pRF size at specific eccentricities, which are indicative of cerebral plasticity.
Another line of activity was devoted to assess brain response at rest in a series of longitudinal tests, analyzing synchrony of activity across areas as well as long-range anatomical connections. To investigate temporal-dependent functional changes, we have adopted a novel method to analyze resting-state data: dynamic functional connectivity. We have therefore applied the method to healthy participants. We have also performed the first meta-analytic activation likelihood estimation of fMRI responsive areas in patients with V1 damage and blindsight that enabled us to identify for the first time the most promising regions in terms of preserved response without V1 and highest potential to take over its functions. In addition to group analyses, we proceeded to in-depth analyses of individual subjects. We advanced in this direction, reporting that one informative case of blindsight has previously undescribed changes of cortical thickness in peri-calcarine cortex, an anatomical hallmark of structural plasticity.
Capitalizing of previous knowledge and initial animal evidence, we have defined a behavioural training protocol for rehabilitation of visual field defect due to V1 damage, combined with analysis of white matter changes. The protocol has been finally accepted as registered report. Interdisciplinary developments are also testified by a number of review papers in top interdisciplinary journals that have contributed to the theoretical definition of consciousness and its neural correlates, thus paving the way to future empirical developments and identification of major achievements and challenges in fields such as neuroscience, ethology, psychology and philosophy.
In sum, the most of the goals envisaged for the initial stages of the project have been fully achieved, and we have created the conditions to progress smoothly to the next stages in the coming months.
The project is characterized by a series of novel methodologies and their integration, as well as progresses beyond state of the art. Analyzing fMRI signal similarly to the way tuning properties are ascribed to neurons in physiology has made possible to assess how responses properties change when the same stimulus is processed with or without awareness in the intact and damaged brain. We are currently characterizing different dimensions of brain plasticity, those involving the formation or strengthening of long-range connections between areas, and those related to the settling of coherence and synchrony in their functional activity. The emerging picture describes the brain with a damage to the visual system as having higher degrees of post-lesional flexibility higher than previously thought. We expect, by the end of the project, to be able to steer these compensatory changes toward directions that enable a genuine, though partial, restitution to conscious visual functions in the previously blind fields.
Recent advances in machine learning and artificial intelligence have opened up new ways of thinking about neural computation. Deep neural networks offer an unprecedented opportunity to model the functioning of specific neural structures as well as their changes due to damage. We have therefore developed a convolutional neural network model of the superior colliculus; a key structure for non-conscious perception after V1 damage. This is the first deep learning model of a visual subcortical structure that is biologically plausible and tailored to reproduce its connectional and functional properties on the superior colliculus. We will make the artificial neural network and all related scripts accessible, and we believe this can trigger a wave of progress in AI of visual functions.
Before the end of the project, we expect to fully exploit the potential of an animal model of visual awareness to establish a comprehensive understanding of the neural mechanisms sustaining vision with and without damage to the visual cortex. We will capitalize on this knowledge to devise and test active interventions to enhance compensatory mechanisms able to recover creditable visual functions after brain damage.
Recent advances in machine learning and artificial intelligence have opened up new ways of thinking about neural computation. Deep neural networks offer an unprecedented opportunity to model the functioning of specific neural structures as well as their changes due to damage. We have therefore developed a convolutional neural network model of the superior colliculus; a key structure for non-conscious perception after V1 damage. This is the first deep learning model of a visual subcortical structure that is biologically plausible and tailored to reproduce its connectional and functional properties on the superior colliculus. We will make the artificial neural network and all related scripts accessible, and we believe this can trigger a wave of progress in AI of visual functions.
Before the end of the project, we expect to fully exploit the potential of an animal model of visual awareness to establish a comprehensive understanding of the neural mechanisms sustaining vision with and without damage to the visual cortex. We will capitalize on this knowledge to devise and test active interventions to enhance compensatory mechanisms able to recover creditable visual functions after brain damage.