Periodic Reporting for period 1 - CorticalSpaceShift (How altered sensory experience changes the cortex: plasticity processes in the visual cortex andtheir relation to ecological real-life events under shifted perception condition) Período documentado: 2018-09-01 hasta 2020-08-31 Resumen del contexto y de los objetivos generales del proyecto Our lifetime experience and past interactions with the world shape the way we act and perceive. How do these interactions forge our brain? And how does our brain adapt in order to function in an altered environment? The CorticalSpaceShift project aims to discover how virtual reality (VR) training can modulate subsequent brain activity and connectivity in healthy individuals and brain-damaged patients. The inspiration for the project comes from a rehabilitation treatment for a unique neuropathological syndrome called ‘Hemispatial neglect’ (‘neglect’). In this syndrome, right hemisphere damage (usually following a stroke) causes patients an inability to attend to and perceive sensory inputs from the left side of space. A prominent hypothesis maintains that a general imbalance in activity and connection between the two hemispheres stands in the basis of hemispatial neglect. Correspondingly, the most promising rehabilitation tool for ameliorating neglect symptoms is wearing prismatic lenses that induce a right lateral shift in the visual inputs while patients are performing a visuo-motor task ('prism adaptation'), resulting in an adaptive leftward correction of motor action to compensate for this deviation (‘adaptation aftereffects’). After prism removal, patients exhibit a re-balancing of spatial behaviour, manifested in motor tasks, visual perception, auditory perception, and even spatial cognitive tasks. While re-balancing spatial behaviour in neglect patients, prism adaptation is able to quickly induce long-lasting spatial biases in healthy individuals. However, how these behavioural changes manifest in the brain was still not elucidated. In the current project, we have created a VR-based version of prism adaptation, which can induce more powerful and experimentally controlled adaptation experience for both healthy individuals and neglect patients. The project focused on two main research questions:1) How would VR adaptation change spontaneous and movie-driven brain activity in healthy individuals? Could we temporarily induce unbalance between hemispheres with a brief VR training experience? 2) Could we use VR-adaptation to re-balance spontaneous and movie-driven brain activity in neglect patients? Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha During the course of the project, we have created an innovative VR-based setup for inducing sensory-motor adaptation. In this setup, participants had to catch dynamic targets (tennis balls) with a virtual hand. After several trials, the virtual hand shifted laterally with respect to the participants' own hand, forcing participants to adapt their reaching movements in the direction opposite the shift in order to catch the tennis balls (Figure 1). We used this setup to induce a brief adaptation training for healthy individuals and long-term rehabilitation training with neglect patients. We have published a paper describing the VR-adaptation setup and its behavioural aftereffects (Wilf et al., 2020), and a clinical trial comprising our paradigm is about to be launched by our collaborators at ‘MindMaze’ biotechnology company to test effectivity of rehabilitation of stroke survivors and neurological patients with spatial deficits at the Lausanne University Hospital. In order to unravel the neural aftereffects of our VR-adaptation training, we recorded brain activity under identical conditions before and after adaptation experience using neuroimaging methods. Brain activity was recorded under several conditions: 1) Free viewing of a sequence of short naturalistic videoclips. 2) Spontaneous brain activity while participants rest with their eyes closed.We found that when healthy individuals were watching naturalistic videos following VR-adaptation with a rightward shift, activity in their right hemisphere visual cortex was enhanced as compared to following VR training with no shift. Since right visual cortex processes visual information from the left portion of space, this effect reflects enhanced visual representation of the left portion of space following VR-adaptation. Furthermore, the amount of right hemisphere activity enhancement was strongly correlated with the amount of behavioural aftereffects measured in our group of participants, suggesting a link between behavioural and brain modulation induced by VR-adaptation experience. We next explored the effect of adaptation on spontaneous brain activity without task or sensory stimulation. To validate our VR setup, we initially measured the change in spontaneous activity following exposure to prism adaptation goggles outside VR. We discovered that prism adaptation modulated the connections between large-scale functional brain networks – namely the networks controlling attention, and the network responsible for self-referential processes (Wilf et al., 2019). We then recorded spontaneous activity in three groups of healthy participants before and after VR training with either rightward shift, leftward shift, or no shift. We found that VR-adaptation again causes disconnections between large-scale networks in the cortex – the attention network and the self-referential network. Interestingly, the disconnection was more pronounced in the hemisphere contralateral to the shift induced (left hemisphere for rightward shift and right hemisphere for leftward shift) and between the hemispheres. The group who trained with no shift showed no modulation of spontaneous activity. Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha) Our results provide fascinating evidence for the ability to change the adult brain with a brief virtual reality training. Specifically, we have shown that VR-adaptation can unbalance brain activity between the two hemispheres, causing “neglect-like” characteristics of brain activity. During naturalistic viewing, only right visual cortex activity was enhanced following training with rightward VR-adaptation, and during spontaneous activity, functional disconnection between large scale networks was hemisphere-specific, depending on the side of the VR-adaptation shift. Additionally, we have found a strong correlation between brain and behavioural modulations following VR-adaptation, suggesting that a brief VR-adaptation training can induce a deep change in how our brain represents the space around us. On a clinical point of view, additional data from neglect patients will reveal whether similar brain modulation processes are occurring in a damaged brain, but in contrary to healthy individuals, lead to a beneficial outcome of re-balancing between the hemispheres. The VR-adaptation setup is now available for rehabilitation in the clinics and at the bedside, and will potentially even be available at home in a relatively short time window.