Grid cells are place-modulated neurons that encode the location of an agent in space, relying on the integration of various sensorimotor signals from the body. Of note, the integration of those signals is also fundamental for the agent's conscious experience of selfhood, referred to as bodily self-consciousness (BSC). Although both grid cells and BSC systems are related to the brain mechanisms of self-location and are based on multimodal signal integration, their interplay has never been investigated. My thesis aimed at revealing their links in humans by assessing the impact of BSC modulations on grid cell-like representation (GCLR): an fMRI proxy of grid cell activity in entorhinal cortex (EC). In Study 1, I assessed whether manipulation on BSC, specifically enhancing self-identification, affects GCLR during spatial navigation in a virtual reality (VR) environment. I implemented a novel fMRI paradigm integrating a spatial navigation task with online BSC manipulation through a motion-mimicking avatar. The data showed a significant reduction of GCLR as well as improved spatial navigation performance in the condition with the self-identified avatar, linking entorhinal grid cell activity and BSC through bodily self-motion cues provided online during spatial navigation. These behavioral and neural changes were further associated with increased activity in posterior parietal and retrosplenial cortex, collectively suggesting the impact of BSC on a distributed spatial navigation networks in the human brain. Consistent with the previous BSC research, in Study1, I observed illusory drifts in experienced self-location toward the self-identified avatar. In Study2, I further investigated whether illusory self-location changes would be sufficient to elicit GCLR in the absence of active spatial navigation. Adopting the Full-body illusion (FBI) paradigm to the MRI scanner, my data extend changes in self-location related to multisensory stimulation and demonstrated that these indeed evoke GCLR. Although the amplitude of GCLR during the FBI was smaller than the one during virtual navigation, their grid orientations were similar. These data suggest that the brain mechanisms underlying the BSC-induced illusory self-location are similar and comparable, albeit weaker, to the ones during virtual navigation.Temporal Interference (TI) stimulation is a novel method that can excite or inhibit neurons in the deep brain by combining high-frequency electrical fields. Building on the previous studies, in study3, I probed the causal link between GCLR and spatial navigation by applying TI stimulation to EC of participants while they were performing a VR navigation task in the scanner. The preliminary results showed that their spatial navigation was improved by excitatory stimuli compared to the control, while it deteriorated during the inhibition. Besides, I found that modulated GCLR was also associated with improved performance in the excitatory condition. Together, these data provide the first causal link between GCLR and spatial navigation, showing potential future avenues for navigation enhancement in humans. To summarize, I investigated BSC and grid cell systems jointly in humans and, for the first time, uncovered their links through robust evidence based on both behavioral and neuroimaging data. My thesis shed new light on the research of both systems which are closely intermingled but have hitherto been considered separately.
EPFL2021
