Changes in spatial self-consciousness elicit grid cell-like representation in the entorhinal cortex.

Grid cells in the entorhinal cortex (EC) encode an individual's location in space, integrating both environmental and multisensory bodily cues. Notably, body-derived signals are also primary signals for the sense of self. While studies have demonstrated that continuous application of visuo-tactile bodily stimuli can induce perceptual shifts in self-location, it remains unexplored whether these illusory changes suffice to trigger grid cell-like representation (GCLR) within the EC, and how this compares to GCLR during conventional virtual navigation. To address this, we systematically induced illusory drifts in self-location toward controlled directions using visuo-tactile bodily stimulation, while maintaining the subjects' visual viewpoint fixed (absent conventional virtual navigation). Subsequently, we evaluated the corresponding GCLR in the EC through functional MRI analysis. Our results reveal that illusory changes in perceived self-location (independent of changes in environmental navigation cues) can indeed evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation in the same virtual room. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues.

Physical Body Orientation Impacts Virtual Navigation Experience and Performance.

Most human navigation studies in MRI rely on virtual navigation. However, the necessary supine position in MRI makes it fundamentally different from daily ecological navigation. Nonetheless, until now, no study has assessed whether differences in physical body orientation (BO) affect participants' experienced BO during virtual navigation. Here, combining an immersive virtual reality navigation task with subjective BO measures and implicit behavioral measures, we demonstrate that physical BO (either standing or supine) modulates experienced BO. Also, we show that standing upright BO is preferred during spatial navigation: participants were more likely to experience a standing BO and were better at spatial navigation when standing upright. Importantly, we report that showing a supine virtual agent reduces the conflict between the preferred BO and physical supine BO. Our study provides critical, but missing, information regarding experienced BO during virtual navigation, which should be considered cautiously when designing navigation studies, especially in MRI.

Optical EUS Activation to Relax Sensitized Micturition Response.

This study aims to activate the external urethral sphincter (EUS), which plays a critical role in micturition control, through optogenetics and to determine its potential contribution to the stabilization of sensitized micturition activity. The viral vector (AAV2/8-CMV-hChR2(H134R)-EGFP) is utilized to introduce light-gated ion channels (hChR2/H134R) into the EUS of wild-type C57BL/6 mice. Following the induction of sensitized micturition activity using weak acetic acid (0.1%) in anesthetized mice, optical stimulation of the EUS muscle tissue expressing channel rhodopsin is performed using a 473 nm laser light delivered through optical fibers, and the resulting changes in muscle activation and micturition activity are examined. Through EMG (electromyography) measurements, it is confirmed that optical stimulation electrically activates the EUS muscle in mice. Analysis of micturition activity using cystometry reveals a 70.58% decrease in the micturition period and a 70.27% decrease in the voiding volume due to sensitized voiding. However, with optical stimulation, the micturition period recovers to 101.49%, and the voiding volume recovered to 100.22%. Stimulation of the EUS using optogenetics can alleviate sensitized micturition activity and holds potential for application in conjunction with other micturition control methods.

Targeted photothrombotic subcortical small vessel occlusion using in vivo real-time fiber bundle endomicroscopy in mice.

The development of an accurate subcortical small vessel occlusion model for pathophysiological studies of subcortical ischemic stroke is still insignificant. In this study, in vivo real-time fiber bundle endomicroscopy (FBEµ) was applied to develop subcortical photothrombotic small vessel occlusion model in mice with minimal invasiveness. Our FBFµ system made it possible to precisely target specific blood vessels in deep brain and simultaneously observe the clot formation and blood flow blockage inside the target blood vessel during photochemical reactions. A fiber bundle probe was directly inserted into the anterior pretectal nucleus of the thalamus in brain of live mice to induce a targeted occlusion in small vessels. Then, targeted photothrombosis was performed using a patterned laser, observing the process through the dual-color fluorescence imaging. On day one post occlusion, infarct lesions are measured using TTC staining and post hoc histology. The results show that FBEµ applied to targeted photothrombosis can successfully generate a subcortical small vessel occlusion model for lacunar stroke.

Perspective: Present and Future of Virtual Reality for Neurological Disorders.

Since the emergence of Virtual Reality technology, it has been adopted in the field of neurology. While Virtual Reality has contributed to various rehabilitation approaches, its potential advantages, especially in diagnosis, have not yet been fully utilized. Moreover, new tides of the Metaverse are approaching rapidly, which will again boost public and research interest and the importance of immersive Virtual Reality technology. Nevertheless, accessibility to such technology for people with neurological disorders has been critically underexplored. Through this perspective paper, we will briefly look over the current state of the technology in neurological studies and then propose future research directions, which hopefully facilitate beneficial Virtual Reality studies on a wider range of topics in neurology.

Sense of self impacts spatial navigation and hexadirectional coding in human entorhinal cortex.

Grid cells in entorhinal cortex (EC) encode an individual's location in space and rely on environmental cues and self-motion cues derived from the individual's body. Body-derived signals are also primary signals for the sense of self and based on integrated sensorimotor signals (proprioceptive, tactile, visual, motor) that have been shown to enhance self-centered processing. However, it is currently unknown whether such sensorimotor signals that modulate self-centered processing impact grid cells and spatial navigation. Integrating the online manipulation of bodily signals, to modulate self-centered processing, with a spatial navigation task and an fMRI measure to detect grid cell-like representation (GCLR) in humans, we report improved performance in spatial navigation and decreased GCLR in EC. This decrease in entorhinal GCLR was associated with an increase in retrosplenial cortex activity, which was correlated with participants' navigation performance. These data link self-centered processes during spatial navigation to entorhinal and retrosplenial activity and highlight the role of different bodily factors at play when navigating in VR.