Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality.

ABSTRACT: Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, requiring sometimes the addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatiotemporal patterns of SCS-induced paresthesia. In this cross-sectional prospective interventional study, 15 patients with severe chronic pain and an SCS implant underwent congruent SCS-VR (personalized visual feedback of the perceived SCS-induced paresthesia displayed on the patient's virtual body) and 2 control conditions (incongruent SCS-VR and VR alone). We demonstrate the efficacy of neuromodulation-enhanced VR for the treatment of chronic pain by showing that congruent SCS-VR reduced pain ratings on average by 44%. Spinal cord stimulation-VR analgesia was stronger than that in both control conditions (enabling stronger analgesic effects than incongruent SCS-VR analgesia or VR alone) and kept increasing over successive stimulations, revealing the selectivity and consistency of the observed effects. We also show that analgesia persists after congruent SCS-VR had stopped, indicating carry over effects and underlining its therapeutic potential. Linking latest VR technology with recent insights from the neuroscience of body perception and SCS neuromodulation, our personalized new SCS-VR platform highlights the impact of immersive digiceutical therapies for chronic pain.Registration: clinicaltrials.gov, Identifier: NCT02970006.

First-person body view modulates the neural substrates of episodic memory and autonoetic consciousness: A functional connectivity study.

Episodic memory (EM) is classically conceived as a memory for events, localized in space and time, and characterized by autonoetic consciousness (ANC) allowing to mentally travel back in time and subjectively relive an event. Building on recent evidence that the first-person visual co-perception of one's own body during encoding impacts EM, we used a scene recognition task in immersive virtual reality (VR) and measured how first-person body view would modulate peri-encoding resting-state fMRI, EM performance, and ANC. Specifically, we investigated the impact of body view on post-encoding functional connectivity in an a priori network of regions related either to EM or multisensory bodily processing and used these regions in a seed-to-whole brain analysis. Post-encoding connectivity between right hippocampus (rHC) and right parahippocampus (rPHC) was enhanced when participants encoded scenes while seeing their body. Moreover, the strength of connectivity between the rHC, rPHC and the neocortex displayed two main patterns with respect to body view. The connectivity with a sensorimotor fronto-parietal network, comprising primary somatosensory and primary motor cortices, correlated with ANC after - but not before - encoding, depending on body view. The opposite change of connectivity was found between rHC, rPHC and the medial parietal cortex (from being correlated with ANC before encoding to an absence of correlation after encoding), but irrespective of body view. Linking immersive VR and fMRI for the study of EM and ANC, these findings suggest that seeing one's own body during encoding impacts the brain activity related to EM formation by modulating the connectivity between the right hippocampal formation and the neocortical regions involved in the processing of multisensory bodily signals and self-consciousness.

Subjective feeling of re-experiencing past events using immersive virtual reality prevents a loss of episodic memory.

INTRODUCTION: Personally meaningful past episodes, defined as episodic memories (EM), are subjectively re-experienced from the natural perspective and location of one's own body, as described by bodily self-consciousness (BSC). Neurobiological mechanisms of memory consolidation suggest how initially irrelevant episodes may be remembered, if related information makes them gain importance later in time, leading for instance, to a retroactive memory strengthening in humans. METHODS: Using an immersive virtual reality system, we were able to directly manipulate the presence or absence of one's body, which seems to prevent a loss of initially irrelevant, self-unrelated past events. RESULTS AND CONCLUSION: Our findings provide an evidence that personally meaningful memories of our past are not fixed, but may be strengthened by later events, and that body-related integration is important for the successful recall of episodic memories.

First-person view of one's body in immersive virtual reality: Influence on episodic memory.

Episodic memories (EMs) are recollections of contextually rich and personally relevant past events. EM has been linked to the sense of self, allowing one to mentally travel back in subjective time and re-experience past events. However, the sense of self has recently been linked to online multisensory processing and bodily self-consciousness (BSC). It is currently unknown whether EM depends on BSC mechanisms. Here, we used a new immersive virtual reality (VR) system that maintained the perceptual richness of life episodes and fully controlled the experimental stimuli during encoding and retrieval, including the participant's body. Our data reveal a classical EM finding, which shows that memory for complex real-life like scenes decays over time. However, here we also report a novel finding that delayed retrieval performance can be enhanced when participants view their body as part of the virtual scene during encoding. This body effect was not observed when no virtual body or a moving control object was shown, thereby linking the sense of self, and BSC in particular, to EMs. The present VR methodology and the present behavioral findings will enable to study key aspects of EM in healthy participants and may be especially beneficial for the restoration of self-relevant memories in future experiments.

From microscopy data to in silico environments for in vivo-oriented simulations.

ABSTRACT: : In our previous study, we introduced a combination methodology of Fluorescence Correlation Spectroscopy (FCS) and Transmission Electron Microscopy (TEM), which is powerful to investigate the effect of intracellular environment to biochemical reaction processes. Now, we developed a reconstruction method of realistic simulation spaces based on our TEM images. Interactive raytracing visualization of this space allows the perception of the overall 3D structure, which is not directly accessible from 2D TEM images. Simulation results show that the diffusion in such generated structures strongly depends on image post-processing. Frayed structures corresponding to noisy images hinder the diffusion much stronger than smooth surfaces from denoised images. This means that the correct identification of noise or structure is significant to reconstruct appropriate reaction environment in silico in order to estimate realistic behaviors of reactants in vivo. Static structures lead to anomalous diffusion due to the partial confinement. In contrast, mobile crowding agents do not lead to anomalous diffusion at moderate crowding levels. By varying the mobility of these non-reactive obstacles (NRO), we estimated the relationship between NRO diffusion coefficient (Dnro) and the anomaly in the tracer diffusion (α). For Dnro=21.96 to 44.49 µm2/s, the simulation results match the anomaly obtained from FCS measurements. This range of the diffusion coefficient from simulations is compatible with the range of the diffusion coefficient of structural proteins in the cytoplasm. In addition, we investigated the relationship between the radius of NRO and anomalous diffusion coefficient of tracers by the comparison between different simulations. The radius of NRO has to be 58 nm when the polymer moves with the same diffusion speed as a reactant, which is close to the radius of functional protein complexes in a cell.