IE-Map: a novel in-vivo atlas and template of the human inner ear

Brain atlases and templates are core tools in scientific research with increasing importance also in clinical applications. Advances in neuroimaging now allowed us to expand the atlas domain to the vestibular and auditory organ, the inner ear. In this study, we present IE-Map, an in-vivo template and atlas of the human labyrinth derived from multi-modal high-resolution magnetic resonance imaging (MRI) data, in a fully non-invasive manner without any contrast agent or radiation. We reconstructed a common template from 126 inner ears (63 normal subjects) and annotated it with 94 established landmarks and semi-automatic segmentations of all relevant macroscopic vestibular and auditory substructures. We validated the atlas by comparing MRI templates to a novel CT/micro-CT atlas, which we reconstructed from 21 publicly available post-mortem images of the bony labyrinth. Templates in MRI and micro-CT have a high overlap, and several key anatomical measures of the bony labyrinth in IE-Map are in line with micro-CT literature of the inner ear. A quantitative substructural analysis based on the new template, revealed a correlation of labyrinth parameters with total intracranial volume. No effects of gender or laterality were found. We provide the validated templates, atlas segmentations, surface meshes and landmark annotations as open-access material, to provide neuroscience researchers and clinicians in neurology, neurosurgery, and otorhinolaryngology with a widely applicable tool for computational neuro-otology

The human egomotion network.

All volitional movement in a three-dimensional space requires multisensory integration, in particular of visual and vestibular signals. Where and how the human brain processes and integrates self-motion signals remains enigmatic. Here, we applied visual and vestibular self-motion stimulation using fast and precise whole-brain neuroimaging to delineate and characterize the entire cortical and subcortical egomotion network in a substantial cohort (n=131). Our results identify a core egomotion network consisting of areas in the cingulate sulcus (CSv, PcM/pCi), the cerebellum (uvula), and the temporo-parietal cortex including area VPS and an unnamed region in the supramarginal gyrus. Based on its cerebral connectivity pattern and anatomical localization, we propose that this region represents the human homologue of macaque area 7a. Whole-brain connectivity and gradient analyses imply an essential role of the connections between the cingulate sulcus and the cerebellar uvula in egomotion perception. This could be via feedback loops involved updating visuo-spatial and vestibular information. The unique functional connectivity patterns of PcM/pCi hint at central role in multisensory integration essential for the perception of self-referential spatial awareness. All cortical egomotion hubs showed modular functional connectivity with other visual, vestibular, somatosensory and higher order motor areas, underlining their mutual function in general sensorimotor integration

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health