Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

BackgroundThe invasive nature of the current methods for monitoring of intracranial pressure (ICP) has prevented their use in many clinical situations. Several attempts have been made to develop methods to monitor ICP non-invasively. The aim of this study is to assess the relationship between ultrasound-based non-invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients.Methods and findingsThis was a prospective, single-cohort observational study of patients admitted to a tertiary neurocritical care unit. Patients with brain injury requiring invasive ICP monitoring were considered for inclusion. nICP was assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd). A total of 445 ultrasound examinations from 64 patients performed from 1 January to 1 November 2016 were included. The median age of the patients was 53 years (range 37–64). Median Glasgow Coma Scale at admission was 7 (range 3–14), and median Glasgow Outcome Scale was 3 (range 1–5). The mortality rate was 20%. ONSD and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on FVd did not correlate with ICP significantly. Combining the 2 strongest nICP predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R = 0.80). The ability to detect intracranial hypertension (ICP ≥ 20 mm Hg) was highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88–0.95). The combination of ONSD and FVsv methods showed a statistically significant improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90–0.97, p = 0.01). Major limitations are the heterogeneity and small number of patients included in this study, the need for specialised training to perform and interpret the ultrasound tests, and the variability in performance among different ultrasound operators.ConclusionsOf the studied ultrasound nICP methods, ONSD is the best estimator of ICP. The novel combination of ONSD ultrasonography and vTCD of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension.

A fundamental question in neuroscience is how brain organisation gives rise to humans' unique cognitive abilities. Although complex cognition is widely assumed to rely on frontal and parietal brain regions, the underlying mechanisms remain elusive: current approaches are unable to disentangle different forms of information processing in the brain. Here, we introduce a powerful framework to identify synergistic and redundant contributions to neural information processing and cognition. Leveraging multimodal data including functional MRI, PET, cytoarchitectonics and genetics, we reveal that synergistic interactions are the fundamental drivers of complex human cognition. Whereas redundant information dominates sensorimotor areas, synergistic activity is closely associated with the brain's prefrontal-parietal and default networks; furthermore, meta-analytic results demonstrate a close relationship between highlevel cognitive tasks and synergistic information. From an evolutionary perspective, the human brain exhibits higher prevalence of synergistic information than non-human primates. At the macroscale, we demonstrate that high-synergy regions underwent the highest degree of evolutionary cortical expansion. At the microscale, human-accelerated genes promote synergistic interactions by enhancing synaptic transmission. These convergent results provide critical insights that synergistic neural interactions underlie the evolution and functioning of humans' sophisticated cognitive abilities, and demonstrate the power of our widely applicable information decomposition framework..

Highlights LSD untethers functional connectivity from the constraint of structural connectivity. Increased small-worldness of brain networks predicts LSD-induced ego-dissolution. LSD has time-specific effects on brain network integration and segregation. LSD increases the complexity of segregated brain states. Results bridge pharmacodynamics, subjective experience and brain dynamics.