Large-scale intrinsic brain systems have been identified for exteroceptive senses (e.g., sight, hearing, touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic/interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic/interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain’s functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness.

Large-scale intrinsic brain systems have been identified for exteroceptive senses (e.g., sight, hearing, touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic/interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic/interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain's functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms * Corresponding authors: ian_kleckner@urmc.rochester.edu, l.barrett@neu.edu. ǂ Shared senior authorshipAuthor contributions: The study was designed by all the authors, analyzed by all the authors, and the manuscript was written by I.R.K. and L.F.B with comments and edits from other authors. Competing interests:The authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Hum Behav. Author manuscript; available in PMC 2017 October 24.Published in final edited form as: Nat Hum Behav. 2017 ; 1: . doi:10.1038/s41562-017-0069. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe brain contains intrinsic systems for processing exteroceptive sensory inputs from the world, such as vision, audition, and proprioception/touch (e.g., 1 ). Accumulating evidence indicates that these systems work via the principles of predictive coding (e.g., 2-7 ), where sensations are anticipated and then corrected by sensory inputs from the world. The brain, as a generative system, models the world by predicting, rather than reacting to, sensory inputs.Predictions guide action and perception by continually constructing possible representations of the immediate future based on their prior probabilities relative to the present context 8,9 . We and others have recently begun studying the hypothesis that ascending sensory inputs from the organs and systems within the body's internal milieu are similarly anticipated and represented (i.e., autonomic visceral and vascular function, neuroendocrine fluctuations, and neuroimmune function) [10][11][12][13][14][15][16] . These sensations are referred to as interoception [17][18][19] .Engineering studies of neural design 20 , alo...

BackgroundThe receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells.MethodsMelanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice. The ratios of CD3+CD8+ cytotoxic T cells, CD49b+NK cells, CD4+CD25+FoxP3+ Tregs and Gr1+CD11b+ MDSCs in tumor-DLN or spleen were examined by flow cytometry. After the co-culture of B16 cells and CD8+ T cells, the effects of Notch1 on the proliferation and activation of T cells were assessed by CCK8 assay, CFSE dilution and Chromium-release test. The mRNA expression and supernatant secretion of immunosuppressive cytokines, TGF-β1, VEGF, IL-10 and IFN-γ were measured by RT-PCR and ELISA, respectively.ResultsDownregulation or overexpression of Notch1 in B16 melanoma cells inhibited or promoted tumor growth in immunocompetent mice, respectively. Notch1 expression in B16 melanoma cells inhibited the infiltration of CD8+ cytotoxic T lymphocytes and NK cells and reduced IFN-γ release in tumor tissue. It could also enhance B16 cell-mediated inhibition of T cell proliferation and activation, and upregulate PD-1 expression on CD4+ and CD8+ T cells. The percentage of CD4+CD25+FoxP3+ Tregs and Gr1+CD11b+MDSCs were significantly increased in tumor microenvironment, and all these were attributed to the upregulation of TGF-β1.ConclusionThese findings suggested that Notch1 signaling in B16 melanoma cells might inhibit antitumor immunity by upregulation of TGF-β1.

The electrochemical stability of electrolytes is essential to the working potential of supercapacitors. Ionic liquids (ILs) are being considered as safe alternatives to current organic electrolytes and attracting extensive interests owing to their inflammability, widened potential windows, and superior ionic conductivity. Novel supercapacitors with IL electrolytes exhibit attractive energy density and can be utilized in various energy storage systems. Most previous studies focused on electrochemical performances, while rare attentions were devoted to energy storage process details or mechanisms. This review comprehensively summarizes the latest progress on formulated IL electrolytes for different types of supercapacitors, with an emphasis on the intrinsic understanding of the related energy storage mechanisms. Subsequently, comparisons of various IL-based liquid-state electrolytes as well as the state-of-the-art advancements in optimizing ILs electrolytes are introduced. The authors attempt to reveal the inherent correlation between the usage of IL electrolytes and the properties of supercapacitors via referenced works. Some emerging applications of ionogel electrolytes based on conventional polymers and poly(IL)s for flexible supercapacitors are also presented, including the existing problems. In addition, challenges and future perspectives of research in this field are highlighted.