An Integrative Tinnitus Model Based on Sensory Precision.

Tinnitus is a common disorder that often complicates hearing loss. Its mechanisms are incompletely understood. Current theories proposing pathophysiology from the ear to the cortex cannot individually - or collectively - explain the range of experimental evidence available. We propose a new framework, based on predictive coding, in which spontaneous activity in the subcortical auditory pathway constitutes a 'tinnitus precursor' which is normally ignored as imprecise evidence against the prevailing percept of 'silence'. Extant models feature as contributory mechanisms acting to increase either the intensity of the precursor or its precision. If precision (i.e., postsynaptic gain) rises sufficiently then tinnitus is perceived. Perpetuation arises through focused attention, which further increases the precision of the precursor, and resetting of the default prediction to expect tinnitus

Singular projective varieties and quantization

By the quantization condition compact quantizable Kaehler manifolds can be embedded into projective space. In this way they become projective varieties. The quantum Hilbert space of the Berezin-Toeplitz quantization (and of the geometric quantization) is the projective coordinate ring of the embedded manifold. This allows for generalization to the case of singular varieties. The set-up is explained in the first part of the contribution. The second part of the contribution is of tutorial nature. Necessary notions, concepts, and results of algebraic geometry appearing in this approach to quantization are explained. In particular, the notions of projective varieties, embeddings, singularities, and quotients appearing in geometric invariant theory are recalled.Comment: 21 pages, 3 figure

Spectral Grouping of Electrically Encoded Sound Predicts Speech-in-Noise Performance in Cochlear Implantees

\ua9 2023, The Author(s). Objectives: Cochlear implant (CI) users exhibit large variability in understanding speech in noise. Past work in CI users found that spectral and temporal resolution correlates with speech-in-noise ability, but a large portion of variance remains unexplained. Recent work on normal-hearing listeners showed that the ability to group temporally and spectrally coherent tones in a complex auditory scene predicts speech-in-noise ability independently of the audiogram, highlighting a central mechanism for auditory scene analysis that contributes to speech-in-noise. The current study examined whether the auditory grouping ability also contributes to speech-in-noise understanding in CI users. Design: Forty-seven post-lingually deafened CI users were tested with psychophysical measures of spectral and temporal resolution, a stochastic figure-ground task that depends on the detection of a figure by grouping multiple fixed frequency elements against a random background, and a sentence-in-noise measure. Multiple linear regression was used to predict sentence-in-noise performance from the other tasks. Results: No co-linearity was found between any predictor variables. All three predictors (spectral and temporal resolution plus the figure-ground task) exhibited significant contribution in the multiple linear regression model, indicating that the auditory grouping ability in a complex auditory scene explains a further proportion of variance in CI users’ speech-in-noise performance that was not explained by spectral and temporal resolution. Conclusion: Measures of cross-frequency grouping reflect an auditory cognitive mechanism that determines speech-in-noise understanding independently of cochlear function. Such measures are easily implemented clinically as predictors of CI success and suggest potential strategies for rehabilitation based on training with non-speech stimuli

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/ gamma) were demonstrated in primary auditory cortex in medial Heschl’s gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions

Sequence learning modulates neural responses and oscillatory coupling in human and monkey auditory cortex

Learning complex ordering relationships between sensory events in a sequence is fundamental for animal perception and human communication. While it is known that rhythmic sensory events can entrain brain oscillations at different frequencies, how learning and prior experience with sequencing relationships affect neocortical oscillations and neuronal responses is poorly understood. We used an implicit sequence learning paradigm (an “artificial grammar”) in which humans and monkeys were exposed to sequences of nonsense words with regularities in the ordering relationships between the words. We then recorded neural responses directly from the auditory cortex in both species in response to novel legal sequences or ones violating specific ordering relationships. Neural oscillations in both monkeys and humans in response to the nonsense word sequences show strikingly similar hierarchically nested low-frequency phase and high-gamma amplitude coupling, establishing this form of oscillatory coupling—previously associated with speech processing in the human auditory cortex—as an evolutionarily conserved biological process. Moreover, learned ordering relationships modulate the observed form of neural oscillatory coupling in both species, with temporally distinct neural oscillatory effects that appear to coordinate neuronal responses in the monkeys. This study identifies the conserved auditory cortical neural signatures involved in monitoring learned sequencing operations, evident as modulations of transient coupling and neuronal responses to temporally structured sensory input

Communication : where evolutionary linguistics went wrong

In this article we offer a detailed assessment of current approaches to the origins of language, with a special focus on their historical and theoretical underpinnings. It is a widely accepted view within evolutionary linguistics that an account of the emergence of human language necessarily involves paying special attention to its communicative function and its relation to other animal communication systems. Ever since Darwin, some variant of this view has constituted the mainstream version in evolutionary linguistics; however, it is our contention in this article that this approach is seriously flawed, and that "animal communication" does not constitute a natural kind on which a sound theoretical model can be built. As a consequence, we argue that this communicative perspective is better abandoned in favor of a structural/formal approach based on the notion of homology, and that some interesting and unexpected similarities may be found by applying this venerable comparative method founded in the 19th century by Richard Owen

Is adolescent body mass index and waist circumference associated with the food environments surrounding schools and homes? A longitudinal analysis

Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status. Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and ‘other retail outlets’ located within a 1 km radius of an individual’s home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period. Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations. Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies

A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello