Voltage-sensitive dye imaging reveals tonotopic organization of auditory cortex spontaneous activity

Imaging neural activity across a large (several mm) cortical area with high temporal and spatial resolution is desirable, for example in the auditory system to measure cortical processing across a broad frequency spectrum. Voltage-sensitive dye imaging (VSDI) has a unique combination of properties making this possible, but so far studies have been limited to studying simple sparsely-presented sensory stimuli. We demonstrate the feasibility of long-acquisition VSDI (using the dye RH-1691) in auditory cortex while presenting complex time-varying acoustic stimuli or silence. Using a dense array of partially-overlapping 50 ms tone pips (8 frequencies per octave spanning six octaves), we obtained high-resolution spectrotemporal receptive fields (STRFs) simultaneously across the majority of the guinea pig primary auditory cortical fields (A1 and DC). Long epochs of spontaneous activity were also measured, permitting a comparison of spontaneous activity patterns with functional architecture. By grouping all pixels in areas A1 and DC according to sound frequency preference (obtained from STRFs), we reveal that spontaneous activity (such as cortical spindles) show complex spatial patterns, which are organized according to sound frequency preference within and across cortical areas. More specifically, spontaneous activity correlation decreases as frequency preference diverges within A1 or DC; but additionally, pixels in A1 are also highly correlated with (even far-away) pixels in DC sharing similar frequency preference. These properties of patterned cortical spontaneous activity constrain mechanistic hypotheses regarding their genesis. Beyond these observations, the feasibility of VSDI with continuous stimulation or silence permits measuring population activity during long-lasting sound patterns, which is necessary for examining cortical dynamics and sensory-context dependent processing

Did Kant suffer from misophonia?

Misophonia is a disorder of decreased tolerance to specific sounds, often produced by humans but not always, which can trigger intense emotional reactions (anger, disgust etc.). This relatively prevalent disorder can cause a reduction in the quality of life. The causes of misophonia are still unclear. In this article, we develop a hypothesis suggesting that misophonia can be caused by a failure in the organization of the perceived world. The perceived world is the result of both the structure of human thought and the many conditioning factors that punctuate human life, particularly social conditioning. It is made up of abstract symbols that map the world and help humans to orient himself in a potentially dangerous environment. In this context, the role of social rules acquired throughout life is considerable. Table manners, for example, are a set of deeply regulated and controlled behaviors (it’s considered impolite to eat with the mouth open and to make noise while eating), which contribute to shape the way the perceived world is organized. So it’s not surprising to find sounds from the mouth (chewing etc.) among the most common misophonic sound triggers. Politeness can be seen as an act of obedience to moral rules or courtesy, which is a prerequisite for peaceful social relations. Beyond this example, we also argue that any sound can become a misophonic trigger as long as it is not integrated into the perceived ordered and harmonious world, because it is considered an “anomaly,” i.e., a disorder, an immorality or a vulgarity

Civilisation of manners and misophonia

Misophonia is a disorder of tolerance to specific sounds (i.e. trigger sounds), such as chewing, throat clearing or breathing sounds, produced by humans, which can trigger intense emotional reactions (anger, disgust). This relatively prevalent disorder can cause a reduction in the quality of life. The causes of misophonia are still unclear. In this article, we develop a “social” hypothesis based on the work of Norbert Elias. Misophonia would be an exaggerated reaction to behaviours (of others) that have been subject to rigorous social conditioning, which are supposed to be strictly regulated and repressed. The social rules imposed by society, accompanying the long process of pacification and increasing interdependence between individuals over the centuries, would be at the origin of this conditioning. The function of this conditioning, achieved mainly through shame and disgust, would be to preserve social cohesion, through the strict training of behaviour. It is indeed imperative to control oneself, to act in a thoughtful and balanced way, to spare others by taking into account their expectations, in short to behave in a “courteous” way. Imposed and less spontaneous behaviour creates a sense of modesty and distance between individuals. The obligation to strictly regulate behaviour and affect in public contributes to the creation of an interiority, an "inner self". The feeling of intrusion by others is a collateral effect of this process of distancing and individualisation. The rigorous integration of the social rule by the misophonic subject may account for the fact that any violation of the rule is considered unacceptable. In order to put an end to the unpleasant situation, i.e. to the intrusion generated by the “encroachment” of others, the subject has no other choice but to flee or to attack the author of the sound

A Systematic Review of Existing Clinical Guidelines for the Assessment and Treatment of Tinnitus in Adults

Background: Though clinical guidelines for assessment and treatment of chronic subjective tinnitus do exist, a comprehensive review of those guidelines has not been performed. The objective of this review was to identify current clinical guidelines, and compare their recommendations for the assessment and treatment of subjective tinnitus in adults. Method: We systematically searched a range of sources for clinical guidelines (as defined by the Institute of Medicine, United States) for the assessment and/or treatment of subjective tinnitus in adults. No restrictions on language or year of publication were applied to guidelines. Results: Clinical guidelines from Denmark, Germany, Sweden, The Netherlands, and the United States were included in the review. There was a high level of consistency across the guidelines with regard to recommendations for audiometric assessment, physical examination, use of a validated questionnaire(s) to assess tinnitus related distress, and referral to a psychologist when required. Cognitive behavioral treatment for tinnitus related distress, use of hearing aids in instances of hearing loss and recommendations against the use of medicines were consistent across the included guidelines. Differences between the guidelines centered on the use of imaging in assessment procedures and sound therapy as a form of treatment for tinnitus distress respectively. Conclusion: Given the level of commonality across tinnitus guidelines from different countries the development of a European guideline for the assessment and treatment of subjective tinnitus in adults seems feasible. This guideline would have the potential to benefit the large number of clinicians in countries where clinical guidelines do not yet exist, and would support standardization of treatment for patients across Europe

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Innovations in Doctoral Training and Research on Tinnitus:The European School on Interdisciplinary Tinnitus Research (ESIT) Perspective

Tinnitus is a common medical condition which interfaces many different disciplines, yet it is not a priority for any individual discipline. A change in its scientific understanding and clinical management requires a shift toward multidisciplinary cooperation, not only in research but also in training. The European School for Interdisciplinary Tinnitus research (ESIT) brings together a unique multidisciplinary consortium of clinical practitioners, academic researchers, commercial partners, patient organizations, and public health experts to conduct innovative research and train the next generation of tinnitus researchers. ESIT supports fundamental science and clinical research projects in order to: (1) advancing new treatment solutions for tinnitus, (2) improving existing treatment paradigms, (3) developing innovative research methods, (4) performing genetic studies on, (5) collecting epidemiological data to create new knowledge about prevalence and risk factors, (6) establishing a pan-European data resource. All research projects involve inter-sectoral partnerships through practical training, quite unlike anything that can be offered by any single university alone. Likewise, the postgraduate training curriculum fosters a deep knowledge about tinnitus whilst nurturing transferable competencies in personal qualities and approaches needed to be an effective researcher, knowledge of the standards, requirements and professionalism to do research, and skills to work with others and to ensure the wider impact of research. ESIT is the seed for future generations of creative, entrepreneurial, and innovative researchers, trained to master the upcoming challenges in the tinnitus field, to implement sustained changes in prevention and clinical management of tinnitus, and to shape doctoral education in tinnitus for the future

Planck 2015 results. XX. Constraints on inflation

We present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey. The Planck full mission temperature data and a first release of polarization data on large angular scales measure the spectral index of curvature perturbations to be n s = 0.968 ± 0.006 and tightly constrain its scale dependence to dn s /dlnk = −0.003 ± 0.007 when combined with the Planck lensing likelihood. When the high-ℓ polarization data is included, the results are consistent and uncertainties are reduced. The upper bound on the tensor-to-scalar ratio is r 0.002 <0.11 (95% CL), consistent with the B-mode polarization constraint r<0.12 (95% CL) obtained from a joint BICEP2/Keck Array and Planck analysis. These results imply that V(ϕ)∝ϕ 2 and natural inflation are now disfavoured compared to models predicting a smaller tensor-to-scalar ratio, such as R 2 inflation. Three independent methods reconstructing the primordial power spectrum are investigated. The Planck data are consistent with adiabatic primordial perturbations. We investigate inflationary models producing an anisotropic modulation of the primordial curvature power spectrum as well as generalized models of inflation not governed by a scalar field with a canonical kinetic term. The 2015 results are consistent with the 2013 analysis based on the nominal mission data