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We investigated auditory, dorsal attention, and default mode networks in adults with tinnitus and hearing loss in a resting state functional connectivity study. Data were obtained using continuous functional magnetic resonance imaging (fMRI) while the participants were at \"rest\" and were not performing any task. Participants belonged to one of three groups: middle-aged adults with tinnitus and mild-to-moderate high frequency hearing loss (TIN), age-matched controls with normal hearing and no tinnitus (NH), and a second control group with mild-to-moderate high frequency hearing loss without tinnitus (HL). After standard preprocessing, (a) a group independent component analysis (ICA) using 30 components and (b) a seeding-based connectivity analysis were conducted. In the group ICA, the default mode network was the only network to display visual differences between subject groups. In the seeding analysis, we found increased connectivity between the left parahippocampus and the auditory resting state network in the TIN group when compared to NH controls. Similarly, there was also an increased correlation between the right parahippocampus and the dorsal attention network when compared to HL controls. Other group differences in this attention network included decreased correlations between the seed regions and the right supramarginal gyrus in TIN patients when compared to HL controls. In the default mode network, there was a strong decrease in correlation between the seed regions and the precuneus when compared to both control groups. The findings of this study identify specific alterations in the connectivity of the default mode, dorsal attention, and auditory resting state networks due to tinnitus. The results suggest that therapies for tinnitus that mitigate the increased connectivity of limbic regions with auditory and attention resting state networks and the decreased coherence of the default mode network could be effective at reducing tinnitus-related distress.

Biochemical approaches revealed that tetraspanins are multi-regulatory proteins forming a web, where they act in tetraspanin-enriched-microdomains (TEMs). A microscopic criterion differentiating between web and TEMs is lacking. Using super-resolution microcopy, we identify co-assemblies between the tetraspanins CD9 and CD81 and CD151 and CD81. CD9 assemblies contain as well the CD9/CD81-interaction partner EWI-2. Moreover, CD9 clusters are proximal to clusters of the CD81-interaction partner CD44 and CD81-/EWI-2-interacting ezrin–radixin–moesin proteins. Assemblies scatter unorganized across the cell membrane; yet, upon EWI-2 elevation, they agglomerate into densely packed arranged-crowds in a process independent from actin dynamics. In conclusion, microscopic clusters are equivalent to biochemical tetraspanin-assemblies, defining in their entirety the tetraspanin web. Cluster-agglomeration enriches tetraspanins, which makes agglomerations to a microscopic complement of TEMs. The microscopic classification of tetraspanin assemblies advances our understanding of this enigmatic protein family, whose members play roles in a plethora of cellular functions, diseases, and pathogen infections.

We present a novel approach to test for heteroscedasticity of a nonstationary time series that is based on Gini’s mean difference of logarithmic local sample variances. In order to analyse the large sample behaviour of our test statistic, we establish new limit theorems for U-statistics of dependent triangular arrays. We derive the asymptotic distribution of the test statistic under the null hypothesis of a constant variance and show that the test is consistent against a large class of alternatives, including multiple structural breaks in the variance. Our test is applicable even in the case of nonstationary processes, assuming a locally stationary mean function. The performance of the test and its comparatively low computation time are illustrated in an extensive simulation study. As an application, we analyse Google Trends data, monitoring the relative search interest for the topic “global warming.”

Subjective, chronic tinnitus, the perception of sound in the absence of an external source, commonly occurs with many comorbidities, making it a difficult condition to study. Hearing loss, often believed to be the driver for tinnitus, is perhaps one of the most significant comorbidities. In the present study, white matter correlates of tinnitus and hearing loss were examined. Diffusion imaging data were collected from 96 participants—43 with tinnitus and hearing loss (TIN HL ), 17 with tinnitus and normal hearing thresholds (TIN NH ), 17 controls with hearing loss (CON HL ) and 19 controls with normal hearing (CON NH ). Fractional anisotropy (FA), mean diffusivity and probabilistic tractography analyses were conducted on the diffusion imaging data. Analyses revealed differences in FA and structural connectivity specific to tinnitus, hearing loss, and both conditions when comorbid, suggesting the existence of tinnitus-specific neural networks. These findings also suggest that age plays an important role in neural plasticity, and thus may account for some of the variability of results in the literature. However, this effect is not seen in tractography results, where a sensitivity analysis revealed that age did not impact measures of network integration or segregation. Based on these results and previously reported findings, we propose an updated model of tinnitus, wherein the internal capsule and corpus callosum play important roles in the evaluation of, and neural plasticity in response to tinnitus.

Resting state functional connectivity (RS-FC) studies of tinnitus are useful tools for identifying neural mechanisms and potential treatment options for patients. Building on our previous work demonstrating the replicability of RS-FCin individuals with tinnitus and controls, we attempted to investigate the factors leading to published inconsistent findings by examining resting state networks in participant groups across two different study sites: civilians recruited from the University of Illinois Urbana-Champaign; and military-affiliated participants recruited at the Hearig Center of Excellence at Lackland Airforce Base in San Antonio, Texas. Multiple analyses were performed: an overall analysis comparing tinnitus and control participants combined across the sites, and subgroup analyses based on hearing loss, severity, and site. In general, the tinnitus group at the military site exhibited a more profound effect of severity and less so of hearing, compared to their civilian counterparts. More specifically, while changes to the dorsal attention network were observed in the civilian group, the military tinnitus group exhibited alterations to the default mode, emotion processing, and sensory networks. Our study reiterates the impact of severity and hearing loss on neural networks of tinnitus and further supports the need to account for demographic variables such as age and profession.

Speech-in-noise (SiN) recognition difficulties are often reported in patients with tinnitus. Although brain structural changes such as reduced gray matter (GM) volume in auditory and cognitive processing regions have been reported in the tinnitus population, it remains unclear how such changes influence speech understanding, such as SiN performance. In this study, pure-tone audiometry and Quick Speech-in-Noise test were conducted on individuals with tinnitus and normal hearing and hearing-matched controls. T1-weighted structural MRI images were obtained from all participants. After preprocessing, GM volumes were compared between tinnitus and control groups using whole-brain and region-of-interest analyses. Further, regression analyses were performed to examine the correlation between regional GM volume and SiN scores in each group. The results showed decreased GM volume in the right inferior frontal gyrus in the tinnitus group relative to the control group. In the tinnitus group, SiN performance showed a negative correlation with GM volume in the left cerebellum (Crus I/II) and the left superior temporal gyrus; no significant correlation between SiN performance and regional GM volume was found in the control group. Even with clinically defined normal hearing and comparable SiN performance relative to controls, tinnitus appears to change the association between SiN recognition and regional GM volume. This change may reflect compensatory mechanisms utilized by individuals with tinnitus who maintain behavioral performance.

The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions. To achieve this, the chemical and physical attributes of the substrates should mimic the natural tissue environment and allow control of their biological properties. Herein, recent advances in the development of materials to study/manipulate stem cells, both in vitro and in vivo, are described with a focus on the novelty of the substrates’ properties, and on application of substrates to direct stem cells. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

Difficulties with consumer engagement are a common barrier to implementing trauma-focused evidence-based psychotherapies (TF-EBPs). Potential methods of increasing engagement include utilizing a stage-based treatment approach, and involving consumers in implementation efforts. This mixed method study explored consumers’ perspectives on a stage-based TF-EBP, Dialectical Behavior Therapy (DBT) with the DBT Prolonged Exposure (DBT PE) protocol. Nineteen DBT consumers in two public mental health agencies targeted for implementation of DBT + DBT PE participated in focus groups and completed questionnaires assessing treatment preferences and expectancies. Consumers reported positive treatment expectancies and a strong preference for DBT with DBT PE (89.5%) over DBT alone (5.3%) or PE alone (5.3%). This was primarily due to beliefs about the treatment’s efficacy, a perceived need for PTSD treatment, and the stage-based approach. Consumer-focused strategies for increasing uptake and reach of TF-EBPs are discussed.

Delivering Dialectical Behavior Therapy (DBT) with adherence to the manual is a critical aspect of quality assurance and leads to better outcomes for clients. However, DBT is a challenging treatment to deliver adherently as it requires therapists to learn many strategies and to know when and how to apply them effectively. To date, little is known about the degree to which therapists in routine care deliver DBT adherently or what adherence challenges may be most common in these settings. This paper presents data from two studies in which the DBT Adherence Coding Scale (Linehan, M. M., & Korslund, K. E. (2003). Dialectical behavior therapy adherence coding scale manual. University of Washington.) was used to evaluate 158 DBT individual therapy sessions delivered by 63 therapists to 78 clients in routine practice (non-academic or research) settings. Nearly all therapists (98.4%) had read the DBT manual and attended DBT workshops (M = 17.9 days). Across studies, therapists delivered DBT individual therapy slightly below adherence on average (M = 3.96, SD = 0.18; cut-off for adherence = 4.00). Overall, 54.4% of sessions were adherent and 45.6% of sessions were non-adherent. On average, therapists exhibited highest adherence for acceptance-oriented strategies, moderate adherence for structural strategies, and lowest adherence for change-oriented and dialectical strategies. Informed by these results, we provide recommendations for how to improve adherence for the strategies most frequently delivered non-adherently as well as how to increase use of underutilized strategies.

The overall goal of the study was to identify functional and behavioral differences between individuals with higher tinnitus distress and individuals with lower tinnitus distress. Subsequent exploratory analyses were conducted to investigate the role physical activity may have on the observed results between high and low distress groups. The purpose of the experiment was to identify brain regions to be targeted in future intervention studies for tinnitus. A total of 32 individuals with varying levels of tinnitus severity were recruited from the Urbana-Champaign area. Volunteers were divided into higher tinnitus distress (HD) and lower tinnitus distress (LD) groups. Note that these groups also significantly differed based on physical activity level and were subsequently stratified into higher and lower physical activity level subgroups for exploratory analysis. While in a functional magnetic resonance imaging (fMRI) scanner, subjects listened to affective sounds classified as pleasant, neutral or unpleasant from the International Affective Digital Sounds database. The HD group recruited amygdala and parahippocampus to a greater extent than the LD group when listening to affective sounds. The LD group engaged frontal regions to a greater extent when listening to the affective stimuli compared to the HD group. Both higher physical activity level subgroups recruited more frontal regions, and both lower levels of physical activity subgroups recruited more limbic regions respectively. Individuals with lower tinnitus distress may utilize frontal regions to better control their emotional response to affective sounds. Our analysis also suggests physical activity may contribute to lower tinnitus severity and greater engagement of the frontal cortices. We suggest that future intervention studies focus on changes in the function of limbic and frontal regions when evaluating the efficacy of treatment. Additionally, we recommend further investigation concerning the impact of physical activity level on tinnitus distress.