Cortico-limbic morphology separates tinnitus from tinnitus distress

Tinnitus is a common auditory disorder characterized by a chronic ringing or buzzing “in the ear.”Despite the auditory-perceptual nature of this disorder, a growing number of studies have reported neuroanatomical differences in tinnitus patients outside the auditory-perceptual system. Some have used this evidence to characterize chronic tinnitus as dysregulation of the auditory system, either resulting from inefficient inhibitory control or through the formation of aversive associations with tinnitus. It remains unclear, however, whether these “non-auditory” anatomical markers of tinnitus are related to the tinnitus signal itself, or merely to negative emotional reactions to tinnitus (i.e., tinnitus distress). In the current study, we used anatomical MRI to identify neural markers of tinnitus, and measured their relationship to a variety of tinnitus characteristics and other factors often linked to tinnitus, such as hearing loss, depression, anxiety, and noise sensitivity. In a new cohort of participants, we confirmed that people with chronic tinnitus exhibit reduced gray matter in ventromedial prefrontal cortex (vmPFC) compared to controls matched for age and hearing loss. This effect was driven by reduced cortical surface area, and was not related to tinnitus distress, symptoms of depression or anxiety, noise sensitivity, or other factors. Instead, tinnitus distress was positively correlated with cortical thickness in the anterior insula in tinnitus patients, while symptoms of anxiety and depression were negatively correlated with cortical thickness in subcallosal anterior cingulate cortex (scACC) across all groups. Tinnitus patients also exhibited increased gyrification of dorsomedial prefrontal cortex (dmPFC), which was more severe in those patients with constant (vs. intermittent) tinnitus awareness. Our data suggest that the neural systems associated with chronic tinnitus are different from those involved in aversive or distressed reactions to tinnitus

Hyporheic Exchange and Water Chemistry of Two Arctic Tundra Streams of Contrasting Geomorphology

The North Slope of Alaska’s Brooks Range is underlain by continuous permafrost, but an active layer of thawed sediments develops at the tundra surface and beneath streambeds during the summer, facilitating hyporheic exchange. Our goal was to understand how active layer extent and stream geomorphology influence hyporheic exchange and nutrient chemistry. We studied two arctic tundra streams of contrasting geomorphology: a high-gradient, alluvial stream with riffle-pool sequences and a low-gradient, peat-bottomed stream with large deep pools connected by deep runs. Hyporheic exchange occurred to ~50 cm beneath the alluvial streambed and to only ~15 cm beneath the peat streambed. The thaw bulb was deeper than the hyporheic exchange zone in both stream types. The hyporheic zone was a net source of ammonium and soluble reactive phosphorus in both stream types. The hyporheic zone was a net source of nitrate in the alluvial stream, but a net nitrate sink in the peat stream. The mass flux of nutrients regenerated from the hyporheic zones in these two streams was a small portion of the surface water mass flux. Although small, hyporheic sources of regenerated nutrients help maintain the in-stream nutrient balance. If future warming in the arctic increases the depth of the thaw bulb, it may not increase the vertical extent of hyporheic exchange. The greater impacts on annual contributions of hyporheic regeneration are likely to be due to longer thawed seasons, increased sediment temperatures or changes in geomorphology

Influence of Morphology and Permafrost Dynamics on Hyporheic Exchange in Arctic Headwater Streams under Warming Climate Conditions

We investigated surface-subsurface (hyporheic) exchange in two morphologically distinct arctic headwater streams experiencing warming (thawing) sub-channel conditions. Empirically parameterized and calibrated groundwater flow models were used to assess the influence of sub-channel thaw on hyporheic exchange. Average thaw depths were at least two-fold greater under the higher-energy, alluvial stream than under the lowenergy, peat-lined stream. Alluvial hyporheic exchange had shorter residence times and longer flowpaths that occurred across greater portions of the thawed sediments. For both reaches, the morphologic (longitudinal bed topography) and hydraulic conditions (surface and groundwater flow properties) set the potential for hyporheic flow. Simulations of deeper thaw, as predicted under a warming arctic climate, only influence hyporheic exchange until a threshold depth. This depth is primarily determined by the hydraulic head gradients imposed by the stream morphology. Therefore, arctic hyporheic exchange extent is likely to be independent of greater sub-stream thaw depths

Predictors of orbital convergence in primates: A test of the snake detection hypothesis of primate evolution

Traditional explanations for the evolution of high orbital convergence and stereoscopic vision in primates have focused on how stereopsis might have aided early primates in foraging or locomoting in an arboreal environment. It has recently been suggested that predation risk by constricting snakes was the selective force that favored the evolution of orbital convergence in early primates, and that later exposure to venomous snakes favored further degrees of convergence in anthropoid primates. Our study tests this snake detection hypothesis (SDH) by examining whether orbital convergence among extant primates is indeed associated with the shared evolutionary history with snakes or the risk that snakes pose for a given species. We predicted that orbital convergence would be higher in species that: 1) have a longer history of sympatry with venomous snakes, 2) are likely to encounter snakes more frequently, 3) are less able to detect or deter snakes due to group size effects, and 4) are more likely to be preyed upon by snakes. Results based on phylogenetically independent contrasts do not support the SDH. Orbital convergence shows no relationship to the shared history with venomous snakes, likelihood of encountering snakes, or group size. Moreover, those species less likely to be targeted as prey by snakes show significantly higher values of orbital convergence. Although an improved ability to detect camouflaged snakes, along with other cryptic stimuli, is likely a consequence of increased orbital convergence, this was unlikely to have been the primary selective force favoring the evolution of stereoscopic vision in primates

Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning

Understanding the spatial organization of tissues is of critical importance for both basic and translational research. While recent advances in tissue imaging are opening an exciting new window into the biology of human tissues, interpreting the data that they create is a significant computational challenge. Cell segmentation, the task of uniquely identifying each cell in an image, remains a substantial barrier for tissue imaging, as existing approaches are inaccurate or require a substantial amount of manual curation to yield useful results. Here, we addressed the problem of cell segmentation in tissue imaging data through large-scale data annotation and deep learning. We constructed TissueNet, an image dataset containing >1 million paired whole-cell and nuclear annotations for tissue images from nine organs and six imaging platforms. We created Mesmer, a deep learning-enabled segmentation algorithm trained on TissueNet that performs nuclear and whole-cell segmentation in tissue imaging data. We demonstrated that Mesmer has better speed and accuracy than previous methods, generalizes to the full diversity of tissue types and imaging platforms in TissueNet, and achieves human-level performance for whole-cell segmentation. Mesmer enabled the automated extraction of key cellular features, such as subcellular localization of protein signal, which was challenging with previous approaches. We further showed that Mesmer could be adapted to harness cell lineage information present in highly multiplexed datasets. We used this enhanced version to quantify cell morphology changes during human gestation. All underlying code and models are released with permissive licenses as a community resource

Direct effects of diazepam on emotional processing in healthy volunteers

RATIONALE: Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness. OBJECTIVES: The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers. MATERIALS AND METHODS: Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured. RESULTS: Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention. CONCLUSIONS: At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety

[Comment] Redefine statistical significance

The lack of reproducibility of scientific studies has caused growing concern over the credibility of claims of new discoveries based on “statistically significant” findings. There has been much progress toward documenting and addressing several causes of this lack of reproducibility (e.g., multiple testing, P-hacking, publication bias, and under-powered studies). However, we believe that a leading cause of non-reproducibility has not yet been adequately addressed: Statistical standards of evidence for claiming discoveries in many fields of science are simply too low. Associating “statistically significant” findings with P < 0.05 results in a high rate of false positives even in the absence of other experimental, procedural and reporting problems. For fields where the threshold for defining statistical significance is P<0.05, we propose a change to P<0.005. This simple step would immediately improve the reproducibility of scientific research in many fields. Results that would currently be called “significant” but do not meet the new threshold should instead be called “suggestive.” While statisticians have known the relative weakness of using P≈0.05 as a threshold for discovery and the proposal to lower it to 0.005 is not new (1, 2), a critical mass of researchers now endorse this change. We restrict our recommendation to claims of discovery of new effects. We do not address the appropriate threshold for confirmatory or contradictory replications of existing claims. We also do not advocate changes to discovery thresholds in fields that have already adopted more stringent standards (e.g., genomics and high-energy physics research; see Potential Objections below). We also restrict our recommendation to studies that conduct null hypothesis significance tests. We have diverse views about how best to improve reproducibility, and many of us believe that other ways of summarizing the data, such as Bayes factors or other posterior summaries based on clearly articulated model assumptions, are preferable to P-values. However, changing the P-value threshold is simple and might quickly achieve broad acceptance