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Sevasemten (EDG-5506) is a selective inhibitor of fast skeletal muscle myosin, designed to protect skeletal muscle from contraction-induced injury in Becker and Duchenne muscular dystrophy. In a Phase 1b open-label study (ARCH, NCT05160415), adults with BMD (N=12) were administered 10-20 mg of sevasemten daily for up to 24 months. We previously observed rapid reductions in muscle injury biomarkers, including creatine kinase (CK) and fast skeletal Troponin I (TNNI2), which were maintained through 12 months. Here, we used Somascan proteomic analysis to assess changes in muscle injury biomarkers and muscle fiber type-specific proteins with continued treatment up to 24 months. We also characterize the plasma proteomic changes characteristic of chronic sevasemten administration. Circulating levels of TNNI2 and CK decreased significantly (p = 0.01 and 0.05, respectively) after short-term sevasemten treatment (1 – 2 months) and were maintained at low levels throughout the study period of 24 months. Similarly, an expanded set of proteins specific to contraction-induced skeletal muscle injury were quickly and robustly reduced following sevasemten treatment through the duration of the study. Further, reduced levels of proteins suggestive of muscle protection were associated with fast fiber-specific subsets over that of slow fiber subsets. Multivariate analysis also identified a subset of proteins that were specific to chronic administration that were observed to be unchanged at short-term time points. This subset was highly enriched with proteins associated with inflammatory and tissue remodeling processes. Several individual proteins associated with pro- or anti-inflammatory responses were shifted towards levels seen in sex-matched unaffected individuals. We demonstrate that circulating indicators of muscle injury are reduced after short-term sevasemten therapy and maintained through 24 months of treatment. Further, we show that chronic treatment with sevasemten elicits changes to inflammatory proteomic signatures that shift towards those seen in healthy individuals. [ABSTRACT FROM AUTHOR]

Fast (Type II) muscle fibers are affected early and disproportionately in dystrophinopathies. Sevasemten (EDG-5506) is an orally administered, once daily, investigational product that modulates fast skeletal muscle myosin and, in DMD disease models, decreased muscle damage biomarkers and fibrosis while increasing muscle strength and activity. ARCH is a 24-month Phase 1b open-label study of sevasemten, assessing safety, pharmacokinetics, biomarkers of muscle damage and functional measures in adults with Becker. Twelve ambulatory adults with Becker received daily oral doses of sevasemten. At baseline, North Star Ambulatory Assessment (NSAA) ranged from 5 to 31 (mean 15.5). Decreased muscle mass was evident by low serum creatinine and DXA lean muscle mass. After 24 months, sevasemten was well tolerated without serious adverse events, withdrawals due to AEs, or dose modifications. Rapid (within 1-2 months) reductions in biomarkers of muscle damage were sustained to 24 months, including creatine kinase, myoglobin and fast skeletal muscle troponin I. Alongside acute and chronic biomarker changes, trends toward functional improvement were noted with NSAA with a mean change of -0.2 versus an expected decline of -2.4 or more as predicted from natural history (Bello 2016, Van de Velde 2021, De Wel 2024). The 100-meter timed test and grip strength were unchanged over 24 months. In summary, sevasemten was well tolerated with rapid and sustained reductions in biomarkers of muscle damage. Treatment resulted in acute and sustained reductions in muscle damage biomarkers. Functional improvements compared to the expected natural history decline in the NSAA score were observed. Phase 2 trials in BMD and DMD are ongoing (NCT05291091 and NCT05540860) including a pivotal cohort in Becker. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have indicated that virtual treatments for eating disorders (EDs) are roughly as effective as are in-person treatments; the present nonrandomized study aimed to expand on the current body of evidence by comparing outcomes from a virtual day treatment program with those of an in-person program in an adult ED sample., Method: Participants were 109 patients who completed at least 60% of day treatment sessions (n = 55 in-person and n = 54 virtual). Outcome measures included ED and comorbid symptoms, and motivation., Results: Linear mixed models showed that global EDE-Q scores decreased during treatment (AIC = 376.396, F = 10.94, p = 0.002), irrespective of treatment modality (p = 0.186). BMI significantly increased over time (AIC = 389.029, F = 27.97, p < 0.001), with no effect of treatment modality (p = 0.779)., Discussion: Our findings suggest that the virtual delivery of day treatments produces comparable outcomes to those obtained using in-person formats, and that virtual formats may represent a pragmatic treatment option, especially in situations in which access to in-person care is limited., (© 2024 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural "blueprints" may fundamentally constrain neuroplastic change, e.g. in response to sensory deprivation. Here, we trained 12 blind participants and 14 sighted participants in echolocation over a 10-week period, and used MRI in a pre-post design to measure functional and structural brain changes. We found that blind participants and sighted participants together showed a training-induced increase in activation in left and right V1 in response to echoes, a finding difficult to reconcile with the view that sensory cortex is strictly organized by modality. Further, blind participants and sighted participants showed a training induced increase in activation in right A1 in response to sounds per se (i.e. not echo-specific), and this was accompanied by an increase in gray matter density in right A1 in blind participants and in adjacent acoustic areas in sighted participants. The similarity in functional results between sighted participants and blind participants is consistent with the idea that reorganization may be governed by similar principles in the two groups, yet our structural analyses also showed differences between the groups suggesting that a more nuanced view may be required., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change. The aim of the present study was to describe the development and examine the psychometric properties, user satisfaction and rated potentials for practical use of our application., Methods: The content of our application was based on concepts derived from self-determination theory, the transtheoretical model of change, and cognitive theory. The application was developed by a multidisciplinary team of clinicians, researchers, staff members and individuals with lived ED experience, each being involved in all steps of the application's development. We tested validity, reliability, satisfaction and perceived feasibility for clinical implementation in an independent sample of 15 patients with an ED and 13 clinicians specialized in ED treatment. Psychometric properties were evaluated using descriptive statistics, correlations, content validity indices and intraclass coefficients. Differences in satisfaction ratings and perceived potential for clinical implementation of the application between clinicians and patients were examined using Mann-Whitney U tests., Results: The digital application showed excellent validity (mean i-CVI: .93, range: .86-.96) and internal reliability (all Cronbach alpha's > .88). Patients and clinicians both considered the application acceptable, appropriate, and feasible for use in clinical practice., Conclusions: Findings suggest that our transdiagnostic interactive application has excellent psychometric properties. Furthermore, patients and clinicians alike were positive about the possible use of the application in clinical practice. The next step will be to investigate the application's effectiveness as an intervention to promote autonomous motivation and to facilitate remission in people on the waitlist for specialized ED treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Despite availability of evidence-based treatments for eating disorders (EDs), individuals with EDs often do not receive informed treatment. Training of non-specialized clinicians by experienced professionals through knowledge exchange (KE) programs is an effective way to enhance accessibility to evidence-based treatments for EDs. The authors conducted a qualitative analysis of factors that facilitated or impeded the uptake of an ED-focused KE program. Semi-structured interviews were conducted with mental health professionals (n = 43) and managers (n = 11) at 13 community mental-health sites at which the KE program was offered. Data were analyzed using a qualitative content analysis. Key facilitators identified were management support for the program and building competence through ongoing supervision of clinicians. Main barriers were limited access to ED patients to treat and having insufficient time to apply ED interventions in front-line settings. The results provide insights into the practical imperatives involved in implementing a KE initiative for ED treatment., (© 2022. National Council for Mental Wellbeing.)

In the investigation of the brain areas involved in human spatial navigation, the traditional focus has been on visually guided navigation in sighted people. Consequently, it is unclear whether the involved areas also support navigational abilities in other modalities. We explored this possibility by testing whether the occipital place area (OPA), a region associated with visual boundary-based navigation in sighted people, has a similar role in echo-acoustically guided navigation in blind human echolocators. We used fMRI to measure brain activity in 6 blind echolocation experts (EEs; five males, one female), 12 blind controls (BCs; six males, six females), and 14 sighted controls (SCs; eight males, six females) as they listened to prerecorded echolocation sounds that conveyed either a route taken through one of three maze environments, a scrambled (i.e., spatiotemporally incoherent) control sound, or a no-echo control sound. We found significantly greater activity in the OPA of EEs, but not the control groups, when they listened to the coherent route sounds relative to the scrambled sounds. This provides evidence that the OPA of the human navigation brain network is not strictly tied to the visual modality but can be recruited for nonvisual navigation. We also found that EEs, but not BCs or SCs, recruited early visual cortex for processing of echo acoustic information. This is consistent with the recent notion that the human brain is organized flexibly by task rather than by specific modalities. SIGNIFICANCE STATEMENT There has been much research on the brain areas involved in visually guided navigation, but we do not know whether the same or different brain regions are involved when blind people use a sense other than vision to navigate. In this study, we show that one part of the brain (occipital place area) known to play a specific role in visually guided navigation is also active in blind human echolocators when they use reflected sound to navigate their environment. This finding opens up new ways of understanding how people navigate, and informs our ability to provide rehabilitative support to people with vision loss., (Copyright © 2023 the authors.)

Click-based echolocation can support mobility and orientation in people with vision impairments (VI) when used alongside other mobility methods. Only a small number of people with VI use click-based echolocation. Previous research about echolocation addresses the skill of echolocation per se to understand how echolocation works, and its brain basis. Our report is the first to address the question of professional practice for people with VI, i.e., a very different focus. VI professionals are well placed to affect how a person with VI might learn about, experience or use click-based echolocation. Thus, we here investigated if training in click-based echolocation for VI professionals might lead to a change in their professional practice. The training was delivered via 6-h workshops throughout the UK. It was free to attend, and people signed up via a publicly available website. We received follow-up feedback in the form of yes/no answers and free text comments. Yes/no answers showed that 98% of participants had changed their professional practice as a consequence of the training. Free text responses were analysed using content analysis, and we found that 32%, 11.7% and 46.6% of responses indicated a change in information processing, verbal influencing or instruction and practice, respectively. This attests to the potential of VI professionals to act as multipliers of training in click-based echolocation with the potential to improve the lives of people with VI. The training we evaluated here could feasibly be integrated into VI Rehabilitation or VI Habilitation training as implemented at higher education institutions (HEIs) or continuing professional development (CPD)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Thaler, Di Gregorio and Foresteire.)

Objectives: Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion., Methods: We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED., Results: Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups ( Q  < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3 , CSGALNACT1, NEGR1 , NR1H3 ) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation., Conclusions: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.

Purpose: Self-determination theory suggests that autonomous motivation for change (i.e., motivation that is internal and self-endorsed) can be enhanced in therapeutic contexts by clinicians acting in an autonomy supportive manner. While previous research has established a link between autonomy support (AS) and autonomous motivation in enhancing outcomes in eating disorder (ED) treatment, few studies have examined factors that support or hinder therapists' ability to be autonomy supportive in the context of an ED therapeutic encounter. The goal of the present study was to conduct a qualitative analysis of personal and contextual factors that facilitated or hindered therapists' ability to provide autonomy supportive interventions., Methods: Semi-structured interviews were conducted with 10 therapists conducting outpatient psychotherapy at a specialized eating disorders treatment program. Data were analyzed using thematic analysis., Results: The most frequently noted facilitators were organizational support of AS interventions and patients' engagement and motivation for treatment. The most frequently noted barriers were patients' personality variables such as patients that exhibit passive and help-rejecting behaviours, as well as therapists feeling overwhelmed due to a high workload., Conclusion: Our results provide insight into the factors that facilitate and impede the utilization of an autonomy supportive approach in specialized ED treatment and can be used to inform future quantitative research on such factors., Level of Evidence: Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Here, we report novel empirical results from a psychophysical experiment in which we tested the echolocation abilities of nine blind adult human experts in click-based echolocation. We found that they had better acuity in localizing a target and used lower intensity emissions (i.e., mouth clicks) when a target was placed 45° off to the side compared with when it was placed at 0° (straight ahead). We provide a possible explanation of the behavioral result in terms of binaural-intensity signals, which appear to change more rapidly around 45°. The finding that echolocators have better echo-localization off axis is surprising, because for human source localization (i.e., regular spatial hearing), it is well known that performance is best when targets are straight ahead (0°) and decreases as targets move farther to the side. This may suggest that human echolocation and source hearing rely on different acoustic cues and that human spatial hearing has more facets than previously thought.

Although treatment dropout is common among patients with eating disorders, very few studies have examined predictors of non-completion in day treatment. We investigated various potential predictors of dropout from adult day treatment. Participants were 295 adult patients with a diagnosis of Anorexia Nervosa (restricting or binge-eating/purging subtype), Bulimia Nervosa (BN), Other Specified Feeding or Eating Disorder, or Avoidant Restrictive Food Intake Disorder. Predictors included eating-disorder characteristics, motivation at the commencement of treatment, Body Mass Index (BMI), time spent in treatment and personality dimensions. Logistic regression analyses showed that for patients with a BMI of less than 20 at the start of treatment, low BMI was a significant predictor of staff-initiated termination due to not meeting weight gain goals. Furthermore, completing less than 6 weeks of treatment was associated with staff-initiated termination. For the whole sample, those with higher changes in weight over the course of treatment were less likely to terminate prematurely. None of the other predictor variables yielded significant results. Results of the current study highlight characteristics of patients who are more likely not to complete day treatment and can help identify patients who may be at risk for not succeeding in multi-diagnostic day treatment programs., (© 2021 Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: Findings show virtual therapy (conducted using internet-based videoconferencing techniques) to be a viable alternative to in-person therapy for a variety of mental-health problems. COVID-19 social-distancing imperatives required us to substitute virtual interventions for in-person sessions routinely offered in our outpatient eating disorder (ED) program-and afforded us an opportunity to compare the two treatment formats for clinical efficacy., Methods: Using self-report assessments, we compared outcomes in a historical sample of 49 adults with heterogeneous EDs (treated in-person over 10-14 weeks in individual and group therapies) to those of 76 patients receiving comparable virtual treatments, at distance, during the COVID-19 outbreak. Linear mixed models were used to study symptom changes over time and to test for differential effects of treatment modality., Results: Participants in both groups showed similar improvements on eating symptoms, levels of weight gain (in individuals in whom gain was indicated), and satisfaction with services., Discussion: Our results suggest that short-term clinical outcomes with virtual and in-person ED therapies are comparable, and point to potentials of virtual therapy for situations in which geographical distance or other barriers impede physical access to trained therapists or specialized treatments., (© 2021 Wiley Periodicals LLC.)

What factors are important in the calibration of mental representations of auditory space? A substantial body of research investigating the audiospatial abilities of people who are blind has shown that visual experience might be an important factor for accurate performance in some audiospatial tasks. Yet, it has also been shown that long-term experience using click-based echolocation might play a similar role, with blind expert echolocators demonstrating auditory localization abilities that are superior to those of people who are blind and who do not use click-based echolocation by Vercillo et al. (Neuropsychologia 67: 35-40, 2015). Based on this hypothesis we might predict that training in click-based echolocation may lead to improvement in performance in auditory localization tasks in people who are blind. Here we investigated this hypothesis in a sample of 12 adult people who have been blind from birth. We did not find evidence for an improvement in performance in auditory localization after 10 weeks of training despite significant improvement in echolocation ability. It is possible that longer-term experience with click-based echolocation is required for effects to develop, or that other factors can explain the association between echolocation expertise and superior auditory localization. Considering the practical relevance of click-based echolocation for people who are visually impaired, future research should address these questions., (© 2021. The Author(s).)

Understanding the factors that determine if a person can successfully learn a novel sensory skill is essential for understanding how the brain adapts to change, and for providing rehabilitative support for people with sensory loss. We report a training study investigating the effects of blindness and age on the learning of a complex auditory skill: click-based echolocation. Blind and sighted participants of various ages (21-79 yrs; median blind: 45 yrs; median sighted: 26 yrs) trained in 20 sessions over the course of 10 weeks in various practical and virtual navigation tasks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, sighted people performed better than those who were blind in some cases, although our analyses suggest that this might be better explained by the younger age (or superior binaural hearing) of the sighted group. Importantly, however, neither age nor blindness was a limiting factor in participants' rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing. Overall, our results suggest that the ability to learn click-based echolocation is not strongly limited by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss., Competing Interests: The authors have declared that no competing interests exist.

Making sense of the world requires perceptual constancy-the stable perception of an object across changes in one's sensation of it. To investigate whether constancy is intrinsic to perception, we tested whether humans can learn a form of constancy that is unique to a novel sensory skill (here, the perception of objects through click-based echolocation). Participants judged whether two echoes were different either because: (a) the clicks were different, or (b) the objects were different. For differences carried through spectral changes (but not level changes), blind expert echolocators spontaneously showed a high constancy ability (mean d' = 1.91) compared to sighted and blind people new to echolocation (mean d' = 0.69). Crucially, sighted controls improved rapidly in this ability through training, suggesting that constancy emerges in a domain with which the perceiver has no prior experience. This provides strong evidence that constancy is intrinsic to human perception. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The human brain may use recent sensory experience to create sensory templates that are then compared to incoming sensory input, that is, "knowing what to listen for." This can lead to greater perceptual sensitivity, as long as the relevant properties of the target stimulus can be reliably estimated from past sensory experiences. Echolocation is an auditory skill probably best understood in bats, but humans can also echolocate. Here we investigated for the first time whether echolocation in humans involves the use of sensory templates derived from recent sensory experiences. Our results showed that when there was certainty in the acoustic properties of the echo relative to the emission, either in temporal onset, spectral content or level, people detected the echo more accurately than when there was uncertainty. In addition, we found that people were more accurate when the emission's spectral content was certain but, surprisingly, not when either its level or temporal onset was certain. Importantly, the lack of an effect of temporal onset of the emission is counter to that found previously for tasks using nonecholocation sounds, suggesting that the underlying mechanisms might be different for echolocation and nonecholocation sounds. Importantly, the effects of stimulus certainty were no different for people with and without experience in echolocation, suggesting that stimulus-specific sensory templates can be used in a skill that people have never used before. From an applied perspective our results suggest that echolocation instruction should encourage users to make clicks that are similar to one another in their spectral content. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness., Method: We compared plasma levels of one-carbon metabolism nutrients across women with active AN (AN-Active: n = 53), in remission from AN (AN-Remitted: n = 40), or who had no eating-disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre- to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating-disorder symptoms were assessed by interview and self-report., Results: Compared to NED individuals, AN-Active individuals exhibited significantly elevated B12 and (less-reliably) betaine. In AN-Active individuals, lower BMI was associated with higher B12., Discussion: The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects., (© 2020 Wiley Periodicals, Inc.)

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to psychiatric disorder phenotypes, such as anorexia nervosa (AN). The oxytocin receptor (OXTR) gene is epigenetically regulated, and studies have shown associations between OXTR and social behaviours in various samples, including women with AN. The present study examined differential levels of methylation at various CG sites of the OXTR gene in 69 women with active AN (AN-Active), 21 in whom AN was in remission (AN-Rem) and 35 with no eating disorder (NED). Within each group, we explored the correlation between methylation and measures of social behaviour such as insecure attachment and social avoidance. Hypermethylation of a number of CG sites was seen in AN-Active participants as compared with AN-Rem and NED participants. In the AN-Rem sample, methylation at CG27501759 was significantly positively correlated with insecure attachment (r = .614, p = .003, permutation Q = 0.008) and social avoidance (r = .588, p = .005, permutation Q = 0.0184). Our results highlight differential methylation of the OXTR gene among women with AN, those in remission from AN, and those who never had AN and provide some evidence of associations between OXTR methylation and social behaviour in women remitted from AN., (© 2019 John Wiley & Sons, Ltd and Eating Disorders Association.)

People use sensory, in particular visual, information to guide actions such as walking around obstacles, grasping or reaching. However, it is presently unclear how malleable the sensorimotor system is. The present study investigated this by measuring how click-based echolocation may be used to avoid obstacles while walking. We tested 7 blind echolocation experts, 14 sighted, and 10 blind echolocation beginners. For comparison, we also tested 10 sighted participants, who used vision. To maximize the relevance of our research for people with vision impairments, we also included a condition where the long cane was used and considered obstacles at different elevations. Motion capture and sound data were acquired simultaneously. We found that echolocation experts walked just as fast as sighted participants using vision, and faster than either sighted or blind echolocation beginners. Walking paths of echolocation experts indicated early and smooth adjustments, similar to those shown by sighted people using vision and different from later and more abrupt adjustments of beginners. Further, for all participants, the use of echolocation significantly decreased collision frequency with obstacles at head, but not ground level. Further analyses showed that participants who made clicks with higher spectral frequency content walked faster, and that for experts higher clicking rates were associated with faster walking. The results highlight that people can use novel sensory information (here, echolocation) to guide actions, demonstrating the action system's ability to adapt to changes in sensory input. They also highlight that regular use of echolocation enhances sensory-motor coordination for walking in blind people. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cue combination occurs when two independent noisy perceptual estimates are merged together as a weighted average, creating a unified estimate that is more precise than either single estimate alone. Surprisingly, this effect has not been demonstrated compellingly in children under the age of 10 years, in contrast with the array of other multisensory skills that children show even in infancy. Instead, across a wide variety of studies, precision with both cues is no better than the best single cue - and sometimes worse. Here we provide the first consistent evidence of cue combination in children from 7 to 10 years old. Across three experiments, participants showed evidence of a bimodal precision advantage (Experiments 1a and 1b) and the majority were best-fit by a combining model (Experiment 2). The task was to localize a target horizontally with a binaural audio cue and a noisy visual cue in immersive virtual reality. Feedback was given as well, which could both (a) help participants judge how reliable each cue is and (b) help correct between-cue biases that might prevent cue combination. Crucially, our results show cue combination when feedback is only given on single cues - therefore, combination itself was not a strategy learned via feedback. We suggest that children at 7-10 years old are capable of cue combination in principle, but must have sufficient representations of reliabilities and biases in their own perceptual estimates as relevant to the task, which can be facilitated through task-specific feedback., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The functional specializations of cortical sensory areas were traditionally viewed as being tied to specific modalities. A radically different emerging view is that the brain is organized by task rather than sensory modality, but it has not yet been shown that this applies to primary sensory cortices. Here, we report such evidence by showing that primary 'visual' cortex can be adapted to map spatial locations of sound in blind humans who regularly perceive space through sound echoes. Specifically, we objectively quantify the similarity between measured stimulus maps for sound eccentricity and predicted stimulus maps for visual eccentricity in primary 'visual' cortex (using a probabilistic atlas based on cortical anatomy) to find that stimulus maps for sound in expert echolocators are directly comparable to those for vision in sighted people. Furthermore, the degree of this similarity is positively related with echolocation ability. We also rule out explanations based on top-down modulation of brain activity-e.g. through imagery. This result is clear evidence that task-specific organization can extend even to primary sensory cortices, and in this way is pivotal in our reinterpretation of the functional organization of the human brain.

Some people who are blind have trained themselves in echolocation using mouth clicks. Here, we provide the first report of psychophysical and clicking data during echolocation of distance from a group of 8 blind people with experience in mouth click-based echolocation (daily use for > 3 years). We found that experienced echolocators can detect changes in distance of 3 cm at a reference distance of 50 cm, and a change of 7 cm at a reference distance of 150 cm, regardless of object size (i.e. 28.5 cm vs. 80 cm diameter disk). Participants made mouth clicks that were more intense and they made more clicks for weaker reflectors (i.e. same object at farther distance, or smaller object at same distance), but number and intensity of clicks were adjusted independently from one another. The acuity we found is better than previous estimates based on samples of sighted participants without experience in echolocation or individual experienced participants (i.e. single blind echolocators tested) and highlights adaptation of the perceptual system in blind human echolocators. Further, the dynamic adaptive clicking behaviour we observed suggests that number and intensity of emissions serve separate functions to increase SNR. The data may serve as an inspiration for low-cost (i.e. non-array based) artificial 'cognitive' sonar and radar systems, i.e. signal design, adaptive pulse repetition rate and intensity. It will also be useful for instruction and guidance for new users of echolocation.

Objective: Although hospitalization is sometimes necessary when treating individuals with anorexia nervosa, the available literature provides limited guidance to inform decisions surrounding optimal components or duration of inpatient treatments. We report observational data comparing outcomes of two inpatient treatments. The first was longer and more strictly structured around a Contingency Management Protocol (CMP) emphasizing external incentives for achieving weight-restoration goals; the second was a shorter Autonomy Support Protocol (ASP) that progressively increased patient autonomy around meal management without external incentives., Method: We compared data from 41 patients who participated in the ASP to a historical sample of 41 patients treated using the CMP. At admission, discharge, and post-treatment follow-up, participants completed the Eating Disorder Examination Questionnaire and the Behavior and Symptom Identification Scale-32, and we measured height and weight to compute body mass index., Results: Multilevel modeling analyses that controlled for time in treatment and time in follow-up indicated the two protocols yielded equivalent in-treatment gains and post-treatment loss of gains., Discussion: Our results indicate that shorter inpatient stays emphasizing autonomous control over eating behavior may yield outcomes that are equivalent to those of lengthier, more stringent, and more costly approaches implicating external incentives and controls., (© 2019 Wiley Periodicals, Inc.)

Patients with injury to early visual cortex or its inputs can display the Riddoch phenomenon: preserved awareness for moving but not stationary stimuli. We provide a detailed case report of a patient with the Riddoch phenomenon, MC. MC has extensive bilateral lesions to occipitotemporal cortex that include most early visual cortex and complete blindness in visual field perimetry testing with static targets. Nevertheless, she shows a remarkably robust preserved ability to perceive motion, enabling her to navigate through cluttered environments and perform actions like catching moving balls. Comparisons of MC's structural magnetic resonance imaging (MRI) data to a probabilistic atlas based on controls reveals that MC's lesions encompass the posterior, lateral, and ventral early visual cortex bilaterally (V1, V2, V3A/B, LO1/2, TO1/2, hV4 and VO1 in both hemispheres) as well as more extensive damage to right parietal (inferior parietal lobule) and left ventral occipitotemporal cortex (VO1, PHC1/2). She shows some sparing of anterior occipital cortex, which may account for her ability to see moving targets beyond ~15 degrees eccentricity during perimetry. Most strikingly, functional and structural MRI revealed robust and reliable spared functionality of the middle temporal motion complex (MT+) bilaterally. Moreover, consistent with her preserved ability to discriminate motion direction in psychophysical testing, MC also shows direction-selective adaptation in MT+. A variety of tests did not enable us to discern whether input to MT+ was driven by her spared anterior occipital cortex or subcortical inputs. Nevertheless, MC shows rich motion perception despite profoundly impaired static and form vision, combined with clear preservation of activation in MT+, thus supporting the role of MT+ in the Riddoch phenomenon., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: This study explored state-related tendencies in DNA methylation in people with anorexia nervosa., Methods: We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained post-intervention methylation data from 52 of the women from the active group., Results: Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction., Limitations: Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use., Conclusion: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components., Competing Interests: A. Labbe and R. Joober are members of the journal editorial board; they were not involved in the evaluation or acceptence of this manuscript for publication. R. Joober reports clinician-​scientist salary awards from Fonds de recherche du Quebec outside the scope of this work. He participates on the advisory boards and speakers bureaus of Pfizer, Janssen Ortho, Otsuka, Lundbeck, Purdue and Myelin and has received honoraria from those companies. He also reports honoraria from Shire and royalties from Henry Stewart Talks. No other authors have declared competing interests., (© 2019 Joule Inc. or its licensors)

Humans are effective at dealing with noisy, probabilistic information in familiar settings. One hallmark of this is Bayesian Cue Combination: combining multiple noisy estimates to increase precision beyond the best single estimate, taking into account their reliabilities. Here we show that adults also combine a novel audio cue to distance, akin to human echolocation, with a visual cue. Following two hours of training, subjects were more precise given both cues together versus the best single cue. This persisted when we changed the novel cue's auditory frequency. Reliability changes also led to a re-weighting of cues without feedback, showing that they learned something more flexible than a rote decision rule for specific stimuli. The main findings replicated with a vibrotactile cue. These results show that the mature sensory apparatus can learn to flexibly integrate new sensory skills. The findings are unexpected considering previous empirical results and current models of multisensory learning.

We describe the implementation and impact of a province-wide program of knowledge exchange (KE), aimed at developing capacity for the treatment of people with eating disorders (EDs). The program is designed to equip clinicians working in nonspecialized health-care installations with skills to evaluate and treat people with EDs. Trainings were conducted at 21 institutions. The majority of clinicians reported satisfaction with the KE program and indicated that the trainings enhanced their confidence and ability to treat patients with EDs. A subset of clinicians received case supervision with a specialist ED therapist and followed patients with EDs (n = 119). Treated patients showed significant improvements on eating and depressive symptoms, and reported satisfaction with the treatments they received.

The original version of this article unfortunately contained a mistake in EAT-26 values under "Patients Receiving Treatment for an ED in their Sector" section.

Objective: Across diverse clinical problems, therapists' autonomy support has been found to increase patients' autonomous motivation for change. Being self-motivated has, in turn, been linked to superior treatment response. In people undergoing outpatient eating disorder (ED) treatment, we examined associations among ratings of autonomy support received from therapists and other carers, self-reported engagement in therapy, and clinical outcomes., Method: Ninety-seven women with anorexia nervosa, bulimia nervosa, or a related ED provided measures of motivational status and clinical symptoms at the beginning and end of time-limited (12-16 weeks) segments of specialized treatment. At mid-treatment, patients also rated the extent to which they perceived their individual therapists, group therapists, group-therapy peers, family members, friends, and romantic partners as being autonomy supportive., Results: Overall, multiple regression analyses indicated autonomy support to moderate (rather than mediate) the link between initial autonomous motivation and later change in autonomous motivation-with results indicating that, independently of ED diagnosis or treatment intensity, greater perceived autonomy support (from therapists and nontherapists alike) coincided with larger increases in autonomous motivation over the course of therapy. In turn, higher autonomous motivation at end-of-therapy coincided with larger reductions in eating symptoms., Discussion: Findings suggest that the experience of autonomy support (from therapists and nontherapists) is associated with increasing motivation in people undergoing ED treatment, and that becoming self-motivated is linked to better outcomes. Such results indicate that support from therapists, relatives, and peers can favorably influence personal engagement in individuals undergoing ED treatment., (© 2017 Wiley Periodicals, Inc.)

Echolocation is the ability to use sound-echoes to infer spatial information about the environment. Some blind people have developed extraordinary proficiency in echolocation using mouth-clicks. The first step of human biosonar is the transmission (mouth click) and subsequent reception of the resultant sound through the ear. Existing head-related transfer function (HRTF) data bases provide descriptions of reception of the resultant sound. For the current report, we collected a large database of click emissions with three blind people expertly trained in echolocation, which allowed us to perform unprecedented analyses. Specifically, the current report provides the first ever description of the spatial distribution (i.e. beam pattern) of human expert echolocation transmissions, as well as spectro-temporal descriptions at a level of detail not available before. Our data show that transmission levels are fairly constant within a 60° cone emanating from the mouth, but levels drop gradually at further angles, more than for speech. In terms of spectro-temporal features, our data show that emissions are consistently very brief (~3ms duration) with peak frequencies 2-4kHz, but with energy also at 10kHz. This differs from previous reports of durations 3-15ms and peak frequencies 2-8kHz, which were based on less detailed measurements. Based on our measurements we propose to model transmissions as sum of monotones modulated by a decaying exponential, with angular attenuation by a modified cardioid. We provide model parameters for each echolocator. These results are a step towards developing computational models of human biosonar. For example, in bats, spatial and spectro-temporal features of emissions have been used to derive and test model based hypotheses about behaviour. The data we present here suggest similar research opportunities within the context of human echolocation. Relatedly, the data are a basis to develop synthetic models of human echolocation that could be virtual (i.e. simulated) or real (i.e. loudspeaker, microphones), and which will help understanding the link between physical principles and human behaviour.

Eating disorders (EDs) are characterized by intense preoccupation with shape and weight and maladaptive eating practices. The complex of symptoms that characterize EDs often arise through the activation of latent genetic potentials by environmental exposures, and epigenetic mechanisms are believed to link environmental exposures to gene expression. This chapter provides an overview of genetic factors acting in the etiology of EDs. It then provides a background to the hypothesis that epigenetic mechanisms link stresses such as obstetric complications and childhood abuse as well as effects of malnutrition to eating disorders (EDs). The chapter then summarizes the emerging body of literature on epigenetics and EDs-mainly studies on DNA methylation in samples of anorexia and bulimia. The available evidence base suggests that an epigenetically informed perspective contributes in valuable ways to the understanding of why people develop EDs.

Bats and dolphins are known for their ability to use echolocation. They emit bursts of sounds and listen to the echoes that bounce back to detect the objects in their environment. What is not as well-known is that some blind people have learned to do the same thing, making mouth clicks, for example, and using the returning echoes from those clicks to sense obstacles and objects of interest in their surroundings. The current review explores some of the research that has examined human echolocation and the changes that have been observed in the brains of echolocation experts. We also discuss potential applications and assistive technology based on echolocation. Blind echolocation experts can sense small differences in the location of objects, differentiate between objects of various sizes and shapes, and even between objects made of different materials, just by listening to the reflected echoes from mouth clicks. It is clear that echolocation may enable some blind people to do things that are otherwise thought to be impossible without vision, potentially providing them with a high degree of independence in their daily lives and demonstrating that echolocation can serve as an effective mobility strategy in the blind. Neuroimaging has shown that the processing of echoes activates brain regions in blind echolocators that would normally support vision in the sighted brain, and that the patterns of these activations are modulated by the information carried by the echoes. This work is shedding new light on just how plastic the human brain is. WIREs Cogn Sci 2016, 7:382-393. doi: 10.1002/wcs.1408 For further resources related to this article, please visit the WIREs website., (© 2016 Wiley Periodicals, Inc.)

Epigenetic mechanisms are believed to link environmental exposures to gene expression, and in so doing, to provide a physical basis for the activation, by life experiences, of mental-health problems. This paper provides a background to the hypothesis that epigenetic mechanisms link life stresses (perinatal, childhood and adult) and effects of malnutrition to the eating disorders (EDs). The paper reviews literature bearing upon the putative link between epigenetic factors and ED development, and examines ways in which epigenetic alterations could account for risk of eating disturbances and commonly associated behavioral and emotional problems. Ultimately, we propose that epigenetic processes provide an intriguing (although hypothetical) biological "platform" upon which ED-relevant effects of perinatal insults, life stresses, and consequences of malnutrition may be registered, and argue that an epigenetically informed understanding may explain why EDs are triggered and maintained by excessive caloric restraint, why they coincide so frequently with mood- and impulse-regulation problems, and why they tend to become increasingly entrenched over time. Finally, we comment on the clinical relevance and implications of an epigenetically informed model of ED etiology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: We explored the effect of autonomous and controlled motivation on outcomes for patients undergoing inpatient treatment for Anorexia Nervosa (AN)., Method: Data on 80 patients with AN were available for the start of treatment, and for 49 at end of treatment. Patients completed measures of autonomous and controlled motivation, eating disorder symptoms and attitudes, and comorbid psychopathology at the start and end of treatment., Results: Patients showed significant improvements on eating symptoms and comorbid psychopathology over the course of treatment. Autonomous motivation was a significant predictor of change in severity of eating symptoms and attitudes such that patients with higher pre-treatment levels of autonomous motivation showed larger post-treatment reductions on these indices. No such effects were associated with controlled motivation., Discussion: This study highlights a relationship between autonomous motivation and outcome in an inpatient setting. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:626-629)., (© 2016 Wiley Periodicals, Inc.)

Substance abuse is common in individuals with bulimia-spectrum (binge-purge) eating disturbances, a co-occurrence that has been attributed to shared neurobiological substrates--notably alterations in dopaminergic activity. We examined the implications of variations of selected, dopamine-relevant polymorphisms (DRD2 Taq1A, DRD4 7R, and COMT) for risk of substance abuse in women with binge-purge eating syndromes. We genotyped 183 women (66.1% showing full-threshold BN and 33.9% showing sub-syndromic variants), and assessed lifetime presence of alcohol, cannabis, cocaine, and stimulant abuse or dependence using structured interviews. Tests for main and interaction effects of various allele combinations revealed that individuals who carried high function COMT and low-function DRD4 7R alleles (a combination expected to be associated with higher risk) did indeed show more lifetime substance abuse and, specifically, more cannabis abuse. Our findings suggest that a gene combination that, in theory, codes for low levels of dopaminergic neurotransmission coincides with sensitivity to substance abuse in a sample displaying binge-purge eating-disorder variants., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants' was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation.

It is still an open question if the auditory system, similar to the visual system, processes auditory motion independently from other aspects of spatial hearing, such as static location. Here, we report psychophysical data from a patient (female, 42 and 44 years old at the time of two testing sessions), who suffered a bilateral occipital infarction over 12 years earlier, and who has extensive damage in the occipital lobe bilaterally, extending into inferior posterior temporal cortex bilaterally and into right parietal cortex. We measured the patient's spatial hearing ability to discriminate static location, detect motion and perceive motion direction in both central (straight ahead), and right and left peripheral auditory space (50° to the left and right of straight ahead). Compared to control subjects, the patient was impaired in her perception of direction of auditory motion in peripheral auditory space, and the deficit was more pronounced on the right side. However, there was no impairment in her perception of the direction of auditory motion in central space. Furthermore, detection of motion and discrimination of static location were normal in both central and peripheral space. The patient also performed normally in a wide battery of non-spatial audiological tests. Our data are consistent with previous neuropsychological and neuroimaging results that link posterior temporal cortex and parietal cortex with the processing of auditory motion. Most importantly, however, our data break new ground by suggesting a division of auditory motion processing in terms of speed and direction and in terms of central and peripheral space., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Research associates maternal stress exposures (especially when occurring late in gestation) with heightened risk of subsequent emotional and behavioral problems in affected offspring. However, as yet, no study has examined the association between prenatal maternal stress (PNMS) and affected children's risk of anorexia- or bulimia-type eating disturbances., Objective: To study the influences of PNMS on later disordered eating in exposed offspring., Method: We used the Eating Attitudes Test (EAT)-26 to measure eating attitudes and behaviors in 54 thirteen-year olds whose mothers had been exposed, while pregnant with these children, to the 1998 Quebec Ice Storm-a natural disaster regarded as a model of exposure to severe environmental stress. Mothers' stress was measured shortly after exposure to the storm using established indices of objective and subjective stress., Results: Hierarchical multiple linear regression analyses indicated that once variance owing to children's body mass index and sex was accounted for, stress exposures during the third trimester of pregnancy predicted elevated EAT-26 scores in affected children-perhaps even more so when levels of objective stress were high., Discussion: Third trimester exposure to PNMS, especially when objectively severe, seems to be associated with increased eating-disorder-linked manifestations in affected early adolescents., (© 2015 Wiley Periodicals, Inc.)