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Abstract Sex and gender are inadequately considered in health and medical research, policy and practice, leading to preventable disparities in health and wellbeing. Several global institutions, journals, and funding bodies have developed policies and guidelines to improve the inclusion of diverse participants and consideration of sex and gender in research design and reporting and the delivery of clinical care. However, according to recent evaluations, these policies have had limited impact on the inclusion of diverse research participants, adequate reporting of sex and gender data and reducing preventable inequities in access to, and quality provision of, healthcare. In Australia, the Sex and Gender Policies in Medical Research (SGPMR) project aims to address sex and gender bias in health and medical research by (i) examining how sex and gender are currently considered in Australian research policy and practice; (ii) working with stakeholders to develop policy interventions; and (iii) understanding the wider impacts, including economic, of improved sex and gender consideration in Australian health and medical research. In this paper we describe the development of a theory of change (ToC) for the SGPMR project. The ToC evolved from a two-stage process consisting of key stakeholder interviews and a consultation event. The ToC aims to identify the pathways to impact from improved consideration of sex and gender in health and medical research, policy and practice, and highlight how key activities and policy levers can lead to improvements in clinical practice and health outcomes. In describing the development of the ToC, we present an entirely novel framework for outlining how sex and gender can be appropriately considered within the confines of health and medical research, policy and practice.

Abstract Background Refeeding syndrome is the gravest possible medical complication in malnourished patients undergoing refeeding in the hospital. We previously reported that males with malnutrition secondary to eating disorders required more calories and had longer hospital stays than females; however, sex differences in electrolyte abnormalities indicating refeeding syndrome risk remain unknown. The objective of this study was to assess differences in electrolyte abnormalities indicating refeeding syndrome risk among male and female adolescents and young adults with eating disorders hospitalized for medical instability. Methods We retrospectively reviewed the electronic medical records of 558 patients aged 9–25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability between May 2012 and August 2020. Serum was drawn per standard of care between 5 and 7 am each morning and electrolyte abnormalities indicating refeeding syndrome risk were defined as: hypophosphatemia (

Abstract The term ‘perspective’ in the context of economic evaluations and costing studies in healthcare refers to the viewpoint that an analyst has adopted to define the types of costs and outcomes to consider in their studies. However, there are currently notable variations in terms of methodological recommendations, definitions, and applications of different perspectives, depending on the objective or intended user of the study. This can make it a complex area for stakeholders when interpreting these studies. Consequently, there is a need for a comprehensive overview regarding the different types of perspectives employed in such analyses, along with the corresponding implications of their use. This is particularly important, in the context of low-and-middle-income countries (LMICs), where practical guidelines may be less well-established and infrastructure for conducting economic evaluations may be more limited. This article addresses this gap by summarising the main types of perspectives commonly found in the literature to a broad audience (namely the patient, payer, health care providers, healthcare sector, health system, and societal perspectives), providing their most established definitions and outlining the corresponding implications of their uses in health economic studies, with examples particularly from LMIC settings. We then discuss important considerations when selecting the perspective and present key arguments to consider when deciding whether the societal perspective should be used. We conclude that there is no one-size-fits-all answer to what perspective should be used and the perspective chosen will be influenced by the context, policymakers'/stakeholders’ viewpoints, resource/data availability, and intended use of the analysis. Moving forward, considering the ongoing issues regarding the variation in terminology and practice in this area, we urge that more standardised definitions of the different perspectives and the boundaries between them are further developed to support future studies and guidelines, as well as to improve the interpretation and comparison of health economic evidence.

Abstract Background Clinical trials using psilocybin therapy to treat anorexia nervosa (AN) are currently underway. The safety and tolerability of psilocybin is of utmost importance in individuals with AN who may present unique medical vulnerabilities. The purpose of this review is to describe how the common physiologic adverse effects of psilocybin may impact medical complications experienced by individuals with AN in clinical trials of psilocybin therapy. Main body The physiologic underpinnings of common adverse effects following psilocybin administration are described, including tachycardia, hypertension, electrocardiogram changes, nausea, headache, and lightheadedness. These anticipated physiologic changes are described in relation to the common medical correlates seen in individuals with AN. Risk mitigation strategies for each adverse effect are proposed. Conclusion Early evidence suggests that psilocybin therapy is well-tolerated in individuals with AN. Understanding the unique medical complications of AN, and how they may be impacted by common physiologic adverse effects of psilocybin administration, leads to tailored risk mitigation strategies to enhance safety and tolerability of this novel intervention.

Abstract The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Abstract Background Binge-eating disorder (BED) is the most common eating disorder phenotype and is linked to several negative health outcomes. Yet, little is known about the social epidemiology of BED, particularly in early adolescence. The objective of this study was to examine the associations between sociodemographic characteristics and BED and binge-eating behaviors in a large, national cohort of 10–14-year-old adolescents in the United States (U.S.) Methods We conducted a cross-sectional analysis of two-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study (2018 − 2020) that included 10,197 early adolescents (10 − 14 years, mean 12 years) in the U.S. Multivariable logistic regression models were used to assess the associations between sociodemographic characteristics and BED and binge-eating behaviors, defined based on the Kiddie Schedule for Affective Disorders and Schizophrenia. Results In this early adolescent sample (48.8% female, 54.0% White, 19.8% Latino/Hispanic, 16.1% Black, 5.4% Asian, 3.2% Native American, 1.5% Other), the prevalence of BED and binge-eating behaviors were 1.0% and 6.3%, respectively. Identifying as gay or bisexual (compared to heterosexual; adjusted odds ratio [AOR]: 2.25, 95% CI 1.01–5.01) and having a household income of less than $75,000 (AOR: 2.05, 95% CI: 1.21–3.46) were associated with greater odds of BED. Being male (AOR: 1.28, 95% CI: 1.06–1.55), of Native American (AOR: 1.60, 95% CI: 1.01–2.55) descent, having a household income less than $75,000 (AOR: 1.34, 95% CI: 1.08–1.65), or identifying as gay or bisexual (AOR for ‘Yes’ Response: 1.95, 95% CI: 1.31–2.91 and AOR for ‘Maybe’ Response: 1.81, 95% CI: 1.19–2.76) were all associated with higher odds of binge-eating behaviors. Conclusion Several sociodemographic variables showed significant associations with binge-eating behaviors, which can inform targeted screening, prevention, and education campaigns for BED among early adolescents.

Abstract Background No guidelines currently exist that represent a standardization of care for Avoidant/Restrictive Food Intake Disorder (ARFID) on an inpatient service. Unique features of this diagnosis (e.g., sensory sensitivity contributing to involuntary emesis) suggest that established protocols that were developed for anorexia nervosa might be less effective for adolescents with ARFID. To inform improved inpatient medical stabilization and care for these patients, we first provide an overview of clinical characteristics for patients with ARFID who presented to a pediatric hospital for inpatient eating disorder care. We use these descriptives to outline the rationale for, and executions of, modifications to an inpatient protocol designed to flexibly meet the needs of this clinical population. Methods Chart review with descriptive statistics were conducted for patients who had received an ARFID diagnosis from March 2019 to March 2023 (N = 32, aged 9–23). We then present a case series (n = 3) of adolescents who either transitioned to a novel adjusted protocol from an original standard of care on the inpatient service, or who received only the standard protocol. Results The sample was aged M(SD) = 15.6 (3.3) years, 53% male, and a majority (69%) presented with the ARFID presentation specific to fear of negative consequences. On average, patients had deviated from their growth curve for just over two years and presented with mean 76% of their estimated body weight. Of those requiring nasogastric tube insertion during admission (n = 8, 25%), average duration of tube placement was 15 days. From within this sample, case series data suggest that the adjusted protocol will continue to have a positive impact on care trajectory among adolescents admitted for ARFID including improved weight gain, reduction of emesis, and improved food intake. Conclusions Findings demonstrate the likely need to tailor established medical inpatient protocols for those with ARFID given different symptom presentation and maintenance factors compared to patients with anorexia nervosa. Further research is warranted to explore the longer-term impact of protocol changes and to inform standardization of care for this high priority clinical population across care sites.

Abstract Economic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources’ opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource’s value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.

Purpose – This experimental study aimed to examine the effects of annotating a historical text as a reading comprehension strategy on student academic achievement in an eighth-grade social studies class. Design/methodology/approach – A mixed-method design was used to collect quantitative and qualitative data sequentially. First, the authors collected quantitative data with a series of pre- and post-tests from all student participants during a six-week instructional time frame. Next, the authors collected quantitative and qualitative data with a survey from teacher and intervention group student participants. Quantitative data were analyzed to evaluate the mean differences in participants' test scores and survey responses. Finally, qualitative data from open-ended survey questions were transcribed and analyzed using an inductive approach to supplement the quantitative findings and develop a holistic picture of the participants' learning experiences. Findings – The results showed that the annotating strategy increased student engagement, reading comprehension and thus academic achievement in social studies. Annotating helped students visualize key points, break down complex texts and slow down when reading complex historical texts. As a result, it helped students focus, think critically and discourse to understand complex content. Research limitations/implications – The study was conducted with eighth-grade students in one middle school in South Georgia. Practical implications – The findings of this study provide evidence that the reading comprehension strategy of annotating is a valuable teaching and learning tool for daily use in social studies classrooms. Social implications – Educators must prepare students to use reading comprehension strategies such as annotating in all content areas and not only in a traditional academic setting. Originality/value – This study adds to the current body of research and undergirds reading comprehension strategies used to improve the learning outcomes in content other than reading.

Plain English summary Medical complications of eating disorders in males are understudied compared to females. Little is known about vitamin D levels in male adolescents and young adults with eating disorders. We studied vitamin D levels in male and female adolescents and young adults hospitalized at the University of California, San Francisco between 2012 and 2020. We found that 44% of males had low vitamin D levels. Despite nearly half of males having low vitamin D, few were receiving calcium, vitamin D, or multivitamin supplementation prior to the hospitalization. White race, prior calcium or vitamin D supplementation, and higher calcium levels were associated with higher vitamin D levels. Medical providers should consider assessing for low vitamin D levels among males and females with eating disorders.

BackgroundWhile the assessment of acute medical stability in patients with eating disorders should never be minimized, careful attention toward other specific age-related consequences of malnutrition can improve psychological outcomes and reduce long-term, potentially irreversible medical complications, like linear growth impairment.ReviewWhile the impact of malnutrition on linear growth is widely recognized, emerging data highlight consensus in several key areas: the time from onset to time of diagnosis, age at illness onset, pubertal stage at illness onset, and adequacy of weight restoration to achieve catch-up growth. This review provides concrete and actionable steps to help providers identify and explore deviations in expected growth and development while prioritizing early and aggressive weight restoration to provide the best opportunity for catch-up linear growth in patients with eating disorders.ConclusionThe impact of restrictive eating disorders on growth and development cannot be overstated, particularly in pre- and peripubertal patients. While many consequences of malnutrition are reversible, the loss of genetic height potential may prove irreversible without early and aggressive weight restoration.

Context: Body mass index (BMI) is a useful tool for measuring body composition. It is unclear whether high BMI is a favourable indicator in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). Objective: To investigate the prognostic significance of BMI in patients with mRCC treated with ICIs in a systematic review and meta-analysis. Evidence acquisition: Ovid MEDLINE, Embase, and Web of Science were systematically searched in July 2021, and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence synthesis: A total of 517 nonduplicate citations were screened by title and abstract, followed by full-text screening of 57 candidate articles to determine whether each study met the eligibility criteria. Overall, a total of 2281 patients from eight studies were included in the systematic review and meta-analysis. BMI levels were compared with overall survival (OS) and progression-free survival (PFS) in seven and three studies, respectively. Overweight/obese BMI was significantly associated with better OS compared to normal BMI (adjusted hazard ratio [aHR] 0.77, 95% confidence intervals [CI] 0.65–0.91; p = 0.002). A similar trend was observed for PFS (aHR 0.66, 95% CI 0.44–1.00; p = 0.050). There was no statistical heterogeneity or obvious publication bias among these studies. Conclusions: This is the first systematic review and meta-analysis to evaluate the impact of BMI on survival outcomes of patients with mRCC treated with ICIs. To confirm the existence of the obesity paradox for patients with mRCC in the immuno-oncology era, high-quality clinical trials and basic research are warranted. Patient summary: We reviewed published data on survival outcomes of 2281 patients with metastatic kidney cancer treated with immunotherapy drugs in relation to their body mass index (BMI). We found that higher BMI was associated with better survival when compared to normal BMI for this disease setting and treatment strategy.

Summary: Background: There is increasing evidence that the COVID-19 pandemic has impacted adversely on the provision of essential health services. The South East Asia region (SEAR) has experienced extremely high rates of COVID-19 infection, and continues to bear a significant proportion of communicable disease burden worldwide. Methods: We conducted a systematic literature review of quantitative evidence to estimate the impact of COVID-19 on the provision of essential prevention, detection, treatment, and management services for five high-burden infectious diseases across the SEAR. Findings: A total of 2338 studies were reviewed, and 12 studies were included in our analysis, covering six countries across the SEAR (Bhutan, Sri Lanka, Nepal, Myanmar, Thailand, and India) for three conditions of interest (HIV, TB, dengue fever). We identified significant disruption to TB testing (range=25% to 77.9%) and diagnoses (range=50% to 58%) in India, Nepal, and Indonesia; and similar disruptions were observed for screening, new diagnoses and commencing HIV treatment in India and Thailand. There was also drastically reduced case detection for dengue fever (range=75% to 90% disrupted) in Bhutan and Sri Lanka. No studies were identified for malaria nor hepatitis in any country, and nor for any service in the remaining six SEAR countries. Interpretation: We identified evidence of significant disruption to the prevention, diagnoses, treatment, and management of TB, HIV, and dengue fever due to the COVID-19 pandemic across multiple SEAR country settings. This has the potential to set back hard-fought gains in infectious disease control across the region. The lack of evidence for the impact of the pandemic on malaria and hepatitis services, and in the remaining six SEAR countries, is an important evidence gap that should be addressed in order to inform future policy for service protection and pandemic preparedness. Funding: This work was supported by the WHO Sri Lanka Country office.

Summary: Background: COVID-19 has had a profound impact on the health systems of the 11 countries of the WHO South East Asia Region. We conducted a systematic review of studies that used quantitative and comparative approaches to assess the impact of the pandemic on the service provision of four noncommunicable diseases (NCDs) (cancer, cardiovascular disease, chronic respiratory diseases, and diabetes) in the region. Methods: A systematic search was conducted in PubMed, Embase, MedRxiv, and WHO COVID-19 databases in December 2021. The quality of studies was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist and the ROBINS-I risk of bias tool. A narrative synthesis was conducted following the ‘synthesis without meta-analysis’ reporting guidelines. Findings: Two review authors independently screened 5,397 records with 31 studies included, 26 which were cross-sectional studies. Most studies (n=24, 77%) were conducted in India and 19 (61%) were single-site studies. Compared to a pre-pandemic period, 10/17 cancer studies found a >40% reduction in outpatient services, 9/14 cardiovascular disease found a reduction of 30% or greater in inpatient admissions and 2 studies found diagnoses and interventions for respiratory diseases reduced up to 78.9% and 83.0%, respectively. No eligible studies on the impact of COVID-19 on diabetes services were found. Interpretation: COVID-19 has substantially disrupted the provision of essential health services for NCDs in the WHO South East Asia Region, particularly cancer and cardiovascular disease. This is likely to have serious and potentially long-term downstream impacts on health and mortality of those living with or at risk of NCDs in the region. Funding: This work was supported by the WHO Sri Lanka Country Office.

Introduction The Megha Health Insurance Scheme (MHIS) was launched in 2013 in the North-East Indian state of Meghalaya to reduce household out-of-pocket expenditure on health and provide access to high-quality essential healthcare. Despite substantial expansion of the MHIS since the scheme’s inception, there is a lack of comprehensive documentation and evaluation of the scheme’s performance against its Universal Health Care (UHC) objectives. Methods We analysed six years of enrolment and claims data (2013–2018) covering three phases of the scheme to understand the pattern of enrolment, utilisation and care provision under the MHIS during this period. De-identified data files included information on age, sex, district of residence, the district of provider hospital, type of hospital, date of admission, status at discharge, claimed category of care, package codes, and amount claimed. Descriptive statistics were generated to investigate key trends in enrolment, service utilisation, and Government health spending under the MHIS. Results Approximately 55% of the eligible population are currently enrolled in MHIS. Enrolment increased consistently from phase I through III and remained broadly stable across districts, gender, age group and occupation categories, with a small decline in males 19–60 years. Claims were disproportionately skewed towards private provision; 57% of all claims accrued to the 18 empanelled private hospitals and 39% to the 159 public sector facilities. The package ‘General Ward Unspecified’ was responsible for the highest volume of claims and highest financial dispensation across all three phases of the scheme. This likely indicates substantial administrative error and is potentially masking both true burden of disease and accurate financial provision for care under the MHIS. Anti-rabies injections for dog/cat bite contributed to 11% of total claims under MHIS III, and 1.6% of all claims under MHIS II. This warrants investigation to better understand the burden of animal bites on the Meghalayan population and inform the implementation of cost-effective strategies to reduce this burden. Conclusions This paper describes the first analysis of health insurance enrolment and claims data in the state of Meghalaya. The analysis has generated an important evidence base to inform future MHIS enrolment and care provision policies as the scheme expands to provide Universal Health Coverage to the state’s entire population.

Economic evidence is increasingly being used for informing health policies. However, the underlining principles of health economic analyses are not always fully understood by non-health economists, and inappropriate types of analyses, as well as inconsistent methodologies, may be being used for informing health policy decisions. In addition, there is a lack of open access information and methodological guidance targeted to public health professionals, particularly those based in low- and middle-income country (LMIC) settings. The objective of this review is to provide a comprehensive and accessible introduction to economic evaluations for public health professionals with a focus on LMIC settings. We cover the main principles underlining the most common types of full economic evaluations used in healthcare decision making in the context of priority setting (namely cost-effectiveness/cost-utility analyses, cost-benefit analyses), and outline their key features, strengths and weaknesses. It is envisioned that this will help those conducting such analyses, as well as stakeholders that need to interpret their output, gain a greater understanding of these methods and help them select/distinguish between the different approaches. In particular, we highlight the need for greater awareness of the methods used to place a monetary value on the health benefits of interventions, and the potential for such estimates to be misinterpreted. Specifically, the economic benefits reported are typically an approximation, summarising the health benefits experienced by a population monetarily in terms of individual preferences or potential productivity gains, rather than actual realisable or fiscal monetary benefits to payers or society.

We present the case of a 17 year old football player with a 2 week history of left leg weakness and difficulty weight-bearing. Magnetic resonance imaging revealed a well-circumscribed lesion deep to the left iliacus muscle. The patient proceeded to computed tomography-guided biopsy. The likely diagnosis was that of a subperiosteal haematoma of the iliac wing, which was exerting mass effect upon the left femoral nerve resulting in leg pain and weakness. Imaging was repeated at an interval of 1 month, at which time the lesion had almost entirely resolved. Subperiosteal haematoma of the iliac bone is a rare entity but should be considered as a potential diagnosis in young adults, particularly where there is a history of trauma or recent sports injury. Keywords: Subperiosteal haematoma, Iliac bone, Femoral neuropathy, Magnetic resonance imaging, Sports medicine

In order for brain-computer interface (BCI) systems to maximize functionality, users will need to be able to accurately modulate grasp force to avoid dropping heavy objects while also being able to handle fragile items. We present a case-study consisting of two experiments designed to identify whether intracortical recordings from the motor cortex of a person with tetraplegia could predict intended grasp force. In the first task, we were able classify neural responses to attempted grasps of four objects, each of which required similar grasp kinematics but different implicit grasp force targets, with 69% accuracy. In the second task, the subject attempted to move a virtual robotic arm in space to grasp a simple virtual object. For each trial, the subject was asked to grasp the virtual object with the force appropriate for one of the four objects from the first experiment, with the goal of measuring an implicit representation of grasp force. While the subject knew the grasp force during all phases of the trial, accurate classification was only achieved during active grasping, not while the hand moved to, transported, or released the object. In both tasks, misclassifications were most often to the object with an adjacent force requirement. In addition to the implications for understanding the representation of grasp force in motor cortex, these results are a first step toward creating intelligent algorithms to help BCI users grasp and manipulate a variety of objects that will be encountered in daily life.Clinical Trial Identifier: NCT01894802 https://clinicaltrials.gov/ct2/show/NCT01894802.

Abstract Introduction Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. Methods Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age‐matched individuals (n = 26). Results Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. Discussion Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development.

Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries.

Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory ‘foreground’ and ‘background’. Patients with typical amnestic Alzheimer's disease (n = 13) and age-matched healthy individuals (n = 17) underwent functional 3T-MRI using a sparse acquisition protocol with passive listening to auditory stimulus conditions comprising the participant's own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable) analogues of these conditions. Name identification (conditions containing the participant's own name contrasted with spectrally rotated analogues) produced extensive bilateral activation involving superior temporal cortex in both the AD and healthy control groups, with no significant differences between groups. Auditory object segregation (conditions with interleaved name sounds contrasted with superimposed name sounds) produced activation of right posterior superior temporal cortex in both groups, again with no differences between groups. However, the cocktail party effect (interaction of own name identification with auditory object segregation processing) produced activation of right supramarginal gyrus in the AD group that was significantly enhanced compared with the healthy control group. The findings delineate an altered functional neuroanatomical profile of auditory scene analysis in Alzheimer's disease that may constitute a novel computational signature of this neurodegenerative pathology.

Despite considerable evidence for abnormalities of self-awareness in Alzheimer’s disease (AD), the cognitive mechanisms of altered self-processing in AD have not been fully defined. Here we addressed this issue in a detailed analysis of self/non-self-processing in three patients with AD. We designed a novel neuropsychological battery comprising tests of tactile body schema coding, attribution of tactile events to self versus external agents, and memory for self- versus non-self-generated vocal information, administered in conjunction with a daily life measure of self/non-self-processing (the Interpersonal Reactivity Index). Three male AD patients (aged 54 to 68 years; one with a pathogenic mutation in the Presenilin 1 gene, one with a pathogenic mutation in the Amyloid Precursor Protein gene, and one with a CSF protein profile supporting underlying AD pathology) were studied in relation to a group of eight healthy older male individuals (aged 58 to 74 years). Compared to healthy controls, all patients had relatively intact tactile body schema processing. In contrast, all patients showed impaired memory for words previously presented using the patient’s own voice whereas memory for words presented in other voices was less consistently affected. Two patients showed increased levels of emotional contagion and reduced perspective taking on the Interpersonal Reactivity Index. Our findings suggest that AD may be associated with deficient self /non-self differentiation over time despite a relatively intact body image: this profile of altered self-processing contrasts with the deficit of tactile body schema previously described in frontotemporal dementia associated with C9orf72 mutations. We present these findings as a preliminary rationale to direct future systematic study in larger patient cohorts.