Agnosia for accents in primary progressive aphasia.

As an example of complex auditory signal processing, the analysis of accented speech is potentially vulnerable in the progressive aphasias. However, the brain basis of accent processing and the effects of neurodegenerative disease on this processing are not well understood. Here we undertook a detailed neuropsychological study of a patient, AA with progressive nonfluent aphasia, in whom agnosia for accents was a prominent clinical feature. We designed a battery to assess AA's ability to process accents in relation to other complex auditory signals. AA's performance was compared with a cohort of 12 healthy age and gender matched control participants and with a second patient, PA, who had semantic dementia with phonagnosia and prosopagnosia but no reported difficulties with accent processing. Relative to healthy controls, the patients showed distinct profiles of accent agnosia. AA showed markedly impaired ability to distinguish change in an individual's accent despite being able to discriminate phonemes and voices (apperceptive accent agnosia); and in addition, a severe deficit of accent identification. In contrast, PA was able to perceive changes in accents, phonemes and voices normally, but showed a relatively mild deficit of accent identification (associative accent agnosia). Both patients showed deficits of voice and environmental sound identification, however PA showed an additional deficit of face identification whereas AA was able to identify (though not name) faces normally. These profiles suggest that AA has conjoint (or interacting) deficits involving both apperceptive and semantic processing of accents, while PA has a primary semantic (associative) deficit affecting accents along with other kinds of auditory objects and extending beyond the auditory modality. Brain MRI revealed left peri-Sylvian atrophy in case AA and relatively focal asymmetric (predominantly right sided) temporal lobe atrophy in case PA. These cases provide further evidence for the fractionation of brain mechanisms for complex sound analysis, and for the stratification of progressive aphasia syndromes according to the signature of nonverbal auditory deficits they produce

The Language Profile of Behavioral Variant Frontotemporal Dementia

BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker

Auditory spatial processing in Alzheimer's disease.

: The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer's disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer's disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer's disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer's disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer's disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer's disease syndromic spectrum.<br/

Brain disorders and the biological role of music

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration

Defining the neuropsychological and neuroimaging phenotype of behavioural variant frontotemporal dementia

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer’s disease (AD). There exists a paucity of quantifiable, sensitive, and specific biomarkers to detect this disease and track its manifestation and progression. The primary aim of this thesis was to develop and investigate new biomarkers for FTD, and focused on the examination of neuropsychological biomarkers in the behavioural variant of FTD (bvFTD) and their neuroanaotmical correlates. Chapters 4 and 5 explored social cognition in patients with FTD and the neural correlates of this behaviour. bvFTD patients displayed gross dysfunction in the perception of sarcasm and the ability to understand basic social signals, and this mapped onto a larger social cognition neural network that has previously been defined in the literature. These findings delineate a brain network substrate for the social impairment that characterises FTD syndromes. In Chapters 6 and 7, I explored the executive functions of task switching, reaction time, and neural timing in patients with FTD. Results indicated several dissociable executive capacities, which mapped onto discrete neural areas as part of a larger executive function network, suggesting that structures implicated in aspects of executive functioning can be targeted by FTD and may underpin aspects of the bvFTD phenotype. In the final Chapter, I devised a novel battery to examine the bases of psychosis in FTD patients with the C9ORF72 mutation, which demonstrated a specific and unique impairment in the ability to interpret somatosensory proprioceptive information in these patients, which may represent a candidate mechanism for psychosis. The studies described in this thesis contribute to the growing interest in characterising and understanding the neuropsychological phenotypes of bvFTD. Improved understanding of the anatomical associations of neuropsycholgical performance in this patient population could potentially facilitate earlier and more accurate diagnosis and symptom managemen

Profiles of white matter tract pathology in frontotemporal dementia.

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc

Programmatic Environmental Scans: A Survey Based on Program Planning and Evaluation Concepts

Within Extension, environmental scans are most commonly used to assess community or organizational issues or for strategic planning purposes. However, Extension has expanded the use of environmental scans to systematically identify “what programs exist” on a given topic or focus area. Yet, despite recent attention to the topic of environmental scanning in Extension, survey instruments used to conduct environmental scans have not been published. Given the emphasis on implementation of evidence-based practices and programs, having a ready-made survey that can be used to identify programs on a specific topic and that could subsequently lead to an evaluability assessment of those programs would be a useful resource. To encourage the use of environmental scans to identify existing evidence-based programs, this article describes a survey instrument developed for the purpose of scanning for 4-H Healthy Living programs ready for rigorous outcome evaluation and/or national replication. It focuses on the rationale for survey items, as well as provides a summary and definition of those items. The survey tool can be easily adapted for future programmatic environmental scans both within and outside Extension

The 100 most cited articles investigating the radiological staging of oesophageal and junctional cancer: a bibliometric analysis

Objectives Accurate staging of oesophageal cancer (OC) is vital. Bibliometric analysis highlights key topics and publications that have shaped understanding of a subject. The 100 most cited articles investigating radiological staging of OC are identified. Methods The Thomas Reuters Web of Science database with search terms including “CT, PET, EUS, oesophageal and gastro-oesophageal junction cancer” was used to identify all English language, full-script articles. The 100 most cited articles were further analysed by topic, journal, author, year and institution. Results A total of 5,500 eligible papers were returned. The most cited paper was Flamen et al. (n = 306), investigating the utility of positron emission tomography (PET) for the staging of patients with potentially operable OC. The most common research topic was accuracy of staging investigations (n = 63). The article with the highest citation rate (38.00), defined as the number of citations divided by the number of complete years published, was Tixier et al. investigating PET texture analysis to predict treatment response to neo-adjuvant chemo-radiotherapy, cited 114 times since publication in 2011. Conclusion This bibliometric analysis has identified key publications regarded as important in radiological OC staging. Articles with the highest citation rates all investigated PET imaging, suggesting this modality could be the focus of future research

The brain basis of musicophilia: evidence from frontotemporal lobar degeneration.

Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia, and 25 did not exhibit the phenomenon. The syndrome of semantic dementia was relatively over-represented among the musicophilic subgroup. A VBM analysis revealed significantly increased regional gray matter volume in left posterior hippocampus in the musicophilic subgroup relative to the non-musicophilic group (p < 0.05 corrected for regional comparisons); at a relaxed significance threshold (p < 0.001 uncorrected across the brain volume) musicophilia was associated with additional relative sparing of regional gray matter in other temporal lobe and prefrontal areas and atrophy of gray matter in posterior parietal and orbitofrontal areas. The present findings suggest a candidate brain substrate for musicophilia as a signature of distributed network damage that may reflect a shift of hedonic processing toward more abstract (non-social) stimuli, with some specificity for particular neurodegenerative pathologies

Impact of body mass index on survival outcomes of patients with metastatic renal cell carcinoma in the immuno-oncology era: a systematic review and meta-analysis

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