Hearing and dementia: from ears to brain

The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between ‘peripheral’ and ‘central’ hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer’s disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory ‘cognitive stress tests’ and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticit

Inappropriate trusting behaviour in dementia

BACKGROUND: Inappropriate trusting behaviour may have significant social, financial and other consequences for people living with dementia. However, its clinical associations and predictors have not been clarified. Here we addressed this issue in canonical syndromes of frontotemporal dementia (FTD) and Alzheimer’s disease (AD). METHODS: In 34 patients with AD and 73 with FTD (27 behavioural variant (bv)FTD, 22 semantic variant primary progressive aphasia (svPPA), 24 nonfluent/agrammatic variant (nfv)PPA) we recorded inappropriate trusting and other abnormal socio-emotional behaviours using a semi-structured caregiver survey. Patients were comprehensively characterised using a general cognitive assessment and the Revised Self-Monitoring Scale (RSMS; an informant index of socioemotional awareness). RESULTS: Inappropriate trusting was more frequent in svPPA (55%) and bvFTD (44%) than nfvPPA (17%) or AD (24%). After adjusting for age, sex, education and Mini-Mental State Examination (MMSE) score, inappropriate trusting was significantly more likely in svPPA (odds ratio 3.61; 95% confidence interval 1.41–8.75) and bvFTD (3.01, 1.23–6.65) than AD. Significant predictors of inappropriate trusting comprised apathy in svPPA, disinhibition and altered pain responsiveness in bvFTD, and lower MMSE and RSMS (self-presentation) scores in AD. CONCLUSION: Dementia syndromes vary in prevalence and predictors of abnormal trusting behaviour, with implications for clinical counselling and safeguarding

The muon system of the Daya Bay Reactor antineutrino experiment

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Search for a Light Sterile Neutrino at Daya Bay

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Impaired phonemic discrimination in logopenic variant primary progressive aphasia

Logopenic variant primary progressive aphasia (lvPPA) is the least well defined of the major primary progressive aphasia (PPA) syndromes. We assessed phoneme discrimination in patients with PPA (semantic, nonfluent/agrammatic, and logopenic variants) and typical Alzheimer’s disease, relative to healthy age‐matched participants. The lvPPA group performed significantly worse than all other groups apart from tAD, after adjusting for auditory verbal working memory. In the combined PPA cohort, voxel‐based morphometry correlated phonemic discrimination score with grey matter in left angular gyrus. Our findings suggest that impaired phonemic discrimination may help differentiate lvPPA from other PPA subtypes, with important diagnostic and management implications

Processing of Degraded Speech in Brain Disorders

The speech we hear every day is typically “degraded” by competing sounds and the idiosyncratic vocal characteristics of individual speakers. While the comprehension of “degraded” speech is normally automatic, it depends on dynamic and adaptive processing across distributed neural networks. This presents the brain with an immense computational challenge, making degraded speech processing vulnerable to a range of brain disorders. Therefore, it is likely to be a sensitive marker of neural circuit dysfunction and an index of retained neural plasticity. Considering experimental methods for studying degraded speech and factors that affect its processing in healthy individuals, we review the evidence for altered degraded speech processing in major neurodegenerative diseases, traumatic brain injury and stroke. We develop a predictive coding framework for understanding deficits of degraded speech processing in these disorders, focussing on the “language-led dementias”—the primary progressive aphasias. We conclude by considering prospects for using degraded speech as a probe of language network pathophysiology, a diagnostic tool and a target for therapeutic intervention

Comprehension of acoustically degraded emotional prosody in Alzheimer's disease and primary progressive aphasia.

Previous research suggests that emotional prosody perception is impaired in neurodegenerative diseases like Alzheimer's disease (AD) and primary progressive aphasia (PPA). However, no previous research has investigated emotional prosody perception in these diseases under non-ideal listening conditions. We recruited 18 patients with AD, and 31 with PPA (nine logopenic (lvPPA); 11 nonfluent/agrammatic (nfvPPA) and 11 semantic (svPPA)), together with 24 healthy age-matched individuals. Participants listened to speech stimuli conveying three emotions in clear and noise-vocoded forms and had to identify the emotion being conveyed. We then conducted correlation analyses between task performance and measures of socio-emotional functioning. All patient groups showed significant impairments in identifying clear emotional prosody compared to healthy individuals. These deficits were exacerbated under noise-vocoded conditions, with all patient groups performing significantly worse than healthy individuals and patients with lvPPA performing significantly worse than those with svPPA. Significant correlations with social cognition measures were observed more consistently for noise-vocoded than clear emotional prosody comprehension. These findings open a window on a dimension of real-world emotional communication that has often been overlooked in dementia, with particular relevance to social cognition, and begin to suggest a novel candidate paradigm for investigating and quantifying this systematically

Decoding expectation and surprise in dementia: the paradigm of music

Making predictions about the world and responding appropriately to unexpected events are essential functions of the healthy brain. In neurodegenerative disorders, such as frontotemporal dementia and Alzheimer's disease, impaired processing of 'surprise' may underpin a diverse array of symptoms, particularly abnormalities of social and emotional behaviour, but is challenging to characterize. Here, we addressed this issue using a novel paradigm: music. We studied 62 patients (24 female; aged 53-88) representing major syndromes of frontotemporal dementia (behavioural variant, semantic variant primary progressive aphasia, non-fluent-agrammatic variant primary progressive aphasia) and typical amnestic Alzheimer's disease, in relation to 33 healthy controls (18 female; aged 54-78). Participants heard famous melodies containing no deviants or one of three types of deviant note-acoustic (white-noise burst), syntactic (key-violating pitch change) or semantic (key-preserving pitch change). Using a regression model that took elementary perceptual, executive and musical competence into account, we assessed accuracy detecting melodic deviants and simultaneously recorded pupillary responses and related these to deviant surprise value (information-content) and carrier melody predictability (entropy), calculated using an unsupervised machine learning model of music. Neuroanatomical associations of deviant detection accuracy and coupling of detection to deviant surprise value were assessed using voxel-based morphometry of patients' brain MRI. Whereas Alzheimer's disease was associated with normal deviant detection accuracy, behavioural and semantic variant frontotemporal dementia syndromes were associated with strikingly similar profiles of impaired syntactic and semantic deviant detection accuracy and impaired behavioural and autonomic sensitivity to deviant information-content (all P < 0.05). On the other hand, non-fluent-agrammatic primary progressive aphasia was associated with generalized impairment of deviant discriminability (P < 0.05) due to excessive false-alarms, despite retained behavioural and autonomic sensitivity to deviant information-content and melody predictability. Across the patient cohort, grey matter correlates of acoustic deviant detection accuracy were identified in precuneus, mid and mesial temporal regions; correlates of syntactic deviant detection accuracy and information-content processing, in inferior frontal and anterior temporal cortices, putamen and nucleus accumbens; and a common correlate of musical salience coding in supplementary motor area (all P < 0.05, corrected for multiple comparisons in pre-specified regions of interest). Our findings suggest that major dementias have distinct profiles of sensory 'surprise' processing, as instantiated in music. Music may be a useful and informative paradigm for probing the predictive decoding of complex sensory environments in neurodegenerative proteinopathies, with implications for understanding and measuring the core pathophysiology of these diseases

Independent measure of the neutrino mixing angle θ13 via neutron capture on hydrogen at Daya Bay

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