62 research outputs found
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
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
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
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
Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease
Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology
Independent measure of the neutrino mixing angle θ13 via neutron capture on hydrogen at Daya Bay
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