Mechanisms of voice processing in dementia

Perception of nonverbal vocal information is essential in our daily lives. Patients with degenerative dementias commonly have difficulty with such aspects of vocal communication; however voice processing has seldom been studied in these diseases. This thesis comprises a series of linked studies of voice processing in canonical dementias: Alzheimer’s disease, behavioural variant frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. A series of neuropsychological tests were developed to examine perceptual and semantic stages of voice processing and to assess two aspects of accent processing: comprehension of foreign accented speech and recognition of regional and foreign accents; patient performance was referenced to healthy control subjects. Neuroanatomical associations of voice processing performance were assessed using voxel based morphometry. Following a symptom-led approach, a syndrome of progressive associative phonagnosia was characterised in two detailed case studies. Following a disease-led approach, this work was extended systematically to cohorts of patients representing the target diseases and assessing voice processing in relation to other aspects of person recognition (faces and names). This work provided evidence for separable profiles of voice processing impairment in different diseases: associative deficits were particularly severe in semantic dementia, whilst perceptual deficits showed relative specificity for Alzheimer’s disease. Neuroanatomical associations were identified for voice recognition in the right temporal pole and anterior fusiform gyrus, and for voice discrimination in the right inferior parietal lobe. The final phase of this work addressed the neuropsychological and neuroanatomical basis of accent processing, as an important dimension of nonverbal vocal analysis that is not dependent on voice identity. This work provides evidence for impaired processing of accents in progressive nonfluent aphasia and Alzheimer’s with neuroanatomical associations in the anterior and superior temporal lobe. The thesis contributes new information about voice processing in the degenerative dementias and furthers our understanding of the mechanisms of human voice analysis

Accent processing in dementia

Accented speech conveys important nonverbal information about the speaker as well as presenting the brain with the problem of decoding a non-canonical auditory signal. The processing of non-native accents has seldom been studied in neurodegenerative disease and its brain basis remains poorly understood. Here we investigated the processing of non-native international and regional accents of English in cohorts of patients with Alzheimer's disease (AD; n=20) and progressive nonfluent aphasia (PNFA; n=6) in relation to healthy older control subjects (n=35). A novel battery was designed to assess accent comprehension and recognition and all subjects had a general neuropsychological assessment. Neuroanatomical associations of accent processing performance were assessed using voxel-based morphometry on MR brain images within the larger AD group. Compared with healthy controls, both the AD and PNFA groups showed deficits of non-native accent recognition and the PNFA group showed reduced comprehension of words spoken in international accents compared with a Southern English accent. At individual subject level deficits were observed more consistently in the PNFA group, and the disease groups showed different patterns of accent comprehension impairment (generally more marked for sentences in AD and for single words in PNFA). Within the AD group, grey matter associations of accent comprehension and recognition were identified in the anterior superior temporal lobe. The findings suggest that accent processing deficits may constitute signatures of neurodegenerative disease with potentially broader implications for understanding how these diseases affect vocal communication under challenging listening conditions

Auditory object cognition in dementia

The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n = 21), progressive nonfluent aphasia (PNFA; n = 5), logopenic progressive aphasia (LPA; n = 7) and aphasia in association with a progranulin gene mutation (GAA; n = 1), and in healthy age-matched controls (n = 20). Based on a cognitive framework treating complex sounds as 'auditory objects', we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes. (C) 2011 Elsevier Ltd. All rights reserved

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

Melody Processing Characterizes Functional Neuroanatomy in the Aging Brain

The functional neuroanatomical mechanisms underpinning cognition in the normal older brain remain poorly defined, but have important implications for understanding the neurobiology of aging and the impact of neurodegenerative diseases. Auditory processing is an attractive model system for addressing these issues. Here, we used fMRI of melody processing to investigate auditory pattern processing in normal older individuals. We manipulated the temporal (rhythmic) structure and familiarity of melodies in a passive listening, ‘sparse’ fMRI protocol. A distributed cortico-subcortical network was activated by auditory stimulation compared with silence; and within this network, we identified separable signatures of anisochrony processing in bilateral posterior superior temporal lobes; melodic familiarity in bilateral anterior temporal and inferior frontal cortices; and melodic novelty in bilateral temporal and left parietal cortices. Left planum temporale emerged as a ‘hub’ region functionally partitioned for processing different melody dimensions. Activation of Heschl’s gyrus by auditory stimulation correlated with the integrity of underlying cortical tissue architecture, measured using multi-parameter mapping. Our findings delineate neural substrates for analyzing perceptual and semantic properties of melodies in normal aging. Melody (auditory pattern) processing may be a useful candidate paradigm for assessing cerebral networks in the older brain and potentially, in neurodegenerative diseases of later life

Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias

Background Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. Methods We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters—temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)—in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images. Results Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Conclusions Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development

Hearing and dementia

Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia

The Glasgow Voice Memory Test: Assessing the ability to memorize and recognize unfamiliar voices

One thousand one hundred and twenty subjects as well as a developmental phonagnosic subject (KH) along with age-matched controls performed the Glasgow Voice Memory Test, which assesses the ability to encode and immediately recognize, through an old/new judgment, both unfamiliar voices (delivered as vowels, making language requirements minimal) and bell sounds. The inclusion of non-vocal stimuli allows the detection of significant dissociations between the two categories (vocal vs. non-vocal stimuli). The distributions of accuracy and sensitivity scores (d’) reflected a wide range of individual differences in voice recognition performance in the population. As expected, KH showed a dissociation between the recognition of voices and bell sounds, her performance being significantly poorer than matched controls for voices but not for bells. By providing normative data of a large sample and by testing a developmental phonagnosic subject, we demonstrated that the Glasgow Voice Memory Test, available online and accessible fromall over the world, can be a valid screening tool (~5 min) for a preliminary detection of potential cases of phonagnosia and of “super recognizers” for voices