Johanna C. Goll

Progressive logopenic/phonological aphasia: Erosion of the language network

The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. Five of nine patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings is threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.

Non-verbal sound processing in the primary progressive aphasias

Little is known about the processing of non-verbal sounds in the primary progressive aphasias. Here, we investigated the processing of complex non-verbal sounds in detail, in a consecutive series of 20 patients with primary progressive aphasia [12 with progressive non-fluent aphasia; eight with semantic dementia]. We designed a novel experimental neuropsychological battery to probe complex sound processing at early perceptual, apperceptive and semantic levels, using within-modality response procedures that minimized other cognitive demands and matching tests in the visual modality. Patients with primary progressive aphasia had deficits of non-verbal sound analysis compared with healthy age-matched individuals. Deficits of auditory early perceptual analysis were more common in progressive non-fluent aphasia, deficits of apperceptive processing occurred in both progressive non-fluent aphasia and semantic dementia, and deficits of semantic processing also occurred in both syndromes, but were relatively modality specific in progressive non-fluent aphasia and part of a more severe generic semantic deficit in semantic dementia. Patients with progressive non-fluent aphasia were more likely to show severe auditory than visual deficits as compared to patients with semantic dementia. These findings argue for the existence of core disorders of complex non-verbal sound perception and recognition in primary progressive aphasia and specific disorders at perceptual and semantic levels of cortical auditory processing in progressive non-fluent aphasia and semantic dementia, respectively.

Voice processing in dementia: a neuropsychological and neuroanatomical analysis

Voice processing in neurodegenerative disease is poorly understood. Here we undertook a systematic investigation of voice processing in a cohort of patients with clinical diagnoses representing two canonical dementia syndromes: temporal variant frontotemporal lobar degeneration (n = 14) and Alzheimer’s disease (n = 22). Patient performance was compared with a healthy matched control group (n = 35). All subjects had a comprehensive neuropsychological assessment including measures of voice perception (vocal size, gender, speaker discrimination) and voice recognition (familiarity, identification, naming and cross-modal matching) and equivalent measures of face and name processing. Neuroanatomical associations of voice processing performance were assessed using voxel-based morphometry. Both disease groups showed deficits on all aspects of voice recognition and impairment was more severe in the temporal variant frontotemporal lobar degeneration group than the Alzheimer’s disease group. Face and name recognition were also impaired in both disease groups and name recognition was significantly more impaired than other modalities in the temporal variant frontotemporal lobar degeneration group. The Alzheimer’s disease group showed additional deficits of vocal gender perception and voice discrimination. The neuroanatomical analysis across both disease groups revealed common grey matter associations of familiarity, identification and cross-modal recognition in all modalities in the right temporal pole and anterior fusiform gyrus; while in the Alzheimer’s disease group, voice discrimination was associated with grey matter in the right inferior parietal lobe. The findings suggest that impairments of voice recognition are significant in both these canonical dementia syndromes but particularly severe in temporal variant frontotemporal lobar degeneration, whereas impairments of voice perception may show relative specificity for Alzheimer’s disease. The right anterior temporal lobe is likely to have a critical role in the recognition of voices and other modalities of person knowledge.

Structural neuroanatomy of tinnitus and hyperacusis in semantic dementia

Introduction Tinnitus and hyperacusis are common symptoms of excessive auditory perception in the general population; however, their anatomical substrates and disease associations continue to be defined. Patients with semantic dementia (SemD) frequently report tinnitus and hyperacusis but the significance and basis for these symptoms have not been elucidated. Methods 43 patients with a diagnosis of SemD attending a specialist cognitive disorders clinic were retrospectively studied. 14 patients (32% of the cohort) reported at least moderately severe chronic auditory symptoms: seven had tinnitus and a further seven had hyperacusis, and all had brain MRI while symptomatic. MRI data from SemD patients with and without auditory symptoms were compared using voxel based morphometry in order to identify neuroanatomical associations of tinnitus and hyperacusis. Results Compared with SemD patients with no history of auditory symptoms, patients with tinnitus or hyperacusis had relative preservation of grey matter in the posterior superior temporal lobe and reduced grey matter in the orbitofrontal cortex and medial geniculate nucleus. Conclusions Tinnitus and hyperacusis may be a significant issue in SemD. Neuroanatomical evidence in SemD supports previous work implicating a distributed cortico-subcortical auditory and limbic network in the pathogenesis of these abnormal auditory percepts.

Auditory object cognition in dementia.

Highlights ► A study of nonverbal auditory object processing in four dementia syndromes. ► Subjects were assessed using a novel, customised neuropsychological battery. ► Different dementia syndromes lead to distinct auditory processing impairments. ► Evidence is provided for separable stages of nonverbal auditory processing.

Impairments of auditory scene analysis in Alzheimer's disease.

Parsing of sound sources in the auditory environment or ‘auditory scene analysis’ is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer’s disease. However, little information is available concerning auditory scene analysis in Alzheimers disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimers disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimers disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimers disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimers disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimers disease and for delineating cognitive mechanisms that mediate auditory scene analysis both in health and in neurodegenerative disease.

Nonverbal sound processing in semantic dementia: A functional MRI study

Semantic dementia (SD) is a unique neurodegenerative syndrome accompanied by relatively selective loss of the meaning of objects and concepts. The brain mechanisms that underpin the syndrome have not been defined: a better understanding of these mechanisms would inform our understanding of both the organisation of the human semantic system and its vulnerability to neurodegenerative disease. In this fMRI study, we investigated brain correlates of sensory object processing in nine patients with SD compared with healthy control subjects, using the paradigm of nonverbal sound. Compared with healthy controls, patients with SD showed differential activation of cortical areas surrounding the superior temporal sulcus, both for perceptual processing of spectrotemporally complex but meaningless sounds and for semantic processing of environmental sound category (animal sounds versus tool sounds). Our findings suggest that defective processing of sound objects in SD spans pre-semantic perceptual processing and semantic category formation. This disease model illustrates that antero-lateral temporal cortical mechanisms are critical for representing and differentiating sound categories. The breakdown of these mechanisms constitutes a network-level functional signature of this neurodegenerative disease.

Barriers to Social Participation among Lonely Older Adults: The Influence of Social Fears and Identity

Introduction Loneliness among older adults is a major public health problem that may be associated with processes of social participation and identity. This study therefore sought to examine the relationship between social participation and identity in a sample of lonely older adults living independently in London, England. Method An inductive qualitative approach, based on semi-structured interviews and thematic analysis, was employed. Results Participants commonly spoke of barriers to social participation that have been reported elsewhere, including illness/disability, loss of contact with friends/relatives, lack of a supportive community, and lack of acceptable social opportunities. However, novel findings were also derived. In particular, participants commonly minimised the difficulties they faced alone, and described attempts to avoid social opportunities. These behaviours were linked to fears about engaging in social participation opportunities, including fears of social rejection and/or exploitation, and fears of losing valued aspects of identity. Discussion It is concluded that social participation amongst lonely older people will not improve through the removal of previously reported barriers alone; instead, older peoples’ beliefs, fears and identities must be addressed. Suggestions for implementing these findings within community organisations are provided.

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 Alzheimers 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.

Functional neuroanatomy of auditory scene analysis in Alzheimer's disease

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 Alzheimers disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimers disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing ones spoken name) are used to segregate auditory ‘foreground’ and ‘background’. Patients with typical amnestic Alzheimers 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 participants own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable) analogues of these conditions. Name identification (conditions containing the participants 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 Alzheimers disease that may constitute a novel computational signature of this neurodegenerative pathology.