Naming treatment in semantic and logopenic variant PPA

Primary progressive aphasia (PPA) is an acquired impairment of language caused by neurodegenerative disease affecting language regions in the brain. Unlike aphasia caused by stroke, the language impairments in PPA gradually worsen over time as atrophy spreads. Current consensus criteria for diagnosis identify three clinical variants, each of which is associated with a different pathological entity: a semantic variant, with verbal and nonverbal semantic deficits; a logopenic variant, with anomia and phonological working memory problems; and a nonfluent variant, with agrammatism and/or apraxia of speech (Gorno-Tempini et al., 2011; Gorno-Tempini et al., 2004)

Clinical, anatomical and pathological features in the three variants of primary progressive aphasia : a review

Primary progressive aphasias (PPA) are neurodegenerative diseases clinically characterized by an early and relatively isolated language impairment. Three main clinical variants, namely the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA) have been described, each with specific linguistic/cognitive deficits, corresponding anatomical and most probable pathological features. Since the discovery and the development of diagnostic criteria for the PPA variants by the experts in the field, significant progress has been made in the understanding of these diseases. This review aims to provide an overview of the literature on each of the PPA variant in terms of their clinical, anatomical and pathological features, with a specific focus on recent findings. In terms of clinical advancements, recent studies have allowed a better characterization and differentiation of PPA patients based on both their linguistic and non-linguistic profiles. In terms of neuroimaging, techniques such as diffusion imaging and resting-state fMRI have allowed a deeper understanding of the impact of PPA on structural and functional connectivity alterations beyond the well-defined pattern of regional gray matter atrophy. Finally, in terms of pathology, despite significant advances, clinico-pathological correspondence in PPA remains far from absolute. Nonetheless, the improved characterization of PPA has the potential to have a positive impact on the management of patients. Improved reliability of diagnoses and the development of reliable in vivo biomarkers for underlying neuropathology will also be increasingly important in the future as trials for etiology-specific treatments become available

The neural correlates of verbal and nonverbal semantic processing deficits in neurodegenerative disease

Objective—To investigate the neural correlates of verbal and non-verbal semantic processing in neurodegenerative disease. Background—Semantic memory is often impaired in neurodegenerative disease. Neuropsychological and functional neuroimaging studies suggest that the semantic processing of verbal and non-verbal stimuli may depend on partially distinct brain networks. Methods—We examined this possibility using voxel-based morphometry to correlate performance on verbal and non-verbal versions of a semantic association task with regional gray matter atrophy in 144 individuals with a variety of neurodegenerative diseases. Results—Results showed that, regardless of stimulus type, semantic processing correlated with atrophy in both temporal lobes. In addition, material-specific correlations were found in left temporal regions for verbal stimuli and the right fusiform gyrus for non-verbal stimuli. Conclusions—These results provide evidence for a differential role of the left and right hemispheres in the extraction of semantic information from verbal and pictorial representations. Areas in the right inferior temporal lobe may be necessary to access structural descriptions of visually presented object

Phonological processing in primary progressive aphasia

Primary progressive aphasia (PPA) is a debilitating condition wherein speech and language deteriorate as a result of neurodegenerative disease. Three variants of PPA are now recognized, each of which shows a unique constellation of speech-language deficits and pattern of underlying atrophy in the brain (Gorno-Tempini et al., 2011). The variants include a nonfluent/agrammatic type (nfvPPA), characterized by syntactic and motor speech deficits and fronto-insular atrophy in the left hemisphere. The semantic variant (svPPA) shows degradation of semantic knowledge in the context of anterior and inferior temporal lobe atrophy (left hemisphere greater than right). Finally, the more recently characterized logopenic variant (lvPPA) shows impairments in naming and repetition that are thought to be phonological in nature. This variant, associated with atrophy of temporoparietal regions in the left hemisphere, has also been referred to as the “phonological” variant of PPA due to observed deficits on tasks that require phonological storage (i.e., the “phonological loop”) and to the presence of phonological paraphasias in connected speech (Gorno-Tempini et al., 2008). Impaired phonological processing has been considered a unique feature of the logopenic variant of PPA, however, phonological skills have not been thoroughly characterized across the three variants. Recent models of the functional neuroanatomy of language propose two pathways by which speech is processed in the brain (Hickok & Poeppel, 2007). A dorsal pathway involving temporoparietal and posterior frontal structures is thought to be involved in mapping phonological representations onto articulatory representations. A ventral pathway located in the middle and inferior temporal lobes is considered crucial for mapping phonological representations onto lexical-semantic representations. Both the dorsal and ventral streams emanate from a common cortical region in posterior, superior temporal cortex/sulcus that appears critical to the mental representation of phonology. We investigated phonological processing in PPA, with the goal of identifying whether patterns of performance in the different variants support this functional-anatomical framework. Based on our knowledge of the locus of anatomical damage in the subtypes of PPA, we hypothesized that patients with damage to dorsal route structures (nonfluent and logopenic variants) would show greater impairment on phonological processing tasks, whereas patients with damage to ventral route structures (semantic variant) would show relative preservation of phonological abilities

Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy.

Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes

Speech and language markers of neurodegeneration: a call for global equity

In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders. As a complement to classic tests, scalable and low-cost digital tools can capture relevant anomalies automatically, potentially supporting the quest for globally equitable markers of brain health. However, this promise remains unfulfilled due to limited linguistic diversity in scientific works and clinical instruments. Here we argue for cross-linguistic research as a core strategy to counter this problem. First, we survey the contributions of linguistic assessments in the study of primary progressive aphasia and the three most prevalent neurodegenerative disorders worldwide-Alzheimer's disease, Parkinson's disease, and behavioural variant frontotemporal dementia. Second, we address two forms of linguistic unfairness in the literature: the neglect of most of the world's 7000 languages and the preponderance of English-speaking cohorts. Third, we review studies showing that linguistic dysfunctions in a given disorder may vary depending on the patient's language and that English speakers offer a suboptimal benchmark for other language groups. Finally, we highlight different approaches, tools and initiatives for cross-linguistic research, identifying core challenges for their deployment. Overall, we seek to inspire timely actions to counter a looming source of inequity in behavioural neurology

Interpersonal prosodic correlation in frontotemporal dementia.

Communication accommodation describes how individuals adjust their communicative style to that of their conversational partner. We predicted that interpersonal prosodic correlation related to pitch and timing would be decreased in behavioral variant frontotemporal dementia (bvFTD). We predicted that the interpersonal correlation in a timing measure and a pitch measure would be increased in right temporal FTD (rtFTD) due to sparing of the neural substrate for speech timing and pitch modulation but loss of social semantics. We found no significant effects in bvFTD, but conversations including rtFTD demonstrated higher interpersonal correlations in speech rate than healthy controls

Music recognition in frontotemporal lobar degeneration and Alzheimer disease

Objective—To compare music recognition in patients with frontotemporal dementia, semantic dementia, Alzheimer disease, and controls and to evaluate the relationship between music recognition and brain volume. Background—Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music. Methods—Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies. Results—There were no group differences on pitch and melody discrimination tasks. However, patients with semantic dementia had considerable difficulty naming familiar melodies and also scored the lowest when asked to identify pitch errors in the same melodies. Naming familiar melodies, but not other music tasks, was strongly related to measures of semantic memory. Voxelbased morphometry analysis of brain MRI showed that difficulty in naming songs was associated with the bilateral temporal lobes and inferior frontal gyrus, whereas difficulty in identifying pitch errors in familiar melodies correlated with primarily the right temporal lobe. Conclusions—The results support a view that the anterior temporal lobes play a role in familiar melody recognition, and that musical functions are affected differentially across forms of dementia

Semantic and lexical features of words dissimilarly affected by non-fluent, logopenic, and semantic primary progressive aphasia

OBJECTIVE: To determine the effect of three psycholinguistic variables-lexical frequency, age of acquisition (AoA), and neighborhood density (ND)-on lexical-semantic processing in individuals with non-fluent (nfvPPA), logopenic (lvPPA), and semantic primary progressive aphasia (svPPA). Identifying the scope and independence of these features can provide valuable information about the organization of words in our mind and brain. METHOD: We administered a lexical decision task-with words carefully selected to permit distinguishing lexical frequency, AoA, and orthographic ND effects-to 41 individuals with PPA (13 nfvPPA, 14 lvPPA, 14 svPPA) and 25 controls. RESULTS: Of the psycholinguistic variables studied, lexical frequency had the largest influence on lexical-semantic processing, but AoA and ND also played an independent role. The results reflect a brain-language relationship with different proportional effects of frequency, AoA, and ND in the PPA variants, in a pattern that is consistent with the organization of the mental lexicon. Individuals with nfvPPA and lvPPA experienced an ND effect consistent with the role of inferior frontal and temporoparietal regions in lexical analysis and word form processing. By contrast, individuals with svPPA experienced an AoA effect consistent with the role of the anterior temporal lobe in semantic processing. CONCLUSIONS: The findings are in line with a hierarchical mental lexicon structure with a conceptual (semantic) and a lexeme (word-form) level, such that a selective deficit at one of these levels of the mental lexicon manifests differently in lexical-semantic processing performance, consistent with the affected language-specific brain region in each PPA variant

“Looks familiar, but I do not know who she is”:The role of the anterior right temporal lobe in famous face recognition

Processing a famous face involves a cascade of steps including detecting the presence of a face, recognizing it as familiar, accessing semantic/biographical information about the person, and finally, if required, production of the proper name. Decades of neuropsychological and neuroimaging studies have identified a network of occipital and temporal brain regions ostensibly comprising the 'core' system for face processing. Recent research has also begun to elucidate upon an 'extended' network, including anterior temporal and frontal regions. However, there is disagreement about which brain areas are involved in each step, as many aspects of face processing occur automatically in healthy individuals and rarely dissociate in patients. Moreover, some common phenomena are not easily induced in an experimental setting, such as having a sense of familiarity without being able to recall who the person is. Patients with the semantic variant of Primary Progressive Aphasia (svPPA) often recognize a famous face as familiar, even when they cannot specifically recall the proper name or biographical details. In this study, we analyzed data from a large sample of 105 patients with neurodegenerative disorders, including 43 svPPA, to identify the neuroanatomical substrates of three different steps of famous face processing. Using voxel-based morphometry, we correlated whole-brain grey matter volumes with scores on three experimental tasks that targeted familiarity judgment, semantic/biographical information retrieval, and naming. Performance in naming and semantic association significantly correlates with grey matter volume in the left anterior temporal lobe, whereas familiarity judgment with integrity of the right anterior middle temporal gyrus. These findings shed light on the neuroanatomical substrates of key components of overt face processing, addressing issues of functional lateralization, and deepening our understanding of neural substrates of semantic knowledge