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

Phonological Facilitation of Object Naming in Agrammatic and Logopenic Primary Progressive Aphasia (PPA): Evidence for a Phonological Processing Deficit

Naming is a pervasive deficit in primary progressive aphasia. However, the source of such deficits across PPA variants is little understood. In this study, individuals with agrammatic (PPA-G) and logopenic (PPA-L) PPA, along with age-matched controls, performed a picture-word interference task to test for online phonological processing deficits during naming. All groups exhibited phonological facilitation (PF) effects, i.e., speeded picture naming in the presence of phonologically-related words. However, the PPA participants exhibited abnormally large PF effects that also were protracted, compared to the control group. These results suggest that impaired phonological processing may contribute to anomia in PPA-G and PPA-L

Non-verbal episodic memory deficits in primary progressive aphasias are highly predictive of underlying amyloid pathology

Diagnostic distinction of primary progressive aphasias (PPA) remains challenging, in particular for the logopenic (lvPPA) and nonfluent/agrammatic (naPPA) variants. Recent findings highlight that episodic memory deficits appear to discriminate these PPA variants from each other, as only lvPPA perform poorly on these tasks while having underlying amyloid pathology similar to that seen in amnestic dementias like Alzheimer’s disease (AD). Most memory tests are, however, language based and thus potentially confounded by the prevalent language deficits in PPA. The current study investigated this issue across PPA variants by contrasting verbal and non-verbal episodic memory measures while controlling for their performance on a language subtest of a general cognitive screen. A total of 203 participants were included (25 lvPPA; 29 naPPA; 59 AD; 90 controls) and underwent extensive verbal and non-verbal episodic memory testing, with a subset of patients (n = 45) with confirmed amyloid profiles as assessed by Pittsburgh Compound B and PET. The most powerful discriminator between naPPA and lvPPA patients was a non-verbal recall measure (Rey Complex Figure delayed recall), with 81% of PPA patients classified correctly at presentation. Importantly, AD and lvPPA patients performed comparably on this measure, further highlighting the importance of underlying amyloid pathology in episodic memory profiles. The findings demonstrate that non-verbal recall emerges as the best discriminator of lvPPA and naPPA when controlling for language deficits in high load amyloid PPA cases

Brain plasticity in aphasic patients: Intra- and inter-hemispheric reorganisation of the whole linguistic network probed by N150 and N350 components

The present study examined linguistic plastic reorganization of language through Evoked Potentials in a group of 17 non-fluent aphasic patients who had suffered left perisylvian focal lesions, and showed a good linguistic recovery. Language reorganisation was probed with three linguistic tasks (Phonological, Semantic, Orthographic), the early word recognition potential (N150) and the later phonological-related component (N350). Results showed the typical left-lateralised posterior N150 in healthy controls (source: left Fusiform Gyrus), that was bilateral (Semantic) or right sided (Phonological task) in patients (sources: right Inferior/Middle Temporal and Fusiform Gyri). As regards N350, controls revealed different intra- and inter-hemispheric linguistic activation across linguistic tasks, whereas patients exhibited greater activity in left intact sites, anterior and posterior to the damaged area, in all tasks (sources: Superior Frontal Gyri). A comprehensive neurofunctional model is presented, describing how complete intra- and inter-hemispheric reorganisation of the linguistic networks occurs after aphasic damage in the strategically dominant left perisylvian linguistic centres

The relationship between phonological and morphological deficits in Broca's aphasia: further evidence from errors in verb inflection

A previous study of 10 patients with Broca’s aphasia demonstrated that the advantage for producing the past tense of irregular over regular verbs exhibited by these patients was eliminated when the two sets of past-tense forms were matched for phonological complexity (Bird, Lambon Ralph, Seidenberg, McClelland, & Patterson, 2003). The interpretation given was that a generalised phonological impairment was central to the patients’ language deficits, including their poor performance on regular past tense verbs. The current paper provides further evidence in favour of this hypothesis, on the basis of a detailed analysis of the errors produced by these same 10 patients in reading, repetition, and sentence completion for a large number of regular, irregular, and nonce verbs. The patients’ predominant error types in all tasks and for all verb types were close and distant phonologically related responses. The balance between close and distant errors varied along three continua: the severity of the patient (more distant errors produced by the more severely impaired patients); the difficulty of the task (more distant errors in sentence completion > reading > repetition); the difficulty of the item (more distant errors for novel word forms than real verbs). A position analysis for these phonologically related errors revealed that vowels were most likely to be preserved and that consonant onsets and offsets were equally likely to be incorrect. Critically, the patients’ errors exhibited a strong tendency to simplify the phonological form of the target. These results are consistent with the notion that the patients’ relatively greater difficulty with regular past tenses reflects a phonological impairment that is sensitive to the complexity of spoken forms

Comprehension of wh-questions in a case of mixed dementia

We investigated processing of wh-questions and declarative sentences with differing syntactic complexity in a case of mixed dementia (FA). FA was impaired in her ability to understand syntactically complex declarative sentences and syntactically complex wh-questions beginning with which but not complex who questions. This profile, novel in dementia, is similar to that reported for people with agrammatic aphasia and discerns a ‘‘fault line’’ of the language system along a syntactic/semantic paramete

Comprehension of wh-questions in a case of mixed dementia

We investigated processing of wh-questions and declarative sentences with differing syntactic complexity in a case of mixed dementia (FA). FA was impaired in her ability to understand syntactically complex declarative sentences and syntactically complex wh-questions beginning with which but not complex who questions. This profile, novel in dementia, is similar to that reported for people with agrammatic aphasia and discerns a ‘‘fault line’’ of the language system along a syntactic/semantic paramete

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA