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

Multimodal Cuing of Autobiographical Memory in Semantic Dementia

OBJECTIVE: Individuals with semantic dementia (SD) have impaired autobiographical memory (AM), but the extent of the impairment has been controversial. According to one report (Westmacott, Leach, Freedman, & Moscovitch, 2001), patient performance was better when visual cues were used instead of verbal cues; however, the visual cues used in that study (family photographs) provided more retrieval support than do the word cues that are typically used in AM studies. In the present study, we sought to disentangle the effects of retrieval support and cue modality. METHOD: We cued AMs of 5 patients with SD and 5 controls with words, simple pictures, and odors. Memories were elicited from childhood, early adulthood, and recent adulthood; they were scored for level of detail and episodic specificity. RESULTS: The patients were impaired across all time periods and stimulus modalities. Within the patient group, words and pictures were equally effective as cues (Friedman test; χ² = 0.25, p = .61), whereas odors were less effective than both words and pictures (for words vs. odors, χ² = 7.83, p = .005; for pictures vs. odors, χ² = 6.18, p = .01). There was no evidence of a temporal gradient in either group (for patients with SD, χ² = 0.24, p = .89; for controls, χ² \u3c 2.07, p = .35). CONCLUSIONS: Once the effect of retrieval support is equated across stimulus modalities, there is no evidence for an advantage of visual cues over verbal cues. The greater impairment for olfactory cues presumably reflects degeneration of anterior temporal regions that support olfactory memory

Neuropsychological, Behavioral, and Anatomical Evolution in Right Temporal Variant Frontotemporal Dementia: A Longitudinal Single Case Analysis

We examine longitudinal clinical and anatomical data for a patient with the right temporal variant of frontotemporal dementia. The patient received comprehensive clinical evaluations and structural MRI scans over three years. She presented with early behavioral deficits and ultimately developed semantic impairments consistent with the semantic variant of primary progressive aphasia. Imaging revealed early atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that right and left temporal variants reflect early asymmetry of atrophy that may become more bilateral over time, resulting in a mixed clinical picture

An Overview on Primary Progressive Aphasia and Its Variants

We present a review of the literature on Primary Progressive Aphasia (PPA) together with the analysis of neuropschychological and neuroradiologic profiles of 42 PPA patients. Mesulam originally defined PPA as a progressive degenerative disorder characterized by isolated language impairment for at least two years. The most common variants of PPA are: (1) Progressive nonfluent aphasia (PNFA), (2) semantic dementia (SD), (3) logopenic progressive aphasia (LPA). PNFA is characterized by labored speech, agrammatism in production, and/or comprehension. In some cases the syndrome begins with isolated deficits in speech. SD patients typically present with loss of word and object meaning and surface dyslexia. LPA patients have word-finding difficulties, syntactically simple but accurate language output and impaired sentence comprehension. The neuropsychological data demonstrated that SD patients show the most characteristic pattern of impairment, while PNFA and LPA overlap within many cognitive domains. The neuroimaging analysis showed left perisylvian region involvement. A comprehensive cognitive, neuroimaging and pathological approach is necessary to identify the clinical and pathogenetic features of different PPA variants

Anatomical correlates of early mutism in progressive nonfluent aphasia

Patients with progressive nonfluent aphasia (PNFA) can become mute early in the course of the disease. Voxel-based morphometry showed that PNFA is associated with left anterior insula and inferior frontal atrophy. In PNFA with early mutism, volume loss was more prominent in the pars opercularis and extended into the left basal ganglia. Damage to the network of brain regions involved in both coordination and execution of speech causes mutism in PNFA

Deformation-based shape analysis of the hippocampus in the semantic variant of primary progressive aphasia and Alzheimer’s disease

Background Increasing evidence shows that the semantic variant of primary progressive aphasia (svPPA) is characterized by hippocampal atrophy. However, less is known about disease-related morphological hippocampal changes. The goal of the present study is to conduct a detailed characterization of the impact of svPPA on global hippocampus volume and morphology compared with control subjects and patients with Alzheimer’s disease (AD). Methods We measured hippocampal volume and deformation-based shape differences in 22 patients with svPPA compared with 99 patients with AD and 92 controls. Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeT-Brain) was used on MRI images obtained at the diagnostic visit. Results Comparable left and right hippocampal atrophy were observed in svPPA and AD. Deformation-based shape analysis showed a common pattern of morphological deformation in svPPA and AD compared with controls. More specifically, both svPPA and AD showed inward deformations in the dorsal surface of the hippocampus, from head to tail on the left side, and more limited to the anterior portion of the body in the right hemisphere. These results also pointed out that both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. Discussion Our study provides critical new evidence of hippocampal morphological changes in svPPA, similar to those found in AD. These findings highlight the importance of considering morphological hippocampal changes as part of the anatomical profile of patients with svPPA

Observing conversational laughter in frontotemporal dementia.

BackgroundWe performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer's disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking.MethodsPatients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant's own vocalisation ('self' context) or during or shortly after the partner's vocalisation ('partner' context).ResultsIndividuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech comparedwith healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls.ConclusionsLaughter in response to one's own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis

State and trait characteristics of anterior insula time-varying functional connectivity.

The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity varies over time. We implemented a novel approach combining seed-to-whole-brain sliding-window functional connectivity MRI and k-means clustering to assess time-varying functional connectivity of aINS subregions. We studied three independent large samples of healthy participants and longitudinal datasets to assess inter- and intra-subject stability, and related aINS time-varying functional connectivity profiles to dispositional empathy. We identified four robust aINS time-varying functional connectivity modes that displayed both "state" and "trait" characteristics: while modes featuring connectivity to sensory regions were modulated by eye closure, modes featuring connectivity to higher cognitive and emotional processing regions were stable over time and related to empathy measures

Speech and language therapy approaches to managing primary progressive aphasia

The term primary progressive aphasia (PPA) describes a group of neurodegenerative disorders with predominant speech and language dysfunction as their main feature. There are three main variants – the semantic variant, the nonfluent or agrammatic variant and the logopenic variant – each with specific linguistic deficits and different neuroanatomical involvement. There are currently no curative treatments or symptomatic pharmacological therapies. However, speech and language therapists have developed several impairment-based interventions and compensatory strategies for use in the clinic. Unfortunately, multiple barriers still need to be overcome to improve access to care for people with PPA, including increasing awareness among referring clinicians, improving training of speech and language therapists and developing evidence-based guidelines for therapeutic interventions. This review highlights this inequity and the reasons why neurologists should refer people with PPA to speech and language therapists