Semantic Variant Primary Progressive Aphasia: Practical Recommendations for Treatment from 20 Years of Behavioural Research.
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ABSTRACT:
SUBMITTER: Suarez-Gonzalez A
PROVIDER: S-EPMC8699306 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g., it has eight legs) to conceptual (e.g., venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing.
| S-EPMC8241439 | biostudies-literature
Project description:The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA. Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes. Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease.
| S-EPMC6465769 | biostudies-literature
Project description:Data are mixed on whether patients with semantic variant primary progressive aphasia exhibit a category-selective semantic deficit for animate objects. Moreover, there is little consensus regarding the neural substrates of this category-selective semantic deficit, though prior literature has suggested that the perirhinal cortex and the lateral posterior fusiform gyrus may support semantic memory functions important for processing animate objects. In this study, we investigated whether patients with semantic variant primary progressive aphasia exhibited a category-selective semantic deficit for animate objects in a word-picture matching task, controlling for psycholinguistic features of the stimuli, including frequency, familiarity, typicality and age of acquisition. We investigated the neural bases of this category selectivity by examining its relationship with cortical atrophy in two primary regions of interest: bilateral perirhinal cortex and lateral posterior fusiform gyri. We analysed data from 20 patients with semantic variant primary progressive aphasia (mean age = 64 years, S.D. = 6.94). For each participant, we calculated an animacy index score to denote the magnitude of the category-selective semantic deficit for animate objects. Multivariate regression analysis revealed a main effect of animacy (β = 0.52, t = 4.03, P < 0.001) even after including all psycholinguistic variables in the model, such that animate objects were less likely to be identified correctly relative to inanimate objects. Inspection of each individual patient's data indicated the presence of a disproportionate impairment in animate objects in most patients. A linear regression analysis revealed a relationship between the right perirhinal cortex thickness and animacy index scores (β = -0.57, t = -2.74, P = 0.015) such that patients who were more disproportionally impaired for animate relative to inanimate objects exhibited thinner right perirhinal cortex. A vertex-wise general linear model analysis restricted to the temporal lobes revealed additional associations between positive animacy index scores (i.e. a disproportionately poorer performance on animate objects) and cortical atrophy in the right perirhinal and entorhinal cortex, superior, middle, and inferior temporal gyri, and the anterior fusiform gyrus, as well as the left anterior fusiform gyrus. Taken together, our results indicate that a category-selective semantic deficit for animate objects is a characteristic feature of semantic variant primary progressive aphasia that is detectable in most individuals. Our imaging findings provide further support for the role of the right perirhinal cortex and other temporal lobe regions in the semantic processing of animate objects.
| S-EPMC8493104 | biostudies-literature
Project description:As their illness progresses, patients with the semantic variant of Primary Progressive Aphasia (svPPA) frequently exhibit peculiar behaviors indicative of altered visual attention or an increased interest in artistic endeavors. In the present study, we examined changes within and between large-scale functional brain networks that may explain this altered visual behavior. We first examined the connectivity of the visual association network, the dorsal attention network, and the default mode network in healthy young adults (n = 89) to understand the typical architecture of these networks in the healthy brain. We then compared the large-scale functional connectivity of these networks in a group of svPPA patients (n = 12) to a group of age-matched cognitively normal controls (n = 30). Our results showed that the between-network connectivity of the dorsal attention and visual association networks was elevated in svPPA patients relative to controls. We further showed that this heightened between-network connectivity was associated with a decrease in the within-network connectivity of the default mode network, possibly due to progressive degeneration of the anterior temporal lobes in svPPA. These results suggest that focal neurodegeneration can lead to the reorganization of large-scale cognitive networks beyond the primarily affected network(s), possibly contributing to cognitive or behavioral changes that are commonly present as part of the clinical phenotype of svPPA.
| S-EPMC7708956 | biostudies-literature
Project description:Some patients with primary progressive aphasia (PPA) present with various types of hearing deficits. Research on the auditory function and speech sounds in PPA, including temporal, phonemic, and prosodic processing, revealed impairment in some of these auditory processes. Many patients with PPA who present with impaired word recognition subsequently developed non-fluent variant PPA. Herein, we present a patient with semantic variant PPA (svPPA) who demonstrated impaired verbal word discrimination. Audiological examinations revealed normal auditory brainstem responses and slightly impaired pure-tone perception. By contrast, verbal word discrimination and monosyllable identification were impaired, and temporal auditory acuity deteriorated. Analyses of brain magnetic resonance images revealed a significant decrease in the gray matter volume in bilateral superior temporal areas, predominantly on the left, compared with those of patients with typical svPPA, which appeared to be associated with impaired word recognition in our patient.
| S-EPMC9243420 | biostudies-literature
Project description:The objective of the study was to evaluate the prognostic value of regional cerebral blood flow (CBF) measured by arterial spin labeled (ASL) perfusion MRI in patients with semantic variant primary progressive aphasia (svPPA). We acquired pseudo-continuous ASL (pCASL) MRI and whole-brain T1-weighted structural MRI in svPPA patients (N = 13) with cerebrospinal fluid biomarkers consistent with frontotemporal lobar degeneration pathology. Follow-up T1-weighted MRI was available in a subset of patients (N = 8). We performed whole-brain comparisons of partial volume-corrected CBF and cortical thickness between svPPA and controls, and compared baseline and follow-up cortical thickness in regions of significant hypoperfusion and hyperperfusion. Patients with svPPA showed partial volume-corrected hypoperfusion relative to controls in left temporal lobe and insula. svPPA patients also had typical cortical thinning in anterior temporal, insula, and inferior frontal regions at baseline. Volume-corrected hypoperfusion was seen in areas of significant cortical thinning such as the left temporal lobe and insula. Additional regions of hypoperfusion corresponded to areas without cortical thinning. We also observed regions of hyperperfusion, some associated with cortical thinning and others without cortical thinning, including right superior temporal, inferior parietal, and orbitofrontal cortices. Regions of hypoperfusion and hyperperfusion near cortical thinning at baseline had significant longitudinal thinning between baseline and follow-up scans, but perfusion changes in distant areas did not show progressive thinning. Our findings suggest ASL MRI may be sensitive to functional changes not readily apparent in structural MRI, and specific changes in perfusion may be prognostic markers of disease progression in a manner consistent with cell-to-cell spreading pathology.
| S-EPMC5097861 | biostudies-literature
Project description:A wealth of neuroimaging research has associated semantic variant primary progressive aphasia with distributed cortical atrophy that is most prominent in the left anterior temporal cortex; however, there is little consensus regarding which region within the anterior temporal cortex is most prominently damaged, which may indicate the putative origin of neurodegeneration. In this study, we localized the most prominent and consistent region of atrophy in semantic variant primary progressive aphasia using cortical thickness analysis in two independent patient samples (n = 16 and 28, respectively) relative to age-matched controls (n = 30). Across both samples the point of maximal atrophy was located in the same region of the left temporal pole. This same region was the point of maximal atrophy in 100% of individual patients in both semantic variant primary progressive aphasia samples. Using resting state functional connectivity in healthy young adults (n = 89), we showed that the seed region derived from the semantic variant primary progressive aphasia analysis was strongly connected with a large-scale network that closely resembled the distributed atrophy pattern in semantic variant primary progressive aphasia. In both patient samples, the magnitude of atrophy within a brain region was predicted by that region's strength of functional connectivity to the temporopolar seed region in healthy adults. These findings suggest that cortical atrophy in semantic variant primary progressive aphasia may follow connectional pathways within a large-scale network that converges on the temporal pole.
| S-EPMC5278308 | biostudies-literature
Project description:The most recent theories of emotions have postulated that their expression and recognition depend on acquired conceptual knowledge. In other words, the conceptual knowledge derived from prior experiences guide our ability to make sense of such emotions. However, clear evidence is still lacking to contradict more traditional theories, considering emotions as innate, distinct and universal physiological states. In addition, whether valence processing (i.e. recognition of the pleasant/unpleasant character of emotions) also relies on semantic knowledge is yet to be determined. To investigate the contribution of semantic knowledge to facial emotion recognition and valence processing, we conducted a behavioural and neuroimaging study in 20 controls and 16 patients with the semantic variant of primary progressive aphasia, a neurodegenerative disease that is prototypical of semantic memory impairment, and in which an emotion recognition deficit has already been described. We assessed participants' knowledge of emotion concepts and recognition of 10 basic (e.g. anger) or self-conscious (e.g. embarrassment) facial emotional expressions presented both statically (images) and dynamically (videos). All participants also underwent a brain MRI. Group comparisons revealed deficits in both emotion concept knowledge and emotion recognition in patients, independently of type of emotion and presentation. These measures were significantly correlated with each other in patients and with semantic fluency in patients and controls. Neuroimaging analyses showed that both emotion recognition and emotion conceptual knowledge were correlated with reduced grey matter density in similar areas within frontal ventral, temporal, insular and striatal regions, together with white fibre degeneration in tracts connecting frontal regions with each other as well as with temporal regions. We then performed a qualitative analysis of responses made during the facial emotion recognition task, by delineating valence errors (when one emotion was mistaken for another of a different valence), from other errors made during the emotion recognition test. We found that patients made more valence errors. The number of valence errors correlated with emotion conceptual knowledge as well as with reduced grey matter volume in brain regions already retrieved to correlate with this score. Specificity analyses allowed us to conclude that this cognitive relationship and anatomical overlap were not mediated by a general effect of disease severity. Our findings suggest that semantic knowledge guides the recognition of emotions and is also involved in valence processing. Our study supports a constructionist view of emotion recognition and valence processing, and could help to refine current theories on the interweaving of semantic knowledge and emotion processing.
| S-EPMC7805810 | biostudies-literature
Project description:Currently, variant subtyping in primary progressive aphasia (PPA) requires an expert neurologist and extensive language and cognitive testing. Spelling impairments appear early in the development of the disorder, and the three PPA variants (non-fluent - nfvPPA; semantic - svPPA; logopenic - lvPPA) reportedly show fairly distinct spelling profiles. Given the theoretical and empirical evidence indicating that spelling may serve as a proxy for spoken language, the current study aimed to determine whether spelling performance alone, when evaluated with advanced statistical analyses, allows for accurate PPA variant classification. A spelling to dictation task (with real words and pseudowords) was administered to 33 PPA individuals: 17 lvPPA, 10 nfvPPA, 6 svPPA. Using machine learning classification algorithms, we obtained pairwise variant classification accuracies that ranged between 67 and 100%. In additional analyses that assumed no prior knowledge of each case's variant, classification accuracies ranged between 59 and 70%. To our knowledge, this is the first time that all the PPA variants, including the most challenging logopenic variant, have been classified with such high accuracy when using information from a single language task. These results underscore the rich structure of the spelling process and support the use of a spelling task in PPA variant classification.
| S-EPMC6817413 | biostudies-literature
Project description:T1-magnetic resonance imaging (MRI) studies report early atrophy in the left anterior temporal lobe, especially the perirhinal cortex, in semantic variant primary progressive aphasia (svPPA). Improved segmentation protocols using high-resolution T2-MRI have enabled fine-grained medial temporal lobe (MTL) subregional measurements, which may provide novel information on the atrophy pattern and disease progression in svPPA. We aimed to investigate the MTL subregional atrophy pattern cross-sectionally and longitudinally in patients with svPPA as compared with controls and patients with Alzheimer's disease (AD). MTL subregional volumes were obtained using the Automated Segmentation for Hippocampal Subfields software from high-resolution T2-MRIs in 15 svPPA, 37 AD, and 23 healthy controls. All MTL volumes were corrected for intracranial volume and parahippocampal cortices for slice number. Longitudinal atrophy rates of all subregions were obtained using an unbiased deformation-based morphometry pipeline in 6 svPPA patients, 9 controls, and 12 AD patients. Cross-sectionally, significant volume loss was observed in svPPA compared with controls in the left MTL, right cornu ammonis 1 (CA1), Brodmann area (BA)35, and BA36 (subdivisions of the perirhinal cortex). Compared with AD patients, svPPA patients had significantly smaller left CA1, BA35, and left and right BA36 volumes. Longitudinally, svPPA patients had significantly greater atrophy rates of left and right BA36 than controls but not relative to AD patients. Fine-grained analysis of MTL atrophy patterns provides information about the evolution of atrophy in svPPA. These results indicate that MTL subregional measures might be useful markers to track disease progression or for clinical trials in svPPA.
| S-EPMC8018475 | biostudies-literature