Perturbations of language network connectivity in primary progressive aphasia.
Ontology highlight
ABSTRACT:
SUBMITTER: Bonakdarpour B
PROVIDER: S-EPMC6889875 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Perturbations of language network connectivity in primary progressive aphasia.
Bonakdarpour Borna B Hurley Robert S RS Wang Allan R AR Fereira Hernando R HR Basu Anisha A Chatrathi Arjuna A Guillaume Kyla K Rogalski Emily J EJ Mesulam M Marsel MM
Cortex; a journal devoted to the study of the nervous system and behavior 20190909
Aphasias are caused by disruption in structural integrity and interconnectivity within a large-scale distributed language network. We investigated the distribution and behavioral consequences of altered functional connectivity in three variants of primary progressive aphasia (PPA). The goal was to clarify relationships among atrophy, resting connectivity, and the resulting behavioral changes in 73 PPA and 33 control participants. Three core regions of the left perisylvian language network: the i ...[more]
Similar Datasets
Project description:ObjectiveTranscranial direct current stimulation (tDCS) has shown promising results when used as an adjunct to behavioral training in neurodegenerative diseases. However, the underlying neural mechanisms are not understood and neuroimaging evidence from pre/post treatment has been sparse. In this study, we examined tDCS-induced neural changes in a language intervention study for primary progressive aphasia (PPA), a neurodegenerative syndrome with language impairment as the primary clinical presentation. Anodal tDCS was applied to the left inferior frontal gyrus (LIFG). To evaluate the hypothesis that tDCS promotes system segregation, analysis focused on understanding tDCS-induced changes in the brain-wide functional network connectivity of the targeted LIFG.MethodsResting-state fMRI data were obtained from 32 participants with PPA before and after receiving a written naming therapy, accompanied either by tDCS or sham stimulation. We focused on evaluating changes in the global connectivity of the stimulated LIFG-triangularis (LIFG-tri) region given its important role in lexical processing. Global connectivity was indexed by the graph-theoretic measure participation coefficient (PC) which quantifies a region's level of system segregation. The values before and after treatment were compared for each condition (tDCS or Sham) as well as with age-matched healthy controls (n = 19).ResultsHigher global connectivity of the LIFG-tri before treatment was associated with greater dementia severity. After treatment, the tDCS group showed a significant decrease in global connectivity whereas the Sham group's did not change, suggesting specific neural effects induced by tDCS. Further examination revealed that the decrease was driven by reduced connectivity between the LIFG-tri and regions outside the perisylvian language area, consistent with the hypothesis that tDCS enhances the segregation of the language system and improves processing efficiency. Additionally, we found that these effects were specific to the LIFG-tri and not observed in other control regions.ConclusionTDCS-augmented language therapy in PPA increased the functional segregation of the language system, a normalization of the hyper-connectivity observed before treatment. These findings add to our understanding of the nature of tDCS-induced neural changes in disease treatment and have applications for validating treatment efficacy and designing future tDCS and other non-invasive brain stimulation (NIBS) treatments.
| S-EPMC8311858 | biostudies-literature
Project description:Patients with Primary Progressive Aphasia (PPA) may react to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms. We used magnetoencephalography (MEG) to evaluate oscillatory neural responses in sentence comprehension, in patients with PPA and age-matched controls. Participants viewed sentences containing semantically and syntactically anomalous words that evoke distinct oscillatory responses. For age-matched controls, semantic anomalies elicited left-lateralized 8-30?Hz power decreases distributed along ventral brain regions, whereas syntactic anomalies elicited bilateral power decreases in both ventral and dorsal regions. In comparison to controls, patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude, which were correlated with linguistic impairment measured offline. The recruitment of right hemisphere temporo-parietal areas (also found in controls) was correlated with preserved semantic processing abilities, indicating that preserved neural activity in these regions was able to support successful semantic processing. In contrast, syntactic processing was more consistently impaired in PPA, regardless of neural activity patterns, suggesting that this domain of language is particularly vulnerable to the neuronal loss. In addition, we found that delayed peak latencies of oscillatory responses were associated with lower accuracy for detecting semantic anomalies, suggesting that language deficits observed in PPA may be linked to delayed or slowed information processing.
| S-EPMC5964832 | biostudies-other
Project description:Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases' pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.
| S-EPMC10066572 | biostudies-literature
Project description:ObjectiveTo determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA).MethodForty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings-particularly of WMH-are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable.ResultsVisual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P = 0.033) and greater global (P = 0.033) and periventricular (P = 0.049) WMH. High global WMH (P = 0.034) were also correlated with worse sentence repetition skills.ConclusionVisual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure-behavior relationships in PPA than cortical atrophy measures alone.
| S-EPMC7479763 | biostudies-literature
Project description:Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer's disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick's disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.2 ± 2.6 years) and shortest in TDP(A) (7.1 ± 2.4 years). A subset of 68 right-handed participants entered longitudinal investigations. They were classified as logopenic, agrammatic/non-fluent or semantic by quantitative algorithms. Each variant had a preferred but not invariant neuropathological correlate. Seventy-seven per cent of logopenics had ADNC, 56% of agrammatics had corticobasal degeneration/progressive supranuclear palsy or Pick's disease and 89% of semantics had TDP(C). Word comprehension impairments had strong predictive power for determining underlying neuropathology positively for TDP(C) and negatively for ADNC. Cortical atrophy was smallest in corticobasal degeneration/progressive supranuclear palsy and largest in TDP(A). Atrophy encompassed posterior frontal but not temporoparietal cortex in corticobasal degeneration/progressive supranuclear palsy, anterior temporal but not frontoparietal cortex in TDP(C), temporofrontal but not parietal cortex in Pick's disease and all three lobes with ADNC or TDP(A). There were individual deviations from these group patterns, accounting for less frequent clinicopathologic associations. The one common denominator was progressive asymmetric atrophy overwhelmingly favouring the left hemisphere language network. Comparisons of ADNC in typical amnestic versus atypical aphasic dementia and of TDP in type A versus type C revealed fundamental biological and clinical differences, suggesting that members of each pair may constitute distinct clinicopathologic entities despite identical downstream proteinopathies. Individual TDP(C) participants with unilateral left temporal atrophy displayed word comprehension impairments without additional object recognition deficits, helping to dissociate semantic primary progressive aphasia from semantic dementia. When common and uncommon associations were considered in the set of 68 participants, one neuropathology was found to cause multiple clinical subtypes, and one subtype of primary progressive aphasia to be caused by multiple neuropathologies, but with different probabilities. Occasionally, expected clinical manifestations of atrophy sites were absent, probably reflecting individual peculiarities of language organization. The hemispheric asymmetry of neurodegeneration and resultant language impairment in primary progressive aphasia reflect complex interactions among the cellular affinities of the degenerative disease, the constitutive biology of language cortex, familial or developmental vulnerabilities of this network and potential idiosyncrasies of functional anatomy in the affected individual.
| S-EPMC9246707 | biostudies-literature
Project description:Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.
| S-EPMC6041563 | 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:Background and purposeThere are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹?F]-THK5351 retention across all three subtypes and determine the topography of [¹?F]-THK5351 retention correlated with each neurolinguistic score.MethodsWe enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹?F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹?F]-THK5351 retention.ResultsThe nfvPPA patients exhibited higher [¹?F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹?F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹?F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹?F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹?F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹?F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices.ConclusionsThe pattern of [¹?F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
| S-EPMC6785468 | biostudies-literature
Project description:ObjectiveLanguage function test-specific neural substrates in Korean patients with primary progressive aphasia (PPA) might differ from those in other causes of dementia and English-speaking PPA patients. We investigated the correlation between language performance tests and cortical thickness to determine neural substrates in Korean patients with PPA.Materials and methodsNinety-six patients with PPA were recruited from the memory clinic. To acquire neural substrates, we performed linear regression using the scores of each language test as a predictor, cortical thickness as an outcome and age, sex, years of education, and intracranial volume as confounders.ResultsPoor performance in each language function test was associated with lower cortical thickness in specific cortical regions: (1) object naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (2) semantic generative naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (3) phonemic generative naming and the left prefrontal and inferior parietal regions; and (4) comprehension and the left posterior portion of the superior and middle temporal regions. In particular, the neural substrates of the semantic generative naming test in PPA patients, left anterior to mid-portion of the lateral and basal temporal regions, quite differed from those in patients with other causes of dementia.ConclusionOur findings provide a better understanding of the different pathomechanisms for language impairments among PPA patients from those with other causes of dementia.
| S-EPMC9452784 | biostudies-literature
Project description:Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 ± 9 years), non-fluent/agrammatic variant (n = 12, age = 71 ± 8 years) and semantic variant (n = 13, age = 65 ± 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 ± 5 years). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands-delta-theta (2-8 Hz); alpha (8-12 Hz); beta (12-30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variant-specific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network-specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.
| S-EPMC5841154 | biostudies-literature