Dataset Information

Validated automatic speech biomarkers in primary progressive aphasia.

ABSTRACT:

Objective

To automatically extract and quantify specific disease biomarkers of prosody from the acoustic properties of speech in patients with primary progressive aphasia.

Methods

We analyzed speech samples from 59 progressive aphasic patients (non-fluent/agrammatic = 15, semantic = 21, logopenic = 23; ages 50-85 years) and 31 matched healthy controls (ages 54-89 years). Using a novel, automated speech analysis protocol, we extracted acoustic measurements of prosody, including fundamental frequency and speech and silent pause durations, and compared these between groups. We then examined their relationships with clinical tests, gray matter atrophy, and cerebrospinal fluid analytes.

Results

We found a narrowed range of fundamental frequency in patients with non-fluent/agrammatic variant aphasia (mean 3.86 ± 1.15 semitones) compared with healthy controls (6.06 ± 1.95 semitones; P < 0.001) and patients with semantic variant aphasia (6.12 ± 1.77 semitones; P = 0.001). Mean pause rate was significantly increased in the non-fluent/agrammatic group (mean 61.4 ± 20.8 pauses per minute) and the logopenic group (58.7 ± 16.4 pauses per minute) compared to controls. In an exploratory analysis, narrowed fundamental frequency range was associated with atrophy in the left inferior frontal cortex. Cerebrospinal level of phosphorylated tau was associated with an acoustic classifier combining fundamental frequency range and pause rate (r = 0.58, P = 0.007). Receiver operating characteristic analysis with this combined classifier distinguished non-fluent/agrammatic speakers from healthy controls (AUC = 0.94) and from semantic variant patients (AUC = 0.86).

Interpretation

Restricted fundamental frequency range and increased pause rate are characteristic markers of speech in non-fluent/agrammatic primary progressive aphasia. These can be extracted with automated speech analysis and are associated with left inferior frontal atrophy and cerebrospinal phosphorylated tau level.

SUBMITTER: Nevler N

PROVIDER: S-EPMC6331511 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Validated automatic speech biomarkers in primary progressive aphasia.

Nevler Naomi N Ash Sharon S Irwin David J DJ Liberman Mark M Grossman Murray M

Annals of clinical and translational neurology 20181124 1

<h4>Objective</h4>To automatically extract and quantify specific disease biomarkers of prosody from the acoustic properties of speech in patients with primary progressive aphasia.<h4>Methods</h4>We analyzed speech samples from 59 progressive aphasic patients (non-fluent/agrammatic = 15, semantic = 21, logopenic = 23; ages 50-85 years) and 31 matched healthy controls (ages 54-89 years). Using a novel, automated speech analysis protocol, we extracted acoustic measurements of prosody, including fun ...[more]

PMID: 30656179

Similar Datasets

Project description:Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients' personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.

Project description:Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non-fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as 'fluent' or 'non-fluent', however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously. Secondly, we aimed to determine the neuroanatomical correlates of changes along these different dimensions. We recorded, transcribed and analysed speech samples for 50 patients with primary progressive aphasia, along with neurodegenerative and normal control groups. Patients were scanned with magnetic resonance imaging, and voxel-based morphometry was used to identify regions where atrophy correlated significantly with motor speech and linguistic features. Speech samples in patients with the non-fluent variant were characterized by slow rate, distortions, syntactic errors and reduced complexity. In contrast, patients with the semantic variant exhibited normal rate and very few speech or syntactic errors, but showed increased proportions of closed class words, pronouns and verbs, and higher frequency nouns, reflecting lexical retrieval deficits. In patients with the logopenic variant, speech rate (a common proxy for fluency) was intermediate between the other two variants, but distortions and syntactic errors were less common than in the non-fluent variant, while lexical access was less impaired than in the semantic variant. Reduced speech rate was linked with atrophy to a wide range of both anterior and posterior language regions, but specific deficits had more circumscribed anatomical correlates. Frontal regions were associated with motor speech and syntactic processes, anterior and inferior temporal regions with lexical retrieval, and posterior temporal regions with phonological errors and several other types of disruptions to fluency. These findings demonstrate that a multidimensional quantification of connected speech production is necessary to characterize the differences between the speech patterns of each primary progressive aphasic variant adequately, and to reveal associations between particular aspects of connected speech and specific components of the neural network for speech production.

Project description:The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.

Project description:Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer's disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients' brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer's disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer's disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals. Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.

Project description:The consensus criteria for the diagnosis and classification of primary progressive aphasia (PPA) have served as an important tool in studying this group of disorders. However, a large proportion of patients remain unclassifiable whilst others simultaneously meet criteria for multiple subtypes. We prospectively evaluated a large cohort of patients with degenerative aphasia and/or apraxia of speech using multidisciplinary clinical assessments and multimodal imaging. Blinded diagnoses were made using operational definitions with important differences compared to the consensus criteria. Of the 130 included patients, 40 were diagnosed with progressive apraxia of speech (PAOS), 12 with progressive agrammatic aphasia, 9 with semantic dementia, 52 with logopenic progressive aphasia, and 4 with progressive fluent aphasia, while 13 were unclassified. The PAOS and progressive fluent aphasia groups were least impaired. Performance on repetition and sentence comprehension was especially poor in the logopenic group. The semantic and progressive fluent aphasia groups had prominent anomia, but only semantic subjects had loss of word meaning and object knowledge. Distinct patterns of grey matter loss and white matter changes were found in all groups compared to controls. PAOS subjects had bilateral frontal grey matter loss, including the premotor and supplementary motor areas, and bilateral frontal white matter involvement. The agrammatic group had more widespread, predominantly left sided grey matter loss and white matter abnormalities. Semantic subjects had bitemporal grey matter loss and white matter changes, including the uncinate and inferior occipitofrontal fasciculi, whereas progressive fluent subjects only had left sided temporal involvement. Logopenic subjects had diffuse and bilateral grey matter loss and diffusion tensor abnormalities, maximal in the posterior temporal region. A diagnosis of logopenic aphasia was strongly associated with being amyloid positive (46/52 positive). Our findings support consideration of an alternative way of identifying and categorizing subtypes of degenerative speech and language disorders.

Dataset Information

Validated automatic speech biomarkers in primary progressive aphasia.

Objective

Methods

Results

Interpretation

Publications

Validated automatic speech biomarkers in primary progressive aphasia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets