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Background and purposeThe non‐fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV‐1451 was developed for the in‐vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS.MethodsNine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV‐1451. Uptake of [18F]AV‐1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel‐wise in SPM12. Each patient was age‐ and sex‐matched to three controls.ResultsThe agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS.ConclusionsThis cross‐sectional study suggests that [18F]AV‐1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

ObjectivesTo assess [18F]AV‐1451 tau‐PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV‐1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV‐1451, [18F]‐fluorodeoxygluclose (FDG)‐PET and MRI (magnetic resonance imaging) to differentiate the PPA variants.MethodsWe performed statistical parametric mapping of [18F]AV‐1451 across 40 PPA patients (logopenic‐PPA = 14, semantic‐PPA = 13, and agrammatic‐PPA = 13) compared to 80 cognitively normal, Pittsburgh compound B–negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV‐1451 tau‐PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV‐1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility.ResultsLogopenic‐PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic‐PPA, and agrammatic‐PPA. Semantic‐PPA and agrammatic‐PPA showed milder patterns of focal [18F]AV‐1451 uptake. Semantic‐PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic‐PPA. Agrammatic‐PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic‐PPA. The principal component analysis of regional [18F]AV‐1451 indicated two primary dimensions, a severity dimension that distinguished logopenic‐PPA from agrammatic‐PPA and semantic‐PPA, and a frontal versus temporal contrast that distinguishes agrammatic‐PPA and semantic‐PPA cases. Diagnostic utility of [18F]AV‐1451was superior to MRI and at least equal to FDG‐PET.Interpretation[18F]AV‐1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV‐1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV‐1451 may have clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599–611

The current investigation contributes to a perceptual similarity-based approach to dysarthria characterization by utilizing an innovative statistical approach, multinomial logistic regression with sparsity constraints, to identify acoustic features underlying each listener's impressions of speaker similarity. The data-driven approach also permitted an examination of the effect of clinical experience on listeners' impressions of similarity. Listeners, irrespective of level of clinical experience, were found to rely on similar acoustic features during the perceptual sorting task, known as free classification. Overall, the results support the continued advancement of a similarity-based approach to characterizing the communication disorders associated with dysarthria.

Background and purposeIt is believed that progressive Lewy‐type synucleinopathy (LTS) is primarily responsible for the worsening of motor and non‐motor Parkinson's disease (PD) signs and symptoms. Characterization of quantitative electroencephalography (QEEG) abnormalities across the spectrum of LTS to PD dementia (PD‐D) may provide insight into the pathophysiology of PD cortical dysfunction. Here our enlarged EEG database was leveraged to characterize spectral QEEG abnormalities in asymptomatic autopsy‐defined groups of control participants and incidental Lewy body disease (ILBD) and three clinically defined groups of participants with PD (cognitively normal PD, mild cognitive impairment PD, and PD‐D).MethodsThe PD cohort was studied as part of the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). AZSAND utilizes its Brain and Body Donation Program to perform prospective, standardized, regular longitudinal pre‐mortem assessments until death. Resting EEG from subjects was analyzed for spectral domain QEEG measures of background rhythm frequency and global relative power in delta, theta, alpha and beta bands.ResultsThe various spectral QEEG measures showed differential changes specific to the groups compared. Important findings were background rhythm frequency showing the most pairwise differences across the groups, and this also was the only significant difference between control and ILBD. An increase in delta bandpower was characteristic of worsening cognitive deficits.ConclusionsDifferent patterns of change amongst QEEG measures across LTS and PD cognitive states suggest that they correlate with heterogeneous pathophysiologies of cortical dysfunction within the PD clinical spectrum. In addition, the biomarker application of a specific spectral QEEG measure needs to be selectively suited to its study purpose.

Speaker normalization, a process whereby the perceptual system of a listener recalibrates to accommodate individual speakers, is proposed to account for the ease with which we understand speech produced by multiple speakers with different sized and shaped vocal tracts. A variety of vowel-, formant-, and speaker-intrinsic or extrinsic transforms have been proposed to model speaker normalization of vowels produced by multiple speakers (e.g., Mel, Bark, and Lobanov methods). Suitability of such normalization procedures has been examined extensively in non-disordered speaker populations. Unknown at this point, however, is the appropriateness of normalization procedures for transforming spectrally distorted vowels produced by speakers with dysarthria. Thus, we examined the suitability of two transforms, Bark and Lobanov, for normalizing vowels produced by a heterogeneous cohort of 45 speakers with dysarthria. Non-normalized (Hertz) and Bark transformed vowel tokens were classified via discriminant function analysis (DFA) with 55% and 56% accuracy, respectively. Classification accuracy of vowel tokens normalized using Lobanov’s method was 65%. The results of the DFAs were compared to perceptual data, which revealed listeners identified vowel tokens with 71% accuracy. These results suggest vowel-extrinsic and formant- and speaker-intrinsic normalization methods (e.g., Lobanov) are better suited to model speaker normalization of dysarthric vowels.

High-density electroencephalography (EEG) was used to evaluate cortical activity patterns during the auditory processing of speech presented at various levels of degradation in a sentence verification task. 25 healthy participants listened to true-false sentences produced with one of 3 channel levels (1, 6, 16), ranging from unintelligible, moderately intelligible, and highly intelligible. Behavioral data were collected via button press (reaction time and accuracy) for each sentence. The analysis of cortical activation patterns includes 1) the identification of independent components that account for variations of activity associated with degradation levels and 2) the examination of associated event-related potentials. Statistical analyses will be performed on individuals' cortical activity, in tandem with behavioral data. Preliminary results reveal differences in the timing and magnitude of frontal and temporal lobe activation that coincide with task difficulty. Results of the present investigation will inform hypotheses about regions of interest for further investigation and will bear on models of connected speech perception, including the neurobiological underpinnings of individual differences and manifestations in a listener's understanding of degraded speech.

Hypokinetic dysarthria is a common manifestation of Parkinson's disease, which negatively influences quality of life. Behavioral techniques that aim to improve speech intelligibility constitute the bulk of intervention strategies for this population, as the dysarthria does not often respond vigorously to medical interventions. Although several case and group studies generally support the efficacy of behavioral treatment, much work remains to establish a rigorous evidence base. This absence of definitive research leaves both the speech-language pathologist and referring physician with the task of determining the feasibility and nature of therapy for intelligibility remediation in PD. The purpose of this paper is to introduce a novel framework for medical practitioners in which to conceptualize and justify potential targets for speech remediation. The most commonly targeted deficits (e.g., speaking rate and vocal loudness) can be supported by this approach, as well as underutilized and novel treatment targets that aim at the listener's perceptual skills.