Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Abstract

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r(2) = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA.

Figure 1. Visual examples of speech behaviors that are associated with apraxia of speech in the nonfluent variant (A2, B2) rather than the logopenic variant (A1, B1).

In A1 and A2, the blue vertical lines mark the boundaries of the 2 vowels used to measure lexical stress. In B1 and B2, the black line shows vocal intensity (i.e. loudness) and the blue line fundamental frequency (i.e. vocal pitch, uncorrected) during speech; The intensity contour falls and the pitch contour breaks when the voice is silent during unvoiced sounds (e.g. ‘t’, ‘f’) or during pauses in speech. A1: Normal speech rate and lexical stress on polysyllabic words (here, the first ‘a’ vowel in ‘banana’ is very brief and much shorter than the second vowel) and no phonetic distortions; Total sample length 900 msec. A2: Slow speech rate, equal lexical stress on polysyllabic words (here, the two ‘a’ vowels in banana are of similar and longer duration, giving the perception of equal stress), and phonetic distortion on the final ‘n’ (closure of the velopharyngeal port is mistimed, blocking the nasal airflow before the tongue tip drops away from the palate, creating a sound similar to ‘d’); Total sample length 900 msec. B1: Normal speech rate and smooth transitions between syllables; Total sample length 1500 msec, 7 syllables. B2: Slowed speech rate and syllable segregation (here, the transitions between ‘-bout’ and ‘my’ and between ‘my’ and ‘grand’ are longer and more distinct in the nonfluent case), as well as distortion/substitution where the ‘f’ sound is perceived as ‘f’ but is momentarily voiced (short segment of blue line) similar to a ‘v’; Total sample length 1500 msec, 5 syllables.

Figure 2. Pairwise variability of vowel duration as a function of proportion of silence time.

The relationship between median Pairwise Variability Index for vowel duration in weak-strong polysyllabic words (PVI_Duration_WS) and proportion of silence time in reading is shown for patients with logopenic variant (lvPPA) and nonfluent variant (nfvPPA) Primary Progressive Aphasia and healthy age-matched adults. For PVI_Duration_WS, smaller values represent more equal stress across the first two syllables of words. Grey squares mark the 7 of 41 patient cases misidentified by the discriminant function Model 1 (lvPPA cases 6 and 7, nfvPPA cases 23, 26, 27, 28, and 37). PiB+ marks the three nfvPPA patients with contradictory positive findings on Pittsburgh compound B scanning, indicative of Alzheimer pathology and more commonly associated with the logopenic variant. Control participants were not included in the discriminant function analysis but are shown here for comparison.

Figure 3. Pairwise variability of vowel duration as a function of variability of silence duration.

The relationship between median Pairwise Variability Index for vowel duration in weak-strong polysyllabic words (PVI_Duration_WS) and variability of silence duration in reading is shown for patients with logopenic variant (lvPPA) and nonfluent variant (nfvPPA) Primary Progressive Aphasia and healthy age-matched adults. For PVI_Duration_WS, smaller values represent more equal stress across the first two syllables of words. Grey squares mark the 7 of 41 patient cases misidentified by the discriminant function Model 1 (lvPPA cases 6 and 7, nfvPPA cases 23, 26, 27, 28, and 37). PiB+ marks the three nfvPPA patients with contradictory positive findings on Pittsburgh compound B scanning, indicative of Alzheimer pathology and more commonly associated with the logopenic variant. Control participants were not included in the discriminant function analysis but are shown here for comparison.

Figure 4. Pairwise Variability of vowel duration in weak-strong versus strong-weak polsyllable words.

The relationship between median Pairwise Variability Index for vowel duration in weak-strong and strong-weak polysyllabic words (PVI_Duration_WS, PVI_Duration_SW, respectively) for individuals with logopenic variant (lvPPA) and nonfluent variant (nfvPPA) Primary Progressive Aphasia and healthy age-matched adults. Smaller values represent more equal stress (i.e. more similar duration) across the first two syllables of words. Consistent with this, individuals with PVI_Duration_WS less than about 110 and PVI_Duration_SW less than about 80 are confidently diagnosed as nfvPPA by the model. Grey boxes indicate 6 patient cases misclassified in a discriminant function analysis (lvPPA case 6, nfvPPA cases 23, 26, 28 labeled in previous figures, and nfvPPA cases 35 and 41 being the two cases with PVI_Duration_SW values between 80 and 100). The three nfvPPA patients with contradictory positive findings on Pittsburgh compound B scanning were excluded from the analysis and are not shown here. Control participants were not included in the discriminant function analysis but are shown here for comparison.

Figure 5. Brain regions in which grey matter intensity correlates significantly with a composite measure of relative vowel duration in words.

A composite measure of pairwise variability for vowel duration in weak-strong and strong-weak polysyllable words was generated for each participant using weights from the discriminant function Model 2. Voxel-based morphometry analyses using diagnostic category (pooled PPA cohort and healthy control group) as a nuisance variable show that the index significantly covaried with atrophy in precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally. Bilateral atrophy in these areas was detected in the nonfluent variant of primary progressive aphasia but not the logopenic variant. Coloured voxels show regions that were significant in the analysis at P<0.05 FDR corrected. Clusters are overlaid on the MNI standard brain and reported at t>2.41.