Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia

Abstract

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.

Figures

Figure 1

Results of whole brain voxel-based morphometry showing areas of significant atrophy in participants with nfvPPA (n = 9) relative to healthy controls (n = 60). The map was derived by conducting a two-group t-test, with age, sex, total grey matter volume, and scanner as covariates (P < 0.001, uncorrected). Colour bar represents t-values. One participant with nfvPPA could not be scanned because of contraindications.

Figure 2

Primary and secondary treatment outcome measures and standardized tests at each time point. Primary outcome measure: (A) Per cent correct, intelligible scripted words for trained and untrained topics. Secondary outcome measures: (B) Overall per cent intelligible words and (C) Number of grammatical errors per 100 words for trained and untrained topics. (D) Standardized test performance. NAT = Northwestern Anagram Test; WAB = Western Aphasia Battery AQ. Values represent group means. Error bars show standard deviation, and are included for descriptive purposes but not for inference, as significance derived by paired permutation test. Asterisk = significantly different from pretreatment within trained or untrained scripts (P < 0.0125); diamond = significantly different from trained scripts at the same time point (P < 0.0125).

Figure 3

Mean ratings from post-treatment survey. Mean survey responses from patients (n = 10; dark grey) and spouses/caregivers (n = 7; light grey). Error bars represent standard error. See also Box 2.

Figure 4

Volumetric analyses within the inferior frontal gyrus-seeded network. The healthy control inferior frontal gyrus-seeded network is depicted (red, green, and blue; Mandelli et al., 2016). Within that network, regions of significant atrophy in nfvPPA patients relative to healthy controls are indicated in blue (two-group t-test with age, sex, total gray matter volume, and scanner as covariates, P < 0.001, uncorrected) and the left middle/inferior temporal gyrus region of interest that significantly predicted treatment response (d-statistic, controlling for aphasia severity using Western Aphasia Battery AQ) is indicated in green.