Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia

Abstract

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

Keywords: digit span; lexical retrieval; primary progressive aphasia; sentence production; voxel-based morphometry.

Fig. 1

Example of test items extracted from the NAVS VNT (a) and SPPT (b) assessing production of the verb wash (a) and of the passive sentence the woman was kissed by the man (b), respectively.

Fig. 2

Example of test item included in the NAT, assessing production of the sentence the man is kissed by the woman.

Fig. 3

Atrophy maps for all individuals with PPA combined (a) and for each of the three PPA subtypes: PPA-G (b), PPA-L (c), and PPA-S (d). Areas in color indicate regions of significant atrophy (i.e. regions in which gray matter volume in PPA was less than in healthy participants) at the voxelwise FWE-corrected threshold of P < 0.05 (k ≥ 100). The color bar reflects the range of t values (from 0 to 15). The t value corresponding to the statistical significance threshold of choice is 4.760. Lighter colors (e.g. light yellow and white) reflect larger t values, i.e. regions of greater atrophy, whereas darker colors (e.g. dark red) reflect smaller t values, i.e. regions of lesser atrophy.

Fig. 4

Areas of association between gray matter (GM) volume and sentence production accuracy measured using the total score on the NAVS SPPT (a) and the total score on the NAT (b). Both analyses included age, education, duration of disease (i.e. number of years since reported onset of symptoms), scanner, and total intracranial volume, as covariates. Statistical maps were thresholded at an uncorrected voxelwise P < 0.001 and cluster-level FWE correction for multiple comparisons, which corresponded to k ≥ 1086 for the analysis in (a) and to k ≥ 1800 for the analysis in (b). The color bar reflects the range of t values (from 0 to 7). The t value corresponding to the statistical significance threshold of choice is t = 3.180. Lighter colors (e.g. light yellow and white) reflect larger t values, i.e. regions where the association between GM volume and sentence production accuracy was stronger, whereas darker colors (e.g. dark red) reflect smaller t values, i.e. regions of where the association was weaker.

Fig. 5

Percent correct accuracy on language measures used in the study by Lukic et al. (2021), conducted on individuals with stroke-induced aphasia, and in the present study (PPA). WAB-AQ = Western Aphasia Battery – Aphasia Quotient (Kertesz 2007); SPPT = Sentence Production Priming Test (included in the Northwestern Assessment of Verbs and Sentences, NAVS, Thompson 2012); C = canonical sentences; NC = non-canonical sentences. Note that verb production scores were derived from different tests in the two studies (i.e. Northwestern Naming Battery, NNB, Thompson and Weintraub (2014) in Lukic et al. (2021), and NAVS for the present study).