Network anatomy in logopenic variant of primary progressive aphasia

Abstract

The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.

Keywords: Alzheimer's disease; cortical atrophy; intrinsic connectivity networks; logopenic variant; longitudinal study; primary progressive aphasia.

FIGURE 1

Cross‐sectional pattern of cortical atrophy in logopenic variant of primary progressive aphasia (lvPPA) compared to HC. Surface rendering of the atrophy pattern in the mild cohort of lvPPA (n = 15) (a), at the baseline atrophy of the longitudinal cohort (n = 28) (b), and in the total cohort of lvPPA (n = 86). The render is performed with the ggseg toolbox in R (https://lcbc‐uio.github.io/ggseg/) on the Glasser brain atlas. The left inferior parietal region showed the greatest atrophy across all three lvPPA cohorts.

FIGURE 2

Two partially distinct intrinsic connectivity networks (ICNs) associated with naming and repetition deficits in logopenic variant of primary progressive aphasia (lvPPA). The intrinsic connectivity map (Z score) extracted from the HCconn cohort seeded in the left PFm (a) includes areas in the inferior parietal and temporal gyri and in the middle frontal gyrus. The intrinsic connectivity map (Z score) extracted from the HCconn cohort seeded in the left PSL (b) includes areas in the superior and middle temporal gyri and in the lateral frontal pole. The overlap between these two networks includes regions in the perisylvian region, the inferior temporal lobe, and the precuneus (c).

FIGURE 3

Longitudinal change in cortical thickness in the logopenic variant of primary progressive aphasia (lvPPA_long) cohort compared to matched health control (HC) with longitudinal data. The longitudinal change in cortical thickness occurred bilaterally in the auditory lateral temporal cortices, the inferior parietal cortex, in the posterior cingulate cortex, and in the left inferior and middle frontal gyri. The render is performed with the ggseg toolbox in R (https://lcbc‐uio.github.io/ggseg/) on the Glasser brain atlas.

FIGURE 4

Functional connectivity in selected healthy control‐intrinsic connectivity networks (HC‐ICNs) predicts longitudinal cortical change in logopenic variant of primary progressive aphasia (lvPPA). Scatterplots of the correlation between the shortest functional path length from the left PFm, perisylvian language (PSL), and right AICC in the HC group and the longitudinal change in cortical thickness in lvPPA. On the scatterplot, each dot represents the statistical change in cortical thickness in each region of the HCP‐MMP1.0 atlas.