White matter damage in primary progressive aphasias: a diffusion tensor tractography study

Abstract

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.

Figures

Figure 1

(A) Examples of the seeds defined for the left inferior longitudinal fasciculus, SLF and uncinate fasciculus, for a single subject. The regions of interest used as seeds are shown overlaid on the colour-coded maps in DTI native space, which show the principal direction of water diffusivity in white matter. Green was assigned to anterior–posterior, red to left–right and blue to craniocaudal white matter fibres. (B) 3D reconstructions of white matter tracts in a single healthy control. Left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UNC) tracts are superimposed onto the subject’s fractional anisotropy map. L = left.

Figure 2

3D Reconstructions of left SLF components in a single healthy control. Left arcuate fasciculus (AF), frontoangular SLF (SLF-II), frontosupramarginal SLF (SLF-III), temporoparietal SLF (SLF-tp) tracts are overlaid onto the subject’s fractional anisotropy map. L = left.

Figure 3

Probabilistic maps of the language-related tracts from all the subjects included in the study. The tracts are overlaid on a 3D rendering of the MNI standard brain. Only voxels present in at least 10% of the subjects are shown. (A) 3D reconstruction of all-subjects probability maps of left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UNC) seen from left (top) and right (bottom). (B) All-subjects probability maps of bilateral SLF, inferior longitudinal fasciculus and uncinate fasciculus. The colour scale indicates the degree of overlap among subjects. A = anterior.

Figure 4

Subcomponents of the superior longitudinal fasciculus (SLF): all-subjects probability maps. The tracts are overlaid on a 3D rendering of the MNI standard brain. Only voxels present in at least 10% of the subjects are showed. (A) 3D reconstruction of left Arcuate fasciculus (AF), frontoangular SLF (SLF-II), frontosupramarginal SLF (SLF-III), temporoparietal SLF (SLF-tp) seen from left (top) and right (bottom). (B) All-subjects probability maps of bilateral arcuate fasciculus, SLF-II, SLF-III and SLF-tp. The colour scale indicates the degree of overlap among subjects.

Figure 5

Fractional anisotropy (FA) values of each group in the probability maps for left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UNC), overlaid on a standard MNI brain. Only voxels that are in common in at least 20% of the subjects in each group were included in the probability maps. Asterisk denotes significantly different relative to normal controls at P < 0.05. The chromatic scale represents average fractional anisotropy values ranging from lower (violet–blue) to higher values (yellow–red).

Figure 6

Mean diffusivity (MD) values of each group in the probability maps for left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UNC), overlaid on a standard MNI brain. Only voxels that are in common in at least 20% of the subjects in each group were included in the probability maps. Asterisk denotes significantly different relative to normal controls at P < 0.05. The chromatic scale represents average mean diffusivity values ranging from lower (violet–blue) to higher values (yellow–red). MD is measured in mm2/s × 10−3.

Figure 7

Fractional anisotropy values of each group in the probability maps for subcomponents of the left superior longitudinal fasciculus (SLF). Arcuate fasciculus (AF), frontoangular SLF (SLF-II), frontosupramarginal SLF (SLF-III) and temporoparietal SLF (SLF-tp) probability maps were overlaid on a standard MNI brain. Only voxels that are in common in at least 20% of the subjects in each group were included in the probability maps. Asterisk denotes significantly different relative to normal controls at P < 0.05. The chromatic scale represents average fractional anisotropy values, ranging from lower (violet–blue) to higher values (yellow–red).

Figure 8

Mean diffusivity values of each group in the probability maps for subcomponents of the left superior longitudinal fasciculus (SLF). Arcuate fasciculus (AF), frontoangular SLF (SLF-II), frontosupramarginal SLF (SLF-III) and temporoparietal SLF (SLF-tp) probability maps were overlaid on a standard MNI brain. Only voxels that are in common in at least 20% of the subjects in each group were included in the probability maps. Asterisk denotes significantly different relative to normal controls at P < 0.05. The chromatic scale represents average mean diffusivity values, ranging from lower (violet–blue) to higher values (yellow–red). Mean diffusivity is measured in mm2/s × 10−3.