Language networks in semantic dementia

Abstract

Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.

Figure 1

The pattern of white matter atrophy in patients with semantic dementia compared with 48 age-matched healthy controls (P < 0.05, corrected at the cluster level). Regions are superimposed on the MNI standard brain in neurological convention (right is right) WM = white matter.

Figure 2

Reconstructions of white matter tracts in a single healthy control: the left ILF in green, the left uncinate fasciculus in red, the left arcuate fasciculus in cyan, the left fronto-parietal SLF in blue, the genu of the corpus callosum in orange and the splenium of the corpus callosum in yellow. Tracts are superimposed onto the subject's T₁-weighted image normalized into the FA space. CC = corpus callosum

Figure 3

Group probabilistic maps of the language-related white matter tracts from healthy controls and semantic dementia (SemD) patients. Left ILF, uncinate fasciculus, arcuate fasciculus and fronto-parietal SLF are superimposed on the three-dimensional rendering of the MNI standard brain. The colour scale indicates the degree of overlap among subjects.

Figure 4

Group probabilistic maps of the genu and splenium of the corpus callosum from healthy controls and semantic dementia (SemD) patients are shown on the axial sections of the MNI standard brain. The colour scale indicates the degree of overlap among subjects.

Figure 5

(A) Structural MRI of one representative control and each semantic dementia patient (coronal view). (B–D) Left language-related white matter tracts are rendered as maps of MD in one representative control and all patients (B: ILF; C: uncinate fasciculus; D: arcuate fasciculus; E: fronto-parietal SLF). The colour scale represents the MD values going from lower (dark red) to higher values (yellow to white). Maximum damage is present in the anterior portion of the ILF and uncinate fasciculus underlying the temporal pole.

Figure 6

Anatomical correspondence between fronto-parietal SLF and activation for a contrast which highlights sublexical processing in control subjects (A) and semantic dementia patients (B). fMRI activations for the contrast of low-frequency regular words and pseudowords versus rest are shown in green (A) for healthy controls and in blue (B) for semantic dementia patients. The healthy control group and the semantic dementia patients both showed activation of posterior inferior frontal gyrus and inferior parietal cortex. Probabilistic maps of the left fronto-parietal SLF obtained in healthy controls (A) and semantic dementia patients (B) are shown in a colour scale which indicates the degree of overlap among subjects. Results are superimposed on the MNI standard brain in neurological convention (right is right).