A novel frontal pathway underlies verbal fluency in primary progressive aphasia

Abstract

The frontal aslant tract is a direct pathway connecting Broca's region with the anterior cingulate and pre-supplementary motor area. This tract is left lateralized in right-handed subjects, suggesting a possible role in language. However, there are no previous studies that have reported an involvement of this tract in language disorders. In this study we used diffusion tractography to define the anatomy of the frontal aslant tract in relation to verbal fluency and grammar impairment in primary progressive aphasia. Thirty-five patients with primary progressive aphasia and 29 control subjects were recruited. Tractography was used to obtain indirect indices of microstructural organization of the frontal aslant tract. In addition, tractography analysis of the uncinate fasciculus, a tract associated with semantic processing deficits, was performed. Damage to the frontal aslant tract correlated with performance in verbal fluency as assessed by the Cinderella story test. Conversely, damage to the uncinate fasciculus correlated with deficits in semantic processing as assessed by the Peabody Picture Vocabulary Test. Neither tract correlated with grammatical or repetition deficits. Significant group differences were found in the frontal aslant tract of patients with the non-fluent/agrammatic variant and in the uncinate fasciculus of patients with the semantic variant. These findings indicate that degeneration of the frontal aslant tract underlies verbal fluency deficits in primary progressive aphasia and further confirm the role of the uncinate fasciculus in semantic processing. The lack of correlation between damage to the frontal aslant tract and grammar deficits suggests that verbal fluency and grammar processing rely on distinct anatomical networks.

Keywords: aphasia; dementia; freesurfer; frontal aslant tract; language; tractography; white matter.

Figures

Figure 1

The frontal aslant tract (cyan) and the uncinate fasciculus (green) connect regions of the frontal and temporal lobes that show atrophic changes in patients with PPA. In particular the frontal aslant tract connects the pars opercularis of the inferior frontal gyrus (IFG) to the pre-supplementary motor area (pre-SMA) and anterior cingulate cortex. The uncinate connects anterior temporal lobe regions, including amygdala and temporal pole cortex, to the pars orbitalis of the inferior frontal gyrus and the orbitofrontal cortex (OFC). These left hemisphere regions also show significant cortical thinning in patients with PPA compared to control subjects, where yellow represents the most significant atrophy (FDR

Figure 2

Differences in tract-specific measurements of the frontal aslant tract and uncinate fasciculus between control subjects (C) and patients with logopenic (L) non-fluent/agrammatic (G), and semantic (S) variants of PPA. Measurements of the number of streamlines (Nstr), fractional anisotropy (FA) and radial diffusivity (RaD) are reported for the frontal aslant tract (upper row) and the uncinate fasciculus (lower row). *statistically significant different versus control group (P < 0.01); **statistically significant different versus semantic group (P < 0.05); ***statistically significant different versus controls and logopenic group (P < 0.001); †statistically significant different versus all other groups (P < 0.001); ††statistically significant different versus controls and logopenic group (P < 0.001). Coronal images in the middle row show the fractional anisotropy values mapped onto the streamlines of the frontal aslant tract and uncinate fasciculus of a control subjects and two representative patients with PPA with non-fluent/agrammatic and semantic variant.

Figure 3

Correlation between tract-specific measurements of the frontal aslant tract and performances on verbal fluency tests. FA = fractional anisotropy; RaD = radial diffusivity. Mean length of utterance is measured as number of words per sentence.

Figure 4

Correlation between tract-specific measurements of the uncinate fasciculus and performances on semantic processing tests. Nstr = number of streamlines; RaD = radial diffusivity; BNT = Boston Naming Test, PPVT = Peabody Picture Vocabulary Test.