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.

Frontal aslant tract projections to the inferior frontal gyrus

“…FAT's name is derived from its oblique shape and it consists of short association connections between the posterior part of the inferior frontal gyrus (IFG) and the posterior region of the superior frontal gyrus (SFG) [5]. Diffusion tractography imaging (DTI) showed that FAT connects pre-supplementary/supplementary motor area (pre-SMA/SMA) with Broca's region, corresponding to the Brodmann areas 8.9 and 44.45, respectively [3-5, 17, 19].…”

Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer’s Disease

“…Indeed, damages of this bundle have been previously associated with various degrees of speech impairment, from total inability to initiate speech (i.e., mutism) to mild altered fluency [48]. The microstructural damage of FAT was also previously found associated with verbal fluency deficits, mainly in patients with the agrammatic-variant of PPA [14]. In this variant of PPA, patients show several languages' deficits including the "apraxia of speech" [49], a deficit in which the motor engrams needed to produce verbal speech are lost in the absence of motor impairments.…”

“…The role of FAT has been previously investigated in patients showing languages disorders due to different conditions, such as neurodegenerative disorders (e.g. primary progressive aphasia) [14] or focal brain lesions (e.g. brain tumors).…”

“…Probabilistic tractography was performed using PICo [36] to reconstruct the Frontal Aslant tract (FAT), in both right and left hemisphere. Seedpoints and waypoints were defined manually on the coronal FA maps of each participant according to published guidelines [14] (see Figure 1). When defining seed and waypoints, the operator (G.B.G.)…”

“…It is known that FAT plays a role in normal language development, as previously shown in young healthy individuals [13]. There is also some evidence that FAT is involved in language impairments due to primary progressive aphasia (PPA) [14], brain tumors [15,16,17], and stroke [18]. FAT is considered as a part of a "motor stream" mainly involved in speech production [19] and complementing the dorsal and ventral language streams [20].…”