Middle longitudinal fascicle is associated with semantic processing deficits in primary progressive aphasia

The middle longitudinal fascicle (MdLF) is a recently delineated association cortico-cortical fiber pathway in humans, connecting superior temporal gyrus and temporal pole principally with the angular gyrus, and is likely to be involved in language processing. However, the MdLF has not been studied in language disorders as primary progressive aphasia (PPA). We hypothesized that the MdLF will exhibit evidence of neurodegeneration in PPA patients. In this study, 20 PPA patients and 25 healthy controls were recruited in the Primary Progressive Aphasia program in the Massachusetts General Hospital Frontotemporal Disorders Unit. We used diffusion tensor imaging (DTI) tractography to reconstruct the MdLF and extract tract-specific DTI metrics (fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD)) to assess white matter changes in PPA and their relationship with language impairments. We found severe WM damage in the MdLF in PPA patients, which was principally pronounced in the left hemisphere. Moreover, the WM alterations in the MdLF in the dominant hemisphere were significantly correlated with impairments in word comprehension and naming, but not with articulation and fluency. In addition, asymmetry analysis revealed that the DTI metrics of controls were similar for each hemisphere, whereas PPA patients had clear laterality differences in MD, AD and RD. These findings add new insight into the localization and severity of white matter fiber bundle neurodegeneration in PPA, and provide evidence that degeneration of the MdLF contribute to impairment in semantic processing and lexical retrieval in PPA.