Abnormalities of the uncinate fasciculus correlate with behavioral symptoms in primary progressive aphasia. (P6.216)

Objective. Our aim was to investigate the clinical-anatomical correlation between white matter damage in fronto-temporal networks and behavioral symptoms in Primary Progressive Aphasia (PPA).Background. PPA is a clinical syndrome characterized by the progressive breakdown of language functioning, with relative sparing of other cognitive domains, for at least two years from the onset of the disease. Patients with PPA have high risk of developing behavioural problems but the neuroanatomical basis of these symptoms is still unknown.Methods. We used diffusion tractography to define the microstructural organization of the uncinate fasciculus, inferiorior fronto-occipital fasciculus (IFOF) and inferior longitudinal fasciculus (ILF). These tracts represent the principal connections of the orbitofrontal cortex (OFC) and the anterior temporal lobe (ATL), which are frequently affected in dementias associated with behavioural symptoms. We also measured cortical thickness of the OFC and ATL.Results. Thirty-three patients with PPA and twenty-six healthy controls were recruited. We found a statistically significant correlation between all the diffusion measurements (number of streamlines, fractional anisotropy, axial and perpendicular diffusivity) in the left uncinate fasciculus and the severity of total, positive and negative symptoms assessed by the Frontal Behavioral Inventory (FBI). Cortical thickness of the left OFC and ATL cortex were also correlated with negative, positive and total FBI symptoms.Conclusions. Our data indicate that degeneration of the uncinate fasciculus is associated with severity of behavioral symptoms in PPA. The lack of correlation between damage to the ILF/IFOF and behavioral symptoms indicates that emotion and social behaviour rely on a network directly connecting OFC and ATL. These findings could have important implications for early detection and clinical management of behavioral symptoms in degenerative disorders affecting fronto-temporal regions. Disclosure: Dr. D9Anna has nothing to disclose. Dr. Mesulam has received personal compensation for activities with Roberts, Carroll, Feldstein u0026 Peirce Inc. as a consultant. Dr. Thiebaut De Schotten has nothing to disclose. Dr. Jakobsen has nothing to disclose. Dr. Wieneke has nothing to disclose. Dr. Dell9acqua has nothing to disclose. Dr. Rogalski has nothing to disclose. Dr. Catani has nothing to disclose.