Microstructural alteration of the Frontal Aslant Tract in Tourette Syndrome

• The literature lacks consensus on specific white matter tract alterations in Tourette Syndrome. • This study aims to investigate the microstructural integrity of the Frontal Aslant Tract in patients with Tourette Syndrome using Neurite Orientation Dispersion and Density Imaging (NODDI). • Our results show reduced Fractional Anisotropy and Neurite Density, as well as increased Mean Diffusivity, in the bilateral Frontal Aslant Tract of patients compared to healthy controls. • Moreover, this study suggests that diffusion metrics are mutually correlated: FA and ND are directly proportional, and both are inversely proportional to MD and ODI. Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics, affecting up to 1% of the adult population. While its etiology is unknown, increasing evidence highlights the key role of brain connectivity changes. Given its involvement in motor and speech inhibition, the Frontal Aslant Tract (FAT), a white matter tract connecting the posterior Superior and Inferior Frontal Gyri, may present structural alterations in individuals with TS. To investigate this hypothesis, a prospective case-control study was conducted from 2020 to 2023, enrolling 11 consecutive right-handed adults diagnosed with TS at a single referral center, alongside 12 age- and sex-matched healthy controls. We examined microstructural alterations of the FAT using metrics derived from two diffusion MRI techniques: Neurite Orientation Dispersion and Density Imaging (NODDI) and Constrained Spherical Deconvolution (CSD). We also examined correlations between diffusion metrics and clinical scores, as well as relationships among the diffusion metrics within both the TS and control groups. After False Discovery Rate corrections, patients’ bilateral FAT showed reduced Fractional Anisotropy (FA) and Neurite Density (ND), and higher Mean Diffusivity (MD), indicating a more isotropic water diffusion and a decreased density in axons and dendrites. No significant correlations between diffusion metrics and clinical measures were found. FA and ND were positively correlated, and they also showed negative correlations with MD and Orientation Dispersion Index (ODI). These results strongly indicate that patients with TS may have reduced integrity of the bilateral FAT, which could be considered a potential target of stimulation techniques in TS treatment. Data and Code Availability Statement: Raw Data will be made available upon a reasonable request to the corresponding author.