Tourette syndrome (TS) is considered a neurodevelopmental disorder initiated before 18 years old and accompanied by at least one year of motor and phonic tics; defined as, rigid, intermittent, and repetitive movements and vocalizations being the hallmark symptoms of TS. It is reported to be more common and severe in males compared to females, with a prevalence of 0.3–0.9% among children and 0·002–0·08% in adults (Baizabal-Carvallo and Jankovic, 2023; Johnson et al., 2023; Yang et al., 2021). The tics can be either semi-voluntary or involuntary and simple or complex. These tics can be changed in severity under different circumstances. For instance, stress, excitement, or fatigue situations might worsen the tics, whilst physical or mental activity could improve the tic symptoms (Johnson et al., 2023). TS syndrome is characterized by several functional impairments leading to decrements in the quality of life (Kang et al., 2022). Besides, some behavioral comorbidities encompassing attention-deficit hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), and other symptoms related to mood and disruptive behavior are reported to be present in approximately 90% of the TS cases (Cavanna, 2022; Hirschtritt et al., 2015). Despite the unknown exact pathogenesis of its progression, various factors from genetic to neurophysiological mechanisms are proposed to have a role in this regard. Basal ganglion disinhibition and related cortico-striato-thalamo-cortical (CSTC) circuits’ alterations as well as overall sensorimotor processing disruption are known as the most prominent mechanisms underpinning the TS occurrence. Moreover, neurotransmission pathways, particularly dopaminergic, GABA (γ-aminobutyric acid) -ergic, and serotonergic systems are illustrated as other potential drivers contributing to TS progression. Some controversial evidence is also available regarding the role of inhibitory control deficits in its pathogenesis (Cavanna, 2022; Hsu et al., 2020).

Behavioral therapies, pharmacotherapy, or their combination are known to be approved for the treatment of TS. Although some research is being conducted regarding the utilization of deep brain stimulation and non-invasive neuromodulation techniques in the treatment of TS, they have not been validated yet for clinical use. Behavioral therapies using comprehensive behavioral intervention for tics (CBIT) are considered first-line treatment options in TS with convincing outcomes in tic reduction in not only children but also adult populations suffering from TS. It is demonstrated that CBIT can reduce the severity as well as number of tics by 26–31%, revealing almost the same effects as pharmacological treatment (Johnson et al., 2023).

Routine imaging modalities like T1 or T2-weighted magnetic resonance imaging (MRI) have mostly revealed normal brain characteristics in TS patients; whilst, several abnormalities are demonstrated to exist in advanced structural and functional neuroimaging methods. Diffusion MRI (dMRI) is an MRI modality that can provide detailed characterization of white matter microstructural alterations. Several dMRI studies have shown connectivity changes mainly throughout the CSTC circuit structures, encompassing basal ganglion, sensorimotor cortex, corticospinal tracts, motor cortex, and supplementary motor cortex among individuals with TS (Chen et al., 2015; Hsu et al., 2020).

Diffusion magnetic resonance imaging (dMRI) connectometry is a cutting-edge method for assessing the integrity of white matter and investigating microstructural changes linked to specific variables through comprehensive brain analysis (Ghazi Sherbaf et al., 2018; Yeh et al., 2011). This approach relies on the density of water diffusion rather than the diffusion velocity, which traditional diffusion tensor imaging (DTI) utilizes. This shift enables dMRI to achieve superior spatial resolution for delineating white matter pathways, especially in regions with complex fiber arrangements that conventional DTI might neglect or oversimplify by only providing average diffusion metrics (Yeh et al., 2016; Yeh, F.C. et al., 2013). dMRI connectometry introduces the concept of the local connectome, assessing connectivity between adjacent voxels through the spin distribution function (SDF), to overcome the limitations of traditional DTI. This allows for the mapping of local connectivity within fiber pathways, highlighting pathway components that show significant correlations with the research variable. The process converts SDF into quantitative anisotropy (QA), a density-based metric for further analysis, including the extraction of fiber tracts and the assessment of differences or associations with specific variables (Yeh et al., 2016; Yeh, F.C. et al., 2013). Unlike traditional tractography, which relies on average diffusion measures for statistical analysis, dMRI connectometry focuses on detecting significant differences or correlations using QA/SDF and voxel data, enhancing the method's resolution and reducing the likelihood of type 2 errors and susceptibility to partial volume effects (Sanjari Moghaddam et al., 2019). Thus, dMRI connectometry offers enhanced accuracy and innovative insights in non-invasive studies, presenting a promising tool for addressing complex research questions.

The primary focus of the present study is to provide an in-depth analysis of the correlation between dMRI findings and TS severity and to compare the white matter properties among TS versus healthy comparisons. We also aim to shed light on the impacts of behavioral therapy on dMRI findings of individuals with TS.