Tourette Syndrome and Obsessive-Compulsive Disorder: different neural correlates from a multimodal neuroimaging study in drug-naïve children

Background: Tourette syndrome (TS) and early-onset obsessive-compulsive disorder (OCD) are frequently associated and considered to etiologically overlap. However, the nature of this close relationship is largely unknown. Clinical and neuropsychological investigations have offered limited insight as to whether TS and OCD may represent distinct disorders or different phenotypes of a single disease spectrum. Objective: To gain further understanding on TS and OCD pathophysiology, we investigated brain and cerebellar structural and functional connectivity in drug-naïve children with TS without comorbidities (TS-pure), OCD, and with the comorbid condition of TS+OCD. Methods: Drug-naïve children with TS-pure (n=16), TS+OCD (N=14), OCD (N=10), and N=11 age-matched controls underwent 3 Tesla magnetic resonance imaging (MRI). We used diffusion tensor imaging to investigate white matter structural connectivity and resting-state MRI to measure the activity of neural networks at 'rest'. Fractional anisotropy (FA) was analyzed in the cerebellar peduncles and in five supratentorial tracts of interest, i.e., cortico-spinal tract, anterior thalamic radiations, inferior longitudinal fasciculus, corpus callosum, and cingulum. Functional connectivity was examined in the following networks: basal ganglia, sensori-motor, cerebellum, fronto-parietal, default mode, orbito-frontal, and salience, while dentate nucleus functional connectivity was assessed as a measure of cortico-cerebellar interplay. All MRI findings were correlated to symptom severity assessed through the Yale Global Tic Severity Scale (YGTSS) and Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Results: On a structural level, TS-pure and TS+OCD children showed the same pattern of increased FA in all supratentorial tracts and in cerebellar peduncles compared to controls, while OCD exhibited decreased FA. For both TS and OCD, FA in supratentorial tracts was negatively correlated to symptom severity, highlighting the role of white matter organization in symptom expression. On a functional level, TS and TS+OCD were again underpinned by a common pattern of resting state activity. TS-pure/TS+OCD and OCD groups significantly differed in the frontoparietal network, which displayed reduced activity in TS-pure/TS+OCD and increased activity in OCD, compared to controls. For both clinical groups, the degree of involvement of the frontoparietal network directly correlated to disease severity. Lastly, dentate nucleus functional connectivity revealed divergent connectivity patterns between the cerebellum and the prefrontal cortex (reduced in TS-pure/TS+OCD, increased in OCD) in respect to controls, while connectivity between the cerebellum and the thalamus was similarly reduced in all clinical groups, supporting a functional disconnection within the cerebello-thalamo-cortical circuit in both TS and OCD. Conclusions: The study provides evidence for: 1. Different white matter organization in TS and OCD, both in supratentorial bundles as well as in cerebellar peduncles. 2. Different involvement of Fronto-Parietal and Fronto-Cerebellar networks in TS and in OCD. 3. The presence in both disorders of a functional disconnection of the cerebello-thalamo-cortical circuit.