Predicting Clinical Course from Subcortical Shape in Provisional Tic Disorder

The ongoing NewTics study examines children who have had tics for less than 9 months (NT group) - a population on which little research exists. Here, we further investigate relationships between subcortical shape and tic symptom outcomes. 138 children were assessed at baseline and a 12-month follow-up: 79 with NT, 27 tic-free healthy controls (HC), and 32 with chronic tic disorder or Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic metric mapping, and linear regression models were constructed to correlate structural shapes with TTS while accounting for covariates, with relationships mapped onto structure surfaces. When compared to healthy controls, smaller mean volumes were found in the TS group for the caudate, nucleus accumbens, pallidum, and thalamus. NT had smaller mean volumes than controls in the caudate, pallidum, and thalamus. Surface maps illustrate distinct patterns of inward deformation (localized volume loss) in the TS group compared to NT children. In the NT group, a larger hippocampus at baseline significantly correlated with the worsening of tic symptoms at 12 months. Outward deformation in the hippocampus and inward deformation in the accumbens at baseline are also related to worsening tic symptoms at follow-up. Since the NT group has had tics only for a few months, we can rule out the possibility that these subcortical volume differences are caused by living with tics for years; they are more likely related to the cause of tics. These observations constitute some of the first prognostic biomarkers for tic disorders and suggest localized circuitry that may be associated with outcome of tic disorders.