Predicting Clinical Course from Subcortical Shape in Provisional Tic Disorder

The NewTics study examined children at the onset of tic disorder (with tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the shape of subcortical nuclei and tic symptom outcomes. 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 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 baseline structural shapes with follow-up TTS while accounting for covariates, with relationships mapped onto structure surfaces. We found that the NT group had a larger right hippocampus compared to healthy controls. Surface maps illustrate distinct patterns of inward deformation (localized lower volume) in the putamen and outward deformation (localized volume gain) in the thalamus for the NT group compared to healthy controls. We also found distinct patterns of outward deformation in almost all studied structures when comparing the TS group to healthy controls. In the significant vertices of this comparison, the caudate further exhibited an overall trend of greater outward deformation (compared to the template) in the TS group compared to both the NT group and controls. When comparing the NT and TS groups, the NT group showed consistent outward deformation in the caudate, accumbens, putamen, and thalamus. 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. Subsequent analyses including clinical symptoms revealed that a larger pallidum and thalamus at baseline predicted less improvement of tic symptoms in the future. These observations constitute some of the first prognostic biomarkers for tic disorders and suggest that these subregional volume differences may be associated with outcome of tic disorders.