Elucidating the nature and mechanism of tic improvement in tourette syndrome: a pilot study

Abstract

Background: For unclear reasons, many Tourette syndrome (TS) children report near-complete tic remission by young adulthood. Immature maturation of brain networks, observed with resting-state functional MRI (rs-fc-MRI) in adolescents and adults with TS, might evolve to a mature pattern in adults who experience tic improvement or remission. We explored the feasibility of testing this hypothesis in our population of young adult TS males, each with prior clinical assessments completed during childhood as part of a separate TS Association Genetics Consortium study.

Methods: A total of 10 TS males (off tic suppressing drugs for at least 6 months) aged 19-32 years, mean follow-up interval 7.5 (2 to 13) years, and 11 neurologically normal controls were enrolled and underwent 3-Tesla structural and rs-fc-MRI sequences.

Results: The mean change in Yale Global Tic Severity Scale (YGTSS) was -31.5% (total) and -26.6% (YGTSS motor+vocal). Two subjects reported resolution of tic-related disability, with drops from mean 45 to 16.5 (YGTSS-total) and 25 to 11.5 (YGTSS motor+vocal.). Rs-fc-MRI revealed significantly increased connectivity between the ipsilateral anterior and mid cingulate cortex and striatum, increased connectivity between local connections, and decreased connectivity between more distant connections; representing an immature connectivity pattern.

Discussion: Similar to previous reports, we found immature patterns of functional connectivity in adult TS subjects. Despite a lack of complete tic remission, two subjects exhibited dramatic drops in tic severity that correlated with tic-related disability improvement. More work is needed to elucidate the mechanism of such dramatic improvement in TS.

Keywords: ADHD; MRI; OCD; Tourette syndrome; tic.

Figure 1. Flowchart showing data recruitment and analysis.

From 80 subjects with prior YGTSS scores, 10 were imaged, with 9 TS subjects and 10 matched control subjects showing images with acceptable image quality.

Figure 2. Difference in Fisher-transformed Correlation between Samples (Control – TS) for each Pair of 116 regions in the AAL brain atlas.

The blue square in the middle shows significantly higher correlation for TS subjects (p = 0.016) averaging correlation for all connections between occipital lobe regions (ROIs 43–56).

Figure 3. Differences in Correlation as a Function of Strength of Functional “Connection.”

Scatter plot shows difference in correlation (Control – TS) as a function of mean correlation for the connection over all 20 participants.

Figure 4. Differences in Correlation as a Function of Distance of Functional “Connection.”

Scatter plot shows difference in correlation (Control – TS) as a function of distance between the centroids of the ROIs for each functional “connection.”