The Severity and Neural Correlates of Premonitory Urge in Tourette Syndrome: A Systematic Review and Meta-Analysis

Premonitory urge (PU) is an aversive bodily sensation that signals the onset of tic disorder.To our knowledge, PU typically precedes the appearance of tic symptoms, and both age and tic severity are correlated with PU. However, inconsistent findings have also been reported. Hence, we conducted a meta-analysis to examine the relationship among premonitory symptoms, patient age and the severity of tic symptoms, as well as to summarize the research on the neural underpinnings of PU in Tourette syndrome (TS).

We conducted a literature search of relevant studies published between December 2005 and April 2022 using databases such as PubMed, Elsevier, PsycINFO, and Web of Science. Our analysis was carried out using R software with the assistance of the "meta" and "metafor" packages.

Our meta-analysis included 22 studies with a total of 1236 tic disorder patients. The mean Premonitory Urge for Tics Scale (PUTS) score was 20.17, with a 95% confidence interval of [18.14, 21.68]. Through meta-regression, we found that age and tic severity play important moderating roles in PU severity (p < 0.0001). Neuroimaging studies suggest that PU is related to the insula, prefrontal cortex (PFC), anterior cingulate cortex (ACC), and supplementary motor area (SMA), regardless of the structural or functional level.

Our meta-analysis confirmed the positive relationship between the severity of tics and PU and identified age as a significant factor influencing PU. The neural mechanisms underlying PU remain largely unknown, but evidence suggests that the insula, PFC, ACC, and SMA are related regions.