One of the paramount strengths of this study lies in the participant selection. By focusing exclusively on a highly homogeneous group of tic disorder patients, our research endeavors to minimize the variability often seen in more diverse groups. This approach ensures that the observed neuroimaging patterns are more confidently attributed to tic disorders rather than confounded by other co-existing psychiatric conditions. It is already widely known that a notable subset of tic disorder patients is co-diagnosed with OCD. Decades of research were invested on this topic, and even though a clear explanation is yet to be given we are aware that tic disorder patients, OCD patients, and patients with both disorders show many significant differences (Coffey et al. 1998; Lebowitz et al. 2012). We therefore decided to only include patients without OCD to maximize homogeneity.
Our analysis revealed heightened network centrality within the left inferior frontal gyrus pars opercularis. This elevated centrality manifests that this region exhibits increased hubness in patients with tic disorders, suggesting its enhanced significance within their neural network. The pars opercularis of the is the part of the inferior frontal gyrus that is posterior to the ascending ramus of the lateral sulcus, overlying the insular cortex. This region was traditionally known to recognize spoken language constituting a segment of Broca’s area (Schremm et al. 2018), and was also believed to play a central role in executive control and cognitive inhibition (Aron et al. 2004). Recent advancements in neuroimaging have underscored the significance of this region in inhibitory controls (Swick et al. 2008). Notably, lesions in the right inferior frontal gyrus have been correlated with deficits in stop-signal inhibition (Aron et al. 2003). A non-invasive study employing theta burst transcranial magnetic stimulation on this region also revealed augmented inhibitory control in patients with nicotine addiction (Newman-Norlund et al. 2020). Based on these and other related studies, it has been concluded that this region is posited to have a unique association with motor inhibition. Interestingly, the inhibitory function of the right inferior frontal gyrus appears to manifest predominantly in later stages of life, while the left inferior frontal gyrus demonstrates heightened inhibitory activity in children (Bunge et al. 2002). Similar to its right counterpart, lesions of the left inferior frontal gyrus were also linked to deficits in GoNoGo tasks (Swick et al. 2008). Altogether, these findings highlight the critical role of both right and left inferior frontal gyri in response inhibition, a hallmark characteristic that is affected in tic disorder. A recent study observing increased surface curvature of the pars opercularis and the pars triangularis in tic disorder patients compared to controls further substantiates this assertion (McCann et al. 2022). The authors also suggested that abnormalities of this region are possibly associated with vocal tics, since damage to this area may give rise to hesitant speech that is evident in Broca’s aphasia. A diffusion tensor imaging (DTI) study on adults with tic disorder showed decreased fractional anisotropy of several brain regions including the left pars opercularis, further suggesting that alterations of this area are related to the inhibitory impairments in tic disorder (Müller-Vahl et al. 2014). This was also demonstrated in study that observed impaired ability to stop an action while the right pars opercularis was temporarily deactivated by repetitive transcranial magnetic stimulation (Chambers et al. 2006). Collectively, these findings suggest the pars opercularis’s involvement in the inhibitory mechanism governing tics. Increased hubness of this area can be hypothesized to be an acquired change in response to frequent motor tics during the developmental ages.
A study by Openneer et al. also investigated the brain network of tic disorder by comparing patients with tic disorder, ADHD, and healthy controls (Openneer et al. 2020). Patients were also divided into groups with and without a co-diagnosis of ADHD. The authors reported that tic disorder patients with ADHD showed lower local efficiency and clustering coefficients in the default mode network compared to controls, and in the frontoparietal network when compared to ADHD patients. The pars opercularis, which was significant in our study, does not traditionally belong to one of those networks, so our results do not exactly match to these. Our results show increased network centrality in tic disorder patients whereas Openneer et al. reported decreased network centrality in the patient group. Of course, it must be noted that the two studies had different patient groups (all tic disorder patients vs only tic disorder patients with ADHD), but the different results indicate that tic disorder is a complicated mixture of various brain activities.
Our study is not without limitations. First, the small number of enrolled patients is a major limitation of all tic disorder studies. The young age and frequent movement that is innate to tic disorder patients make it difficult to obtain high quality MRI data. Nonetheless, it is crucial to highlight the high homogeneity and drug-naïve status of our patient group. Second, the cross-sectional design of the study made it impossible to verify our results through a prospective time-period.
Our study suggests that the brains of tic disorder patients could show different developmental traces when compared to controls, as they are continuously inhibiting tics during their developmental ages. These findings will aid in unveiling the pathophysiology of tic disorders. Further research and follow up studies are necessary to verify our results and to develop clinical applications.