In children with attention-deficit/hyperactivity disorder, less task-related up-modulation of motor cortex during response inhibition.

Tic disorder is a neurodevelopmental disorder characterized by tics. The waxing-and-waning nature of tics and the variability in treatment response pose considerable challenges in management, highlighting the need for improved understanding of tic disorder pathophysiology and more effective, individualized interventions []. Increasing evidence highlights the role of neuroinflammation in the pathogenesis of tic disorder. Recent studies directly examining cytokines in tic disorder provide evidence of a link between inflammation and tic symptoms. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β have been linked to tic severity, highlighting a connection between immune dysregulation and clinical symptoms []. For instance, Chi . [] observed distinct patterns of cytokine activity across tic severity levels. TNF-α level was positively correlated with total tic scores and phonic tic scores, suggesting its role in the amplification of tic symptoms. Interestingly, IL-1β level was significantly lower in mild tic patients compared to healthy controls, indicating a potentially dynamic role of this cytokine in modulating immune responses during less severe phases of the disorder. Hsu . [] further reported heightened pro-inflammatory cytokine activity, including elevated TNF-α level, in children with tic disorder, supporting the hypothesis that inflammatory pathways exacerbate tic-related symptoms and disrupt cortico-striato-thalamo-cortical (CSTC) circuits. Together, these findings underscore the relevance of TNF-α and IL-1β in the immune-neural interface of tic disorder pathophysiology. A recent network meta-analysis further highlights the increased levels of pro-inflammatory cytokines, including IL-6 and IL-1β, in multiple psychiatric disorders, highlighting potential parallels with immune dysregulation observed in tic disorder []. These processes can disrupt neurodevelopment and contribute to functional impairments by affecting synaptic pruning, neuronal survival, and white matter integrity. In particular, microglial dysregulation in tic disorder has been associated with abnormalities in neuroprotection and inflammatory responses, further exacerbating disruptions within CSTC circuits []. The pathophysiology of tic disorder has been attributed to disruptions in CSTC circuits, which are involved in motor control, inhibitory processes, and habit formation [,]. These circuits encompass the basal ganglia, thalamus, and prefrontal cortex - key areas implicated in tic generation and suppression. Neuroimaging studies, such as diffusion tensor imaging (DTI), have provided evidence of structural abnormalities in these regions. For instance, Yang . [] observed reduced fractional anisotropy (FA) in the corpus callosum and inferior longitudinal fasciculus (ILF) in tic disorder patients, indicating impaired white matter connectivity. Similarly, studies have highlighted alterations in microstructural integrity within the CSTC loop, linking these changes to tic severity and motor dysfunction [,]. However, findings across studies have been inconsistent with variability in sample characteristics, imaging methodologies, and confounding factors such as medication exposure and comorbidities. For example, while several studies report reduced FA in CSTC-related regions, others note no significant differences between tic disorder patients and healthy controls []. These discrepancies underscore the need for further research, particularly in medication-naïve and newly diagnosed pediatric populations, to elucidate the neurodevelopmental trajectory of tic disorder [].