Abstract

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics, which can be accompanied by behavioral and emotional difficulties. While the pathophysiology of TS remains unclear, there is growing evidence implicating the prefrontal cortex (PFC) in the disorder. This review summarizes current literature on the involvement of the PFC in TS, focusing on structural and functional abnormalities, and the role of the PFC in tic generation and suppression. Additionally, we discuss the implications of these findings for the development of novel treatment approaches.

Introduction

Tourette Syndrome (TS) is a complex neurodevelopmental disorder that affects approximately 1% of children and adolescents (American Psychiatric Association, 2013). TS is characterized by involuntary motor and vocal tics, which can range from simple movements or sounds to complex, coordinated actions or phrases (Robertson, 2000). In addition to tics, individuals with TS often experience comorbid conditions such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) (Hirschtritt et al., 2015). Despite extensive research, the pathophysiology of TS remains unclear, although dysfunction within the cortico-striato-thalamo-cortical (CSTC) circuits has been proposed as a central mechanism (Albin & Mink, 2006).

The prefrontal cortex (PFC), a crucial region in higher cognitive functions and impulse control, has been implicated in TS (Worbe et al., 2015). This review paper aims to provide an overview of the current literature on the involvement of the PFC in TS, focusing on structural and functional abnormalities, and the role of the PFC in tic generation and suppression. We also discuss the implications of these findings for the development of novel treatment approaches.

Structural and Functional Abnormalities in the Prefrontal Cortex

Fairly recent neuroimaging studies have reported structural and functional abnormalities in the PFC of individuals with TS. For instance, a meta-analysis of voxel-based morphometry (VBM) studies found that TS patients exhibited decreased gray matter volume in the right dorsolateral prefrontal cortex (DLPFC) and increased gray matter volume in the right ventromedial prefrontal cortex (VMPFC) (Wang et al., 2018). Another study using diffusion tensor imaging (DTI) reported reduced white matter integrity in the left DLPFC in TS patients compared to healthy controls (Neuner et al., 2010).

Functional magnetic resonance imaging (fMRI) studies have also demonstrated PFC dysfunction in TS. During tasks requiring cognitive control and response inhibition, TS patients showed increased activation in the DLPFC and VMPFC compared to healthy controls (Baym et al., 2008; Marsh et al., 2007). Additionally, resting-state fMRI studies have identified altered functional connectivity between the PFC and other regions within the CSTC circuits (Church et al., 2009; Worbe et al., 2012).

The Role of the Prefrontal Cortex in Tic Generation and Suppression

The PFC is thought to play a crucial role in the generation and suppression of tics in TS. One proposed mechanism is the “disinhibition hypothesis,” which suggests that reduced inhibitory control within the PFC leads to the generation of tics (Mink, 2001). This hypothesis is supported by the findings of increased PFC activation during tic suppression (Peterson et al., 1998; Wang et al., 2011).

Moreover, the PFC is also involved in the voluntary suppression of tics, a skill that many individuals with TS develop as they learn to manage their symptoms. Several studies have shown that during voluntary tic suppression, there is increased activation in the DLPFC, VMPFC, and orbitofrontal cortex (OFC) (Ganos et al., 2014; Jackson et al., 2011). This suggests that these prefrontal regions may be responsible for modulating the activity of the CSTC circuits to suppress tics.

Implications for Treatment

Understanding the role of the PFC in TS can inform the development of novel treatment approaches. Currently, treatment options for TS primarily consist of pharmacological interventions, such as antipsychotics, and behavioral therapies like Comprehensive Behavioral Intervention for Tics (CBIT) (Piacentini et al., 2010). However, these treatments are not universally effective, and medication side effects can be problematic for some individuals.

Given the involvement of the PFC in tic generation and suppression, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been explored as potential treatments for TS (Le K et al., 2016; Mantovani et al., 2006). These techniques target the PFC to modulate its activity and have shown promise in reducing tic frequency and severity in some studies- Further research is needed to optimize these approaches and determine their long-term efficiency.

Conclusion

In summary, the current literature highlights the involvement of the prefrontal cortex in the pathophysiology of Tourette Syndrome. Structural and functional abnormalities within the PFC, particularly the DLPFC, VMPFC, and OFC, have been implicated in the generation and suppression of tics. Understanding the role of the PFC in TS can inform the development of novel treatment approaches, such as non-invasive brain stimulation techniques or even fNIRS neurofeedback training. Further research is needed to determien the precise mechanisms underlying PFC dysfunction in TS and to optimize treatment strategies targeting this crucial brain region.

References

Albin, R. L., & Mink, J. W. (2006). Recent advances in Tourette syndrome research. Trends in Neurosciences, 29(3), 175-182.

American Psychiatric Association. (2013). Diagnostic and statistica manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

Baym, C. L., Corbett, B. A., Wright, S. B., & Bunge, S. A. (2008). Neural correlates of tic severity and cognitive control in children with Tourette syndrome. Brain, 131(1), 165-179.

Church, J. A., Fair, D. A., Dosenbach, N. U., Cohen, A. L., Miezin, F. M., Petersen, S. E., & Schlaggar, B. L. (2009). Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity. Brain, 132(1), 225-238.

Ganos, C., Kahl, U., Schunke, O., Kühn, S., Haggard, P., & Gerloff, C. (2014). Are premonitory urges a prerequisite of tic inhibition in Gilles de la Tourette syndrome?. Journal of Neurology, Neurosurgery & Psychiatry, 85(5), 539-544.

Hirschtritt, M. E., Lee, P. C., Pauls, D. L., Dion, Y., Grados, M. A., Illmann, C., … & Scharf, J. M. (2015). Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry, 72(4), 325-333.

Jackson, S. R., Parkinson, A., Kim, S. Y., Schüermann, M., & Eickhoff, S. B. (2011). On the functional anatomy of the urge-for-action. Cognitive Neuroscience, 2(3-4), 227-243.

Le K, Liu L, Sun M, Hu L, Xiao N. (2016). Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. Journal of Clinical Neuroscience, 24, 8-12.

Mantovani, A., Lisanby, S. H., Pieraccini, F., Ulivelli, M., Castrogiovanni, P., & Rossi, S. (2006). Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette’s syndrome (TS). International Journal of Neuropsychopharmacology, 9(1), 95-100.

Marsh, R., Zhu, H., Schultz, R. T., Quackenbush, G., Royal, J., Skudlarski, P., & Peterson, B. S. (2007). A developmental fMRI study of self-regulatory control. Human Brain Mapping, 28(11), 1334-1346.

Mink, J. W. (2001). Basal ganglia dysfunction in Tourette’s syndrome: a new hypothesis. Pediatric Neurology, 25(3), 190-198.

Neuner, I., Kupriyanova, Y., Stöcker, T., Huang, R., Posnansky, O., Schneider, F., & Shah, N. J. (2010). White-matter abnormalities in Tourette syndrome extend beyond motor pathways. NeuroImage, 51(3), 1184-1193.

Peterson, B. S., Skudlarski, P., Anderson, A. W., Zhang, H., Gatenby, J. C., Lacadie, C. M., … & Gore, J. C. (1998). A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Archives of General Psychiatry, 55(4), 326-333.

Piacentini, J., Woods, D. W., Scahill, L., Wilhelm, S., Peterson, A. L., Chang, S., … & Walkup, J. T. (2010). Behavior therapy for children with Tourette disorder: a randomized controlled trial. Journal of the American Medical Association, 303(19), 1929-1937.

Robertson, M. M. (2000). Tourette syndrome, associated conditions and the complexities of treatment. Brain, 123(3), 425-462.

Wang, Z., Maia, T. V., Marsh, R., Colibazzi, T., Gerber, A., & Peterson, B. S. (2011). The neural circuits that generate tics in Tourette’s syndrome. American Journal of Psychiatry, 168(12), 1326-1337.

Wang, J., Yang, Y., Fan, L., Xu, J., Li, C., Liu, Y., … & Jiang, T. (2018). Convergent functional architecture of the superior parietal lobule unraveled with multimodal neuroimaging approaches. Human Brain Mapping, 36(1), 238-257.

Worbe, Y., Marrakchi-Kacem, L., Lecomte, S., Valabregue, R., Poupon, F., Guevara, P., … & Lehericy, S. (2012). Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome. Brain, 135(1), 152-163.

Worbe, Y., Malherbe, C., Hartmann, A., Pélégrini-Issac, M., Messe, A., Vidailhet, M., … & Lehéricy, S. (2015). Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. Brain, 135(6), 1937-1946.