The study was funded by grants from the Tourette Syndrome Association, Tourettes Action, the U.K. Medical Research Council, the National Research Foundation of Korea, and the Korean Ministry of Education, Science and Technology. The authors did not declare any conflicts of interest.
Adviser's Viewpoint
Study Finds Altered Activity
Tourette syndrome (TS) is an age-dependent movement disorder characterized by simple and/or complex motor and vocal tics that have occurred intermittently over a 1-year period. Motor tics usually begin at 3–5 years of age followed by onset of vocal tics several years later. In the mid- to late teen years, approximately one-third of children will stop and have complete resolution of their tics, with another third experiencing significant decrease in symptoms. Although TS occurs in approximately 1%-2% of the pediatric population, it is estimated that as many as 20% of children will have a motor or vocal tic. An important feature of tic phenomenology is the ability of the individual to temporarily suppress the tic and if the effort is sustained, the affected individual may report mental fatigue or exhaustion.
Thus, tics appear to follow a neurodevelopmental sequence characterized by specific ranges of onset, peak, and resolution or amelioration. The latter has given rise to the concept that tics are a “normal” part of the developmental process. That process can be considered part of the adolescents' progressive command of motor, behavioral, and emotional experiences. Dysregulation of these complex control processes can result in the occurrence of the attentional disorders, impulsivity and hyperactivity, and the obsessive thoughts and compulsive actions that are the major comorbidities of TS.
One way to conceive of the active control processes that must take place during development is an alteration in neuronal function and perhaps anatomy, that is, neuroplasticity. As neurologists, we tend to think of neuroplasticity as the brain's response to acquired damage such as stroke or traumatic brain injury or recovery from resective surgery. However, the alteration of brain physiology and anatomy based upon activity in a pathway or network is a fundamental property that literally shapes the nervous system during development. Just as apoptosis eliminates neurons, activity in circuits increases synaptic strength and preservation of the involved neural elements.
MRI has allowed us to explore potential structural and functional alterations that accompany normal development as well as seemingly aberrant states such as TS. Several of the most interesting and reproducible findings from the recent imaging in TS literature include small caudate volumes in children and adults with TS, suggesting that this may be a trait characteristic of refractory tics; thinning of the sensorimotor cortex in children with TS; and enlargement of corpus callosum in adults, but reduction in children with TS.
Recently, the use of modern MRI technology, combined with rigorous behavioral study design and statistical analysis has provided evidence for an active process by which individuals with TS have an enhanced ability to suppress extraneous or conflicting information leading to motor task. In the experiments performed by Dr. Jackson and his colleagues, children with TS exhibited superior control over motor activity when compared with controls, suggesting that their previous cognitive “training” in tic suppression resulted in persistent functional changes. Furthermore, this group had anatomic differences in the white matter of the corpus callosum and forceps minor that correlated with tic severity. Of note, these structures are directly connected to the prefrontal cortex that provides the anatomic substrate for volitional tic suppression. Viewed from the perspective of normal development, the prefrontal cortex is known to be involved in the regulation of motor function. The authors also demonstrate that the right prefrontal cortex has a larger BOLD response during the motor task in which the TS cohort demonstrated better performance.
Taken together, the findings of Dr. Jackson and his associates suggest that the developmental processes by which children learn to control nonvolitional movements are the same that are used to compensate for the excessive motor overflow that characterizes TS. The implications for treatment of both developmental disorders and acquired injury to the nervous system may be profound if existing mechanisms that mediate normal development can be used as part of specific therapeutic regimens.
DR. BUCHHALTER is chief of pediatric neurology and director of the comprehensive pediatric epilepsy program at Phoenix Children's Hospital.
JEFFREY R. BUCHHALTER, M.D., PH.D.