Somatosensory–motor bodily representation cortical thinning in Tourette: Effects of tic severity, age and gender

Abstract

Introduction

Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter.

Methods

66 magnetic resonance imaging scans were acquired from 34 TS subjects (age range 10–25, mean 17.19 ± 4.1) and 32 normal controls (NC) (age range 10–20, mean 16.33 ± 3.56). Brain morphology was assessed using the fully automated CIVET pipeline at the Montreal Neurological Institute.

Results

We report (1) significant cortical thinning in the fronto-parietal and somatosensory–motor cortices in TS relative to NC (p < .05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p < .05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS subjects with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory–motor cortical thickness.

Conclusions

TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.

Introduction

Tourette syndrome (TS) is genetic, neurodevelopmental disorder associated with functional and anatomical abnormalities in the cortico-striatal-thalamic-cortical circuitry (CSTC) (Leckman et al., 1998, Leckman et al., 2001, Sowell et al., 2008, Thomalla et al., 2009). The CSTC circuitry is an organization of 5 parallel loops (i) motor circuit; (ii) occulo-motor circuit; (iii) dorso-lateral prefrontal circuit; (iv) lateral orbitofrontal circuit; (v) and an anterior cingulate (limbic) circuit (Alexander et al., 1986). Each of the circuits originates in a particular cortical area and, through connections with specific regions of the caudate, putamen, globus pallidus, substantia nigra and thalamus, terminates in the same cortical area from which it originated.

The last decade witnessed a boom in neuroimaging findings lending support to the role of the basal ganglia in TS pathophysiology. For example, positron emission tomography demonstrated increased striatal inhibitory D2 receptor activity in TS (Wolf et al., 1996) and functional magnetic resonance imaging reported decreased striatal responsiveness in TS (Peterson et al., 1998). In addition, anatomical neuroimaging results noted that individuals with TS had smaller volumes in specific basal ganglia nuclei and the thalamus when compared with healthy controls (Berthier et al., 1993, Castellanos et al., 1996, Peterson et al., 2001, Peterson et al., 2003, Gerard and Peterson, 2003), and that there is an inverse correlation between caudate volume in childhood and tic severity in early adulthood (Bloch et al., 2005). Nonetheless, there is a discrepancy in the neuroimaging literature. The majority of reported changes are not confirmed consistently across studies. For example, basal ganglia volume has been reported to be decreased in TS (Peterson et al., 2003, Spessot et al., 2004, Plessen et al., 2007). However, Singer et al. (1993) found no significant differences in the absolute volume of any basal ganglia sub-region. Similarly, Wang et al. (2007) also reported no significant difference in basal ganglia volume between TS and normal controls (NC). Frey and Albin (2006) discussed some of the possible causes of such discrepancies, for example, subject age, gender, medications and comorbidities. Indeed, very few studies directly addressed the question of gender differences in the neuroanatomy of TS (Zimmerman et al., 2000, Hong et al., 2002, Peterson et al., 2003).

Relative to the basal ganglia, the prefrontal and parietal cortices have been often relatively neglected in TS literature (Sowell et al., 2008, Thomalla et al., 2009). This is particularly surprising, since (i) Leckman et al. (1991) stated that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex; and (ii) the pre-motor, and orbitofrontal cortices contribute to the motivation, planning, and execution of normal behavioural repertoires (Pandya and Yeterian, 1996). The pre-motor region includes the supplementary motor area, the cortical recipient of motor pathways in the CSTCS that participate in planning and executing motor tasks. Electrical stimulation of this region produces complex movements, vocalizations, and urges to move (Fried et al., 1991). These urges are similar to those that accompany tics. In this vein, using diffusion tensor imaging, Thomalla et al. (2009) concluded that structural changes in the somatosensory system correlate with TS tic severity. Of particular interest to the present study Sowell et al., found cortical thinning in frontal and parietal lobes in TS groups of children relative to controls. The authors concluded that this thinning was most prominent in ventral portions of the sensory and motor homunculi that control the facial, oro-lingual and laryngeal musculature that is commonly involved in tic symptoms. The authors further stated that correlations of cortical thickness in sensorimotor regions with tic symptoms suggest that these brain regions are important in the TS pathogenesis.

The present paper reports the result of on our investigation on cortical thickness across and within 66 subjects, covarying with gender, age and tic severity to further the current understanding of TS neuroanatomy and in an attempt to reduce some of the discrepancies seen in the literature. On one hand, TS is associated with prominent gender differences in clinical and epidemiological expression (Kurlan, 1992). Nordstrom and Burton's findings suggest that hormonal gender differences, apart from the influence of genetic or autoimmune etiologic factors, may be sufficient to aggravate tic severity in TS men (Nordstrom and Burton, 2002). Epidemiological findings demonstrated that TS is more prevalent in men than women (Zahner et al., 1988, Robertson, 1994), its prevalence is estimated to be 1 case per 1000 in boys and 1 case per 10,000 in girls (Awaad, 1999). On the other hand, age is also an important variable to consider in TS pathophysiology. TS typically has a prepubertal onset. Symptoms usually begin with transient bouts of simple motor tics between the ages of 3 and 8 with transient periods of intense eye blinking or some other facial tics. Phonic tics such as repetitive bouts of sniffing or throat clearing may also begin as early as 3 years of age (Leckman et al., 1998). By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. The worst period in TS symptoms is between the ages of 10 and 12 years of age. Interestingly, TS in many patients shows a marked reduction by the age of 19 or 20 (Kerbeshian and Burd, 1992, Coffey et al., 2000, Pappert et al., 2003). However, less than 20% of cases continue to experience clinically impairing tics as adults.

À priori, we predicted thinning of the cortex in brain regions involved in TS symptomatology (i.e., prefrontal and parietal cortices). This prediction is based on (1) TS clinical symptomatology; (2) the Leckman et al. (1991) hypothesis. In addition, we predicted a gender (TS boys showing thinner cortex correlating with tic severity) and age (thinning of the fronto-parietal cortices with age) effects. Cortical thickness analysis involves analyzing in vivo changes in the width of the cortical grey matter (GM) layer that covers the brain. Such a technique involves extracting polygonal meshes of the inner and outer boundary of this layer and employing a distance metric between the surfaces to measure thickness (Lerch and Evans, 2005). Hence, cortical thickness analysis captures a real physical quantity that is easy to interpret and localize.