Review article
Neuropsychological aspects of Tourette syndrome: A review

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Abstract

Tourette syndrome (TS) is assumed to result from frontostriatal dysfunction, which would be expected to result in impairments in neuropsychological functions. This possibility has been explored in a number of studies that have assessed the performance of patients with TS within major cognitive domains and on tests involving executive functioning. We aim to summarize the main findings of these studies while evaluating the influence of task limitations and potentially critical confounding factors such as the presence of comorbidity. Although there is clearly a need for improved study design, we tentatively suggest that there is considerable evidence for cognitive impairment in a subgroup of patients, and that some difficulties seem to be intrinsic to TS. These impairments may reflect dysfunction of the anterior cingulate network within the frontostriatal pathway.

Introduction

Tourette syndrome (TS) is a neurodevelopmental disorder that is most commonly diagnosed in childhood or early adolescence [1]. The core symptoms of TS include multiple motor tics and one or more phonic tics, which last for more than a year. The tics may be simple or complex in nature and vary in number, frequency, and severity over time. Comorbid disorders include anxiety, depression, learning difficulties, and sleep disorders, although attention deficit/hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are most common [2].

Tics may reflect changes in striatal functioning [3], and studies of patients with TS have indicated structural changes within the basal ganglia such as decreased volume of the left side of the caudate, putamen, and globus pallidus [4], and decreased striatal metabolism [5]. Striatal changes may result in dysfunction within frontostriatal circuits, which are formed through connections between the striatum and different regions of the frontal cortex [6]. Dysfunction within circuits involving cortical motor regions is likely to lead to tics. However, three of these parallel circuits involve frontal areas that are likely to subserve cognitive functions—the lateral orbitofrontal cortex, the dorsolateral prefrontal cortex, and the anterior cingulate cortex—and dysfunction within these circuits may lead to cognitive impairments [7]. Support for frontal dysfunction in TS has been provided by studies indicating changes in the activity and metabolism of this region [5], [8], [9].

Frontostriatal dysfunction has been associated with significant deficits in cognitive functions in other disorders of the basal ganglia such as Parkinson's disease [10], [11], [12] and Huntington's disease [13], [14]. A considerable number of studies have similarly shown patients with TS to have related cognitive impairments. However, the exact nature of the deficits attributable to TS, rather than to comorbid disorders, has yet to be elucidated.

This review will summarize findings in core domains (visual perceptual, motor, attention, memory, and learning) and will then discuss patients' performance on tasks involving higher cognitive or executive functions (working memory, fluency, planning, shifting, and inhibition). The discussion will focus on the possible implications of patients' deficits on dysfunction within three specific frontostriatal pathways involving the dorsolateral prefrontal, orbitofrontal, and anterior cingulate cortices. The dorsolateral prefrontal cortex is implicated in cognitive flexibility [15], memory [16], and attentional processes [17]; orbitofrontal dysfunction is more selectively associated with deficits in reinforcement and reversal learning tasks [18]; and the anterior cingulate cortex is important for conflict monitoring and resolution [19] and is active during tasks involving response inhibition [20].

Recent factor analytic studies [21] have shown that there may be more than one TS phenotype. Among these, the “pure TS” phenotype (patients with “uncomplicated” TS, i.e., without comorbid psychiatric conditions) has been consistently replicated [2], [22], [23] and accounts for about 10% of patients diagnosed with TS in both community [24] and clinical [25] settings. Due to the high rates of comorbidity in TS, many studies have included patients with symptoms of ADHD or OCD. Patients with ADHD alone may exhibit deficits in response inhibition [26], working memory [27], and cognitive flexibility [28], while OCD has been associated with poor reversal learning [29] in addition to inhibitory dysfunction [30]. Special attention has been paid to the issue of comorbidity, although we will consider the potential influence of other sample and task limitations. Despite these difficulties, some preliminary conclusions about the nature and basis of cognitive impairment in TS can be drawn.

Section snippets

Perceptual, motor, and visuomotor performance

The most relevant studies providing support for difficulties in fine-motor, perceptual, and visuomotor skills are shown in Table 1. A number of studies have reported that children with TS exhibit deficits in visuomotor integration skills based on performance on the Beery Visual Motor Integration Test (Beery VMI) [31], although one study reported no impairment [32]. Furthermore, some of these studies have indicated that patients' deficits are unlikely to be due to comorbid ADHD [33], [34]. The

Attention

A number of studies have provided evidence for the presence of attentional deficits in TS, and the most relevant findings are listed in Table 2. The presence of comorbid ADHD plays a central role in the investigation of possible attentional impairment in TS. Channon et al. [46] found that a group of adults with TS performed poorly on attentional tasks including the Trail Making Test (TMT), a serial addition task, and a vigilance test, in comparison to control subjects with an equivalent IQ.

Memory, learning, and decision making

Key studies highlighting the presence of memory deficits have been summarized in Table 3. Evidence for deficits on measures of visual memory performance in TS was provided by Watkins et al. [56], who reported spatial recognition memory deficits in a group of 20 TS patients, among whom only 3 TS patients exhibited comorbid ADHD. Another study found evidence of poor performance on a design-recall task in 32 adolescents with TS [39], and Bornstein [41] reported that adults with TS exhibited

Executive function

Tests of executive function assess higher cognitive abilities such as working memory and response inhibition. Studies providing evidence of possible executive deficits in TS are shown in Table 4. Many executive tasks are thought to involve the dorsolateral prefrontal and anterior cingulate cortices, while the orbitofrontal cortex is most likely to contribute to performance on tasks involving reward-related learning [63]. Patients with other disorders involving frontostriatal dysfunction, such

Problems with measures

If patients do exhibit deficits in fundamental cognitive functions such as learning or memory, it is clear that these difficulties could affect performance in a range of tasks. Patients may perform more poorly on complex tasks because they involve several executive components, and if patients have even subtle deficits in multiple components, these could contribute to impaired performance. For example, it is possible that TS patients' poor performance on shifting or memory tasks may at least

Conclusions

The cognitive deficits exhibited by patients with TS are clearly not as striking as those shown by other patient groups with frontostriatal dysfunction [88], such as patients with Parkinson's disease or Huntington's disease. This may be because these disorders reflect different patterns of dysfunction affecting different frontostriatal pathways, in addition to the fact that the latter two disorders are degenerative and TS is not. Bornstein [41] suggested that a subgroup comprising approximately

Acknowledgments

The authors wish to thank Dr. Ian Mitchell for his insightful comments on earlier versions of this manuscript.

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