We examined neuropsychological functioning of children with TS with and without ADHD in a well-characterized and, to our knowledge, largest to-date sample. There were no differences between children with TS-only and unaffected controls on the measures of response inhibition. This finding is in agreement with the earlier neuropsychological studies 23, 47, 48
and with reports of normal behavioral performance in neuroimaging studies of response inhibition in TS. 12, 49
Using the Stroop task in an event-related functional MRI study, Marsh and colleagues reported that compared to unaffected controls, 51 children and adults with TS had normal behavioral performance but increased activation in the frontostriatal circuitry of response inhibition including right inferolateral prefrontal cortex, left mesial frontal gyrus, left dorsolateral prefrontal cortex, lenticular nucleus, and thalamus. Similar results of increased activation in prefrontal cortex during a cognitive control task were reported in 18 children with TS. 49
It was hypothesized that the lack of impairment in response inhibition represents a manifestation of a neural compensatory mechanism that develops in children with TS as a result of ongoing efforts to inhibit involuntary tics. 12, 13
Our study lends support to the neural compensation hypothesis by demonstrating the lack of impairment in response inhibition in a large sample of children with uncomplicated TS.
Similarly to children with ADHD, children with TS-plus-ADHD revealed deficits in sustained attention as evidenced by lower scores on the Conners’ CPT errors of omission and reaction time variability. However, no significant differences between TS-plus-ADHD and unaffected controls were detected on the Stroop, VMI and Purdue tests suggesting that children with TS plus ADHD are less impaired than children with ADHD alone. Similar findings of greater impairment in children with ADHD without tics compared to children with ADHD-plus-TS on the measures of sustain attention and response inhibition were reported by others. 26, 29, 50
It is possible that greater levels of impairment in children with ADHD alone were caused by an ascertainment bias, that is, children recruited for ADHD were more impaired than children recruited for TS and later diagnosed with both TS and ADHD. However, similar scores on the parent rated severity of ADHD symptoms between these two groups make this interpretation unlikely. There was also no difference in the mean age of ADHD onset between the TS-plus-ADHD group (4.81±1.5 years) and the ADHD-only group (5.14±1.6 years). An alternative explanation of the lack of difference between children with TS-plus-ADHD and healthy controls, by contrast to the difference between the ADHD and healthy controls groups, is that children with TS-plus-ADHD may represent a different neuropsychological endophenotype than children with ADHD without tics. Longitudinal studies can elucidate the utility of this endophenotype for discerning the developmental course of ADHD symptoms in children with TS.
Moderate size reduction in Purdue Test scores can be noted in direct comparison of children with TS-only to unaffected controls (Cohen’s d = 0.50; 0.42 and 0.53 for dominant, nondominant and bimanual performance, respectively). However, these differences fell short of statistical significance when sex was entered as a covariate in the analysis. Significant diagnosis by gender interaction revealed that boys but not girls with TS-only were impaired in their dominant hand Purdue performance. Because impaired Purdue performance in childhood was shown to predict tic severity in adulthood, 43
our finding of the gender difference in Purdue performance in children with TS suggests that tics may have different developmental trajectories in boys and in girls. Performance on the Purdue Pegboard Test, a task of motor speed and dexterity, is associated with activation of frontal, sensorimotor and premotor cortices in both hemispheres. 51
Diminished sex differences in the frontoparietal regions were reported in TS 52
and a recent study reported thinning of the frontoparietal cortex in boys relative to girls with TS 53
suggesting that cortical morphology in girls may be associated with better tic control. Our result highlights the importance of investigating the effects of gender on the pathophysiology of TS.
The finding of unimpaired functioning on the VMI test is at odds with the previously published results. 17
It is possible that the small sample size of the TS without ADHD group (n=16) and elevated VMI scores in the control group (Mean Standard Score=105.3; SD=12.4) may be responsible for the significant difference between these groups in our previous study. It is also possible that the recognition of visuoperceptual deficits in TS in the early studies led to educational services, 54
which may be reflected in normalized VMI performance in this study.
Children with ADHD without tics differed from healthy controls on all dependent variables measures except Connors CPT errors of commission and reaction time. This is consistent with report of impaired interference control, 55
visual-motor integration 56
and fine-motor coordination, 57
and small magnitude of effect size on the Conners’ CPT in children with ADHD. 58
Because TS co-occurs with OCD in 20 to 60 percent of clinically referred cases and both disorders are etiologically related, 59
children with co-occurring OCD were included in the study and the diagnosis was entered in analysis as covariate. In agreement with earlier studies, the presence of co-occurring OCD was not associated with neurocognitive impairment. 21
Several limitations should be noted. The first limitation pertains to sample composition. Subjects with TS were ascertained from a specialty clinic, which may not reflect the full breath of TS phenomenology. Similarly, the ADHD sample was ascertained in part from the CHADD organization. Children in families who participate in voluntary organizations may represent a biased sample. In addition, the sample included mostly middle class Caucasian subjects and the results may not be generalizable to other populations. The second limitation concerns the composition of the neuropsychological battery. It is possible that tasks with greater inhibitory demands than traditional Stroop and CPT may be more sensitive to performance deficits. To this end, task complexity was shown to increase response inhibition deficits in children with ADHD. 60
Recent studies in TS also suggested that inhibitory deficits emerge under increasingly complex conditions of the Hayling task. 61, 62
Other areas of executive functioning such as extra-dimensional set shifting may be impaired in TS and merit investigation. 63
However, the goal of this study was to examine neuropsychological performance on well-established tasks in a large sample in order to enhance compatibility with previous neurocognitive and recent neuroimaging studies. The third limitation includes lack of observational measures of tics, particularly during performance of the neuropsychological tasks. It has long been assumed that the occurrence of tics such as blinking and head jerks during testing may interfere with the performance on tasks of attention, speed and coordination. Indeed, it is plausible that a subject experiencing a bout of tics during a timed task may evidence decreased performance. Direct tic counts during neuropsychological testing would make it possible to investigate the association of the number of tics during performance of the task with the results. Our findings of unimpaired performance on the Conners’ CPT, Stroop and VMI suggest that even if the tics were present during these tests, it did not significantly affect the results. This finding is also congruent with reports of lower likelihood of involuntary tics when individuals with TS are engaged in activities that require focused attention and purposeful movement. 64
Finally, the cross-sectional design makes it impossible to determine the directionality of associations between the variables.