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    • Two key findings are as follows First

    2018-11-07

    Two key findings are as follows: First, motor threshold values do not differ in individuals with TS relative to matched controls (Orth, 2009) (c.f. reference (Orth and Rothwell, 2009)). Importantly, it is suggested that equivalent RMTs in TS patients and controls indicates that neural populations recruited by TMS at threshold are in the same state in both samples (Orth, 2009). Second, a number of studies have demonstrated that the gain of motor cortical excitability is reduced in individuals with TS. This is the case for both TMS-induced increases in motor excitability (i.e., TMS recruitment curves) (Orth et al., 2008; Draper et al., 2014) and gains in motor excitability during motor preparation, immediately preceding the execution of volitional movements (Heise et al., 2010; Draper et al., 2015). Importantly, the gain in cortical excitability is thought to depend upon the distribution of excitability within the population of corticospinal AMD-070 (i.e., recruitment of neurons with different levels of excitability): thus it is concluded that a shallower gain function in TS reflects a reduction in the spread of excitability within this population (Orth, 2009). Importantly, the relationship between individual TMS measurement values and tic severity scores in TS has been examined, however the evidence is rather mixed. Orth and colleagues reported, in a study of adults with TS, that the individual slope values for TMS recruitment curves were positively associated with some measures of complex, phonic, and finger tics (Heise et al., 2010). By contrast, they reported that clinical tic rating scales (i.e., the Yale Global Tic Severity Scale [YGTSS] (Leckman et al., 1989)) and other video measures (e.g., the Modified Rush Video Scale (Goetz et al., 1999)) were not associated with tic severity. It is important to note that the majority of studies investigating cortical excitability and physiological inhibition in TS using TMS techniques have been conducted in adults with TS and must therefore be interpreted with some caution for the following reasons. First, TS is a disorder of childhood onset that typically follows a developmental time course in which in the majority of individuals, tics are absent or relatively mild by early adulthood. Adults with TS can be viewed therefore as unrepresentative of the more general TS population (i.e. children and adolescents with the disorder), but may nevertheless constitute an important group in which the clinical phenotype is stable and the compensatory plastic changes thought to bring about increased control over tic severity during adolescence (Jackson et al., 2011) have either failed to occur or have been ineffective. Second, brain imaging studies have consistently demonstrated that while there are widespread alterations in brain structure and function associated with TS (for review see Plessen et al., 2009), these effects differ quite markedly for adult and child samples, and have often been diametrically opposite (Plessen et al., 2009). Given the above, it is important to investigate whether the findings demonstrated in TMS studies investigating cortical excitability and physiological inhibition in adults with TS are replicated in children and adolescents with TS.
    Method
    Results
    Discussion First, in contrast to previous studies in adult TS patients (Orth et al., 2008; Orth, 2009) that reported that motor thresholds in individuals with TS and neurologically normal controls were equivalent, we demonstrated that motor thresholds were significantly higher in individuals with TS compared to age-matched controls. Furthermore, we demonstrated that between-group differences in motor threshold were most apparent in younger individuals with TS, were absent in young adults with TS, and that threshold values were significantly predicted by age within the TS group. Motor threshold is thought to reflect the excitability of a population of corticospinal neurons that project to the targeted muscle, and to depend on the axonal membrane properties of neurons at the site of stimulation and the membrane properties of post-synaptic neurons (Orth, 2009; Ziemann, 2013). Previous findings, demonstrating that motor thresholds are equivalent in adults with TS and neurologically normal controls (Orth et al., 2008; Heise et al., 2010), have been interpreted as indicating that these properties are not different (i.e., they are in a similar state) in individuals with TS (Orth, 2009).