Cheryl Richards edited Pathophysiology.md  about 8 years ago

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The issue of how comorbidities affect a variety of measures was seen in a study of TS children and adolescents \cite{25631951}. Compared to age-matched controls the TS group did significantly worse on the parent-rated Social Responsiveness Scale which measures social impairment. They also significantly longer to complete forms of the Trail Making Tests. However, of the 31 TS subjects, 11 had OCD, 18 had ADHD and 9 had an anxiety disorder. Once these co-occurring conditions were taken into account the group differences on the Trail Making Tests and the Social Responsiveness Scale were no longer significant.  Many factors affect tic frequency and two studies examined the effects of attention on tic  frequency. The role of attention on tic frequency was examined under several conditions /citep{25185800}. In the first study mean tic frequencies were significantly higher for 12 TS subjects compared to baselines when they were alone in a room. Then they were recorded while looking at themselves in a mirror. A second study was performed to determine whether the increase in frequency was due to increased attention to the tics themselves or just due to increased self-awareness. In addition to the conditions from the first study the 16 subjects were also shown videos of themselves while they were not ticcing. Tic frequency was again lower during the baseline compared to the mirror condition. Tic frequency was lower when subjects were watching the video of themselves while not ticcing. The authors suggest that future treatments stressing attention to states when patients experience fewer tics. Another study of TS adults \cite{25486384} compared tic frequency while subjects were engaged in tasks that involved attending to particular fingers, colored circles, or whether a tic had occurred during a specific 2 second interval during tic suppression and free ticcing conditions. Not suprisingly the greatest tics were seen during a baseline free ticcing condition. During the attention tasks, tic frequency was greatest while they focused on their tics and decreased tic frequency on the color attention condition and the greatest decrease on the finger attention condition. When subjects suppressed their tics, they reduced their baseline tic frequency and they exhibited similar frequencies across all attention conditions.  A three-stage instrumental-learning paradigm was used to compare antipsychotic-medicated and unmedicated TS adults with a control group \citep{26490329}. First, subjects learned to associate six different stimuli with six specific outcome pictures and a specific response (i.e., left or right key press). During the second stage, subjects were presented with two outcomes with an indication that one outcome was devalued so that it was no longer associated with point rewards and subjects had to press the key associated with the outcome that would still generate points. During the third stage (i.e., "slip-of-action" stage) the six comes were presented simultaneously with indications that two were devalued so that responding to the associated stimuli would no longer be rewarded with points. Subjects were instructed to press the correct key associated with stimuli associated with the still valued outcomes and withhold the response for stimuli associated with devalued outcomes. Subjects also did a Go-No Go task in which two of six cueing stimuli were devalued with instructions to withhold the key press response when the devalued stimulus was presented. This task provided determined whether excessive "slips of action" were related to a working memory deficit or deficient response inhibition rather than outcome devaluation insensitivity. There were no group performance differences for the first two stages of the instrumental learning task or on the baseline Go-NoGo task. However, unmedicated patients showed a significantly higher response rate to devalued outcomes compared to controls in Bonferroni-corrected post hoc analyses while there was no difference between medicated subjects and controls. In addition, in unmedicated subjects tic severity was correlated with response rates to devalued outcomes and was also correlated with stronger structural connectivity between the right supplementary motor cortex and the posterior putamen. The influence of comorbidities was minimized by excluding subjects with ADHD from the study. In addition, the results obtained in this study contrasted with results on similar tasks obtained with subjects with pure obsessive-compulsive disorder without tics. Delorme et al. argued that over-reliance on habits in pure OCD is associated with impaired knowledge of response-outcome associations while this type of learning was intact in both TS groups in this study and concluded that unmedicated TS subjects tend to engage in enhanced habit formation.