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### Animal models  Rodent and monkey tic models have been developed in an attempt to study the mechanisms involved in tic generation more directly and a number of studies were published in 2015 using mice.  In a rodent model removing about half of the cholinergic interneurons in the dorsolateral striatum produced increased fragmented grooming behavior in response to a repeated unpredictable acoustic startle stimuli and increased repetitive sniffing in response to D-amphetamine challenge \citep{25561540}. Ablation in the dorsomedial striatum did not produce similar deficits. None of the experimental conditions produced a change in prepulse inhibition. Another rodent model was used to determine to what extent cortical input and striatal input affected the temporal and spatial properties of motor tics \citep{26674861}. Biccuculline injections into the anterior striatal motor region produced focal tics in the forelimb area. The medium spiny neurons (MSNs) and the fast spiking interneurons exhibited increased activity during tics. Almost all of the MSNs were only active during the tics while a minority of the FSIs exhibited a decrease in activity. About half of the globus pallidus neurons demonstrated increased activity during the tic while the rest showed only inhibition or a combination of inhibition and excitation. Short bursts of high-frequency stimulus pulses were applied at random intervals to the region of the primary motor cortex representing the forelimb. Stimulation was provided before and after the bicuculline injections. The results suggested that the precise timing of tic occurrence was related to the summation of incoming excitatory cortical input and the time since the previous tic. These results supported the idea that the corticostrial network is fundamentally associated with tic occurrence. 
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### Neuroimaging and electrophysiology studies  Neuroimaging and electrophysiology studies continue to be a focus of many researchers since they provide information about the functional and structural differences between TS and control subjects.  An important (though frustrating) recent finding was that even very small head movements can cause artifactual findings in structural MRI \citep{25498430} . Neroimaging scans were performed on 12 healthy adults while they were still or engaged in specific types of movements including nodding, headshaking and a movement that they invented and then repeated during the scan run. Even during scans when subjects remained still, there was an average of 3 mm/s RMSpm (RMS displacement per minute), but it was significantly higher during the motion conditions. In general there was a 1-3% local volume loss for each 1 mm/s RMSpm increase. The greatest thickness reductions were found in the pre- and post-central cortex, in the temporal lobes and pole, and enthorhinal and parahippocampal regions. Increased thickness associated with motion was seen in regions associated with deep sulci such as the medial orbital frontal and lateral frontal areas. Recommendations were made to reduce head motion during scans as much as possible and then control for motion in the statistical analysis, along with using correlational analyses to determine the associations between head motion and the predictors of interest. A more recent article \citep{26654788} described the development of a system for motion tracking and prospective motion correction, and mentions similar systems that are available for other scanner platforms. The challenges using neuroimaging techniques to study pediatric and clinical subjects are described in detail along with various strategies that can be used to collect high-quality data \citep{26754461}. Many researchers have used a variety of experimental paradigms to study motor response inhibition since tic expression seems related to motor inhibition. In healthy adults performance on a stop-signal task and a continuous performance task was examined using positron emission tomography to measure striatal D1- and D2-type receptor availability \citep{25878272}. Stop-signal reaction time was negatively correlated with both D1- and D2-type receptor activation in both the associative striaum and the sensory motor striatum. Neither D1- nor D2-type receptor activation was associated with Go reaction time or Stop signal reaction time on the continuous performance task suggesting that these two tasks are associated with different neurochemical mechanisms related to motor response inhibition.