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### Electrophysiology   Local field potentials associated with spontaneous tics were studied in 3 patients during DBS surgery \citep{25435514}. In all 3 patients repetitive thalamo-cortical coherent activity was present from 800 to 1500 msec prior to tic-associated muscle contractions. The frequency range affected varied among the patients and there were also ongoing intermittent intra-thalamic coherences that were not synchronized to the tics. The authors speculated that specific DBS targets may not matter as much as whether the target is part of the striato-pallido-thalamo-cortical network. Since However, since  these patients were older and had very severe and complex tics, the authors acknowledge that it is not yet  clearat this point  to what extent these results generalize to the TS population as a whole. | **Title** | **Comment** |  |:----------|:------------|  |Event-related potentials in TS and chronic tic disorder  \citep{26531497} |Both TS and chronic tic disorder groups exhibited similar increased increases in  parietal and central activation event-related potentials,  adding tothe  evidence thatthe distinction between  TS and CTD maynot  beparticularly useful.|  | Event-related topography and  the effect of comorbidities same illness.|  |  \citep{Germain_2015} | Reduced P300 amplitudes in frontal regions were related to TS-associated comorbidities rather than to TS itself. ||  ### Pharmacological studies  Dopamine GABA  involvement was studied  in tic generation has been a long-standing focus of 23  TS researchers. Several recent studies sought to elucidate the role of dopamine in the basal ganglia. Positron emission tomography (PET) was used to investigate striatal D2/D3 dopamine receptors children, aged 8-12, and 67 controls  using a D2/D3 receptor antagonist and an agonist battery of vibrotactile tasks  with preferential binding to D3 dopamine receptors \citep{25788222} in TS subjects and controls. As expected, binding potential for a subset of  the D3 preferential agonist was greater children (19 with TS, 25 controls) also undergoing GABA-edited magnetic resonance spectroscopy (MRS) \citep{26041822}. Lower GABA concentration  in the ventral striatum while it was right sensorimotor cortex correlated with  greaterfor the D2/D3 receptor antagonist in the  motor and associative regions of the dorsal striatum. However, no differences were found for these 3 regions when the TS subjects were compared with the controls, and there tic severity (\(r=-0.55\)). There  were no significant correlations differences  between binding potentials and tic severity. Although the authors discuss the possibility that endogenous dopamine levels might have influenced the results or that striatal dopamine receptors are involved only in a subset of TS patients, they conclude that their results challenge the widely held view that striatal dopamine receptors have a fundamental role in TS pathophysiology. Two studies examined D1 and D2 receptors in healthy adults. Striatal D1- and D2-type receptor availability was measured groups  onstop-signal and continuous performance tasks \citep{25878272}. Stop-signal  reaction timewas negatively correlated with both D1-  and D2-type receptor availability in the the associative and sensory motor regions of the striatum. In contrast, neither D1- nor D2-type receptor availability was associated with performance on the continuous performance task, suggesting baseline amplitude discrimination threshold. However, TS children showed impaired tactile adaptation. The authors suggest  that stop-signal and continuous performance tasks are associated with different neurochemical mechanisms related to motor response inhibition. In a study of healthy adults learning from positive outcomes was positively correlated with D1 receptor binding in the putamen MRS GABA  and caudate while there was an inverted U-shaped relationship (i.e., r2=0.19) between learning from negative outcomes and D2R binding in the putamen \citep{25562824}. A dietary manipulation that reduced dopamine precursor levels significantly improved learning from negative outcomes. These results were interpreted as providing evidence that dopamine acts as a reward prediction error signal rather than tactile measures might useful  as a saliency signal. biomarkers of treatment response.  GABA involvement Positron emission tomography (PET)  was studied used to investigate striatal D2/D3 dopamine receptor availability  in23  TS children, aged 8-12, subjects  and67  controls using a battery of vibrotactile tasks D2/D3 receptor antagonist ( \([^{11}C]\)raclopride) and an agonist  with a subset of preferential binding to D3Rs (\([^{11}C]\)(+)PHNO) \citep{25788222}. No differences were found for these 3 regions when  the children (i.e., 19 TS subjects were compared  withTS, 25 controls) also undergoing GABA-edited magnetic resonance spectroscopy (MRS) \citep{26041822}. Lower GABA concentration in  the right sensorimotor cortex was associated with greater motor tic severity (r=-0.55). There controls, and there  were no significant differences correlations  between groups on reaction time receptor availability  and baseline amplitude discrimination threshold. However, TS children showed impaired tactile adaptation. tic severity.  The authors suggest conclude that their results challenge the widely held view that striatal dopamine receptors have a fundamental role in TS pathophysiology, though they acknowledge  that MRS GABA endogenous dopamine levels may have influenced the results since these radiotracers are displaceable by physiological synaptic concentrations of dopamine.   Two studies examined dopamine D1  and tactile measures might useful as biomarkers D2-like receptors in healthy adults, measuring D1R and D2R availability during stop-signal and continuous performance tasks \citep{25878272}. Stop-signal reaction time was negatively correlated with both D1R and D2R receptor availability in the the associative and sensory motor regions of the striatum. In contrast, neither D1R nor D2R receptor availability was associated with performance on the continuous performance task, suggesting that stop-signal and continuous performance tasks are associated with different neurochemical mechanisms related to motor response inhibition. In a study  of treatment response. healthy adults, learning from positive outcomes was positively correlated with D1R binding in the putamen and caudate while there was an inverted U-shaped relationship ( \(r^2=0.19\) ) between learning from negative outcomes and D2R binding in the putamen \citep{25562824}. A dietary manipulation that reduced dopamine precursor levels significantly improved learning from negative outcomes. These results were interpreted as providing evidence that dopamine acts as a reward prediction error signal rather than as a saliency signal.  A detailed review focuses on histaminergic modulation of striatal function its possible role in TS \citep{26275849}. The authors suggest that, during wakefulness and increased attention, histaminergic neurons will be more active with the result that the striatum will be more responsive to thalamostriatal input and and feed-forward inhibition will dominate. Several lines of evidence related to the role of histamine in TS were discussed. A family linkage study identified a rare mutation in the gene encoding histidine decarboxylase. HDC transgenic mice exhibit decreased pre-pulse inhibition of startle responses and an increase in a variety of amphetamine-induced stereotypies that were prevented by pretreatment with histamine infusion or use of haloperidol. Reduced histamine production was suggested to produce dopaminergic disregulation of the basal ganglia and sympotoms similar to those seen in TS.