Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by the presence of motor and vocal tics. Major pathophysiological theories posit a dysfunction of the cortico-striato-thalamo-cortical circuits as being a representative hallmark of the disease. Recent evidence suggests a more widespread dysfunction of brain networks in TS including the cerebellum and going even beyond classic motor pathways.In order to characterize brain network dysfunction in TS, in this study we investigated functional and effective-like connectivity as well as topological changes of basal ganglia-thalamo-cortical and cortico-cerebellar brain networks. We collected resting-state fMRI data from 28 TS patients (age: 32 ± 11 years) and 28 age-matched, healthy controls (age: 31 ± 9 years). Region of interest based (ROI-ROI) bivariate correlation and ROI-ROI bivariate regression were employed as measures of functional and effective-like connectivity, respectively. Graph theoretical measures of centrality (degree, cost, betweenness centrality), functional segregation (clustering coefficient, local efficiency) and functional integration (average path length, global efficiency) were used to assess topological brain network changes.In this study, TS patients exhibited increased basal ganglia-cortical and thalamo-cortical connectivity, reduced cortico-cerebellar connectivity, and an increase in parallel communication through the basal ganglia, thalamus and cerebellum (increased global efficiency). Additionally, we observed a reduction in serial information transfer (reduction in average path length) within the default mode and the salience network.In summary, our findings show that TS is characterized by increased connectivity and functional integration of multiple basal ganglia-thalamo-cortical circuits, suggesting a predominance of excitatory neurotransmission and a lack of brain maturation. Moreover, topological changes of cortico-cerebellar and brain networks involved in interoception may be underestimated neural correlates of tics and the crucial premonitory urge feeling.

Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder that can have a detrimental impact on the health-related quality of life of children with the condition. To date no patient-reported health-related quality of life measures have been developed for children and adolescents in the English language. This study validated the first disease-specific scale for the quantitative assessment of health-related quality of life in 118 children and adolescents with Gilles de la Tourette syndrome (C&A-GTS-QOL) following language adaptation from Italian to English in the United Kingdom. Standard statistical methods were used to test the psychometric properties of the rating scale. Principal component factor analyses led to the identification of six health-related quality of life domains (cognitive, copro-phenomena, psychological, physical, obsessive-compulsive, and activities of daily living), explaining 66.7% of the overall variance. The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability; validity was supported by interscale correlations (range 0.2-0.7), confirmatory factor analysis, and correlation patterns with other rating scales and clinical variables.

Depotentiation (DP) is a crucial mechanism for the tuning of memory traces once LTP (Long Term Potentiation) has been induced via learning, artificial procedures, or other activities. Putative unuseful LTP might be abolished via this process. Its deficiency is thought to play a role in pathologies, such as drug induced dyskinesia. However, since it is thought that it represents a mechanism that is linked to the susceptibility to interference during consolidation of a memory trace, it is an important process to consider when therapeutic interventions, such as psychotherapy, are administered. Perhaps a person with an abnormal depotentiation is prone to lose learned effects very easily or on the other end of the spectrum is prone to overload with previously generated unuseful LTP. Perhaps this process partly explains why some disorders and patients are extremely resistant to therapy. The present study seeks to quantify the relationship between LTP and depotentiation in the human brain by using transcranial magnetic stimulation (TMS) over the cortex of healthy participants. The results provide further evidence that depotentiation can be quantified in humans by use of noninvasive brain stimulation techniques. They provide evidence that a nonfocal rhythmic on its own inefficient stimulation, such as a modified thetaburst stimulation, can depotentiate an associative, focal spike timing-dependent PAS (paired associative stimulation)-induced LTP. Therefore, the depotentiation-like process does not seem to be restricted to specific subgroups of synapses that have undergone LTP before. Most importantly, the induced LTP seems highly correlated with the amount of generated depotentiation in healthy individuals. This might be a phenomenon typical of health and might be distorted in brain pathologies, such as dystonia, or dyskinesias. The ratio of LTP/DP might be a valuable marker for potential distortions of persistence versus deletion of memory traces represented by LTP-like plasticity.

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