Project 2: Longitudinal development of perception-action integration in GTS: in search for mechanisms underlying symptom remission

抽动秽语综合征（GTS）是一种典型的神经发育障碍，通常始于学龄早期。在许多患者中，症状在青春期部分或完全缓解，在相当大比例的患者中，症状持续到成年期，然后甚至可能恶化。症状缓解和持续存在个体差异的原因尚不清楚。确定预测哪些GTS儿童/青少年更有可能缓解以及哪些有发展为持续性GTS的风险的生物标志物可能会深刻影响患者管理。因此，在这些生物标志物表明症状缓解的患者中，宽容的态度和一般措施，包括应对策略，心理咨询和短暂的对症药理措施可能就足够了。然而，在可能存在症状持续性的患者中，可能需要更强化的干预措施，以促进补偿性认知策略，包括除一般手段外的认知行为治疗。在第一个资助期广泛研究的感知-动作处理是一个有吸引力的生物标志物，因为感知和运动过程的异常结合已经成为GTS的关键发现。持续性GTS的成人表现出与抽搐频率相关的结合强度增加，这表明事件文件编码与抽搐的存在（或持续性）之间存在紧密的病理生理学联系。另一方面，事件文件编码在患有GTS的儿童和青少年的行为水平上是正常的，尽管潜在的神经激活模式与年龄匹配的健康对照不同，这表明结合强度增加作为感知-动作整合过程的神经发育缺乏的可能标志并不是GTS人群整体的特征，而是那些症状持续到成年的GTS患者。在第二个资助期内，项目2专注于GTS的发展方面，旨在确定感知-行动整合的纵向发展变化模式，以区分发展正常化过程（症状缓解）和持续非典型发展过程（导致成年后症状持续存在或恶化）。这将使用建立的行为范例和伴随的EEG调查，包括RIDE分解EEG数据分析，振荡EEG活动和源定位的分析来解决。

Gilles de la Tourette syndrome (GTS) is a prototype neurodevelopmental disorder typically commencing in early school age. In many patients symptoms partially or completely remit during adolescence, in a considerable proportion of patients the symptoms persist into adulthood and may then even deteriorate. The reasons for individual differences in symptom remission and persistence are unclear. Identifying biological markers predicting which children / adolescents with GTS are more likely to undergo remission and which are at risk of developing persisting GTS may profoundly affect patient management. Thus, in patients, in whom such biological markers indicate symptom remission a permissive attitude and general measures including coping strategies, psychosocial counselling, and transient symptomatic pharmacological measures may suffice. However, in patients with likely symptom persistence more intensive interventions to foster compensatory cognitive strategies including cognitive behavioral treatment in addition to general means may be required. Perception-action processing, extensively studied in the first funding period, is an attractive biological marker because abnormal binding of perceptual and motor processes has emerged as a key finding in GTS. Adults with persisting GTS showed an increased binding strength correlating with tic frequency suggesting a tight pathophysiological link between event file coding and the presence (or persistence) of tics. On the other hand, event file coding was normal at the behavioral level in children and adolescents with GTS, although underlying neural activation patterns differed from age-matched healthy controls suggesting that increased binding strength as a possible sign of lack of neurodevelopment of perception-action integration processes is not a characteristic of the GTS population as a whole, but rather of those GTS patients with symptoms persisting into adulthood. Focusing on developmental aspects of GTS in the second funding period, Project 2 aims to identify patterns of longitudinal developmental changes in perception-action integration that differentiate between processes of developmental normalization underlying symptom remission and those of continuing atypical development leading to symptom persistence or deterioration in adulthood. This will be addressed using established behavioral paradigms and concomitant EEG investigations including RIDE-decomposed EEG data analysis, analysis of oscillatory EEG activity and source localization.