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

妥瑞氏综合征（GTS）是一种典型的神经发育障碍，通常发生在学龄早期。许多患者的症状在青春期部分或完全缓解，相当一部分患者的症状持续到成年，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。识别生物标志物，预测哪些患有GTS的儿童/青少年更有可能获得缓解，哪些有发展为持续性GTS的风险，可能会对患者管理产生深远影响。因此，在这些生物标记表明症状缓解的患者中，宽容的态度和包括应对策略、心理社会咨询和短暂症状性药物措施在内的一般措施可能就足够了。然而，对于可能症状持续的患者，除了一般手段外，可能需要更强化的干预措施来促进代偿性认知策略，包括认知行为治疗。知觉-动作加工在第一个资助期被广泛研究，是一个有吸引力的生物标记，因为知觉和运动过程的异常结合已经成为GTS的一个关键发现。持续GTS的成人与抽动频率相关的结合强度增加，表明事件文件编码与抽动的存在（或持续）之间存在紧密的病理生理联系。另一方面，GTS儿童和青少年的事件文件编码在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可能是感知-行动整合过程缺乏神经发育的标志，而不是GTS人群整体的特征，而是那些症状持续到成年的GTS患者的特征。在第二个资助期关注GTS的发展方面，项目2旨在确定感知-行动整合的纵向发展变化模式，以区分发育正常化的潜在症状缓解过程和导致成年期症状持续或恶化的持续非典型发展过程。这将通过已建立的行为范式和伴随的脑电图研究来解决，包括分解的脑电图数据分析、振荡脑电图活动分析和源定位。

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.