Neural Mechanisms of Trust and Dyadic Interaction in BPD

IP3的目的是使用超扫描来识别BPD患者在人际过程受损期间大脑间的异常活动和连接，这使得可以同时测量两个互动的人的大脑活动。在第一个资助期间，我们建立了一种新的、可推广的、健壮的、无假设的分析方法，用于超扫描数据，同时收集健康对照和患者的数据。最初的调查选择了联合注意(JA)任务，因为它代表了一种基本的、简单的、发展早期的特别是人类社会互动的形式。来自两个健康样本的数据显示，在JA期间，大脑系统之间的耦合出现，这是真正互动的受试者所独有的，在时间和空间上具有高度的特殊性，集中在右侧的颞顶交界处(RTPJ)。在我们的第一项研究中，目前涉及22个BPD对，由患者与一个对照参与者互动形成，我们发现JA期间的神经耦合参数受疾病状态的影响。在JA期间，没有观察到涉及BPD受试者的二联体之间的显著耦合，这提供了BPD中社会信息的早期处理阶段的第一个观察到的中断。此外，对第二项研究的初步分析，多轮信任游戏显示，当BPD患者参与互动时，rTPJ耦合也有类似的减少。这一结果可能表明，我们发现了一种社会互动的基本神经机制，即脑间耦合，这种机制在非常基本的社交互动中已经在BPD患者中受损，但在所有复杂程度上都会影响社会功能。JA障碍在自闭症谱系障碍(ASD)中得到了广泛的研究。最近，有报道称BPD患者亚群也符合ASD标准。因此，测试JA期间耦合度降低是否也可以在ASD患者中观察到，以及我们是否发现了影响BPS和ASD社会功能的共同机制，这将是有趣的。因此，我们现在的目标是进一步表征和探索JA期间的神经耦合及其在BPD患者中的障碍。我们将首先调查BPD和ASD患者在JA期间神经耦合障碍、ASD临床特征和社会功能之间的关系。其次，我们将研究JA期间偶联障碍的遗传基础，特别强调催产素受体基因(OXTR)的作用。第三，我们将调查疾病过程中签名的变化，观察缓解的BPD患者的更大样本；第四，我们将更详细地调查交界线二联体内的JA。此外，为了将rTPJ功能与社会互动直接联系起来，我们将在BPD和ASD患者中进行一项先导性研究，在该研究中，我们使用经颅磁刺激(TMS)来兴奋该区域，并测试在社会互动过程中对神经耦合参数的影响。

Aim of IP3 is the identification of abnormal interbrain activity and connectivity during impaired interpersonal processes in BPD using hyperscanning which permits the measurement of brain activity simultaneously in two interacting people. During the first funding period, we established a new, generalizable, robust and hypothesis-free analysis method for hyperscanning data while collecting data from both healthy controls and patients. A Joint Attention (JA) task was chosen for the initial investigation, since it represents a fundamental, simple and developmentally early form of specifically human social interaction. Data from two healthy samples showed that during JA, coupling between brain systems emerges that is unique to truly interacting subjects, and temporally and spatially highly specific, centering on the right temporo-parietal junction (rTPJ). In our first study, currently involving 22 BPD pairs, formed from patient interacting with one control participant, we found that neural coupling parameters during JA were affected by illness status. No significant coupling in dyads involving a BPD subject was observable during JA, providing the first observation of a disruption in this early processing stage of social information in BPD. In addition, initial analysis of the 2nd study, a multi-round trust game showed a comparable reduction in rTPJ coupling when BPD patients were involved in the interaction. This result might indicate that we identified a fundamental neural mechanism of social interaction, interbrain coupling, which is already impaired in BPD patients in very basal kinds of social interaction but affects social functioning on all levels of complexity. Disturbed JA has been extensively investigated in autism spectrum disorders (ASD). Recently a subgroup BPD patients has been described that also meets the criteria for ASD. It would therefore be interesting to test whether the reduced coupling during JA can also be observed in ASD patients and whether we identified a shared mechanism affecting social functioning in BPS and ASD. Therefore, we now aim to further characterize and explore neural coupling during JA and its disturbance in BPD patients. We will first investigate associations between disturbed neural coupling during JA, clinical ASD features and social functions in BPD and ASD patients. Second, we will investigate the genetic underpinnings of impaired coupling during JA specifically emphasizing the role of the oxytocin receptor gene (OXTR). Third, we will investigate the change of the signature over the course of the disorder looking on a larger sample of remitted BPD patients and fourth, we will investigate JA within borderline dyads in more details. In addition, to directly relate rTPJ function to social interaction, we will conduct a pilot study in BPD and ASD patients, where we use transcranial magnetic stimulation (TMS) to excite the region and test resulting effects on neural coupling parameters during social interaction.