Functional segregation in the default mode network:The left and right TPJ in attention, semantic and social processing

15年前，功能神经成像技术的出现使人们意外地发现了默认模式网络(DMN)。尽管在健康和疾病方面取得了相当大的研究进展，但作为人脑能量消耗的主要来源，这个网络几乎只被作为一个凝聚力单位来研究。特别是，很少有人意识到DMN内的右侧和左侧颞顶交界处(TPJ)在认知、解剖学和临床角度上存在分歧。三个拟议的工作包专注于左侧和右侧TPJ在不同认知过程中的因果作用。实验任务将促使注意重新定向、语义加工和心理理论作为典型过程，体现更广泛的认知领域--注意、语言理解和社会认知。已建立的心理学范式将通过与注意(已知为右侧TPJ激活)、语义处理(已知为左侧TPJ激活)和社会认知(已知为双侧TPJ激活)相关的任务，在这个主要的大脑网络中触发偏侧化的神经反应。在任务处理过程中，通过对左侧或右侧TPJ施加重复的经颅磁刺激(RTMS)，健康大脑中的这些神经反应将受到因果干扰。RTMS还将与功能神经成像相结合，以探索健康系统中适应性的短期重组和可塑性。TPJ节点的诱发功能障碍预计会导致DMN动力学的功能活动和连接性改变，这些改变是针对正在进行的任务。该方法利用先前发表的每个认知领域研究的基于坐标的激活似然荟萃分析，通过量化靶区定义来利用先验知识。该方法是多模式的，通过结合注意、语义和社会认知表现的神经成像与元分析约束的rTMS扰动。最后，通过使用先进的统计学习方法分析神经成像结果，该方法是多变量的。这些方法将模拟i)DMN的节点间交互模式(即，组-稀疏图套索和动态因果建模)，ii)单个DMN节点的激活模式的局部差异(探照灯分析)，以及iii)复杂的大脑-行为关系(与任务绩效的Lasso/Ridge/ElasticNet回归)。这样，数据驱动的自下而上和实验自上而下的方法将紧密地交织在一起，以阐明DMN中的功能分离。在通过多变量统计分析进行分析的不同认知操作中，关键区域的扰动有望产生新的洞察力。系统水平上的诱导可塑性效应将有助于更好地理解大脑机制的一般特性，这些机制允许在对局灶性功能障碍的反应中进行快速功能补偿。

The advent of functional neuroimaging techniques has enabled the serendipity discovery of the default-mode network (DMN) 15 years ago. Despite considerable research progress in healthy and disease, this network, a major source of energy consumption in the human brain, has almost exclusively been studied as a cohesive unit. In particular, it has seldom been appreciated that the right and left temporo-parietal junction (TPJ) within the DMN are diverging from cognitive, anatomical, and clinical perspectives.The three proposed work packages focus on the causal role of the left and right TPJ across diverse cognitive processes. Experimental tasks will prompt attentional reorienting, semantic processing and theory of mind as archetypical processes that exemplify the broader cognitive domains attention, language comprehension and social cognition. Established psychological paradigms will trigger lateralized neural responses within this major brain network by tasks related to attention (known for right-lateralized TPJ activation), semantic processing (known for left-lateralized TPJ activation) and social cognition (known for bilateral TPJ activation). These neural responses in the healthy brain will be causally perturbed by applying repetitive transcranial magnetic stimulation (rTMS) to the either left or right TPJ during task processing. rTMS wil also be combined with functional neuroimaging to probe adaptive short-term reorganization and plasticity in the healthy system. The induced dysfunction in the TPJ node is expected to entail functional activity and connectivity alterations of DMN dynamics that are specific to the ongoing task.The approach exploits prior knowledge by quantitative target region definition using coordinate-based activation likelihood meta-analysis of previously published studies in each cognitive domain. The approach is multimodal by combining neuroimaging of attentional, semantic and social cognitive performance with meta-analytically constrained rTMS perturbations. Finally, the approach is multivariate by analyzing the neuroimaging results using advanced statistical-learning methods. These methods will model i) between-node interaction patterns of the DMN (i.e., group-sparse graph lasso and dynamic causal modeling), ii) local differences in activation patterns of individual DMN nodes (searchlight analysis), and iii) complex brain-behavior relationships (Lasso/Ridge/ElasticNet regression with task performance). In this way, data-driven bottom-up and experimental top-down methods will be closely intertwined to elucidate functional segregation in the DMN. New insight is expected to emerge from the perturbation of the key regions during distinct cognitive operations that are analyzed by multivariate statistical analyses. Induced plasticity effects on the system level will contribute to a better understanding of general properties of brain mechanisms that allow for rapid functional compensation in response to focal dysfunctions.