Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai 200433, China.
School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai, China.
Neuroimage Clin. 2020;28:102377. doi: 10.1016/j.nicl.2020.102377. Epub 2020 Aug 7.
Triple network dysfunction theory of schizophrenia postulates that the interaction between the default-mode and the fronto-parietal executive network is disrupted by aberrant salience signals from the right anterior insula (rAI). To date, it is not clear how the proposed resting-state disruption translates to task-processing inefficiency in subjects with schizophrenia. Using a contiguous resting and 2-back task performance fMRI paradigm, we quantified the change in effective connectivity that accompanies rest-to-task state transition in 29 clinically stable patients with schizophrenia and 31 matched healthy controls. We found an aberrant task-evoked increase in the influence of the rAI to both executive (Cohen's d = 1.35, p = 2.8 × 10) and default-mode (Cohen's d = 1.22, p = 1.5 × 10) network regions occur in patients when compared to controls. In addition, the effective connectivity from middle occipital gyrus (dorsal visual cortex) to insula is also increased in patients as compared with healthy controls. Aberrant insula to executive network influence is pronounced in patients with more severe negative symptom burden. These findings suggest that control signals from rAI are abnormally elevated and directed towards both task-positive and task-negative brain regions, when task-related demands arise in schizophrenia. This aberrant, undiscriminating surge in salience signalling may disrupt contextually appropriate allocation of resources in the neuronal workspace in patients with schizophrenia.
精神分裂症的三重网络功能障碍理论假设，默认模式网络和额顶执行网络之间的相互作用被右侧前岛叶（rAI）的异常显著信号破坏。迄今为止，尚不清楚所提出的静息状态中断如何转化为精神分裂症患者在任务处理中的效率低下。使用连续的静息和 2 -back 任务表现 fMRI 范式，我们量化了 29 名临床稳定的精神分裂症患者和 31 名匹配的健康对照组在从静息状态到任务状态转变过程中伴随的有效连接变化。我们发现，与对照组相比，患者在执行（Cohen's d = 1.35，p = 2.8×10）和默认模式（Cohen's d = 1.22，p = 1.5×10）网络区域中，任务诱发的 rAI 影响出现异常增加。此外，与健康对照组相比，患者中从中脑枕叶（背侧视觉皮层）到岛叶的有效连接也增加了。与健康对照组相比，具有更严重阴性症状负担的患者，岛叶对执行网络的影响更为明显。这些发现表明，当精神分裂症患者出现与任务相关的需求时，来自 rAI 的控制信号会异常升高，并指向任务阳性和任务阴性的大脑区域。这种异常的、无差别的显著信号激增可能会破坏精神分裂症患者神经元工作空间中资源的情境适当分配。
