Dynamically Allocated Hub in Task-Evoked Network Predicts the Vulnerable Prefrontal Locus for Contextual Memory Retrieval in Macaques.
Dynamically Allocated Hub in Task-Evoked Network Predicts the Vulnerable Prefrontal Locus for Contextual Memory Retrieval in Macaques.
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DOI：
10.1371/journal.pbio.1002177
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发表时间：
2015-06
期刊：
影响因子：
9.8
通讯作者：
Miyashita Y
中科院分区：
文献类型：
--
作者：
Osada T;Adachi Y;Miyamoto K;Jimura K;Setsuie R;Miyashita Y
神经影像学和神经生理学研究表明，在特定的记忆任务中，前额叶皮层（PFC）的多个区域被激活，但PFC损伤后的损伤严重程度在很大程度上取决于哪个激活区域受损。病变部位和损伤之间的关键关系尚未给出明确的机制解释。虽然最近的工作提出，一个全脑网络包含的枢纽，发挥整合作用，在皮层信息处理，这个框架依赖于解剖结构为基础的结构网络不能占脆弱的位点为特定的任务，损伤会带来损害。在这里，我们假设：（i）激活的PFC区动态地形成一个有序的网络集中在一个任务特定的“功能枢纽”和（ii）病变有效的网站对应于“功能枢纽”，但不是一个任务不变的“结构枢纽”。为了验证这些假设，我们进行了功能性磁共振成像实验猕猴执行时间上下文记忆任务。我们发现，激活区形成了一个层次枢纽为中心的网络的基础上任务诱发的定向连接，不同的解剖网络反映轴突投影模式。使用一种新的基于支持向量机的模拟损伤方法，我们估计损伤后的每个区域的严重程度，这符合猕猴的背景记忆损伤（损伤后的9/46 d区，但不是在8Ad区）的已知解离。损伤的预测严重程度是成比例的网络“枢纽”的虚拟病变区的任务诱发的定向连接网络，而不是在解剖网络已知的示踪剂研究。我们的结果表明，除了静态的解剖枢纽之外，前额叶皮质区域动态地、合作地塑造了一个以枢纽为中心的功能网络，以根据认知过程重新分配损伤有效部位。这些发现将为精确预测人类大脑损伤或手术干预的行为影响奠定基础。猕猴执行记忆提取任务时的全脑活动模式表明，动态皮层网络中的任务特定功能中枢比任务不变结构中枢更好地预测脑损伤的任务特定后果。大脑额叶前部（前额叶皮层）受损的患者会遭受严重的记忆缺陷。神经影像学和神经生理学研究表明，在特定的记忆任务中，前额叶皮层的多个区域被激活。然而，前额叶皮层损伤后记忆缺陷的严重程度在很大程度上取决于哪一个激活区域受损;只有一小部分激活区域的损伤实际上会导致记忆缺陷。目前尚不清楚为什么一些激活区域是“病变有效”的，而另一些则不是。在这里，通过使用功能性磁共振成像（fMRI）来测量猕猴在记忆任务期间的全脑活动，我们发现激活的区域和它们之间的任务特异性功能连接形成了一个以枢纽为中心的分层网络。该动态网络中的特定任务“功能枢纽”准确地对应于记录良好的病变有效部位，并避免邻近的非病变有效部位。定量地，预测的记忆障碍的严重程度是成比例的功能网络中，而不是在解剖网络，这是静态确定的轴突投影模式的病变区域的网络“hubness”。我们的研究结果表明，前额叶皮层的区域动态地形成了一个以枢纽为中心的网络，根据特定记忆任务的认知要求，将病变有效部位从静态解剖枢纽中重新分配。
Neuroimaging and neurophysiology have revealed that multiple areas in the prefrontal cortex (PFC) are activated in a specific memory task, but severity of impairment after PFC lesions is largely different depending on which activated area is damaged. The critical relationship between lesion sites and impairments has not yet been given a clear mechanistic explanation. Although recent works proposed that a whole-brain network contains hubs that play integrative roles in cortical information processing, this framework relying on an anatomy-based structural network cannot account for the vulnerable locus for a specific task, lesioning of which would bring impairment. Here, we hypothesized that (i) activated PFC areas dynamically form an ordered network centered at a task-specific “functional hub” and (ii) the lesion-effective site corresponds to the “functional hub,” but not to a task-invariant “structural hub.” To test these hypotheses, we conducted functional magnetic resonance imaging experiments in macaques performing a temporal contextual memory task. We found that the activated areas formed a hierarchical hub-centric network based on task-evoked directed connectivity, differently from the anatomical network reflecting axonal projection patterns. Using a novel simulated-lesion method based on support vector machine, we estimated severity of impairment after lesioning of each area, which accorded well with a known dissociation in contextual memory impairment in macaques (impairment after lesioning in area 9/46d, but not in area 8Ad). The predicted severity of impairment was proportional to the network “hubness” of the virtually lesioned area in the task-evoked directed connectivity network, rather than in the anatomical network known from tracer studies. Our results suggest that PFC areas dynamically and cooperatively shape a functional hub-centric network to reallocate the lesion-effective site depending on the cognitive processes, apart from static anatomical hubs. These findings will be a foundation for precise prediction of behavioral impacts of damage or surgical intervention in human brains. Patterns of whole-brain activity while macaques perform a memory retrieval task show that the task-specific functional hub in the dynamic cortical network predicts the task-specific consequences of brain damage better than a task-invariant structural hub does. Patients with lesions in the front part of the brain’s frontal lobe—the prefrontal cortex—suffer from severe memory deficits. Neuroimaging and neurophysiology studies have revealed that multiple areas in the prefrontal cortex are activated during a specific memory task. However, the severity of the memory deficit after a lesion in the prefrontal cortex largely depends on which of the activated areas is damaged; lesions in only a fraction of the activated areas actually lead to memory deficits. It is currently unknown why some activated areas are “lesion effective” and others are not. Here, by using functional magnetic resonance imaging (fMRI) to measure macaque whole-brain activity during a memory task, we found that the activated areas and the task-specific functional connectivity among them formed a hierarchical network centered on a hub. The task-specific “functional hub” in this dynamic network accurately corresponds to the well-documented lesion-effective site and avoids the neighboring non-lesion-effective sites. Quantitatively, the predicted severity of memory impairment is proportional to the network “hubness” of the lesioned area in the functional network, rather than in the anatomical network, which is statically determined by axonal projection patterns. Our results suggest that the areas of the prefrontal cortex dynamically shape a hub-centric network, reallocating the lesion-effective site apart from the static anatomical hubs depending on the cognitive requirements of the specific memory task.
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