The Hammersmith Hospital, London, W12 0NN, UK.
Brain. 2011 Aug;134(Pt 8):2233-47. doi: 10.1093/brain/awr175.
Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at 'rest'. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of 'resting' state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In addition, functional connectivity at rest also predicted patterns of brain activation during later performance of the task. As expected, patients showed widespread white matter damage compared with controls. Lower default mode network functional connectivity was seen in those patients with more evidence of diffuse axonal injury within the adjacent corpus callosum. Taken together, our results demonstrate altered patterns of functional connectivity in cognitive networks following injury. The results support a direct relationship between white matter organization within the brain's structural core, functional connectivity within the default mode network and cognitive function following brain injury. They can be explained by two related changes: a compensatory increase in functional connectivity within the default mode network; and a variable degree of structural disconnection that modulates this change in network function.
创伤性脑损伤常导致认知障碍，限制康复。这些损伤的潜在病理生理学尚不清楚，这限制了临床评估和管理。在这里，我们使用磁共振成像来测试以下假设：（i）创伤性脑损伤导致关键认知网络内的功能连接异常；（ii）这些变化与认知表现相关；（iii）弥漫性轴索损伤引起的结构连接变化影响这些网络内的功能连接。我们研究了 20 名创伤性脑损伤后慢性期患者与年龄匹配的对照组。使用功能磁共振成像详细研究网络功能，分析区域脑激活以及网络内脑区的相互作用（功能连接）。我们在患者执行简单选择反应任务和“休息”时研究他们。由于功能连接反映了潜在的结构连接，因此使用扩散张量成像来量化轴索损伤，并测试结构损伤是否与功能变化相关。与年龄匹配的对照组相比，患者组表现出典型的信息处理和注意力障碍。患者能够准确地完成任务，但反应速度较慢且变化较大。两组任务激活的脑区相似，但患者默认模式网络内的去激活更大，表明认知负荷增加。然后使用静息状态功能磁共振成像的多元分析来研究在没有明确任务表现的情况下是否存在网络功能变化。总的来说，患者组默认模式网络的功能连接增加。功能连接最高的患者认知障碍最小。此外，静息状态下的功能连接也可以预测以后执行任务时的脑激活模式。正如预期的那样，与对照组相比，患者显示出广泛的白质损伤。在相邻胼胝体中弥漫性轴索损伤证据较多的患者中，默认模式网络的功能连接较低。总的来说，我们的研究结果表明，损伤后认知网络的功能连接模式发生了改变。这些结果支持大脑结构核心内的白质组织、默认模式网络内的功能连接以及脑损伤后的认知功能之间的直接关系。它们可以用两个相关的变化来解释：默认模式网络内功能连接的代偿性增加；以及调节这种网络功能变化的结构连接的不同程度。
