Department of Neuroscience, University of Pisa, Pisa, Italy.
Exp Neurol. 2012 Mar;234(1):169-80. doi: 10.1016/j.expneurol.2011.12.024. Epub 2011 Dec 27.
The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended cortical damage within the motor circuit of ALS patients. The functional changes in non-primary motor cortices pertaining to fronto-parietal circuit suggest an over-recruitment of a pre-existing physiological sensory-motor network. However, the concomitant fronto-parietal cortical atrophy arises the possibility that such a hyper-activation reflects cortical hyper-excitability due to loss of inhibitory inter-neurons.
利用磁共振成像（MRI）技术收集的关于肌萎缩侧索硬化症（ALS）大脑皮质运动损伤的结构和功能数据存在争议。事实上，一些结构 MRI 研究显示，在运动前回的灰质（GM）萎缩病灶，甚至在早期阶段，而其他研究则没有。大多数 ALS 的功能性 MRI（fMRI）研究报告了运动前皮质的过度激活，而在初级运动皮质的激活方面则得到了矛盾的结果。我们旨在通过结构和功能相结合的方法研究 ALS 患者的皮质运动回路。20 名明确诊断为 ALS 的患者和 16 名健康受试者接受了结构检查，采集了 3D T1 加权序列，并在手握力任务中用右手、左手和双手同时执行时进行 fMRI 检查。T1 加权图像通过基于体素的形态测量法（VBM）进行分析，与对照组相比，ALS 患者的皮质 GM 减少了几个簇，包括中央前回和中央后回、额上、中、下回、辅助运动区、顶叶上、中、下回和颞叶，双侧，但右侧更广泛。与对照组相比，ALS 患者初级感觉运动皮质和额背侧运动前区的激活明显降低。VBM 显示的皮质萎缩焦点与激活减少的区域相匹配。fMRI 分析还显示，腹侧运动前额叶区和顶叶皮质的激活增强，与额顶叶运动回路有关，与疾病进展速度相平行，并与皮质萎缩区域相匹配。额顶叶回路的过度激活是不对称的，主要发生在左侧半球。VBM 和 fMRI 确定了 ALS 患者运动回路中扩展的皮质损伤的结构和功能标志物。与额顶叶回路相关的非初级运动皮质的功能变化表明，一个预先存在的生理感觉运动网络的过度招募。然而，同时发生的额顶叶皮质萎缩提出了这样一种可能性，即这种过度激活反映了由于抑制性中间神经元丧失而导致的皮质过度兴奋性。
