Behavioral studies investigating fundamental cognitive abilities provide evidence that processing speed accounts for large proportions of performance variability between individuals. Processing speed decline is a hallmark feature of the cognitive disruption observed in healthy aging and in demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica, and Wilson's disease. Despite the wealth of evidence suggesting a central role for processing speed in cognitive decline, the neural mechanisms of this fundamental ability remain unknown. Intact neurovascular coupling, acute localized blood flow increases following neural activity, is essential for optimal neural function. We hypothesized that efficient coupling forms the neural basis of processing speed. Because MS features neural-glial-vascular system disruption, we used it as a model to test this hypothesis. To assess the integrity of the coupling system, we measured blood-oxygen-level-dependent (BOLD) signal in healthy controls (HCs) and MS patients using a 3T MRI scanner while they viewed radial checkerboards that flickered periodically at 8 Hz. To assess processing speed and cognitive function, we administered a battery of neuropsychological tests. While MS patients exhibited reduced ΔBOLD with reductions in processing speed, no such relationships were observed in HCs. To further investigate the mechanisms that underlie ΔBOLD-processing speed relationships, we assessed the physiologic components that constitute ΔBOLD signal (i.e., cerebral blood flow, ΔCBF; cerebral metabolic rate of oxygen, ΔCMRO2; neurovascular coupling ratio) in speed-preserved and -impaired MS patients. While ΔCBF and ΔCMRO2 showed no group-differences, the neurovascular coupling ratio was significantly reduced in speed-impaired MS patients compared to speed-preserved MS patients. Together, these results suggest that neurovascular uncoupling might underlie cognitive slowing in MS and might be the central pathogenic mechanism governing processing speed decline.

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人类处理速度差异的神经血管基础：使用多发性硬化症的模型系统方法

调查基本认知能力的行为研究提供的证据表明，处理速度在个体之间的表现差异中占很大比例。处理速度下降是在健康老龄化和脱髓鞘疾病（如多发性硬化症 (MS)、视神经脊髓炎和威尔逊病）中观察到的认知障碍的标志性特征。尽管有大量证据表明处理速度在认知能力下降中起着核心作用，但这种基本能力的神经机制仍然未知。完整的神经血管耦合、急性局部血流量随着神经活动而增加，对于最佳神经功能至关重要。我们假设有效耦合构成了处理速度的神经基础。因为 MS 具有神经-胶质-血管系统破坏的特征，我们用它作为模型来检验这个假设。为了评估耦合系统的完整性，我们使用 3T MRI 扫描仪测量了健康对照 (HC) 和 MS 患者的血氧水平依赖性 (BOLD) 信号，同时他们查看了以 8 Hz 周期性闪烁的径向棋盘格。为了评估处理速度和认知功能，我们进行了一系列神经心理学测试。虽然 MS 患者表现出随着处理速度降低而降低的 ΔBOLD，但在 HC 中没有观察到这种关系。为了进一步研究 ΔBOLD 处理速度关系背后的机制，我们评估了构成 ΔBOLD 信号的生理成分（即脑血流量，ΔCBF；脑氧代谢率，ΔCMRO2；神经血管耦合比）多发性硬化症患者。虽然 ΔCBF 和 ΔCMRO2 没有显示出组间差异，但与保持速度的 MS 患者相比，速度受损的 MS 患者的神经血管耦合率显着降低。总之，这些结果表明神经血管解偶联可能是 MS 认知减慢的基础，并且可能是控制处理速度下降的主要致病机制。