Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-University of Frankfurt, Frankfurt, Germany.
Prog Neurobiol. 2011 Dec;95(4):557-69. doi: 10.1016/j.pneurobio.2011.05.008. Epub 2011 Jun 22.
During the last two decades, imaging of neural activation has become an invaluable tool for assessing the functional organization of the human brain in vivo. Due to its widespread application in neuroscience, functional neuroimaging has raised the interest of clinical researchers in its possible use as a diagnostic biomarker. A hallmark feature of many neurodegenerative diseases is their chronic non-linear dynamic and highly complex preclinical course. Neurodegenerative diseases unfold over years to decades through clinically silent and asymptomatic stages of early adaptive, compensatory to pathophysiological (i.e. actively neurodegenerative) and decompensatory mechanisms in the brain - phases that are increasingly being considered as critical for primary and secondary preventive and therapeutic measures. Emerging evidence supports the concept of a potentially fully reversible functional phase that may precede the onset of micro- and macrostructural and cognitive decline, a potentially late-stage "neurodegenerative" phase of a primary neurodegenerative disorder. Alzheimer's disease serves as an ideal model to test this hypothesis supported by the neural network model of the healthy and diseased brain. Being highly dynamic in nature, brain activation and neuronal network functional connectivity represent not only candidate diagnostic but also candidate surrogate markers for interventional trials. Potential caveats of functional imaging are critically reviewed with focus on confound variables such as altered neurovascular coupling as well as parameters related to task- and study design.
在过去的二十年中，神经激活成像已成为评估人类大脑功能组织的一种非常有价值的工具。由于其在神经科学中的广泛应用，功能神经影像学引起了临床研究人员对其作为诊断生物标志物的潜在用途的兴趣。许多神经退行性疾病的一个显著特征是其慢性非线性动态和高度复杂的临床前过程。神经退行性疾病通过临床无症状和无症状的早期适应性、对大脑病理生理（即主动神经退行性）和代偿性机制的代偿、以及失代偿阶段，在数年内展开——这些阶段越来越被认为对原发性和继发性预防和治疗措施至关重要。新出现的证据支持这样一种概念，即可能存在一个完全可逆的功能阶段，该阶段可能先于微观和宏观结构以及认知能力下降的发生，这是原发性神经退行性疾病的潜在晚期“神经退行性”阶段。阿尔茨海默病是检验这一假说的理想模型，该假说得到了健康和患病大脑的神经网络模型的支持。由于其本质上具有高度动态性，大脑激活和神经元网络功能连接不仅代表了候选诊断标志物，也代表了干预试验的候选替代标志物。本文批判性地回顾了功能影像学的潜在局限性，重点关注改变的神经血管耦联等混淆变量以及与任务和研究设计相关的参数。
