Neuropsychology and Neuroscience Laboratory, Kessler Foundation Research Center, 300 Executive Drive, Suite 70, West Orange, NJ 07052, USA.
Mult Scler. 2013 Feb;19(2):199-208. doi: 10.1177/1352458512448267. Epub 2012 Jun 8.
Patients with multiple sclerosis (MS) suffer memory impairment but the link between MS-related neuroanatomical changes (brain atrophy) and memory is relatively weak.
The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate task-induced default network (DN) deactivation as a neurophysiologic biomarker of memory functioning in MS.
Twenty-eight MS patients underwent high-resolution MRIs to measure brain atrophy (third ventricle width, cerebral gray matter, cerebral white matter, parenchymal fraction, and thalamic, caudate, hippocampal, and amygdala volumes), and fMRI blood oxygen level dependent (BOLD) signal to measure DN deactivation during sustained attention relative to rest. Neuropsychological assessment of episodic memory was performed on a separate day. We used hierarchical regression to predict memory, with age, education, and depression in step one, brain atrophy within step two, DN activity within step three, and the interaction between brain atrophy and DN activity in step four.
Brain atrophy predicted worse memory but DN activity independently predicted memory over-and-above measurements of brain atrophy (R (2)=0.108), with greater DN activity (lesser deactivation) linked to better memory. A significant brain atrophy by DN activity interaction indicated a stronger relationship between memory and DN activity among patients with more advanced disease, at which point higher DN activity protects patients from disease/atrophy-related memory impairment. To establish specificity, we showed no relationship between DN activity and non-memory cognition, and no relationship between non-DN brain activity and memory.
Maintenance of DN activity during sustained attention was supported as a sensitive and specific neurophysiologic biomarker of episodic memory functioning in MS, even when controlling for neuroanatomical changes (brain atrophy).
多发性硬化症（MS）患者会出现记忆障碍，但 MS 相关神经解剖变化（脑萎缩）与记忆之间的联系相对较弱。
本研究旨在使用功能磁共振成像（fMRI）来研究任务诱发的默认网络（DN）去激活作为 MS 患者记忆功能的神经生理生物标志物。
28 名 MS 患者接受了高分辨率 MRI 检查，以测量脑萎缩（第三脑室宽度、脑灰质、脑白质、实质分数以及丘脑、尾状核、海马和杏仁核体积），以及 fMRI 血氧水平依赖（BOLD）信号，以测量与休息相比持续注意力期间的 DN 去激活。在另一天进行了情景记忆的神经心理学评估。我们使用分层回归来预测记忆，在第一步中使用年龄、教育和抑郁，在第二步中使用脑萎缩，在第三步中使用 DN 活性，在第四步中使用脑萎缩和 DN 活性的相互作用。
脑萎缩预测记忆更差，但 DN 活性独立于脑萎缩测量值预测记忆（R²=0.108），DN 活性更高（去激活程度更低）与记忆更好相关。脑萎缩与 DN 活性的显著相互作用表明，在疾病更严重的患者中，记忆与 DN 活性之间的关系更强，此时更高的 DN 活性可保护患者免受疾病/萎缩相关的记忆障碍。为了建立特异性，我们表明 DN 活性与非记忆认知之间没有关系，非-DN 脑活动与记忆之间也没有关系。
即使在控制神经解剖变化（脑萎缩）的情况下，持续注意力期间 DN 活性的维持也支持作为 MS 患者情景记忆功能的敏感和特异性神经生理生物标志物。
