Franzmeier Nicolai, Göttler Jens, Grimmer Timo, Drzezga Alexander, Áraque-Caballero Miguel A, Simon-Vermot Lee, Taylor Alexander N W, Bürger Katharina, Catak Cihan, Janowitz Daniel, Müller Claudia, Duering Marco, Sorg Christian, Ewers Michael
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität MünchenMunich, Germany.
Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technische Universität MünchenMunich, Germany.
Front Aging Neurosci. 2017 Aug 7;9:264. doi: 10.3389/fnagi.2017.00264. eCollection 2017.
Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.
储备指的是在神经病理学程度不成比例的情况下相对保留认知的现象，例如在阿尔茨海默病中。储备背后假定的功能性神经基质是左侧外侧额叶皮质（LFC，布罗德曼区6/44）的全局功能连接性。静息态功能磁共振成像评估的LFC全局连接性与保护因素（教育）以及轻度认知障碍（MCI）中记忆的更好维持相关。由于LFC是调节其他网络活动的额顶叶控制网络的枢纽，因此问题在于LFC与特定网络而非全脑的连接性是否是储备的基础。我们对24名MCI患者和16名健康对照（HC）以及一个独立验证样本（23名MCI/32名HC）进行了静息态功能磁共振成像评估。计算了基于种子点的LFC与七个主要静息态网络（即额顶叶、边缘系统、背侧注意、躯体运动、默认模式、腹侧注意、视觉）的连接性，储备被量化为在考虑年龄和海马萎缩后的残差记忆表现。在两个MCI样本中，LFC活动与默认模式网络（DMN）呈反相关，但与背侧注意网络（DAN）呈正相关。受教育程度越高，预测的LFC-DMN连接性（反相关）和LFC-DAN连接性越强。更强的LFC-DMN和LFC-DAN连接性各自预测了更高的储备，在两个MCI样本中均一致。未检测到LFC与其他网络连接性的关联。这些新结果扩展了我们之前关于LFC全局功能连接性的发现，表明LFC与两个核心记忆网络DAN和DMN的特定连接性增强了MCI患者记忆领域的储备。
