Alderson Thomas, Kehoe Elizabeth, Maguire Liam, Farrell Dervla, Lawlor Brian, Kenny Rose A, Lyons Declan, Bokde Arun L W, Coyle Damien
Intelligent Systems Research Centre, University Ulster, Derry, United Kingdom.
Trinity College Institute of Neuroscience and Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Front Aging Neurosci. 2017 Nov 8;9:370. doi: 10.3389/fnagi.2017.00370. eCollection 2017.
Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adults with aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impaired thalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.
阿尔茨海默病（AD）及其前驱状态遗忘型轻度认知障碍（aMCI）的特征是区域间白质纤维通路广泛异常，以及默认模式网络（DMN）静息态功能连接和有效连接的并行破坏。在健康受试者中，DMN与任务阳性网络的相互作用受丘脑调节，这表明aMCI中基于任务的DMN失活异常可能是丘脑 - 皮质白质回路受损的结果。因此，本文采用多模态方法来评估健康对照（HCs）相对于aMCI患者丘脑与DMN组件之间的白质完整性以及相关的有效连接。26名HC和20名患有aMCI的老年人使用高角分辨率扩散加权采集协议进行了结构、功能和扩散MRI扫描。使用独立成分分析（ICA）识别每个受试者的DMN，并计算丘脑与DMN节点之间的静息态有效连接。采用约束球面反卷积（CSD）纤维束成像研究丘脑与DMN之间的白质完整性变化。发现丘脑白质投射纤维至后DMN组件后扣带回皮质（PCC）和外侧顶下叶（IPL）存在明显的结构缺陷，同时从左丘脑到左IPL的有效连接显著降低。至关重要的是，丘脑 - 皮质白质回路受损与记忆表现相关。丘脑 - 皮质结构破坏伴随着IPL和PCC皮质 - 皮质有效连接的显著降低。在DMN节点之间未发现结构缺陷。DMN后部异常活动可能由丘脑白质连接变化驱动；AD病理学影响的丘脑核与DMN后部节点之间紧密的解剖学和功能关联支持了这一观点。我们得出结论，aMCI中功能失调的DMN后部活动与皮质 - 丘脑 - 皮质处理中断以及基于丘脑的海马疾病因子向皮质枢纽的传播一致。
