Gao Yurui, Xu Lyuan, Schilling Kurt G, Choi Soyoung, Chen Ran, Li Yikang, Li Muwei, Zu Zhongliang, Ding Zhaohua, Anderson Adam W, Gore John C
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA, 37232.
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA, 37235.
Res Sq. 2025 May 7:rs.3.rs-6597153. doi: 10.21203/rs.3.rs-6597153/v1.
There is increasing recognition that blood oxygenation level dependent (BOLD) signals are detectable in white matter (WM) and reflect an important, heretofore overlooked functional activity in the brain, but their biophysical origins remain understudied and poorly understood. By integrating several disparate, multimodal data sets, we established the associations of resting state BOLD signals with key microstructural, hemodynamic and metabolic features in WM. In particular, we identified the roles of myelination and fiber type in modulating BOLD effects, and derived relationships between measurements of BOLD signal power and cerebral blood volume, flow, oxygen extraction and metabolic rate of oxygen consumption, which are predicted using a simple theory and then verified empirically. Our findings demonstrate that myelin selectively influences the fractional amplitude of low-frequency fluctuations (fALFF) in BOLD signals, and that differences in myelin content account for variations in their temporal spectra and hemodynamic response functions, but these in turn are qualitatively different in association versus projection fibers. Other determinants of BOLD in WM are further revealed by converging biological, genomic and neurochemical evidence, including measurements of neurite and mitochondrial densities. Moreover, analyses of images of the optic nerve from human subjects confirm that BOLD activations evoked by visual stimuli are preferentially localized to unmyelinated portions, with minimal responses in fully myelinated regions of the same nerve, suggesting a myelin-dependent requirement for BOLD effects in WM.
人们越来越认识到，在白质（WM）中可检测到血氧水平依赖（BOLD）信号，这些信号反映了大脑中一种重要的、迄今为止被忽视的功能活动，但其生物物理起源仍未得到充分研究且了解甚少。通过整合多个不同的多模态数据集，我们建立了静息态BOLD信号与WM中关键微观结构、血流动力学和代谢特征之间的关联。特别是，我们确定了髓鞘形成和纤维类型在调节BOLD效应中的作用，并推导了BOLD信号功率测量值与脑血容量、血流、氧提取和氧消耗代谢率之间的关系，这些关系通过一个简单理论进行预测，然后通过实验验证。我们的研究结果表明，髓鞘选择性地影响BOLD信号中低频波动的分数振幅（fALFF），髓鞘含量的差异解释了其时间频谱和血流动力学响应函数的变化，但这些变化在联合纤维和投射纤维中在性质上是不同的。WM中BOLD的其他决定因素通过生物学、基因组学和神经化学证据的汇聚进一步揭示，包括神经突和线粒体密度的测量。此外，对人类受试者视神经图像的分析证实，视觉刺激诱发的BOLD激活优先定位于无髓鞘部分，而在同一神经的完全髓鞘化区域中反应最小，这表明WM中BOLD效应存在髓鞘依赖性需求。
