van Nieuwenhuizen Helena, Chesebro Anthony G, Polizu Claire, Clarke Kieran, Strey Helmut H, Weistuch Corey, Mujica-Parodi Lilianne R
Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY, 11790, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Imaging Neurosci (Camb). 2024;2. doi: 10.1162/imag_a_00163. Epub 2024 May 8.
Aging is associated with impaired signaling between brain regions when measured using resting-state fMRI. This age-related destabilization and desynchronization of brain networks reverses itself when the brain switches from metabolizing glucose to ketones. Here, we probe the mechanistic basis for these effects. First, we confirmed their robustness across measurement modalities using two datasets acquired from resting-state EEG (: standard diet, 20-80 years, N = 201; : individually weight-dosed and calorically-matched glucose and ketone ester challenge, , N = 36). Then, using a multiscale conductance-based neural mass model, we identified the unique set of mechanistic parameters consistent with our clinical data. Together, our results implicate potassium (K) gradient dysregulation as a mechanism for age-related neural desynchronization and its reversal with ketosis, the latter finding of which is consistent with direct measurement of ion channels. As such, the approach facilitates the connection between macroscopic brain activity and cellular-level mechanisms.
使用静息态功能磁共振成像（fMRI）测量时，衰老与脑区之间信号传递受损有关。当大脑从代谢葡萄糖转变为代谢酮体时，这种与年龄相关的脑网络不稳定和去同步化会自行逆转。在此，我们探究这些效应的机制基础。首先，我们使用从静息态脑电图（EEG）获取的两个数据集（：标准饮食，20 - 80岁，N = 201；：个体化体重给药且热量匹配的葡萄糖和酮酯激发试验，，N = 36），证实了它们在不同测量方式下的稳健性。然后，使用基于多尺度电导的神经团块模型，我们确定了与我们的临床数据一致的独特机制参数集。总之，我们的结果表明钾（K）梯度失调是与年龄相关的神经去同步化及其通过酮症逆转的一种机制，后者的发现与离子通道的直接测量结果一致。因此，该方法有助于宏观脑活动与细胞水平机制之间的联系。
