UCL Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AZ, UK; UCL Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
UCL Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AZ, UK; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Haidian District, Beijing 100871, China.
Curr Biol. 2023 Nov 6;33(21):4650-4661.e7. doi: 10.1016/j.cub.2023.09.047. Epub 2023 Oct 11.
Path integration (PI) is impaired early in Alzheimer's disease (AD) but reflects multiple sub-processes that may be differentially sensitive to AD. To characterize these sub-processes, we developed a novel generative linear-angular model of PI (GLAMPI) to fit the inbound paths of healthy elderly participants performing triangle completion, a popular PI task, in immersive virtual reality with real movement. The model fits seven parameters reflecting the encoding, calculation, and production errors associated with inaccuracies in PI. We compared these parameters across younger and older participants and patients with mild cognitive impairment (MCI), including those with (MCI+) and without (MCI-) cerebrospinal fluid biomarkers of AD neuropathology. MCI patients showed overestimation of the angular turn in the outbound path and more variable inbound distances and directions compared with healthy elderly. MCI+ were best distinguished from MCI- patients by overestimation of outbound turns and more variable inbound directions. Our results suggest that overestimation of turning underlies the PI errors seen in patients with early AD, indicating specific neural pathways and diagnostic behaviors for further research.
路径整合（PI）在阿尔茨海默病（AD）早期受损，但反映了多个亚过程，这些亚过程可能对 AD 有不同的敏感性。为了描述这些亚过程，我们开发了一种新的生成线性-角度 PI 模型（GLAMPI），以适应健康老年人在沉浸式虚拟现实中执行三角形完成任务的传入路径，这是一种流行的 PI 任务，使用真实运动。该模型拟合七个参数，反映与 PI 不准确相关的编码、计算和产生误差。我们比较了年轻参与者和老年参与者以及轻度认知障碍（MCI）患者（包括有（MCI+）和没有（MCI-）AD 神经病理学脑脊液生物标志物的患者）之间的这些参数。与健康老年人相比，MCI 患者在传出路径中的角度转弯估计过高，传入距离和方向变化更大。MCI+与 MCI-患者的区别在于，MCI+患者在传出路径的转弯估计过高，传入方向的变化更大。我们的研究结果表明，在早期 AD 患者中，PI 误差的基础是转弯估计过高，这表明存在特定的神经通路和诊断行为，值得进一步研究。
