Hohenfeld Christian, Nellessen Nils, Dogan Imis, Kuhn Hanna, Müller Christine, Papa Federica, Ketteler Simon, Goebel Rainer, Heinecke Armin, Shah N Jon, Schulz Jörg B, Reske Martina, Reetz Kathrin
Department of Neurology, RWTH Aachen University, Aachen, Germany.
Institute of Neuroscience and Medicine (INM-4, 6), Research Centre Jülich GmbH, Jülich, Germany.
Front Neurol. 2017 Aug 9;8:384. doi: 10.3389/fneur.2017.00384. eCollection 2017.
Cognitive decline is characteristic for Alzheimer's disease (AD) and also for healthy ageing. As a proof-of-concept study, we examined whether this decline can be counteracted using real-time fMRI neurofeedback training. Visuospatial memory and the parahippocampal gyrus (PHG) were targeted.
Sixteen healthy elderly subjects (mean age 63.5 years, SD = 6.663) and 10 patients with prodromal AD (mean age 66.2 years, SD = 8.930) completed the experiment. Four additional healthy subjects formed a sham-feedback condition to validate the paradigm. The protocol spanned five examination days (T1-T5). T1 contained a neuropsychological pre-test, the encoding of a real-world footpath, and an anatomical MRI scan of the brain. T2-T4 included the fMRI neurofeedback training paradigm, in which subjects learned to enhance activation of the left PHG while recalling the path encoded on T1. At T5, the neuropsychological post-test and another anatomical MRI brain scan were performed. The neuropsychological battery included the Montreal Cognitive Assessment (MoCA); the Visual and Verbal Memory Test (VVM); subtests of the Wechsler Memory Scale (WMS); the Visual Patterns Test; and Trail Making Tests (TMT) A and B.
Healthy elderly and patients with prodromal AD showed improved visuospatial memory performance after neurofeedback training. Healthy subjects also performed better in a working-memory task (WMS backward digit-span) and in the MoCA. Both groups were able to elicit parahippocampal activation during training, but no significant changes in brain activation were found over the course of the training. However, Granger-causality-analysis revealed changes in cerebral connectivity over the course of the training, involving the parahippocampus and identifying the precuneus as main driver of activation in both groups. Voxel-based morphometry showed increases in grey matter volumes in the precuneus and frontal cortex. Neither cognitive enhancements, nor parahippocampal activation were found in the control group undergoing sham-feedback.
These findings suggest that cognitive decline, either related to prodromal AD or healthy ageing, could be counteracted using fMRI-based neurofeedback. Future research needs to determine the potential of this method as a treatment tool.
认知衰退是阿尔茨海默病（AD）以及健康衰老的特征。作为一项概念验证研究，我们考察了是否可以使用功能磁共振成像神经反馈训练来对抗这种衰退。研究针对视觉空间记忆和海马旁回（PHG）。
16名健康老年人（平均年龄63.5岁，标准差=6.663）和10名前驱期AD患者（平均年龄66.2岁，标准差=8.930）完成了该实验。另外4名健康受试者组成假反馈组以验证该范式。实验方案涵盖五个检查日（T1 - T5）。T1包含神经心理学预测试、一条现实世界人行道的编码以及脑部解剖磁共振成像扫描。T2 - T4包括功能磁共振成像神经反馈训练范式，在此过程中受试者学习在回忆T1编码的路径时增强左侧PHG的激活。在T5，进行神经心理学后测试以及另一项脑部解剖磁共振成像扫描。神经心理学测试组合包括蒙特利尔认知评估（MoCA）；视觉和言语记忆测试（VVM）；韦氏记忆量表（WMS）的子测试；视觉模式测试；以及连线测验（TMT）A和B。
健康老年人和前驱期AD患者在神经反馈训练后视觉空间记忆表现有所改善。健康受试者在工作记忆任务（WMS倒序数字广度）和MoCA测试中也表现得更好。两组在训练期间均能够引发海马旁回激活，但在训练过程中未发现脑激活有显著变化。然而，格兰杰因果分析显示在训练过程中大脑连接性发生了变化，涉及海马旁回，并确定楔前叶是两组激活的主要驱动因素。基于体素的形态学测量显示楔前叶和额叶皮质的灰质体积增加。接受假反馈的对照组未发现认知增强或海马旁回激活。
这些发现表明，无论是与前驱期AD相关还是与健康衰老相关的认知衰退，都可以通过基于功能磁共振成像的神经反馈来对抗。未来的研究需要确定这种方法作为一种治疗工具的潜力。
