健康与遗传心理学研究室知识库

目的：正常老化往往伴随多种认知功能衰退，其中情节记忆是受老化影响最严重的认知功能之一。前额叶(尤其是背外侧前额叶，DLPFC)是负责情节记忆的主要脑区之一，该脑区的神经结构和功能改变是情节记忆老化的神经基础。从脑结构上看，老年人大脑灰质体积萎缩，白质连接完整性下降，其中表现最明显的是前额叶。从脑功能上看，在进行认知任务时，老年人局部脑区出现过度激活现象，这种现象可能反映的是大脑功能对认知功能的补偿机制。然而，老年人大脑保留一定可塑性。例如，以往研究发现认知干预可以提高老年人行为成绩，同时促进其大脑结构、功能改变。此外，经颅直流电刺激(tDCS)作为一种非侵入式无创性脑刺激技术，逐渐引起研究者的关注。该技术可以通过调节目标脑区的神经元活动，进而改善认知功能。尽管已有证据表明，tDCS刺激前额叶皮层可以提高老年人情节记忆成绩，但现有研究仍然存在不一致的结果。更重要的是，已有研究只观察了行为表现的变化，对于tDCS影响情节记忆潜在的脑机制尚未有关注。

方法：本研究结合横断元分析研究和纵向干预研究，从行为和脑的层面，深入探讨了tDCS是否能促进健康老年人情节记忆及其脑机制。研究一检索并汇总现有的探讨tDCS与老年人情节记忆关系的研究，通过定量元分析考察tDCS的记忆促进效果，以及其中的调节因素。研究二至研究五采用严格的随机对照试验，对健康老年人的左侧DLPFC实施为期10天的tDCS神经调控，通过一系列记忆行为指标和脑功能、脑结构指标，系统探讨tDCS干预能否改善健康老年人记忆功能，以及潜在的神经机制。

结果：研究一的结果显示，tDCS对健康老年人和临床群体老年人的记忆功能均有积极的提升作用，效果具有保持性。效应量会受到被试群体的年龄以及电极面积、电流强度、刺激时机、刺激偏侧性等参数的影响。研究二考察了tDCS干预对老年人记忆成绩的影响，结果显示，tDCS显著提高了项目记忆和联结记忆成绩，干预效果能维持至少三个月。研究三考察了tDCS干预对情节记忆提取阶段大脑神经活动的影响，发现干预之后老年人DLPFC及附近的前额叶区域、入探讨了tDCS是否能促进健康老年人情节记忆及其脑机制。研究一检索并汇总现有的探讨tDCS与老年人情节记忆关系的研究，通过定量元分析考察tDCS的记忆促进效果，以及其中的调节因素。研究二至研究五采用严格的随机对照试验，对健康老年人的左侧DLPFC实施为期10天的tDCS神经调控，通过一系列记忆行为指标和脑功能、脑结构指标，系统探讨tDCS干预能否改善健康老年人记忆功能，以及潜在的神经机制。

结果：研究一的结果显示，tDCS对健康老年人和临床群体老年人的记忆功能均有积极的提升作用，效果具有保持性。效应量会受到被试群体的年龄以及电极面积、电流强度、刺激时机、刺激偏侧性等参数的影响。研究二考察了tDCS干预对老年人记忆成绩的影响，结果显示，tDCS显著提高了项目记忆和联结记忆成绩，干预效果能维持至少三个月。研究三考察了tDCS干预对情节记忆提取阶段大脑神经活动的影响，发现干预之后老年人DLPFC及附近的前额叶区域、前扣带回在记忆提取时激活强度增加，激活强度变化值与记忆成绩增益正相关。研究四考察tDCS干预对老年人静息状态下大脑功能连接的影响，发现干预之后位于大脑前部的种子点与大脑后部皮层，尤其是默认网络的功能连接下降，连接变化值与记忆成绩增益负相关。研究五考察tDCS干预对老年人大脑结构的影响，发现干预之后大脑内侧前额叶和额中回区域灰质体积增加，体积变化值和记忆成绩增益正相关。

结论：老年人大脑具有可塑性，tDCS可以调节记忆提取时的大脑神经活动、大尺度脑网络间功能连接，并延缓大脑灰质结构萎缩，从而改善老年人情节记忆功能。

Objective: Normal aging is accompanied by a variety of cognitive decline, and episodic memory is one of the most seriously disrupted cognitive functions by aging. The prefrontal cortex, especially the dorsal lateral prefrontal cortex (DLPFC), is the core region responsible for episodic memory. The impairment of episodic memory is generally attributed to declines in structure and functioning of the prefrontal cortex. Regard to the structure of the aging brain, the volume of gray matter shrinkage and the white matter integrity is disconnection. Regard to the functioning of the aging brain, older adults show regional overactivation than younger adults during cognitive tasks, which may signal functional compensation for cognition. Fortunately, the aging brain retains plasticity. Effective cognitive interventions can improve the cognitive and brain functions in the elderly. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation, which can be used to improve cognitive function by modulating the neural activity in target regions. Though previous studies have provided supporting evidence that tDCS on the prefrontal cortex enhanced episodic memory in older subjects, the existing literature is inconsistent. More importantly, it remains unclear that how tDCS modulates the brain of structure and functioning involved in episodic memory tasks.

Methods: The present study investigated the effects of tDCS on episodic memory and its underlying mechanisms by using cross-sectional meta-analysis and interventional data. Study 1 as a meta-analysis, summarized the existing studies and aimed to provide a quantitative assessment of the efficacy of tDCS on modulating memory functions in the elderly. The modulator factors that influenced the efficacy of tDCS were also analyzed. Studies 2 - 5 conducted a rigid randomized controlled trial design for the intervention study, in which healthy older adults received either 10 sessions of anodal or sham stimulation over the left DLPFC. A series of behavior and neuroimaging data were collected to systematically assess the behavioral and neural consequences of multiple-session tDCS in older adults.

Results: In study 1, compared to the sham group, the tDCS group obtained significant memory improvements for both healthy and clinical groups. The improvement of performance can last for a long time. Effects of tDCS were moderated by age of participants, the area of the electrode surface, stimulation laterality, stimulation timing, and current intensity. Study 2 explored the effect of tDCS on the memory performance as well as its lasting effect. Results showed that compared with the control group, older adults in the intervention group indicated greater item and associative memory gains. The improvement could be detected three months later. Study 3 investigated the impact of tDCS on neural activity. The fMRI results revealed that the intervention group increased regional brain activity during memory retrieval in the DLPFC and other prefrontal cortex as well as the anterior cingulate cortex. The improvement in neural activity positively correlated with memory enhancement. Study 4 investigated the impact of tDCS on functional connectivity, demonstrating that the connectivity between the prefrontal cortex and the posterior brain, especially the default mode network, decreased after tDCS. The decreased connectivity values negatively correlated with memory improvement. Study 5 explored the influence of tDCS on the volume of gray matter and found that the volume in the bilateral prefrontal cortex increased following tDCS. The increased volume was positively correlated with memory enhancement.

Conclusion: The aging brain is malleable. tDCS provides a promising approach to improve episodic memory performance in healthy older adults, by modulating brain activity related to memory processing and functional connectivity of large-scale brain network, as well as brain structure.