Integrated Program in Neuroscience, McGill University, Montréal, Quebec H3A 1A1, Canada.
Douglas Mental Health University Institute, Verdun, Quebec H4H 1R3, Canada.
J Neurosci. 2023 Dec 13;43(50):8756-8768. doi: 10.1523/JNEUROSCI.0663-23.2023.
Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife. This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.
随着年龄的增长，女性的编码和提取丰富空间情境细节的能力（情节记忆）会明显下降，而大多数女性正是在中年时期经历自然绝经。然而，关于绝经状态如何影响中年绝经前和绝经后女性在编码和提取时与情节记忆相关的大脑活动，以及观察到的任何大脑活动和记忆表现的组间差异是否与组内的实际年龄相关，我们知之甚少。我们进行了一项与情景记忆相关的事件相关任务 fMRI 研究，以解决这一知识空白。多变量行为偏最小二乘法被用于研究 31 名绝经前女性（年龄范围为 39.55-53.30 岁；平均年龄为 44.28 岁；年龄标准差为 3.12 岁）和 41 名绝经后女性（年龄范围为 46.70-65.14 岁；平均年龄为 57.56 岁；年龄标准差为 3.93 岁）的大脑活动与年龄和检索准确性的相关性。我们发现，绝经后状态以及绝经后的年龄增长与较低的空间情境记忆有关。fMRI 分析表明，只有在绝经后女性中，年龄的增长与编码和提取过程中枕颞叶、海马旁回和顶下小叶皮质活动的减少以及较差的空间情境记忆表现有关。相比之下，只有绝经前女性在角回、中线皮质区域和前额叶皮质的编码和提取活动中存在重叠，与更好的空间情境检索准确性相关。这些结果强调了绝经状态和中年时的实际年龄如何影响情景记忆及其神经相关性。这是第一项研究绝经前和绝经后状态如何影响情景记忆编码和提取的神经相关性，以及实际年龄如何影响任何观察到的组间相似性和差异性的 fMRI 研究。我们发现，绝经状态（内分泌年龄）和实际年龄都会影响空间情境记忆及其神经相关性。绝经状态直接影响了在编码和提取过程中，顶下小叶、海马旁回和枕颞叶皮质的与年龄相关和与表现相关的相关性的方向。此外，我们发现只有绝经前女性在提取时，中线皮质、前额叶和角回的编码相关活动会出现皮质再现。这表明，与绝经后相比，绝经前的空间情境记忆能力可能依赖于不同的大脑系统。
