Abstract: Mnemonic discrimination (MD) refers to the ability to accurately distinguish similar memory experiences. Currently, mnemonic similarity task (MST) is commonly employed to measure and study MD. Previous neuroimaging studies have shown that MD relies on a neural computing mechanism known as pattern separation, which enables the transformation of similar and overlapping input patterns into distinctive representations.
Extensive research has long been focused on exploring the contribution of the hippocampus to MD and pattern separation, particularly emphasizing the roles of the dentate gyrus and CA3 subfields within the hippocampus. However, recent years have yielded a compilation of insights indicating that pattern separation is not only dependent on the hippocampus, but rather a concerted effort involving multiple structures within the medial temporal lobe. The processing of highly overlapping information begins prior to hippocampal engagement, with object-related information traversing the perirhinal and lateral entorhinal cortices, while spatial or contextual information navigating the parahippocampal and medial entorhinal cortices. Here, initial separation occurs, promoting subsequent pattern separation within the hippocampal DG/CA3 subregion. Additionally, we have also come to understand that MD could be supported by large-scale brain networks. Besides pattern separation, the occipital regions play a crucial role in fine-grained perceptual representation, while the prefrontal cortex is essential for monitoring and cognitive control, both of which are also vital for achieving MD.
The elderly tend to exhibit a noticeable decline in MD due to aging and aging-related pathologies. Previous studies have demonstrated that hippocampal dysfunction significantly contributes to this deficit. Early disruptions of hippocampal microstructure and progressive atrophy of the DG/CA3 subfields are closely linked to the decline of MD. Furthermore, the hyperactivation of the DG/CA3 subregions due to reduced neural efficiency, as well as abnormal functional connectivity between the hippocampus and other medial temporal lobe structures, could also exacerbate this decline. Aging-related changes in other brain regions, such as hypoactivation in the entorhinal cortex, fiber loss of the perforant path, damage to structural and functional integrity of the prefrontal cortex, along with alterations in functional connectivity within the default mode network, are also associated with the decline of MD. In addition, given its reliance on the medial temporal lobe, MD can reflect abnormal brain structural damage and functional deterioration in the early stages of cognitive impairment. This enables MST to hold significant potential in early identification of cognitive impairment.
To further explore the causes of the decline of MD in the elderly, future studies should employ more advanced imaging techniques like ultra-high field functional magnetic resonance imaging technology to separately investigate the impact of aging in the DG and CA3 subregions on MD. It is also critical to research more about the cognitive neural mechanisms underlying the impact of neocortical dysfunction on MD, with a particular focus on age-related changes in cortical-hippocampal interaction mechanisms. Large-scale prospective cohorts should also be established to validate the effectiveness of MST in early identification of cognitive impairment.

Key words: mnemonic discrimination, pattern separation, aging, cognitive neural mechanism, cognitive impairment