Moore Tara L, Medalla Maria, Iba Ez Sara, Wimmer Klaus, Mojica Chromewell A, Killiany Ronald J, Moss Mark B, Luebke Jennifer I, Rosene Douglas L
bioRxiv. 2023 Feb 8:2023.02.07.527321. doi: 10.1101/2023.02.07.527321.
Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age and these impairments correlate with changes in biophysical properties of L3 pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of Layer 3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.
与年龄相关的认知能力下降在人类和恒河猴中早在中年就会出现。具体而言,老年人在执行功能(EF)和工作记忆(WM)任务上的表现具有错误频率更高、记忆跨度更短、持续性反应频率增加、反馈利用受损以及处理速度降低等特点。然而,衰老如何精确地对这些认知功能的特定方面产生不同影响,以及介导认知的不同脑区如何受到影响,目前还不太清楚。已知前额叶皮层(PFC)介导EF和WM,并且是一个容易受到与年龄相关的神经元形态改变影响的区域。在当前的研究中,我们表明EF和WM任务的表现随年龄出现了显著变化,并且这些损伤与外侧前额叶皮层(LPFC)第3层锥体神经元的生物物理特性变化相关。具体来说,与之前的研究一致,LPFC第3层锥体神经元的兴奋性随年龄显著增加。此外,LPFC神经元这种与年龄相关的过度兴奋性与WM任务中与年龄相关的表现下降显著相关,但与EF任务无关。当前的研究描述了与年龄相关的WM和EF任务表现,并深入探讨了可能是WM和EF随年龄变化基础的神经基质。