A hippocampal-anterior thalamic circuit associated with learning rate in ageing

Memory normally declines with ageing and these age-related cognitive changes are associated with changes in brain structure. Episodic memory retrieval has been widely studied during ageing, whereas learning has received less attention. Here we examined the neural correlates of learning rate in ageing. Our study sample consisted of 982 cognitively healthy female and male older participants from the Vallecas Project cohort, without a clinical diagnosis of mild cognitive impairment or dementia. The learning rate across three consecutive verbal memory (Free and Cued Selective Reminding Test) recall trials was used as a predictor of grey matter (GM) and white matter (WM) volume using voxel-based morphometry, and WM microstructure using tract-based spatial statistics on fractional anisotropy (FA) and mean diffusivity (MD) measures. Immediate recall improved by 1.4 items per trial on average, and this learning rate was faster in women and negatively associated with age. Structurally, hippocampal and anterior thalamic GM volume correlated positively with learning rate. Learning also correlated with the integrity of WM microstructure (high FA and low MD) in an extensive network of tracts including bilateral anterior thalamic radiation, fornix, and long-range tracts. These results suggest that structural GM and WM characteristics, centred on a hippocampal-anterior thalamic circuit, support learning capacity in ageing. Specifically, reduced volume and microstructure may explain some of the age-related memory deficits that result from impaired learning. Significance statement A detailed understanding of age-related memory changes is crucial in an increasingly ageing population, in which memory decline is prevalent. Whilst memory performance is usually quantified by the ability to correctly retrieve information, memory impairment could be caused by a reduced ability to learn or encode information. In a cohort of cognitively healthy ageing participants, we found an association between verbal learning rate and grey matter volume and white matter microstructure in the limbic system. These findings establish the neural underpinnings of the often-overlooked learning phase of the memory process and have important implications for our understanding of neurobiological changes in healthy ageing and their cognitive phenotypes. ### Competing Interest Statement The authors have declared no competing interest.