Putamen Stiffness Declines with Age and Is Associated with Implicit Sequence Learning Outcomes

Background/Objectives: Sequence learning, the ability to pick up on regularities in our environment to facilitate behavior, is critically dependent on striatal structures in the brain, with the putamen emerging as a critical hub for implicit sequence learning. As the putamen is known to shrink with age, and age-related declines in sequence learning abilities are common, it has been hypothesized that the structural integrity of the putamen is likely related to sequence learning outcomes. However, the structural literature is sparse. One reason may be that traditional structural imaging measures, like volume, are not sufficiently sensitive to measure changes that are related to performance outcomes. We propose that magnetic resonance elastography (MRE), an emerging neuroimaging tool that provides quantitative measures of microstructural integrity, may fill this gap. Methods: In this study, both sequence learning abilities and the structural integrity of the putamen were assessed in 61 cognitively healthy middle-aged and older adults (range: 45–78 years old). Sequence learning was measured via performance on the Serial Reaction Time Task. Putamen integrity was assessed in two ways: first, via standard structural volume assessments, and second, via MRE measures of tissue integrity. Results: Age significantly correlated with both putamen volume and stiffness but not sequence learning scores. While sequence learning scores did not correlate with volume, MRE-derived measures of putamen stiffness were significantly correlated with learning outcomes such that individuals with stiffer putamen showed higher learning scores. A series of control analyses were performed to highlight the specificity and sensitivity of this putamen stiffness–sequence learning relationship. Conclusions: Together these data indicate that microstructural changes that occur in the putamen as we age may contribute to changes in sequence learning outcomes.