Medial temporal contributions to learning, retrieval, and accuracy monitoring in verbal memory

Abstract

AbstractBackgroundVerbal memory profiles are commonly characterized as reflective of frontal or medial temporal dysfunction in clinical practice. Frontal‐subcortical patterns are marked by intrusion errors and impoverished recall that improves with cueing and recognition. However, retrieval deficits, intrusion errors, and impoverished learning are also seen in disorders affecting the medial temporal lobes (MTL), such as Alzheimer’s disease. The aim of the current study was to determine the relative contribution of prefrontal and MTL structural integrity to verbal memory patterns typically attributed to frontal or MTL dysfunction in a mixed neurodegenerative sample.Method1148 participants at the UCSF Memory and Aging Center completed the CVLT‐III‐Short Form, and an MRI (T1‐weighted) scan. Participants varied in neurodegenerative syndrome. 55 functionally intact older adults were included for comparison. MRI analyses focused on a priori regions of interest including dorsolateral prefrontal cortex (DLPFC) and MTL regions (Hippocampus, Parahippocampal Gyrus, and Entorhinal Cortex). Linear regression models assessed the relative contribution of DLPFC and MTL volumes to six CVLT metrics of interest: 1. Benefit from multiple learning trials 2. Learning Slope 3. Cued Recall Gains 4. Total Intrusions 5. Recognition Gains 6. Response Bias.ResultsAlthough participants with smaller DLPFC volumes exhibited a greater benefit from recognition, as would be expected based on commonly characterized frontally‐mediated retrieval deficits, DLPFC volume was not associated with benefit from cueing, intrusions, or response bias. In contrast, patients with smaller MTL volumes benefited less from cued recall and recognition, and the relative contribution of MTL volume was 1.5‐2 times larger than DLPFC. Furthermore, only MTL volume was associated with intrusion errors and benefit from multiple learning trials. Performance was not associated with either region of interest in the control group.ConclusionWhile the current findings support the association between retrieval deficits and prefrontal integrity, they highlight the prominent contribution of MTL to commonly characterized frontal memory deficits, including improvements with repetition, cueing, and recognition. When interpreting verbal memory patterns in neurodegenerative samples, consideration of both PFC and MTL integrity is warranted.