Interindividual Variability In Memory Performance Is Related To Cortico-Thalamic Networks During Memory Encoding And Retrieval

Encoding new memories relies on functional connections between the medial temporal lobe and the frontoparietal cortices. Multi-scan fMRI showed changes in these functional connections before and after memory encoding, potentially influenced by the thalamus. As different thalamic nuclei are interconnected with distinct cortical networks, we hypothesized that variations in cortico-thalamic recruitment may impact individual memory performance. We used a multi-scan fMRI protocol including a resting-state scan followed by an associative memory task encompassing encoding and retrieval phases, in two independent samples of healthy adults (N 1 =29, mean age=26, males=35%; N 2 =108; mean age=28, males=52%). Individual activity and functional connectivity were analyzed in the native space to minimize registration bias. By modeling the direct and indirect effects of cortico-thalamic recruitment on memory using Structural Equation Modeling, we showed a positive association between resting-state functional connectivity of the medial thalamic subdivision within the frontoparietal network and memory performance across samples (effect size R 2 ranging between 0.27 and 0.36; p-values between 0.01 and 4e-05). This direct relationship was mediated by decreased activation of the anterior subdivision during encoding ( R 2 ranging between 0.04 and 0.2; p-values between 0.05 and 0.006) and by increased activation of the medial subdivision during retrieval ( R 2 ranging between 0.04 and 0.2; p-values between 0.05 and 0.004). Moreover, three distinct clusters of individuals displayed different cortico-thalamic patterns across memory phases. We suggest that associative memory encoding relies on the distinct cortico-thalamic pathways involving medial thalamic recruitment and suppression of anterior subdivision to support the successful encoding of new memories. Significance statement Every person is unique in their learning process and related brain functional organization. Prior research has mainly aimed to find shared patterns in how the brain responds to external stimuli, often overlooking individual behavioral differences. We hypothesized that individuals may recruit different neural resources supporting their learning abilities. We investigated whether specific brain configurations are beneficial to individual memory performance. We found that the baseline configuration of select cortico-thalamic networks involving the medial thalamic subdivision supports memory performance via the indirect effects of the anterior thalamic subdivision deactivation and medial activation during the memory task. We propose that cortico-thalamic functioning involving the anterior and medial thalamus underlies interindividual variability in associative memory encoding.