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Improvements in the learning rate of the Verbal Memory Transfer task, but not the Navigation Transfer task, were found to correlate with lateral hippocampal volume but not with anterior and posterior hippocampus (using average volume between pre and post-test).

Consistent findings were obtained when analyzing hemispheric hippocampal volumes (see MTL subregions and either the average number Appendix 3—figure 3). Specifically, a significant positive correlation was observed between the learning rate in the Verbal Memory group and both left hippocampal volume (r(23) = 0.568, p-FDR=.014) and right hippocampal volume (r(23) = 0.601, p-FDR=.007), while no significant correlations were found for the Navigation (left: r(25) = 0.038, p-FDR=0.858; right: r(25) = 0.008, p-FDR=0.970) or Video Control group (left: r(19) = –0.123, p-FDR=0.858; right: r(19) = –0.163, p=0.758), after controlling for sex and site as covariates. Fisher’s z-tests revealed that the positive correlation in the Verbal Memory group was significantly stronger than that in the Navigation group even after controlling for sex and site (left hippocampus: Z=1.942, p-FDR=0.039; right hippocampus: Z=2.326, p-FDR=0.015) and Video Control group (left hippocampus: Z=2.234, p-FDR=0.038; right hippocampus: Z=2.702, p-FDR=0.010) while no significant difference was observed between the Navigation group and Video Control group (left hippocampus: Z=–0.439, p=0.669; right hippocampus: Z=–0.553, p-FDR=0.710).

An analysis was conducted to assess the correlation between anterior and posterior hippocampal volumes and changes in learning rate on the verbal memory transfer task. However, the improvement in learning rate demonstrated no significant correlation with either anterior or posterior hippocampal volume in any of the three groups (ps >0.232, Appendix 2—table 4). This lack of correlation remained consistent after accounting for the influence of sex and site as covariates (ps >0.114).

We also correlated hippocampal volume and MTL subregions with the change in the average number of words recalled, number of trials to criterion, and slope from linear regression (see Appendix 1) between the post-test and pre-test for the verbal memory transfer task. The analysis revealed no significant correlations between hippocampal volume or MTL subregions and either the average number of words recalled or the number of trials to criterion (Appendix 2—tables 6 and 7), regardless of whether sex and site were included as covariates. However, when correlating slope with hippocampal volume, a positive correlation was found for the Verbal Memory group (total hippocampal volume: r=0.552, p=0.006; left hippocampus: r=0.502, p=0.015;right hippocampus: r=0.561, p=0.005, Appendix 2—table 8), however, no such correlation was found for the Navigation group (total hippocampus: r=0.094, p=0.656; left hippocampus: r=0.114, p=0.586; right hippocampus: r=0.073, p=0.727) and Video Control (total hippocampus: r=–0.239, p=0.325; left hippocampus: r=–0.217, p=0.372; right hippocampus: r=–0.238, p=0.326) even after controlling for sex and site as covariates.

We also correlated hippocampal volume with the change in learning rate from the post-test and pre-test for the navigation transfer task. No significant correlations were found between total hippocampal volume and changes in learning rate in any of the three conditions (Navigation: r(25) = –0.27, p=0.181; Verbal Memory: r(24) = –0.31, p=0.129; Video Control: r(17) = 0.124, p=0.612), regardless of whether sex and site were included as covariates. Similar no significant correlations were observed for both left hippocampal volume (Navigation: r(25) = –0.25, p=0.214; Verbal Memory: r(24) = –0.29, p=0.160; Video Control: r(17) = 0.25, p=0.310) and right hippocampal volume (Navigation: r(25) = –0.27, p=0.167; Verbal Memory: r(24) = –0.302, p=0.142; Video Control: r(17) = –0.018, p=0.940), regardless of whether sex and site were included as covariates. We also did not find any significant correlations when examining hippocampal subfields or surrounding MTL subregions (p’s>0.20, Appendix 2—table 5).

The relationship between total hippocampal volume, MTL subregion volumes, and changes in performance on the navigation transfer task was assessed through correlational analyses, focusing on path error, overall pointing error, between-environment pointing error, within-environment pointing error, and map accuracy. These analyses demonstrated a lack of significant associations between hippocampal volume and MTL subregions and any of the behavioral metrics under consideration (Appendix 2—table 9, Appendix 2—tables 10–13), regardless of the inclusion of sex and site as covariates.

Improvements in the learning rate of the Verbal Memory Transfer task, but not the Navigation Transfer task, were found to correlate with both total hippocampal volume and the volume of the CA2/3/DG subfield (using volume data only from the pre-test). We examined the hypothesis that baseline hippocampal volume might be associated with either verbal or navigation performance. For this analysis, we utilized the hippocampal volume (or subfield volume) obtained for each participant at pre-test, rather than averaging volumes across pre and post-test. We then assessed the relationship between hippocampal volumes at pre-test and the change in learning rate from pre-test to post-test for both the Verbal Memory transfer task and the Navigation Transfer task.

We found a marginal correlation in the verbal memory training group between the pre-test total hippocampal volume and the observed improvement in verbal memory performance from pre- to post-test (r(23) = 0.352, p=0.084). Further analysis accounting for sex and site as covariates revealed a significant positive correlation between total hippocampal volume and the learning rate in the Verbal Memory condition (r(23) = 0.545, p=0.007). This effect was specific to the verbal memory training; no significant correlation was identified for either the Navigation condition (r(25) = 0.072, p=.721) or the Video condition (r(19) = –0.209, pP=0.362); the same result was observed when controlling for covariates (Navigation condition: r(25) = 0.082, p=0.695; Video condition: r(19) = –0.144, p=0.555). Consistent findings were obtained when analyzing hemispheric hippocampal volumes. Specifically, a significant positive correlation was observed between the learning rate in the Verbal Memory condition and both left hippocampal volume (r(23) = 0.504, p=0.014) and right hippocampal volume (r(23) = 0.545, p=0.007), while no significant correlations were found for the Navigation condition (left: r(25) = 0.122, p=0.561; right: r(25) = 0.045, p=0.832) or Video Control condition (left: r(19) = –0.084, p=0.734; right: r(19) = –0.187, p=0.444), after controlling for sex and site as covariates.

We further examined the correlation between CA23DG volume and learning rate change. The CA23DG subfield showed a positive correlation with the change in learning rate from pre to post-test in the verbal memory transfer task of the Verbal Memory condition (r(23) = 0.504, p=0.01), suggesting that individuals in the Verbal Memory condition with larger CA23DG volumes exhibited greater improvements in memory performance from pre- to post-test. This correlation persisted even after controlling for sex and site as covariates (r(23) = 0.439, p=0.036). No significant correlations were observed for the CA23DG subfield in the Navigation (r(25) = 0.007, p=0.972) or Video Control conditions (r(19) = –0.05, p=0.828), regardless of whether sex and site were included as covariates.

Fisher’s z-tests revealed that the positive correlation in the Verbal Memory condition was significantly stronger than that in the Navigation even after controlling for sex and site (total hippocampus: Z=1.793, p=0.037; left hippocampus: Z=1.464, p=0.072; right hippocampus: Z=1.919, p=0.027; CA23DG: Z=1.687, p=0.046) and Video conditions (total hippocampus: Z=2.382, p=0.009; left hippocampus: Z=2.009, p=0.022; right hippocampus: Z=2.518, p=0.006; CA23DG: Z=1.766, p=0.038), while no significant difference was observed between the Navigation and Video Control conditions (total hippocampus: Z=–0.731, p=0.768; left hippocampus: Z=–0.662, p=0.746; right hippocampus: Z=–0.750, p=0.773; CA23DG: Z=–0.214, p=0.585).

Improvements in the learning rate of the Verbal Memory Transfer task, but not the Navigation Transfer task, were found to correlate with both total hippocampal volume and the volume of the CA2/3/DG subfield (using volume data only from the post-test). We examined the hypothesis that baseline hippocampal volume may be associated with either verbal or navigation performance. For this analysis, we utilized the hippocampal volume (or subfield volume) obtained for each participant at post-test, rather than averaging volumes across pre-test and post-test. We then assessed the relationship between hippocampal volumes at post-test and the change in learning rate from pre-test to post-test for both the Verbal Memory transfer task and the Navigation transfer task.

We found a marginal correlation in the verbal memory training group between the post-test total hippocampal volume and the observed improvement in verbal memory performance from pre- to post-test (r(23) = 0.360, p=0.078). Further analysis accounting for sex and site as covariates revealed a significant positive correlation between total hippocampal volume and the learning rate in the Verbal Memory condition (r(23) = 0.623, p=0.001). This effect was specific to the verbal memory training; no significant correlation was identified for either the Navigation condition (r(25) = –0.009, p=0.965) or the Video Control condition (r(19) = –0.178, p=0.439); the same was true when controlling for covariates (Navigation condition: r(25) = 0.000, p=0.999; Video Control condition r(18) = –0.083, p=0.736). Consistent findings were obtained when analyzing hippocampal volumes by hemisphere. Specifically, a significant positive correlation was observed between the learning rate in the Verbal Memory condition and both left hippocampal volume (r(23) = 0.597, p=0.003) and right hippocampal volume (r(23) = 0.594, p=0.003), while no significant correlations were found for the Navigation (left: r(25) = 0.026, p=0.901; right: r(24) = –0.023, p=0.912) or Video Control conditions (left: r(19) = –0.036, p=0.883; right: r(18) = –0.109, p=0.656), after controlling for sex and site as covariates.

We further examined the correlation between CA23DG volume and learning rate change. The CA23DG subfield showed a positive correlation with the change in learning rate from pre to post-test in the verbal memory transfer task of the Verbal Memory condition (r(23) = 0.545, p=0.005), suggesting that individuals in the Verbal Memory condition with larger CA23DG volumes exhibited greater improvement in memory performance from pre to post-test. This correlation persisted even after controlling for sex and site as covariates (r(23) = 0.537, p=0.008). No significant correlations were observed for the CA23DG subfield in the Navigation (r(25) = –0.027, p=0.894) or Video Control conditions (r(19) = –0.110, p=0.634), regardless of whether sex and site were included as covariates.

Fisher’s z-tests revealed that the positive correlation in the Verbal Memory condition was significantly stronger than that in the Navigation group even after controlling for sex and site (total hippocampus: Z=2.473, p=0.007; left hippocampus: Z=2.243, p=0.012; right hippocampus: Z=2.398, p=0.008; CA23DG: Z=2.209, p=0.014) and the Video Control condition (total hippocampus: Z=2.558, p=0.005; left hippocampus: Z=2.280, p=0.011; right hippocampus: Z=2.498, p=0.006; CA23DG: Z=2.337, p=0.014), while no significant difference was observed between the Navigation and the Video conditions (total hippocampus: Z=–0.266, p=0.605; left hippocampus: Z=–0.2, p=0.841; right hippocampus: Z=–0.276, p=0.609; CA23DG: Z=–0.291, p=0.615).