White matter integrity correlates of implicit sequence learning in healthy aging

Abstract

Previous research has identified subcortical (caudate, putamen, hippocampus) and cortical (dorsolateral prefrontal cortex, DLPFC; frontal motor areas) regions involved in implicit sequence learning, with mixed findings for whether these neural substrates differ with aging. The present study used diffusion tensor imaging (DTI) tractography to reconstruct white matter connections between the known gray matter substrates, and integrity of these tracts was related to learning in the alternating serial reaction time task (ASRT) in younger and healthy older adults. Both age groups showed significant sequence learning (better performance to predictable, frequently occurring vs. less frequent events), with an age-related difference in the late learning stage. Caudate-DLPFC and hippocampus-DLPFC tract integrity were related to ASRT sequence learning, and these brain-behavior relationships did not differ significantly between age groups. Additionally, age-related decreases in caudate-DLPFC tract integrity mediated age-related differences in late stage sequence learning. Together, these findings complement studies of gray matter substrates underlying implicit sequence learning, and provide evidence for similar white matter integrity-sequence learning relationships in younger and healthy older adults.

Figure 1

Population maps illustrate locations of the three bilateral tracts of interest in younger (upper) and older (lower) adults. Individual tracts in diffusion space were transformed into standard space and overlaid on the standard MNI152 2 mm³ brain. To remove spurious tracts, images were thresholded to show only voxels common to at least two younger (red-yellow) or older (blue-light blue) adults. Axial slices are presented in radiological orientation (right = left). Note that portions of anterior corona radiata (caudate-DLPFC), anterior thalamic radiata (caudate-DLPFC, hippocampus-DLPFC), and superior thalamic and superior corona radiata (putamen-SMA) are included in these tracts.

Figure 2

Learning data for mean of median reaction times for correct trials (left) and proportion of correct responses (right) are presented. Responses to high frequency (black shapes) and low frequency (white shapes) triplets are plotted separately across the three stages of learning in younger (squares) and older (circles) adults. * = Significant age group × triplet type interaction (from an analysis of stage 3 alone) indicating greater learning in younger versus older adults.

Figure 3

Bar graph shows mean FA values for each tract in younger (white) and older (black) adults. * = Significant age group differences in FA are seen in the bilateral caudate-DLPFC tracts.

Figure 4

Scatter plots show correlations between white matter integrity (fractional anisotropy) in the left caudate-DLPFC (upper) and right hippocampus-DLPFC (lower) tracts and triplet type learning scores for stage 2 mean of median reaction time (left) and stage 3 proportion of correct responses (right). * = Significant FA-sequence learning relationships are shown, with separate regression lines for younger (white circles) and older (black circles) adults illustrating how similar these slopes are across age groups. ns = not significant. Note that relationships between left caudate-DLPFC tract FA and sequence learning (stage 3 for accuracy and stage 2 for reaction time) survived Bonferroni correction for six comparisons per tract (i.e., 3 learning stages × 2 behavioral measures per tract; p < .0083).