Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.
Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2 nd and 4 th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (pairedassociate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.Many factors can influence performance on memory tasks and induce inherent between subject variability. For example, when investigating memory consolidation via spatial tasks, general spatial abilities will affect how well subjects perform. General spatial ability and preferred spatial strategy is a sexual dimorphic trait, which is thought to be influenced in utero via the testosterone/oestrogen hormone ratio [1]. This prenatal hormonal ratio does not correlate with sex hormone levels in the adult, making it very difficult to directly measure in memory experiments with adult subjects. Interestingly, this same prenatal hormone ratio also affects the growth of the 4 th digit with higher hormone ratios inducing longer 4 th digits in comparison to the 2 nd digit [2]. More specifically, androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR or activation of ER-α decreases growth of digit 4, which causes a higher 2D:4D ratio; whereas inactivation of ER-α or activation of AR increases growth of digit 4, which leads to a lower 2D:4D ratio. Intriguingly, several genes identified by Zheng et al to be responsible for the 2D:4D ratio also have roles in development of the brain [3]. Thus the ratio between these digits (2D:4D) is an indicator for the hormonal ratio in utero, with lower finger ratios indicating higher testosterone to oestrogen.In a study aimed at investigating memory consolidation effects across different tasks in the same male animals, we noticed early in training while discussing the current state of performance that we had "smart" and "not so smart" rats across different tasks. And in fact, the correlation between probe trial performance in the Delayed-Match-to-Place version of the water maze, with daily switching escape locations [4], and in a flavour-location association task [5] in an open field environment (arena) was significant (n=20, r=0.53, p=0.015; fig 1A; see supplemental materials), suggesting some factor e.g. general spatial ability confounded the performance in both tasks. As a negative correlation between the right (but not left) 2D:4D and spatial performance in the watermaze has been demonstrated in humans [6], we dissected our rat's front paws post-mortem and measured their 2D:4D. And in fact, the right 2D:4D correlated negatively with the performance in both tasks (2D:4D_arena: r=-0.46, p=0.044, 2D:4D_watermaze: r=-0.50, p=0.024; fig 1B,C). Similar to previous human results, there was no such correlation present using the left 2D:4D. Thus we are, to ...
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