2D:4D and spatial abilities: From rats to humans

Abstract

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 ...

Spindle–slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep

“…With a 2 × 2 full‐factorial mixed design we tested system‐wide consolidation processes of a spatial memory paradigm. During fMRI scans, participants engaged in allo‐ or egocentric spatial learning and memory retrieval in a previously validated human analogue of the water maze (Müller et al, 2018; Schoenfeld et al, 2017). Immediately before and after the learning and retrieval sessions, functional connectivity was assessed with resting‐state fMRI.…”

“…Our study follows up on our investigations into the effect of sleep on allocentric and egocentric memory representations in humans and rats (Samanta et al, 2021). Participants performed a human analog of the watermaze (Morris, 1981), a validated paradigm to study different aspects of spatial navigation (Müller et al, 2018; Schoenfeld et al, 2017). Whereas Samanta et al (2021) focused on task‐fMRI data during learning and retrieval, here we focused on resting‐state fMRI and sleep‐EEG data.…”

Sleep Leads to Brain-Wide Neural Changes Independent of Allocentric and Egocentric Spatial Training in Humans and Rats

“…Further, a human analogue of the maze has been developed and there is comparable performance in behavior across both species ( Schoenfeld et al. 2017 ; Müller et al. 2018 ).…”

Sleep leads to system-wide neural changes independent of allo- and egocentric spatial training in humans and rats

“…Only males were chosen since only male rats were used in the previous experiment. Additionally, sex differences studies across both rats and humans [20] have shown sex and menstrual cycle to influence sleep dependent memory consolidation and watermaze training. Participants were recruited through the Radboud Research Participation System.…”

“…We used the watermaze [16], which has been a well-established paradigm to study different aspects of spatial navigation, especially contrasting allo- and egocentric training [7, 17, 18]. Further, a human analog of the maze has been developed and showed comparable performance in behavior across both species [19, 20]. Using the watermaze we tested for the influence of sleep on allo- and egocentric spatial memory training in both rats and humans and investigated the underlying neural signatures with immediate early gene expression analysis in rats and functional MRI in humans.…”