Eye-Movements During Navigation in a Virtual Environment: Sex Differences and Relationship to Sex Hormones.

Sex differences in spatial navigation have been related to different navigation strategies. For example, women are more likely to utilize local landmark-information in the environment compared to men. Furthermore, sex differences appear to be more pronounced when distances need to be judged in Euclidian terms and an allocentric representation of the environment is necessary. This suggests differential attentional processes during spatial navigation in men and women. However, eye-tracking studies on spatial navigation exploring these attentional processes are rare. The present study (39 men and 36 women) set out to investigate sex differences in eye-movements during spatial navigation in a 3D environment using virtual reality goggles. While we observed the expected sex differences in overall navigation performance, women did not benefit from the landmark-based instructions. Gaze fixations were in accordance with the preferred Euclidian strategy in men, but did not confirm the expected landmark-based strategy in women. However, high estradiol levels where related to an increased focus on landmark information. Surprisingly, women showed longer gaze distances than men, although the utilization of distal landmarks has been related to allocentric representations preferred by men. In fact, larger gaze distances related to slower navigation, even though previous studies suggest that the utilization of distal landmarks is beneficial for navigation. The findings are discussed with respect to the utility of virtual reality presentation for studies on sex differences in navigation. While virtual reality allows a full first-person immersion in the environment, proprioceptive and vestibular information is lacking.

Sex and strategy effects on brain activation during a 3D-navigation task.

Sex differences in navigation have often been attributed to the use of different navigation strategies in men and women. However, no study so far has investigated sex differences in the brain networks supporting different navigation strategies. To address this issue, we employed a 3D-navigation task during functional MRI in 36 men and 36 women, all scanned thrice, and modeled navigation strategies by instructions requiring an allocentric vs. egocentric reference frame on the one hand, as well as landmark-based vs. Euclidian strategies on the other hand. We found distinct brain networks supporting different perspectives/strategies. Men showed stronger activation of frontal areas, whereas women showed stronger activation of posterior brain regions. The left inferior frontal gyrus was more strongly recruited during landmark-based navigation in men. The hippocampus showed stronger connectivity with left-lateralized frontal areas in women and stronger connectivity with superior parietal areas in men. We discuss these findings in the light of a stronger recruitment of verbal networks supporting a more verbal strategy in women compared to a stronger recruitment of spatial networks supporting a more spatial strategy use in men. In summary, this study provides evidence that different navigation strategies activate different brain areas in men and women.

Spectral dynamic causal modelling in healthy women reveals brain connectivity changes along the menstrual cycle.

Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects' cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.

The missing link: Global-local processing relates to number-magnitude processing in women.

Number processing and visual hierarchical processing (global-local processing) have much in common. However, the shared aspects of number processing and global-local processing have not been investigated so far. Most visual stimuli are hierarchical with global structures made up of local parts. Processing of global and local aspects occurs in parallel and the global advantage effect indicates faster reactions to global than local aspects. Likewise, multidigit numbers can be represented holistically (whole number magnitudes) or in a decomposed fashion (single digit magnitudes). During comparison of 2-digit numbers, the unit-decade compatibility effect indicates slower responses when the larger number contains the smaller unit digit and has been suggested as a measure of how strongly participants rely on decomposed number representations. However, this interpretation of the compatibility effect is still controversial and a link between global-local processing and the individual tendency to rely on decomposed representations of multidigit numbers remains to be established. To that end we assessed whether the compatibility effect during number comparison was related to various measures of global advantage. To answer this question we drew upon existing data from participants who had completed both, the number comparison task and 2 global-local tasks. Results show that the compatibility effect is indeed negatively related to several measures of global advantage in women, with no evidence for such a relationship in men. These results demonstrate that global-local processing transcends into the numerical domain but also suggest that the compatibility effect reflects different mechanisms in men and women. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Recruiting the right hemisphere: Sex differences in inter-hemispheric communication during semantic verbal fluency.

Sex differences in cognitive functions are heavily debated. Recent work suggests that sex differences do stem from different processing strategies utilized by men and women. While these processing strategies are likely reflected in different brain networks, so far the link between brain networks and processing strategies remains speculative. In the present study we seek for the first time to link sex differences in brain activation patterns to sex differences in processing strategies utilizing a semantic verbal fluency task in a large sample of 35 men and 35 women, all scanned thrice. For verbal fluency, strategies of clustering and switching have been described. Our results show that men show higher activation in the brain network supporting clustering, while women show higher activation in the brain network supporting switching. Furthermore, converging evidence from activation results, lateralization indices and connectivity analyses suggests that men recruit the right hemisphere more strongly during clustering, but women during switching. These results may explain findings of differential performance and strategy-use in previous behavioral studies.

Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach.

Increasing evidence suggests that endogenous sex steroid changes affect human brain functional connectivity, which could be obtained by resting-state fMRI (RS-fMRI). Nevertheless, RS studies on the menstrual cycle (MC) are underrepresented and yield inconsistent results. We attribute these inconsistencies to the use of various methods in exploratory approaches and small sample sizes. Hormonal fluctuations along the MC likely elicit subtle changes that, however, may still have profound impact on network dynamics when affecting key brain nodes. To address these issues, we propose a ROI-based multimodal analysis approach focusing on areas of high functional relevance to adequately capture these changes. To that end, sixty naturally cycling women underwent RS-fMRI in three different cycle phases and we performed the following analyses: (1) group-independent component analyses to identify intrinsic connectivity networks, (2) eigenvector centrality (EC) as a measure of centrality in the global connectivity hierarchy, (3) amplitude of low-frequency fluctuations (ALFF) as a measure of oscillatory activity and (4) seed-based analyses to investigate functional connectivity from the ROIs. For (2)-(4), we applied a hypothesis-driven ROI approach in the hippocampus, caudate and putamen. In the luteal phase, we found (1) decreased intrinsic connectivity of the right angular gyrus with the default mode network, (2) heightened EC for the hippocampus, and (3) increased ALFF for the caudate. Furthermore, we observed (4) stronger putamen-thalamic connectivity during the luteal phase and stronger fronto-striatal connectivity during the pre-ovulatory phase. This hormonal modulation of connectivity dynamics may underlie behavioural, emotional and sensorimotor changes along the MC.

Beyond Biological Sex: Interactive Effects of Gender Role and Sex Hormones on Spatial Abilities.

Sex differences in spatial abilities are well documented, even though their underlying causes are poorly understood. Some studies assume a biological basis of these differences and study the relationship of sex hormone levels to spatial abilities. Other studies assume social influences and study the relationship of gender role (masculinity/femininity) to spatial abilities. Contemporary theories postulate a psychobiosocial model of sex differences in spatial abilities, in which both biological (e.g., hormonal) and psychosocial (e.g., gender role) variables interactively modulate spatial abilities. However, few studies have addressed both aspects simultaneously. Accordingly, the present study explores potential interactive effects between gender role and sex hormones on spatial performance. 41 men and 41 women completed a mental rotation and a virtual navigation task. Sex hormone levels and gender role were assessed in all participants. Sex differences favoring men were observed in both tasks. We found that neither sex hormones nor gender role alone emerged as mediators of these sex differences. However, several interactive effects between gender role and sex hormones were identified. Combined effects of masculinity and testosterone were observed for those variables that displayed sex differences. Participants with both, high masculinity and high testosterone showed the best performance. However, this association was further modulated by biological sex and progesterone levels. Furthermore, we observed an interactive effect of femininity, estradiol and testosterone on response times in both tasks. Consistent across both tasks and irrespective of biological sex, testosterone related to response times in participants with low estradiol levels, depending on their femininity. In participants with low femininity, testosterone was related to slower reaction times, while in participants with higher femininity, testosterone was related to faster reaction times.

Previous contraceptive treatment relates to grey matter volumes in the hippocampus and basal ganglia.

Oral contraceptive (OC) effects on the brain have gained increasing interest, but are highly controversial. Previous studies suggest that OC users have larger hippocampi, parahippocampi, fusiform gyri and Cerebelli. Preliminary evidence from one of those studies even suggests an effect of previous contraceptive use on the hippocampi of women who are not current users of OCs. Furthermore, more recent studies postulate an involvement of previous OC treatment in later development of mood disorders. To address the question whether previous OC treatment affects women's brain structure later in life, high resolution structural images were obtained from 131 naturally cycling women. Among them, 52 women had never used OC before, 52 had previously used one OC for a continuous time period and 27 had previously used multiple contraceptives. The groups did not differ in gray matter volumes. Since endogenous sex hormones modulate gray matter volumes of the hippocampus and basal ganglia along the menstrual cycle, we hypothesize effects of OC use on these areas. Specifically, we hypothesize that a longer duration of previous OC treatment is related to larger hippocampi and larger basal ganglia. Indeed we found the duration of previous OC use to be positively correlated to hippocampal and basal ganglia volumes bilaterally. For the hippocampus, but not for the basal ganglia, this association disappeared after controlling for the time since discontinuation. These results suggest that for the hippocampus, but not for the basal ganglia, effects of previous contraceptive treatment are reversed after a time period comparable to treatment duration. These data question the immediate reversibility of OC effects on brain structure. Accordingly, some changes in the brain due to long-term contraceptive use, while subtle, may be long-lasting.

The cycling brain: menstrual cycle related fluctuations in hippocampal and fronto-striatal activation and connectivity during cognitive tasks.

Estradiol and progesterone vary along the menstrual cycle and exert opposite effects on a variety of neurotransmitter systems. However, few studies have addressed menstrual cycle-dependent changes in the brain. In the present study we investigate menstrual cycle changes in brain activation and connectivity patterns underlying cognition. Thirty-six naturally cycling women underwent functional MRI during two cognitive tasks: spatial navigation and verbal fluency. While no significant performance differences were observed along the menstrual cycle, the changes in brain activation patterns are strikingly similar during both tasks. Irrespective of the task, estradiol boosts hippocampal activation during the pre-ovulatory cycle phase and progesterone boosts fronto-striatal activation during the luteal cycle phase. Connectivity analyses suggest that the increase in right-hemispheric frontal activation is the result of inter-hemispheric decoupling and is involved in the down-regulation of hippocampal activation.

Perspective and strategy interactively modulate sex differences in a 3D navigation task.

Sex differences in navigation performance have been attributed to sex differences in information processing during navigation. Perspective refers to the viewpoint of the navigator, with previous work suggesting that men tend to use an allocentric perspective, while women tend to use an egocentric perspective during navigation. Furthermore, different navigation strategies may be used when moving from point A to B, with previous work suggesting that men tend to use a Euclidian strategy, while women tend to use a landmark-based strategy. However, it has not been studied whether perspective and strategy affect sex differences in navigation interactively or independently of each other. The present study aimed to investigate the interactive effects of perspective and strategy on sex differences in a 3D navigation task. In different levels of the task, perspective and strategy were modulated in a 2 × 2 design via different instructions. Potential mediating effects of video gaming experience and sex hormone levels were addressed. We found that men outperformed women in all levels of the navigation task. However, the male advantage was more pronounced using the allocentric perspective compared to the egocentric perspective. When using the allocentric perspective, men showed better performance using a Euclidian strategy while women showed better performance using a landmark-based strategy. The strategy did not modulate performance under the egocentric perspective. Accordingly, sex differences in navigation were interactively modulated by perspective and strategy. These effects were not explained by sex differences in video gaming experience or sex hormone levels.

Sex Differences in Number Magnitude Processing Strategies Are Mediated by Spatial Navigation Strategies: Evidence From the Unit-Decade Compatibility Effect.

The hybrid model of number magnitude processing suggests that multi-digit numbers are simultaneously processed holistically (whole number magnitudes) and in a decomposed manner (digit magnitudes). Thus, individual tendencies and situational factors may affect which type of processing becomes dominant in a certain individual in a given situation. The unit-decade compatibility effect has been described as indicative of stronger decomposed number processing. This effect occurs during the comparison of two-digit numbers. Compatible items in which the larger number contains the larger unit digit are easier to solve than incompatible items in which the larger number contains the smaller unit digit. We have previously described women show a larger compatibility effect than men. Furthermore, the compatibility effect is modulated by situational factors like the vertical spacing of the presented numbers. However, it has not been addressed whether situational factors and sex affect the unit-decade compatibility effect interactively. We have also demonstrated that the unit-decade compatibility effects relates to global-local processing, which in turn also affects spatial processing strategies. However, a link between spatial processing strategies and the unit-decade compatibility effect has not yet been established. In the present study we investigate, whether sex differences in the unit-decade compatibility effect (i) depend on the vertical spacing between numbers, (ii) are mediated via sex hormone levels of participants, and (iii) relate to sex differences in spatial processing strategies. 42 men and 41 women completed a two-digit number comparison task as well as a spatial navigation task. The number comparison task modulates compatibility and vertical spacing in a 2 × 2 design. The results confirm a larger compatibility effect in women compared to men and with dense compared to sparse spacing. However, no interactive effect was observed, suggesting that these factors modulate number magnitude processing independently. The progesterone/testosterone ratio was related to the compatibility effect, but did not mediate the sex difference in the compatibility effect. Furthermore, spatial processing strategies were related to the compatibility effect and did mediate the sex difference in the compatibility effect. Participants with a stronger focus on landmarks in the spatial navigation task showed a larger compatibility effect.

Subcortical structural changes along the menstrual cycle: beyond the hippocampus.

Animal studies have robustly shown hormone related changes in spine density in various brain areas, specifically the hippocampus. Literature on hormone dependent gray matter volume changes in humans is however less consistent. While various areas have been reported to change along the menstrual cycle in women, many do not survive multiple-comparisons correction and only hippocampal changes have been replicated. We attribute these problems to small sample sizes and inconsistent definitions of menstrual cycle phases. In the present study a large sample of 55 women was scanned three times along their menstrual cycle in concisely defined time windows of hormonal changes. Accordingly this is the first study using a large enough sample size to assess menstrual cycle dependent changes in human brain structure with sufficient power. Results confirm a significant estradiol-dependent pre-ovulatory increase in gray matter volumes of the bilateral hippocampus, but also show a significant, progesterone-dependent increase in gray matter volumes of the right basal ganglia after ovulation. No other areas were affect by hormonal changes along the menstrual cycle. These hormone driven menstrual cycle changes in human brain structure are small, but may be the underlying cause of menstrual cycle dependent changes in cognition and emotion.

Sex differences and functional hemispheric asymmetries during number comparison.

BACKGROUND: Global-local stimuli are hierarchical structures consisting of a larger global structure which is composed of smaller local stimuli. Numbers are also constructed hierarchically, with multi-digit numbers being made up from single digits. During two-digit number comparison, compatible items (larger number contains larger unit digit, e.g., 53 vs. 68) are processed faster and more accurately than incompatible items (smaller number contains larger unit digit, e.g., 58 vs. 63). This so-called unit-decade-compatibility effect has challenged the holistic model of number processing and suggests that the processing of number magnitudes occurs at least in part, decomposed, i.e., separately for each digit. Thus, the compatibility effect is indicative of how decomposed numbers are processed, thereby sharing similarities with traditional global-local processing of hierarchical stimuli. The goal of this study was to investigate whether factors that have been shown to reliably influence global-local processing also affect the compatibility effect during number comparison. Those include visual hemifield, sex, and menstrual cycle phase in women. METHOD: One hundred sixty participants, 77 naturally cycling women and 83 men, completed a two-digit number comparison task twice, with test-sessions time-locked to the early follicular or mid-luteal cycle phase in women. Number comparison stimuli were presented to the right or left hemifield, respectively. RESULTS: We observed a stronger compatibility effect in the right visual hemifield compared to left visual hemifield and in women compared to men, but no evidence for an influence of menstrual cycle phase in women could be found. CONCLUSION: Hemispheric asymmetries in holistic versus decomposed number processing could be demonstrated for the first time, suggesting a similar hemispheric modulation for number magnitude processing as for global-local processing.

Sex Hormones Modulate the Relationship Between Global Advantage, Lateralization, and Interhemispheric Connectivity in a Navon Paradigm.

Sex, stimulus material, and attention condition have previously been related to global advantage (GA; faster responses to global targets than to local targets) on the one hand and lateralization during global-local processing on the other hand. It is presumed that the lateralization of brain functions is either related to the inhibitory influence of the dominant on the nondominant hemisphere or reduced excitation between hemispheres. However, a direct relationship between the GA and lateralization and interhemispheric connectivity has not been previously established. In this study, 58 participants (29 men, 29 naturally cycling women) completed a Navon paradigm, modulating attention condition (divided vs. focused) and stimulus material (letters vs. shapes) during functional magnetic resonance imaging. The size of the GA effect, lateralization indices, interhemispheric connectivity, and sex hormone levels were assessed. In summary, this study suggests that interhemispheric connectivity during global-local processing is affected by sex and material. Furthermore, the relationship between interhemispheric connectivity, lateralization, and behavior was modulated by sex and sex hormones. Results suggest (1) differential roles of interhemispheric connectivity for lateralization in men and women and (2) differential roles of lateralization for behavior in men and women. Importantly, the classic assumption that a more negative connectivity leads to stronger lateralization, which in turn leads to a stronger GA effect, was observed in men, whereas the opposite pattern was found in women. The relationship between connectivity and lateralization was mediated through testosterone levels, whereas the relationship between lateralization and behavior was mediated through progesterone levels. Results are discussed in light of differential functions of inhibitory and excitatory interhemispheric processes in men and women.

Sex and menstrual cycle influences on three aspects of attention.

Sex differences and menstrual cycle influences have been investigated in a variety of cognitive abilities, but results regarding attention are comparably sparse. In the present study, 35 men and 32 naturally cycling women completed three attention tasks, which are commonly used in neuropsychological assessment situations. All participants completed two sessions, which were time-locked to the follicular (low progesterone) and luteal cycle phase (high progesterone) in women. The results reveal higher operation speed during sustained attention in men, but no sex differences in selected and divided attention. Menstrual cycle influences were observed on accuracy in all three tasks. During divided and sustained attention, for which a male advantage was previously reported, accuracy was higher during the early follicular compared to the mid-luteal cycle phase. Furthermore, during selected and sustained attention the learning effect from the first to the second test session was higher in women who started the experiment in their luteal cycle phase. These results suggest a possible role of progesterone in modulating the ability to focus on certain stimulus aspects, while inhibiting others and to sustain attention over a longer period of time.

Spacing and Presentation Modes Affect the Unit-Decade Compatibility Effect During Number Comparison.

The unit-decade compatibility effect has challenged the model of holistic number magnitude processing, suggesting decomposed processing of multi-digit numbers. Recent evidence confirms that decomposed processing of decade and unit magnitudes occurs in parallel. However, the mode of presentation of multi-digit numbers may affect the processing mode (holistic vs. decomposed, parallel vs. sequential). We therefore investigated in two studies, whether presentation mode (vertical, horizontal, or consecutive) or the distance between two vertically presented numbers affects the unit-decade compatibility effect during number comparison. We found that the compatibility effect did not differ significantly between vertical and horizontal presentation, adding to previous results on perceptual generality, but was nonsignificant with consecutive presentation. However, the compatibility effect was significantly smaller, if numbers are spaced further apart. Thus, stimulus size and distance between numbers affect the processing of multi-digit numbers and should be reported in future studies.