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

High-content drug screening in zebrafish xenografts reveals high efficacy of dual MCL-1/BCL-XL inhibition against Ewing sarcoma

Ewing sarcoma is a pediatric bone and soft tissue cancer with an urgent need for new therapies to improve disease outcome. To identify effective drugs, phenotypic drug screening has proven to be a powerful method, but achievable throughput in mouse xenografts, the preclinical Ewing sarcoma standard model, is limited. Here, we explored the use of xenografts in zebrafish for high-throughput drug screening to discover new combination therapies for Ewing sarcoma. We subjected xenografts in zebrafish larvae to high-content imaging and subsequent automated tumor size analysis to screen single agents and compound combinations. We identified three drug combinations effective against Ewing sarcoma cells: Irinotecan combined with either an MCL-1 or an BCL-XL inhibitor and in particular dual inhibition of the anti-apoptotic proteins MCL-1 and BCL-XL, which efficiently eradicated tumor cells in zebrafish xenografts. We confirmed enhanced efficacy of dual MCL-1/BCL-XL inhibition compared to single agents in a mouse PDX model. In conclusion, high-content screening of small compounds on Ewing sarcoma zebrafish xenografts identified dual MCL-1/BCL-XL targeting as a specific vulnerability and promising therapeutic strategy for Ewing sarcoma, which warrants further investigation towards clinical application. Keywords: Anti-apoptotic protein inhibitors; Ewing sarcoma; High-content imaging; Phenotypic drug screening; Zebrafish xenograft

Sex differences in the Kimchi-Palmer task revisited: Global reaction times, but not number of global choices differ between adult men and women

AbstractResearch, directly assessing sex-dependent differences in global versus local processing is sparse, but predominantly suggesting that men show a stronger global processing bias than women. Utilizing the Kimchi-Palmer task however, sex differences in the number of global choices can only be found in children, but not in adults. In the current study 52 men and 46 women completed a computerized version of the Kimchi Palmer task, in order to investigate whether sex-differences in global-local processing in the Kimchi-Palmer task are reflected in choice reaction times rather than choices per se. While no sex differences were found in the number of global choices, we found that especially women are faster in making local choices than men, while men are faster in making global choices than women. We did not find support for the assumption that this sex difference was modulated by menstrual cycle phase of women, since the difference between reaction times to global and local choices was consistent across the menstrual cycle of women. Accordingly there was no relationship between progesterone and global-local processing in the Kimchi-Palmer task. However, like in studies utilizing the Navon task, testosterone was positively related to the number of global choices in both men and women. To our knowledge, this is the first study including reaction times as outcome measure in a Kimchi Palmer paradigm and also the first study demonstrating sex differences in the Kimchi Palmer task in adults

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 22 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.(VLID)356863

Global-local processing relates to spatial and verbal processing: implications for sex differences in cognition

Abstract Sex differences have been reported for a variety of cognitive tasks and related to the use of different cognitive processing styles in men and women. It was recently argued that these processing styles share some characteristics across tasks, i.e. male approaches are oriented towards holistic stimulus aspects and female approaches are oriented towards stimulus details. In that respect, sex-dependent cognitive processing styles share similarities with attentional global-local processing. A direct relationship between cognitive processing and global-local processing has however not been previously established. In the present study, 49 men and 44 women completed a Navon paradigm and a Kimchi Palmer task as well as a navigation task and a verbal fluency task with the goal to relate the global advantage (GA) effect as a measure of global processing to holistic processing styles in both tasks. Indeed participants with larger GA effects displayed more holistic processing during spatial navigation and phonemic fluency. However, the relationship to cognitive processing styles was modulated by the specific condition of the Navon paradigm, as well as the sex of participants. Thus, different types of global-local processing play different roles for cognitive processing in men and women

Frontiers in Psychology / 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.P28261(VLID)340686

Biology of Sex Differences / 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.(VLID)267793

Brain and Language / 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.Andrea Scheuringer, Ti-Anni Harris, Belinda Pletze