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The brain is one of the most prominent examples for structural and functional differences between the left and right half of the body. For handedness and language lateralization, the most widely investigated behavioral phenotypes, only a small fraction of phenotypic variance has been explained by molecular genetic studies. Due to environmental factors presumably also playing a role in their ontogenesis and based on first molecular evidence, it has been suggested that functional hemispheric asymmetries are partly under epigenetic control. This review article aims to elucidate the molecular factors underlying hemispheric asymmetries and their association with inner organ asymmetries. While we previously suggested that epigenetic mechanisms might partly account for the missing heritability of handedness, this article extends this idea by suggesting possible alternatives for transgenerational transmission of epigenetic states that do not require germ line epigenetic transmission. This is in line with a multifactorial model of hemispheric asymmetries, integrating genetic, environmental, and epigenetic influencing factors in their ontogenesis.
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Handedness and language lateralization are the most investigated phenotypes among functional hemispheric asymmetries, i.e. differences in function between the left and the right half of the human brain. Both phenotypes are left hemisphere-dominant, while investigations of the molecular factors underlying right hemisphere-dominant phenotypes are less prominent. In the classical line bisection task, healthy subjects typically show a leftward attentional bias due to a relative dominance of the right hemisphere for visuospatial attention. Based on findings of variations in dopamine-related genes affecting performance in the line bisection task, we first tested whether DNA methylation in non-neuronal tissue in the promoter regions of DBH , SLC6A3 , and DRD2 are associated with line bisection deviation. We replicated the typical behavioral pattern and found an effect of DNA methylation in the DBH promoter region on line bisection deviation in right-aligned trials. A second exploratory analysis indicated that an overall DNA methylation profile of genes involved in dopamine function predicts line bisection performance in right-aligned trials. Genetic variation in dopamine-related genes has been linked to attention deficit hyperactivity disorder (ADHD), a neurodevelopmental trait associated with rightward attentional bias. Overall, our findings point towards epigenetic markers for functional hemispheric asymmetries in non-neuronal tissue not only for left hemisphere-dominant, but also for right hemisphere-dominant phenotypes.
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Handedness is the most investigated form of functional hemispheric asymmetries, but its neural correlates remain unclear. Functional imaging studies suggest differences between left- and right-handers in ipsilateral activation during unilateral hand movements, but do not allow for conclusions on the temporal dimension. In the Tapley and Bryden task, subjects have to draw as many dots as possible on a paper within 20 s using either the left or the right hand. We adapted the task for use during EEG in 36 left- and 36 right-handers. Subjects performed a visually guided response task with each trial consisting of eight motor responses. We investigated the lateralized readiness potential (LRP) at the first and last response of the sequence. Overall, increasing complexity of sequences was associated with earlier and less negative LRP peaks. For the last response, right-handers showed more negative LRP peak amplitudes than left-handers. The effect of handedness on LRP peak amplitude in the first response was modulated by task complexity with a more negative LRP peak amplitude in right-handers than left-handers in simple, but not in medium or complex trials. This effect might be due to more symmetrical processing in right-handers with increasing task complexity. These findings complement previous imaging studies and add a new perspective on the relationship between laterality and schizophrenia, associated with less pronounced LRPs and a higher prevalence of left-handedness.
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Histological studies have reported microstructural hemispheric asymmetries in several cortical areas of the human brain, but reliable in vivo assessment methods have been lacking so far. Here, we used neurite orientation dispersion and density imaging (NODDI) to examine microstructural asymmetries in in vivo and determine if findings are in accordance with what has been reported in histological studies. We examined intra-neurite volume fraction (INVF), neurite orientation dispersion (ODI), and isotropic volume fraction (ISO) asymmetries in two independent samples of healthy adults (n = 269 and n = 251). Over both samples, we found greater left-hemispheric INVF in early auditory, inferior parietal and temporal-parietal-occipital areas. In contrast, we found greater right-hemispheric INVF in the fusiform and inferior temporal gyrus, reflecting what has been reported in histological studies. ODI was asymmetric towards the left hemisphere in frontal areas and towards the right hemisphere in early auditory areas. ISO showed less pronounced asymmetries. There were hardly any effects of sex or handedness on microstructural asymmetry as determined by NODDI. Taken together, these findings suggest substantial microstructural asymmetries in gray matter, making NODDI a promising marker for future genetic and behavioral studies on laterality.
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The ability to speak is a unique human capacity, but where is it located in our brains? This question is closely connected to the pioneering work of Pierre Paul Broca in the 1860s. Based on post-mortem observations of aphasic patients' brains, Broca located language production in the 3rd convolution of the left frontal lobe and thus reinitiated the localizationist view of brain functions. However, contemporary neuroscience has partially rejected this view in favor of a network-based perspective. This leads to the question, whether Broca's findings are still relevant today. In this mini-review, we discuss current and historical implications of Broca's work by focusing on his original contribution and contrasting it with contemporary knowledge. Borrowing from Broca's famous quote, our review shows that humans indeed "speak with the left hemisphere"- but Broca's area is not the sole "seat of articulatory language".
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Social touch is an important aspect of human social interaction - across all cultures, humans engage in kissing, cradling and embracing. These behaviors are necessarily asymmetric, but the factors that determine their lateralization are not well-understood. Because the hands are often involved in social touch, motor preferences may give rise to asymmetric behavior. However, social touch often occurs in emotional contexts, suggesting that biases might be modulated by asymmetries in emotional processing. Social touch may therefore provide unique insights into lateralized brain networks that link emotion and action. Here, we review the literature on lateralization of cradling, kissing and embracing with respect to motor and emotive bias theories. Lateral biases in all three forms of social touch are influenced, but not fully determined by handedness . Thus, motor bias theory partly explains side biases in social touch. However, emotional context also affects side biases, most strongly for embracing. Taken together, literature analysis reveals that side biases in social touch are most likely determined by a combination of motor and emotive biases.
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New findings identified the MORC1 gene as a link between early life stress and major depression. In this study, MORC1 methylation was investigated in 60 healthy human adults (30 women, 30 men) between 19 and 33 years of age. For analysis, DNA was isolated from buccal cells. The results show that DNA methylation in the MORC1 promoter region significantly correlates with the Beck Depression Inventory score in the examined non-clinical population. Sum score of birth complications, however, seems to correlate negatively with methylation. These findings further confirm that MORC1 is a stress sensitive gene and a possible biomarker for depression.
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Handedness is a complex trait influenced by both genetic and non-genetic factors. Asymmetries of DNA methylation and gene expression in the developing foetus are thought to underlie its development. However, its molecular epigenetics are not well understood. We collected buccal cells from adult left- and right-handers ( n = 60) to investigate whether epigenetic biomarkers of handedness can be identified in non-neuronal tissue. We associated DNA methylation in promoter regions of candidate genes with handedness direction. Results indicate that DNA methylation of genes asymmetrically expressed in the foetal brain or spinal cord might play a role within such a multifactorial model. Moreover, we provide tentative evidence that birth stress might be a factor that affects DNA methylation in NEUROD6 , a gene that is asymmetrically expressed in foetal brains.
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Language lateralization is one of the most prominent examples of functional hemispheric asymmetries. Previous studies indicate a significant contribution of factors not related to DNA sequence variation on the development of language lateralization, but the molecular processes underlying this relation are unclear. The Brandler-Paracchini model of hemispheric asymmetries assumes that genes involved in the establishment of ciliogenesis and bodily asymmetries also affect functional hemispheric asymmetries. Thus, genes implicated in this model represent a key target for epigenetic modulation of language lateralization. Here, we analyzed DNA methylation in the KIAA0319 (a gene involved in dyslexia and ciliogenesis) promoter region to investigate whether epigenetic markers of language lateralization can be identified in non-neuronal tissue. We found sex-specific effects of DNA methylation in single CpG sites on language lateralization in the forced-left (FL) and the forced-right (FR), but not on language lateralization in the non-forced (NF) condition of the dichotic listening task. These findings suggest that DNA methylation patterns in the KIAA0319 promoter region might be associated with cognitive control processes that are necessary to perform well in the forced-attention conditions. Furthermore, the assumption of an association between genes involved in ciliogenesis and the ontogenesis of functional hemispheric asymmetries is supported.
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Hemispheric asymmetries represent one of the major organizational principles in vertebrate neurobiology, but their molecular determinants are not well understood. For handedness, the most widely investigated form of hemispheric asymmetries in humans, single gene explanations have been the most popular ontogenetic model in the past. However, molecular genetic studies revealed only few specific genes that explain a small fraction of the phenotypic variance. In contrast, family studies indicated heritability of up to 0.66. It has been suggested that the lack of recognizable genetic heritability is partly accounted for by heritable epigenetic mechanisms. Based on recent neuroscientific findings highlighting the importance of epigenetic mechanisms for brain function and disease, we review recent findings describing non-genetic influences on handedness from conception to childhood. We aim to advance the idea that epigenetic regulation might be the mediating mechanism between environment and phenotype. Recent findings on molecular epigenetic mechanisms indicate that particular asymmetries in DNA methylation might affect asymmetric gene expression in the central nervous system that in turn mediates handedness. We propose that an integration of genes and environment is essential to fully comprehend the ontogenesis of handedness and other hemispheric asymmetries.
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Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.
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Lateralization is a fundamental principle of nervous system organization but its molecular determinants are mostly unknown. In humans, asymmetric gene expression in the fetal cortex has been suggested as the molecular basis of handedness. However, human fetuses already show considerable asymmetries in arm movements before the motor cortex is functionally linked to the spinal cord, making it more likely that spinal gene expression asymmetries form the molecular basis of handedness. We analyzed genome-wide mRNA expression and DNA methylation in cervical and anterior thoracal spinal cord segments of five human fetuses and show development-dependent gene expression asymmetries. These gene expression asymmetries were epigenetically regulated by miRNA expression asymmetries in the TGF-β signaling pathway and lateralized methylation of CpG islands. Our findings suggest that molecular mechanisms for epigenetic regulation within the spinal cord constitute the starting point for handedness, implying a fundamental shift in our understanding of the ontogenesis of hemispheric asymmetries in humans.
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How attractive we find ourselves decides who we target as potential partners and influences our reproductive fitness. Self-perceptions on women’s fertile days could be particularly important. However, results on how self-perceived attractiveness changes across women’s ovulatory cycles are inconsistent and research has seldomly assessed multiple attractiveness-related constructs simultaneously. Here, we give an overview of ovulatory cycle shifts in self-perceived attractiveness, sexual desirability, grooming, self-esteem and positive mood. We addressed previous methodological shortcomings by conducting a large, preregistered online diary study of 872 women (580 naturally cycling) across 70 consecutive days, applying several robustness analyses, and comparing naturally cycling women to women using hormonal contraceptives. As expected, we found robust evidence for ovulatory increases in self-perceived attractiveness and sexual desirability in naturally cycling women. Unexpectedly, we found moderately robust evidence for smaller ovulatory increases in self-esteem and positive mood. Although grooming showed an ovulatory increase descriptively, the effect was small, failed to reach our strict significance level of .01 and was not robust to model variations. We discuss how these results could follow an ovulatory increase in sexual motivation while calling for more theoretical and causally informative research to uncover the nature of ovulatory cycle shifts in the future.
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Research has shown that diverging romantic relationship outcomes of grandiose narcissism can be explained by differential associations of agentic and antagonistic aspects of narcissism. In this study, we wanted to further investigate the underlying mechanisms by examining how narcissists perceive daily situations with their partners. In an online diary, 171 couples reported on 1941 daily situations experienced together. Analyses revealed that agentic narcissism was positively and antagonistic narcissism was negatively related to daily relationship satisfaction. These effects were differentially linked through distinct situation perceptions: Agentic narcissism was positively linked with relationship satisfaction through perceiving daily situations as, for example, containing more romance, sexuality, and love, while antagonistic narcissism was negatively linked with relationship satisfaction through perceiving, for example, more threat, criticism, and accusation. Results are discussed in light of the Narcissistic Admiration and Rivalry Concept and with respect to person–situation transactions in romantic relationships.
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Are ovulatory cycle shifts in women’s mate attraction and preferences robust? What are underlying mechanisms of potential cycle shifts? These questions are the subject of a current scientific debate surrounding the good genes ovulatory shift hypothesis . Here, we report a large, preregistered, within - subjects study, including salivary hormone measure s and conception risk estimates based on luteinizing hormone tests. In four sessions across one ovulatory cycle, N = 257 women (= 1028 sessions) rated the attractiveness of 40 natural male bodies, 40 natural female bodies and 40 objects. Multilevel analyses yield ed weak evidence for ovulatory increases in women’s general attraction, specifically to male bodies, though they are not sy stematically related to changes in steroid hormone levels. Further, w e fou nd no compelling robust evidence for mate pre ference shifts across the cycle, as only one out of many different tests showed some weak evidence for such effects. Mechanisms regulatin g cycle shifts, the impact of our results on developing and revising cycle shift theories, and influences of different methodologies on results are discussed .
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Sexual selection appears to have shaped the acoustic signals of diverse species , including humans . Deep, resonant vocalizations in particular may function in attracting mates and/or intimidating same - sex competitors. Evidence for the se adaptive functions in human males derives predominantly fro m perception studies in which vocal acoustic parameters were manipulated using specialist software. This approach affords tight experimental control but provides little ecological validity, especially when the target acoustic parameters vary naturally with other parameters. Furthermore, such experimental studies provide no information about what acoustic variables indicate about the speaker – that is, why attention to vocal cues may be favored in intrasexual and intersexual contexts. Usi ng voice recordings with high ecological validity from 160 male speakers and biomarkers of condition, including baseline cortisol and testosterone levels, body morphology and strength , we tested a series of pre - registered hypotheses relating to both percep tions and underlying condition of the speaker. We f ou nd negative curvilinear and negative linear relationships between male fundamental frequency ( f o ) and female perceptions of attractiveness and male perceptions of dominance. In addition, cortisol and testosterone negatively interacted in predicting f o , and strength and measures of body size negatively predicted formant frequenc ies ( P f ). M eta - analys es of the present results and those from two previous samples confirmed that f o negatively predict ed testosterone only among men with lower cortisol levels. This research offers empirical evidence of possible evolutionary f unction s for attention to men’s vocal characteristics in contexts of sexual selection.
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Objective: Hormones are often conceptualized as biological markers of individual differences and have been associated with a variety of behavioral indicators and characteristics, such as mating behavior or acquiring and maintaining dominance. However, before researchers create strong theoretical models for how hormones modulate individual and social behavior, information on how hormones are associated with dominant models of personality is needed. Although there have been some studies attempting to quantify the associations between personality traits, testosterone, and cortisol, there are many inconsistencies across these studies. Methods: In this registered report, we examined associations between testosterone, cortisol, and Big Five personality traits. We aggregated 25 separate samples to yield a single sample of 3964 (50.3% women; 27.7% of women were on hormonal contraceptives). Participants completed measures of personality and provided saliva samples for testosterone and cortisol assays. Results: The results from multi-level models and meta-analyses revealed mostly weak, non-significant associations between testosterone or cortisol and personality traits. The few significant effects were still very small in magnitude (e.g., testosterone and conscientiousness: r = −0.05). A series of moderation tests revealed that hormone-personality associations were mostly similar in men and women, those using hormonal contraceptives or not, and regardless of the interaction between testosterone and cortisol (i.e., a variant of the dual-hormone hypothesis). Conclusions: Altogether, we did not detect many robust associations between Big Five personality traits and testosterone or cortisol. The findings are discussed in the context of biological models of personality and the utility of examining heterogeneity in hormone-personality associations.
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People spontaneously judge others’ personality based on their facial appearance and these impressions guide many important decisions. Although the consequences of personality impressions are well documented, studies on the accuracy of personality impressions have yielded mixed results. Moreover, little is known about people’s meta-accuracy (i.e., whether they are aware of their judgment accuracy). Even if accuracy is generally low, meta-accuracy would allow people to rely on their impressions in the right situations. In two studies (one preregistered), we examined the accuracy and meta-accuracy of personality impressions. We addressed three crucial limitations of previous studies (a) by incentivizing accuracy and meta-accuracy, (b) by relying on substantially larger samples of raters and targets (646 participants rating 1,660 faces), and (c) by conducting Bayesian analyses to also quantify evidence for the null hypothesis. Our findings consistently suggest that people show neither accuracy nor meta-accuracy when forming face-based personality impressions.
