Human Handedness Research Articles

Exome-wide analysis implicates rare protein-altering variants in human handedness

Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding regions and may affect gene expression. Implicated genes include several that encode tubulins (microtubule components) or microtubule-associated proteins. Here we examine whether left-handedness is also influenced by rare coding variants (frequencies ≤ 1%), using exome data from 38,043 left-handed and 313,271 right-handed individuals from the UK Biobank. The beta-tubulin gene TUBB4B shows exome-wide significant association, with a rate of rare coding variants 2.7 times higher in left-handers than right-handers. The TUBB4B variants are mostly heterozygous missense changes, but include two frameshifts found only in left-handers. Other TUBB4B variants have been linked to sensorineural and/or ciliopathic disorders, but not the variants found here. Among genes previously implicated in autism or schizophrenia by exome screening, DSCAM and FOXP1 show evidence for rare coding variant association with left-handedness. The exome-wide heritability of left-handedness due to rare coding variants was 0.91%. This study reveals a role for rare, protein-altering variants in left-handedness, providing further evidence for the involvement of microtubules and disorder-relevant genes.

Kin selection as a modulator of human handedness: sex-specific, parental and parent-of-origin effects.

The frequency of left-handedness in humans is ~10% worldwide and slightly higher in males than females. Twin and family studies estimate the heritability of human handedness at around 25%. The low but substantial frequency of left-handedness has been suggested to imply negative frequency-dependent selection, e.g. owing to a 'surprise' advantage of left-handers in combat against opponents more used to fighting right-handers. Because such game-theoretic hypotheses involve social interaction, here we perform an analysis of the evolution of handedness based on kin-selection, which is understood to play a major role in the evolution of social behaviour generally. We show that: (1) relatedness modulates the balance of right-handedness vs. left-handedness, according to whether left-handedness is marginally selfish vs. marginally altruistic; (2) sex differences in relatedness to social partners may drive sex differences in handedness; (3) differential relatedness of parents and offspring may generate parent-offspring conflict and sexual conflict leading to the evolution of maternal and paternal genetic effects in relation to handedness; and (4) differential relatedness of maternal-origin vs. paternal-origin genes may generate intragenomic conflict leading to the evolution of parent-of-origin-specific gene effects - such as 'genomic imprinting' - and associated maladaptation.

Consideration of handedness in human-robot collaboration

In the design of assembly workplaces, considerations regarding handedness and ergonomics play a crucial role. The emergence of human-robot collaboration presents an innovative avenue for enhancing the ergonomic aspects of manual assembly tasks. While initial applications have demonstrated improvements in lifting and holding activities, they often overlook the influence of human handedness. This paper advocates for the adoption of adaptive assembly processes, which offer simple and intuitive robot programming options to enhance workflow efficiency and reduce stress. This study is grounded in two investigations conducted at the Bremen Institute for Mechanical Engineering. The first study, a pilot investigation, aimed to identify indicators of the influence of handedness and ergonomics, laying the groundwork for further research. Building upon these findings, the second study delves into the interaction between workers and collaborative robots during assembly operations. Data collected from 50 participants form the basis for statistical analysis, providing insights into performance factors and self-assessment, as well as external evaluations of ergonomics. A notable finding of this study challenges the assumption of mirrored behavior between presumed left-handed and right-handed individuals. Additionally, the study identifies a subgroup of participants with ambiguous handedness, suggesting a lack of training in their natural handedness. Through these investigations, this paper contributes to our understanding of the intricate relationship between handedness, ergonomics, and human-robot collaboration in assembly workplaces. By addressing these factors comprehensively, we can pave the way for the development of more inclusive and efficient assembly processes.

The evolution and biological correlates of hand preferences in anthropoid primates.

The evolution of human right-handedness has been intensively debated for decades. Manual lateralization patterns in non-human primates have the potential to elucidate evolutionary determinants of human handedness, but restricted species samples and inconsistent methodologies have so far limited comparative phylogenetic studies. By combining original data with published literature reports, we assembled data on hand preferences for standardized object manipulation in 1786 individuals from 38 species of anthropoid primates, including monkeys, apes, and humans. Based on that, we employ quantitative phylogenetic methods to test prevalent hypotheses on the roles of ecology, brain size, and tool use in primate handedness evolution. We confirm that human right-handedness represents an unparalleled extreme among anthropoids and found taxa displaying population-level handedness to be rare. Species-level direction of manual lateralization was largely uniform among non-human primates and did not strongly correlate with any of the selected biological predictors, nor with phylogeny. In contrast, we recovered highly variable patterns of hand preference strength, which show signatures of both ecology and phylogeny. In particular, terrestrial primates tend to display weaker hand preferences than arboreal species. These results challenge popular ideas on primate handedness evolution, including the postural origins hypothesis. Furthermore, they point to a potential adaptive benefit of disparate lateralization strength in primates, a measure of hand preference that has often been overlooked in the past. Finally, our data show that human lateralization patterns do not align with trends found among other anthropoids, suggesting that unique selective pressures gave rise to the unusual hand preferences of our species.

Machine learning of large-scale multimodal brain imaging data reveals neural correlates of hand preference

Lateralization is a fundamental characteristic of many behaviors and the organization of the brain, and atypical lateralization has been suggested to be linked to various brain-related disorders such as autism and schizophrenia. Right-handedness is one of the most prominent markers of human behavioural lateralization, yet its neurobiological basis remains to be determined. Here, we present a large-scale analysis of handedness, as measured by self-reported direction of hand preference, and its variability related to brain structural and functional organization in the UK Biobank (N = 36,024). A multivariate machine learning approach with multi-modalities of brain imaging data was adopted, to reveal how well brain imaging features could predict individual's handedness (i.e., right-handedness vs. non-right-handedness) and further identify the top brain signatures that contributed to the prediction. Overall, the results showed a good prediction performance, with an area under the receiver operating characteristic curve (AUROC) score of up to 0.72, driven largely by resting-state functional measures. Virtual lesion analysis and large-scale decoding analysis suggested that the brain networks with the highest importance in the prediction showed functional relevance to hand movement and several higher-level cognitive functions including language, arithmetic, and social interaction. Genetic analyses of contributions of common DNA polymorphisms to the imaging-derived handedness prediction score showed a significant heritability (h2=7.55%, p <0.001) that was similar to and slightly higher than that for the behavioural measure itself (h2=6.74%, p <0.001). The genetic correlation between the two was high (rg=0.71), suggesting that the imaging-derived score could be used as a surrogate in genetic studies where the behavioural measure is not available. This large-scale study using multimodal brain imaging and multivariate machine learning has shed new light on the neural correlates of human handedness.

A computational model based on corticospinal functional MRI revealed asymmetrically organized motor corticospinal networks in humans

Evolution of the direct, monosynaptic connection from the primary motor cortex to the spinal cord parallels acquisition of hand dexterity and lateralization of hand preference. In non-human mammals, the indirect, multi-synaptic connections between the bilateral primary motor cortices and the spinal cord also participates in controlling dexterous hand movement. However, it remains unknown how the direct and indirect corticospinal pathways work in concert to control unilateral hand movement with lateralized preference in humans. Here we demonstrated the asymmetric functional organization of the two corticospinal networks, by combining network modelling and simultaneous functional magnetic resonance imaging techniques of the brain and the spinal cord. Moreover, we also found that the degree of the involvement of the two corticospinal networks paralleled lateralization of hand preference. The present results pointed to the functionally lateralized motor nervous system that underlies the behavioral asymmetry of handedness in humans.

Lion-tailed macaques show a stable direction and reinforcement of hand preference in simple reaching tasks over several years

Research on hand preference in non-human primates provides information about the evolutionary origin of population-level bias of human handedness. Human hand preference has been shown to remain stable throughout an individual's lifespan. However, the stability of hand preference and its change with age in non-human primates remains questionable. We recorded hand use in lion-tailed macaques (Macaca silenus) during simple reaching tasks in three time periods over six years. We tested the effect of age and body posture on the direction and strength of hand preference in 23 observed individuals. In a subsample of 13 individuals followed for two or three subsequent time periods, we assessed the stability of hand preference across study periods. The direction of hand preference was highly stable; we detected no individuals changing from a left- to right-, or right- to left- preference and repeated quantitative measures of hand preference were correlated among subsequent study periods. Hand preference was, however, reinforced in older individuals and an individual's hand preference was stronger in postures with both hands free for foraging. Stable hand preference at an individual level, and its reinforcement over an individual's lifetime, is emerging as a robust finding across the primate order.

Cognitive and Neurophysiological Models of Brain Asymmetry

Asymmetry is an inherent characteristic of brain organization in both humans and other vertebrate species, and is evident at the behavioral, neurophysiological, and structural levels. Brain asymmetry underlies the organization of several cognitive systems, such as emotion, communication, and spatial processing. Despite this ubiquity of asymmetries in the vertebrate brain, we are only beginning to understand the complex neuronal mechanisms underlying the interaction between hemispheric asymmetries and cognitive systems. Unfortunately, despite the vast number of empirical studies on brain asymmetries, theoretical models that aim to provide mechanistic explanations of hemispheric asymmetries are sparse in the field. Therefore, this Special Issue aims to highlight empirically based mechanistic models of brain asymmetry. Overall, six theoretical and four empirical articles were published in the Special Issue, covering a wide range of topics, from human handedness to auditory laterality in bats. Two key challenges for theoretical models of brain asymmetry are the integration of increasingly complex molecular data into testable models, and the creation of theoretical models that are robust and testable across different species.

Experience-dependent learning of behavioral laterality in the scale-eating cichlid Perissodus microlepis occurs during the early developmental stage

Behavioral laterality—typically represented by human handedness—is widely observed among animals. However, how laterality is acquired during development remains largely unknown. Here, we examined the effect of behavioral experience on the acquisition of lateralized predation at different developmental stages of the scale-eating cichlid fish Perissodus microlepis. Naïve juvenile fish without previous scale-eating experience showed motivated attacks on prey goldfish and an innate attack side preference. Following short-term predation experience, naïve juveniles learned a pronounced lateralized attack using their slightly skewed mouth morphology, and improved the velocity and amplitude of body flexion to succeed in foraging scales during dominant-side attack. Naïve young fish, however, did not improve the dynamics of flexion movement, but progressively developed attack side preference and speed to approach the prey through predation experience. Thus, the cichlid learns different aspects of predation behavior at different developmental stages. In contrast, naïve adults lost the inherent laterality, and they neither developed the lateralized motions nor increased their success rate of predation, indicating that they missed appropriate learning opportunities for scale-eating skills. Therefore, we conclude that behavioral laterality of the cichlid fish requires the integration of genetic basis and behavioral experiences during early developmental stages, immediately after they start scale-eating.

Limb Preference in Animals: New Insights into the Evolution of Manual Laterality in Hominids

Until the 1990s, the notion of brain lateralization—the division of labor between the two hemispheres—and its more visible behavioral manifestation, handedness, remained fiercely defined as a human specific trait. Since then, many studies have evidenced lateralized functions in a wide range of species, including both vertebrates and invertebrates. In this review, we highlight the great contribution of comparative research to the understanding of human handedness’ evolutionary and developmental pathways, by distinguishing animal forelimb asymmetries for functionally different actions—i.e., potentially depending on different hemispheric specializations. Firstly, lateralization for the manipulation of inanimate objects has been associated with genetic and ontogenetic factors, with specific brain regions’ activity, and with morphological limb specializations. These could have emerged under selective pressures notably related to the animal locomotion and social styles. Secondly, lateralization for actions directed to living targets (to self or conspecifics) seems to be in relationship with the brain lateralization for emotion processing. Thirdly, findings on primates’ hand preferences for communicative gestures accounts for a link between gestural laterality and a left-hemispheric specialization for intentional communication and language. Throughout this review, we highlight the value of functional neuroimaging and developmental approaches to shed light on the mechanisms underlying human handedness.

Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish.

Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable. Our previous work has shown that bias is maintained by a habenula-rostral PT circuit and genes associated with Notch signaling. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. We show unbiased behavior is not due to a loss of photo-responsiveness but reduced persistence in same-direction turning. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling disrupts habenula development and turn bias individuality in a dose dependent manner, establishing a direct role of Notch signaling. Last, a mutant allele of a known Notch pathway affecter gene, gsx2, disrupts turn bias individuality, implicating that brain regions independent of the previously established habenula-rostral PT likely contribute to inter-individual variation. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with established neural targets showing sensitivity to specific environmental and gene signaling disruptions. Our results provide new insight into how variation is generated in the vertebrate nervous system.

Random or handedness? Use of laterally paired penises inNalaearwigs (Insecta: Dermaptera: Labiduridae)

AbstractAnimals can show bias in their use of laterally paired organs that do not have any conspicuous anatomical differentiation between the right and left organs. Like right handedness in humans, males of the giant earwig Labidura riparia (Labiduridae: Labidurinae) preferentially (~90%) use the right one of their laterally paired penises for copulation. To elucidate the evolutionary origin of this lateralization, patterns of penis use were examined for the related species of the genus Nala (Labiduridae: Nalinae). In multiple populations and broods of both Nala lividipes and Nala nepalensis, males that were ready to use the right or left penis were equally frequent, providing a striking contrast to Labidura. Surgical ablation of one of the two penises revealed that both penises are functionally competent in N. lividipes. Nevertheless, each male almost consistently used only one of the paired penises, either the right or the left one. Changes in penis use were estimated to occur only once per 64–143 days per male. The present study is the first report of individual-level lateralization for animal genitalia that do not show any conspicuous anatomical differentiation between the right and left organs. Possible advantages of lateralization are discussed in relationship to co-evolution of the genitalia between the sexes.

Repeatability of lateralisation in mosquitofish Gambusia holbrooki despite evidence for turn alternation in detour tests.

Akin to handedness in humans, some animals show a preference for moving to the left or right. This is often attributed to lateralised cognitive functions and eye dominance, which, in turn, influences their behaviour. In fishes, behavioural lateralisation has been tested using detour mazes for over 20years. Studies report that certain individuals are more likely to approach predators or potential mates from one direction. These findings imply that the lateralisation behaviour of individuals is repeatable, but this is rarely confirmed through multiple testing of each individual over time. Here we quantify the repeatability of turning behaviour by female mosquitofish (Gambusia holbrooki) in a double sided T-maze. Each female was tested three times in each of six treatments: when approaching other females, males, or an empty space; and when able to swim freely or when forced to choose by being herded from behind with a net. Although there was no turning bias based on the mean population response, we detected significant repeatability of lateralisation in five of the six treatments (R = 0.251-0.625). This is noteworthy as we also found that individuals tended to alternate between left and right turns, meaning that they tend to move back and forth along one wall of the double-sided T-maze. Furthermore, we found evidence for this wall following when re-analysing data from a previous study. We discuss potential explanations for this phenomenon, and its implications for study design.

An examination of the influence of prenatal sex hormones on handedness: Literature review and amniotic fluid data

Competing theories have posited roles for foetal androgen exposure in the development of human handedness. However, due to practical and ethical considerations, few studies have used hormonal measures to examine this possibility. The current paper reviews this literature and reveals a generally inconsistent pattern of results. We also present data from a longitudinal study of prenatal sex hormone exposure and subsequent handedness. More specifically, we examine correlations between testosterone and estradiol measured from second trimester amniotic fluid and hand preference (Dutch language version of the Edinburgh Handedness Inventory) and hand skill asymmetry (pegboard task) measured at 15 years of age. Prenatal sex hormone exposure was not associated with the direction of hand preference in either males or females. However, in females, high levels of prenatal testosterone were associated with weaker lateralisation of hand skill, and high levels of prenatal estradiol were associated with weaker hand preference. In addition, high levels of prenatal testosterone were associated with increased task duration (i.e., slow hand speed) for the right and left hands of males. The pattern of results observed here is not entirely consistent with any of the main theories linking sex hormones with handedness, suggesting that an association between these variables may be more complex than initially thought.

Equestrian and biomechanical perspectives on laterality in the horse

It has been suggested that one of the underlying causes of asymmetrical performance and left/right bias in sound riding horses is laterality originating in the cerebral cortices described in many species. The aim of this paper is to review the published evidence for inherent biomechanical laterality in horses deemed to be clinically sound and relate these findings to descriptions of sidedness in equestrian texts. There are no established criteria to determine if a horse is left or right dominant but the preferred limb has been defined as the forelimb that is more frequently protracted during stance and when grazing. Findings on left-right differences in forelimb hoof shape and front hoof angles have been linked to asymmetric forelimb ground reaction forces. Asymmetries interpreted as motor laterality have been found among foals and unhandled youngsters, and the consistency or extent of asymmetries seems to increase with age. Expressions of laterality also vary with breed, sex, training and handling, stress, and body shape but there are no studies of the possible link between laterality and lameness. In a recent study of a group of seven dressage horses, a movement pattern in many ways similar to descriptions of sidedness in the equestrian literature, e.g. one hind limb being more protracted and placed more laterally than the other, has been documented. The role of innate laterality versus painful conditions, training, human handedness and simply habit remains to be determined. Understanding the biomechanical manifestations of laterality in healthy horses, including individual variation, would yield a potential basis for how laterality should be taken into account in relation to training/riding and rehabilitation of lameness.

Supplemental Material for Human Handedness: A Meta-Analysis

Supplemental Material for Human Handedness: A Meta-Analysis

Does hand skill asymmetry relate to creativity, developmental and health issues and aggression as markers of fitness?

ABSTRACTA remarkable feature of human handedness at the population level is specialization of the hands, the right hand performing usually better than the left. This specialization might have an evolutionary advantage, because it provides the individual and population with a wider range of skill. We therefore investigated the relationships between hand skill asymmetry and potential markers of Darwinian fitness that have been hypothesized to explain the bias in hand preference: creativity, aggression and developmental and health problems. Over twenty thousand participants (56% left-handers) completed an online survey, including a finger-tapping task to measure hand skill asymmetry. Left-skilled individuals were overall more aggressive than right-skilled individuals and rated themselves as more artistically creative. However, when assessed with a questionnaire, they were less creative on problem solving and equally artistically creative compared to right-skilled individuals, who reported more health problems. Conclusion: we found some evidence for current selection on the direction of lateralization of hand skill although the effect sizes were rather low. Strength of lateralization of hand skill showed only a few associations with fitness proxies. We suggest that Darwinian selection on hand preference (Zickert, Feen, van der, Geuze, & Groothuis, 2018. Fitness costs and benefits associated with hand preference in humans: A large internet study in a Dutch sample. Evolution and Human Behavior, 39, 235–248) and hand skill asymmetry (present study) may be attenuated in modern society.

Handedness in monkeys reflects hemispheric specialization within the central sulcus. An in vivo MRI study in right- and left-handed olive baboons

Handedness, one of the most prominent expressions of laterality, has been historically considered unique to human. This noteworthy feature relates to contralateral inter-hemispheric asymmetries in the motor hand area following the mid-portion of the central sulcus. However, within an evolutionary approach, it remains debatable whether hand preferences in nonhuman primates are associated with similar patterns of hemispheric specialization. In the present study conducted in Old world monkeys, we investigate anatomical asymmetries of the central sulcus in a sample of 86 olive baboons (Papio anubis) from in vivo T1 anatomical magnetic resonance images (MRI). Out of this sample, 35 individuals were classified as right-handed and 28 as left-handed according to their hand use responses elicited by a bimanual coordinated tube task. Here we report that the direction and degree of hand preference (left or right), as measured by this manual task, relates to and correlates with contralateral hemispheric sulcus depth asymmetry, within a mid-portion of the central sulcus. This neuroanatomical manifestation of handedness in baboons located in a region, which may correspond to the motor hand area, questions the phylogenetic origins of human handedness that may date back to their common ancestor, 25–40 millions years ago.

Lateralized display of spontaneous exploratory behaviour induced by novelty in intact rats: Effects of geometrically different environments

Laterality is conceived as a functional property of the brain, where parallel neural circuits modulate complementary aspects of one function. Well known examples are handedness and speech in humans. Laterality also is present in animals indicating a general evolutionary functional aspect and not a single distinctive trait of humans. In the present work, the consistency of one lateralized response in the spontaneous behaviour of exploration, driven by novel environments with different geometrical proportions was studied in rats. Consistency of response was considered when the animal shows the same preferential display in different testing contexts. Three geometrical forms of environments (square, rectangle and T shaped environment) were presented to normal intact rats. Exploratory activity measured by a digital counting device was video-taped in a 3 min duration tests. In these environments, rats had the choice to explore the right or the left aspect of the devices. Results show that in the square box, animals showed a right-biased exploration, and show no preference in the rectangular box, and left-biased exploration in the T shaped environment. Data reveal that animals show inconsistency in the lateralized behavioural response, where the geometrical characteristics of the environment are important to display some biased response.

Handedness in gestural and manipulative actions in male hunter-gatherer Aka pygmies from Central African Republic.

All human populations display a right-biased handedness. Nonetheless, if studies on western populations are plenty, investigations of traditional populations living at subsistence levels are rare. Yet, understanding the geographical variation of phenotypes of handedness is crucial for testing evolutionary hypotheses. We aimed to provide a preliminary investigation of factors affecting handedness in 25 Aka pygmies from Central African Republic when spontaneously gesturing or manipulating food/tools (Nactions = 593). We recorded spontaneous behaviors and characterized individuals' hand preference using GLMM with descriptive variables as target position, task complexity (unimanual/bimanual), task nature (food/tool manipulation, gesture), and task physical/cognitive constraints (precision or power for manipulative actions and informative content for gestures). Individuals were lateralized to the right (93%, N = 15) when manipulating food/tools but not when gesturing. Hand preference was affected by target position but not by task complexity. While nonexplicitly informative gestures were more biased to the right compared to explicitly informative ones, no differences were found within food/tool manipulation (power or precision vs. none). Although we do not intend to assume generalizable results due to our reduced sample, our observations provide additional information on handedness in a contemporary traditional society. Especially, the study mainly evidenced considerable cultural effects in gestures while also supporting theories considering active tool manipulation as one of the overriding factor in human handedness evolution.