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.

triact package for R: analyzing the lying behavior of cows from accelerometer data.

Accelerometers are sensors proven to be useful to analyze the lying behavior of cows. For reasons of algorithm transparency and control, researchers often prefer to use their own data analysis scripts rather than proprietary software. We developed the triact R package that assists animal scientists in analyzing the lying behavior of cows from raw data recorded with a triaxial accelerometer (manufacturer agnostic) attached to a hind leg. In a user-friendly workflow, triact allows the determination of common measures for lying behavior including total lying duration, the number of lying bouts, and the mean duration of lying bouts. Further capabilities are the description of lying laterality and the calculation of proxies for the level of physical activity of the cow. In this publication we describe the functionality of triact and the rationales behind the implemented algorithms. The triact R package is developed as an open-source project and freely available via the CRAN repository.

Effect of breathing conditions on relationships between impairment, breathing laterality and coordination symmetry in elite para swimmers.

The aim was to investigate the effect of breathing conditions and swimming pace on the relationships between the impairment, the breathing laterality and motor coordination symmetry in elite front crawl Para swimmers. Fifteen elite Para swimmers with unilateral physical impairment or with visual impairment and unilateral breathing preference performed eight 25 m using four breathing conditions (every three strokes, every two strokes on preferred and non-preferred breathing side and apnea) at slow and fast paces in a randomized order. Multicamera video system and five sensors have been used to assess arm and leg stroke phases and to compute symmetry of arm coordination (SIIdC) and of leg kick rate (SIKR). Our findings emphasized motor coordination asymmetry whatever the breathing conditions and swimming paces, highlighting the influence of impairment. Multinomial logistic regression exhibited a high probability for motor coordination asymmetry (SIIdC and SIKR) to be present in categories of Para swimmers with impairment and breathing laterality on the same side, suggesting the joined effect of unilateral impairment and unilateral breathing. Moreover, unilateral physical impairment and breathing laterality could also occur on different sides and generate motor coordination asymmetry on different sides and different levels (arms vs. legs). Finally, visual impairment seems amplify the effect of unilateral breathing on motor coordination asymmetry.

Comparison of migraine with left- versus right-sided headache: A cross-sectional study.

OBJECTIVE: The goal of this study was to clarify whether clinical differences exist between patients with migraine who experience headache that is typically left-sided ("left-migraine") versus right-sided ("right-migraine") during attacks. BACKGROUND: Migraine has been associated with unilateral headache for millennia and remains a supportive trait for the clinical diagnosis of migraine of the International Classification of Headache Disorders. It is currently unknown why headache in migraine is commonly unilateral, and whether headache-sidedness is associated with other clinical features. METHODS: This is a cross-sectional study comparing left- versus right-migraine using all available intake questionnaires of new patients evaluated at an academic tertiary headache center over a 20-year period. Eligibility was based on patient written responses indicating the typical location of headache during attacks. In our analyses, the side of headache (left or right) was the predictor variable. The outcomes included various migraine characteristics and psychiatric comorbidities. RESULTS: We identified 6527 patients with migraine, of which 340 met study eligibility criteria. Of these, 48.8% (166/340) had left migraine, and 51.2% (174/340) had right migraine. When comparing patients with left- versus right-migraine, patients with left migraine experienced 3.6 fewer headache-free days (95% confidence interval [CI] 1.3-5.9; p = 0.002) and 2.4 more severe headache days (95% CI 0.8-4.1; p = 0.004) in the previous 4 weeks. No significant differences in age, sex, handedness, migraine characteristics, or psychiatric comorbidities were identified between the two groups. CONCLUSIONS: Patients with migraine with typically left-sided headache during attacks reported a higher burden of headache frequency and severity than those with typically right-sided headache during attacks. These findings may have implications for our understanding of migraine pathophysiology, treatment, and clinical trial design.

Hemispheric asymmetry of hand and tool perception in left- and right-handers with known language dominance.

Regions in the brain that are selective for images of hands and tools have been suggested to be lateralised to the left hemisphere of right-handed individuals. In left-handers, many functions related to tool use or tool pantomime may also depend more on the left hemisphere. This result seems surprising, given that the dominant hand of these individuals is controlled by the right hemisphere. One explanation is that the left hemisphere is dominant for speech and language in the majority of left-handers, suggesting a supraordinate control system for complex motor sequencing that is required for skilled tool use, as well as for speech. In the present study, we examine if this left-hemispheric specialisation extends to perception of hands and tools in left- and right-handed individuals. We, crucially, also include a group of left-handers with right-hemispheric language dominance to examine their asymmetry biases. The results suggest that tools lateralise to the left hemisphere in most right-handed individuals with left-hemispheric language dominance. Tools also lateralise to the language dominant hemisphere in right-hemispheric language dominant left-handers, but the result for left-hemispheric language dominant left-handers are more varied, and no clear bias towards one hemisphere is found. Hands did not show a group-level asymmetry pattern in any of the groups. These results suggest a more complex picture regarding hemispheric overlap of hand and tool representations, and that visual appearance of tools may be driven in part by both language dominance and the hemisphere which controls the motor-dominant hand.

The line bisection bias as a deficit of proportional reasoning - evidence from number line estimation in neglect.

This study aimed to investigate whether neurological patients presenting with a bias in line bisection show specific problems in bisecting a line into two equal parts or their line bisection bias rather reflects a special case of a deficit in proportional reasoning more generally. In the latter case, the bias should also be observed for segmentations into thirds or quarters. To address this question, six neglect patients with a line bisection bias were administered additional tasks involving horizontal lines (e.g., segmentation into thirds and quarters, number line estimation, etc.). Their performance was compared to five neglect patients without a line bisection bias, 10 patients with right hemispheric lesions without neglect, and 32 healthy controls. Most interestingly, results indicated that neglect patients with a line bisection bias also overestimated segments on the left of the line (e.g., one third, one quarter) when dissecting lines into parts smaller than halves. In contrast, such segmentation biases were more nuanced when the required line segmentation was framed as a number line estimation task with either fractions or whole numbers. Taken together, this suggests a generalization of line bisection bias towards a segmentation or proportional processing bias, which is congruent with attentional weighting accounts of line bisection/neglect. As such, patients with a line bisection bias do not seem to have specific problems bisecting a line, but seem to suffer from a more general deficit processing proportions.

Disengagement of attention with spatial neglect: A systematic review of behavioral and anatomical findings.

The present review examined the consequences of focal brain injury on spatial attention studied with cueing paradigms, with a particular focus on the disengagement deficit, which refers to the abnormal slowing of reactions following an ipsilesional cue. Our review supports the established notion that the disengagement deficit is a functional marker of spatial neglect and is particularly pronounced when elicited by peripheral cues. Recent research has revealed that this deficit critically depends on cues that have task-relevant characteristics or are associated with negative reinforcement. Attentional capture by task-relevant cues is contingent on damage to the right temporo-parietal junction (TPJ) and is modulated by functional connections between the TPJ and the right insular cortex. Furthermore, damage to the dorsal premotor or prefrontal cortex (dPMC/dPFC) reduces the effect of task-relevant cues. These findings support an interactive model of the disengagement deficit, involving the right TPJ, the insula, and the dPMC/dPFC. These interconnected regions play a crucial role in regulating and adapting spatial attention to changing intrinsic values of stimuli in the environment.

Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities.

Associations between handedness and brain functional connectivity patterns in children.

Handedness develops early in life, but the structural and functional brain connectivity patterns associated with it remains unknown. Here we investigate associations between handedness and the asymmetry of brain connectivity in 9- to 10-years old children from the Adolescent Brain Cognitive Development (ABCD) study. Compared to right-handers, left-handers had increased global functional connectivity density in the left-hand motor area and decreased it in the right-hand motor area. A connectivity-based index of handedness provided a sharper differentiation between right- and left-handers. The laterality of hand-motor connectivity varied as a function of handedness in unimodal sensorimotor cortices, heteromodal areas, and cerebellum (P < 0.001) and reproduced across all regions of interest in Discovery and Replication subsamples. Here we show a strong association between handedness and the laterality of the functional connectivity patterns in the absence of differences in structural connectivity, brain morphometrics, and cortical myelin between left, right, and mixed handed children.

New origin of life theory may explain biomolecular handedness.

Experiments suggest chemical reaction rates explain how proteins came to be built from left-handed building blocks.

Handedness and effector strength modulate a compatibility effect between stimulus size and response position with manual and vocal responses.

Humans respond more quickly with the left hand to a small stimulus, and with the right hand to a large stimulus, as compared to the reverse mapping (spatial-size association of response codes [SSARC] effect). We investigated the hypothesis that strength differences between the hands contribute to the origin of this effect. Therefore, 80 left-handers and 80 right-handers participated in two experiments. In Experiment 1, participants performed a manual choice-response task in which we manipulated the mapping between physical stimulus size and responding hand. In addition, we measured the strengths of participants' left and right effectors (i.e., finger, hand, and arm). In Experiment 2, we measured the SSARC effect in vocal responses of the same sample. There were four main results. First, participants' dominant effectors were stronger than their nondominant effectors. Second, the SSARC effect occurred in manual and vocal responses with similar size. Third, in both modalities, the SSARC effect was larger in right-handers than in left-handers. Finally, strength differences between effectors (fingers and hands) correlated with the size of the SSARC effect. In sum, results support the hypothesis that functional differences between the hands contribute to the origin of the SSARC effect. In addition, the results suggest that size-space associations have generalized across motor systems, and formed a modality-independent association. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Historical changes in everyday human lifestyles and their effects on hemispheric activation: Speculations on McGilchrist's The Master and His Emissary.

McGilchrist [McGilchrist, I. (2009). The master and His emissary: The divided brain and the making of the modern world. Yale University Press] argued that Western society has undergone a population-level shift from greater right hemisphere influence on cognition to increasingly greater left hemisphere influence over the past few centuries. Four historical lifestyle changes that replaced behaviours associated with right hemisphere activation with behaviours associated with left hemisphere activation may be responsible: (i) shifts from standing to sitting, (ii) from being outdoors to indoors, (iii) from communal to solitary activities, and (iv) from analogue/concrete to holistic/abstract representations.

Left-hand preference in visual artists: A pre-registered observational study on Instagram.

The notion of an increased incidence of left handers among architects and visual artists has inspired both scientific theory building and popular discussion. However, a systematic exploration of the available publications provides, at best, modest evidence for this claim. The present preregistered observational study was designed to reinvestigate the postulated association by examining hand preference of visual artists who share their artistic activities as short video clips ("reels") on the social media platform Instagram. Determining individual hand preference based on five reels for each of N = 468 artists, we identified 42 (8.97%) left handers, suggesting an incidence which is below but statistical comparable to the 10.6% expected for the general population (χ2 = 1.30; p = .25; Cohen's w = 0.05). Also, we did not find any support for the notion that the art created by left-handed artists is of higher quality than art of right handers, as no difference in public endorsement or interest were observed (reflected by the number of likes per post or account followers). Taken together, we do not find any support for difference in artistic engagement or quality between left and right handers.

Sleight of hand: role-differentiated bimanual manipulation speed across infancy.

Role-differentiated bimanual manipulation (RDBM) is a complex behaviour requiring the complementary movement of two hands to achieve a common goal. We investigated the relation of RDBM speed (time to complete a successful RDBM) with a hand preference for acquiring objects (early right, late right, left, no preference), toy type (simple/difficult), age (9-14 months), and hand (right/left) used to perform the RDBM. Changes in RDBM speed across age were examined across different hand preference groups for RDBMs performed on simple toys using the right hand. The analysis revealed that early-right preference infants had a steeper slope than the no preference/left-preference infants. The same was true for right-preference infants (early- and late-) for RDBMs performed on difficult toys using the right hand. A mixed ANOVA revealed that there were decreases in RDBM times across age, therefore infants are faster at performing RDBMs over time, regardless of toy type, hand used, or hand preference. The results of the present study suggest that when exploring the development of hand preference, we should consider the influence of age, hand preference, and hand used.

The Italian version of Edinburgh Handedness Inventory: Translation, transcultural adaptation, and validation in healthy subjects.

Lateralization is a key aspect of brain architecture and handedness is its primary manifestation. The Edinburgh Handedness Inventory (EHI) and the laterality quotient (LQ) assess the direction and consistency of handedness and require translation and cross-cultural adaptation to guarantee construct validity. We developed a standardized Italian EHI version. The developed Italian version was tested on 202 Italian subjects, classified into three hand types based on their LQs: right, mixed, and left. The frequency of left-handedness in Italians and other populations was compared to previous data. LQs from the twenty- and the ten-item original inventories were also compared. We conducted a factorial analysis. Mcdonald's Omega tested internal consistency. The prevalence of left-handedness was 6.4%, consistent with prior findings in Italian samples and other EHI translations. Age was the only socio-demographic variable that significantly affected the LQ. The internal consistency of the Italian EHI was excellent. Handedness is a feature of several cognitive functions and some neuropsychological diseases; it is influenced by socio-demographic and cultural factors and the instrument used to assess it. To provide a consistent and comparable evaluation of the construct, we recommend using this validated Italian translation of the EHI.

Atypical brain lateralization for speech processing at the sublexical level in autistic children revealed by fNIRS.

Autistic children often exhibit atypical brain lateralization of language processing, but it is unclear what aspects of language contribute to this phenomenon. This study employed functional near-infrared spectroscopy to measure hemispheric lateralization by estimating hemodynamic responses associated with processing linguistic and non-linguistic auditory stimuli. The study involved a group of autistic children (N = 20, mean age = 5.8 years) and a comparison group of nonautistic peers (N = 20, mean age = 6.5 years). The children were presented with stimuli with systematically decreasing linguistic relevance: naturalistic native speech, meaningless native speech with scrambled word order, nonnative speech, and music. The results revealed that both groups showed left lateralization in the temporal lobe when listening to naturalistic native speech. However, the distinction emerged between autism and nonautistic in terms of processing the linguistic hierarchy. Specifically, the nonautistic comparison group demonstrated a systematic reduction in left lateralization as linguistic relevance decreased. In contrast, the autism group displayed no such pattern and showed no lateralization when listening to scrambled native speech accompanied by enhanced response in the right hemisphere. These results provide evidence of atypical neural specialization for spoken language in preschool- and school-age autistic children and shed new light on the underlying linguistic correlates contributing to such atypicality at the sublexical level.

Roles of Handedness and Hemispheric Lateralization: Implications for Rehabilitation of the Central and Peripheral Nervous Systems: A Rapid Review.

IMPORTANCE: Handedness and motor asymmetry are important features of occupational performance. With an increased understanding of the basic neural mechanisms surrounding handedness, clinicians will be better able to implement targeted, evidence-based neurorehabilitation interventions to promote functional independence. OBJECTIVE: To review the basic neural mechanisms behind handedness and their implications for central and peripheral nervous system injury. DATA SOURCES: Relevant published literature obtained via MEDLINE. FINDINGS: Handedness, along with performance asymmetries observed between the dominant and nondominant hands, may be due to hemispheric specializations for motor control. These specializations contribute to predictable motor control deficits that are dependent on which hemisphere or limb has been affected. Clinical practice recommendations for occupational therapists and other rehabilitation specialists are presented. CONCLUSIONS AND RELEVANCE: It is vital that occupational therapists and other rehabilitation specialists consider handedness and hemispheric lateralization during evaluation and treatment. With an increased understanding of the basic neural mechanisms surrounding handedness, clinicians will be better able to implement targeted, evidence-based neurorehabilitation interventions to promote functional independence. Plain-Language Summary: The goal of this narrative review is to increase clinicians' understanding of the basic neural mechanisms related to handedness (the tendency to select one hand over the other for specific tasks) and their implications for central and peripheral nervous system injury and rehabilitation. An enhanced understanding of these mechanisms may allow clinicians to better tailor neurorehabilitation interventions to address motor deficits and promote functional independence.

Brain asymmetries from mid- to late life and hemispheric brain age.

The human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evaluate age-related differences in brain asymmetry. Most regional grey and white matter metrics presented asymmetry, which were higher later in life. Informed by these results, we conducted hemispheric brain age (HBA) predictions from left/right multimodal MRI metrics. HBA was concordant to conventional brain age predictions, using metrics from both hemispheres, but offers a supplemental general marker of brain asymmetry when setting left/right HBA into relationship with each other. In contrast to WM brain asymmetries, left/right discrepancies in HBA are lower at higher ages. Our findings outline various sex-specific differences, particularly important for brain age estimates, and the value of further investigating the role of brain asymmetries in brain ageing and disease development.

Assessment of language lateralization in epilepsy patients using the super-selective Wada test.

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.