Rare variants and handedness: spotlight on TUBB4B.

Twin studies suggest that additive genetic effects account for about a quarter of the variance in handedness. Recently, Schijven et al. used exome-wide sequencing to provide evidence for a role of rare protein-coding variants in handedness. These included the gene encoding beta-tubulin, TUBB4B, suggesting that microtubules are relevant for handedness ontogenesis.

Measuring paw preferences in dogs, cats and rats: Design requirements and innovations in methodology.

Studying behavioural lateralization in animals holds great potential for answering important questions in laterality research and clinical neuroscience. However, comparative research encounters challenges in reliability and validity, requiring new approaches and innovative designs to overcome. Although validated tests exist for some species, there is yet no standard test to compare lateralized manual behaviours between individuals, populations, and animal species. One of the main reasons is that different fine-motor abilities and postures must be considered for each species. Given that pawedness/handedness is a universal marker for behavioural lateralization across species, this article focuses on three commonly investigated species in laterality research: dogs, cats, and rats. We will present six apparatuses (two for dogs, three for cats, and one for rats) that enable an accurate assessment of paw preference. Design requirements and specifications such as zoometric fit for different body sizes and ages, reliability, robustness of the material, maintenance during and after testing, and animal welfare are extremely important when designing a new apparatus. Given that the study of behavioural lateralization yields crucial insights into animal welfare, laterality research, and clinical neuroscience, we aim to provide a solution to these challenges by presenting design requirements and innovations in methodology across species.

Cross-hemispheric communication: Insights on lateralized brain functions.

On the surface, the two hemispheres of vertebrate brains look almost perfectly symmetrical, but several motor, sensory, and cognitive systems show a deeply lateralized organization. Importantly, the two hemispheres are connected by various commissures, white matter tracts that cross the brain's midline and enable cross-hemispheric communication. Cross-hemispheric communication has been suggested to play an important role in the emergence of lateralized brain functions. Here, we review current advances in understanding cross-hemispheric communication that have been made using modern neuroscientific tools in rodents and other model species, such as genetic labeling, large-scale recordings of neuronal activity, spatiotemporally precise perturbation, and quantitative behavior analyses. These findings suggest that the emergence of lateralized brain functions cannot be fully explained by largely static factors such as genetic variation and differences in structural brain asymmetries. In addition, learning-dependent asymmetric interactions between the left and right hemispheres shape lateralized brain functions.

A Comparison of Hugging Frequency and Its Association with Momentary Mood Before and During COVID-19 Using Ecological Momentary Assessment.

The COVID-19 pandemic has necessitated a drastic decrease in human social interactions including social touch. One of the most prevalent forms of touch is hugging. Hugging has been demonstrated to benefit both physical and mental well-being. In the present study, we used an ecological momentary assessment approach to assess the relationship between hugging and momentary mood in two independent cohorts sampled prior or during the pandemic. We found that the frequency of hugging was significantly reduced during the pandemic. Using multilevel modeling, we found a significant positive association between momentary mood and daily hugs. This effect was moderated by the cohort, as individuals during the pandemic showed a stronger positive association compared to the cohort sampled prior to the pandemic. While we have to stress that our results are correlational in nature, they potentially indicate that social touch is more beneficial in times of social distancing.

Stability and durability of salivary alpha-amylase across different storage conditions.

Data collection in remote and field settings gains importance and popularity in stress research. Accordingly, existing stress induction paradigms have been successfully adapted to remote and field settings. However, guidelines for the comprehensive assessment of biomarkers such as salivary alpha-amylase (sAA) have yet to be sufficiently established for such contexts. In remote and field settings, swift freezing of saliva samples is not always possible, and samples must be returned to the laboratory for further processing. The current study investigated the robustness of sAA activity against external factors that may affect measurements obtained from saliva samples collected in field and remote settings. We compared sAA activity of samples that were stored in different vials (Salivettes® and Eppendorf® vials) and that were exposed to (1) up to three cycles of freezing and thawing, (2) different temperatures (4 °C, 20 °C, 30 °C, and 40 °C) for 3, 7, 14, or 28 days, or that were (3) sent via postal delivery. Results indicate sAA activity to be susceptible across different temperatures, different time intervals, and different vials. As a systematic pattern, sAA activity seems to decrease in treated samples with this effect being potentiated by more extreme conditions such as higher temperatures and longer time intervals. To conclude, sAA data collected in remote or field settings could be affected systematically by various external variables. Future studies collecting sAA should take factors influencing the durability and stability of sAA into account to ensure reliable and valid measurements of salivary data.

Behavioral lateralization in bipolar disorders: a systematic review.

BACKGROUND: Bipolar disorder (BD) is often seen as a bridge between schizophrenia and depression in terms of symptomatology and etiology. Interestingly, hemispheric asymmetries as well as behavioral lateralization are shifted towards a tendency of left-side or mixed-side bias in schizophrenia whereas no shift is observed in subjects with depression. Given the role of BD with both, (hypo)manic and depressive episodes, investigating hemispheric asymmetries in subjects with BD is an interesting objective. METHOD: A systematic review of studies including measures of behavioral lateralization in the form of handedness, footedness, eyedness, and language lateralization was performed resulting in 25 suitable studies. RESULTS: A broad variety of methods was used to assess behavioral lateralization, especially for eyedness, footedness, and language lateralization hindering the integration of results. Additionally, for hand preference, studies frequently used different cut-off scores and classification systems. Overall, studies do not support alteration in side preference in BD subjects. Studies focusing on differences in handedness demonstrate that subjects show equal rates of right- and non-right-handedness as the general population. Few studies focusing on manic episodes point towards increased left-side bias in ear and eye dominance, but the small sample sizes and conflicting results warrant further investigation. CONCLUSION: The results reinforce that some disorders, such as BD, should not be treated as a homogenous group but sub-groups should be analyzed within the patient's population. Particularly, clinical implications resulting from neuroimaging studies highlight the need to study hemispheric asymmetries given that they may be important to consider for brain stimulation protocols.

Elevated levels of mixed-hand preference in dyslexia: Meta-analyses of 68 studies.

Since almost a hundred years, psychologists have investigated the link between hand preference and dyslexia. We present a meta-analysis to determine whether there is indeed an increase in atypical hand preference in dyslexia. We included studies used in two previous meta-analyses (Bishop, 1990; Eglinton & Annett, 1994) as well as studies identified through PubMed MEDLINE, PsycInfo, Google Scholar, and Web of Science up to August 2022. K = 68 studies (n = 4660 individuals with dyslexia; n = 40845 controls) were entered into three random effects meta-analyses using the odds ratio as the effect size (non-right-handers; left-handers; mixed-handers vs. total). Evidence of elevated levels of atypical hand preference in dyslexia emerged that were especially pronounced for mixed-hand preference (OR = 1.57), although this category was underdefined. Differences in (direction or degree) of hand skill or degree of hand preference could not be assessed as no pertinent studies were located. Our findings allow for robust conclusions only for a relationship of mixed-hand preference with dyslexia.

Roosters do not warn the bird in the mirror: The cognitive ecology of mirror self-recognition.

Touching a mark on the own body when seeing this mark in a mirror is regarded as a correlate of self-awareness and seems confined to great apes and a few further species. However, this paradigm often produces false-negative results and possibly dichotomizes a gradual evolutionary transition of self-recognition. We hypothesized that this ability is more widespread if ecologically tested and developed such a procedure for a most unlikely candidate: chickens (Gallus gallus domesticus). Roosters warn conspecifics when seeing an aerial predator, but not when alone. Exploiting this natural behavior, we tested individual roosters alone, with another male, or with a mirror while a hawk's silhouette flew above them. Roosters mainly emitted alarm calls in the presence of another individual but not when alone or seeing themselves in the mirror. In contrast, our birds failed the classic mirror test. Thus, chickens possibly recognize their reflection as their own, strikingly showing how much cognition is ecologically embedded.

Hand Preference in Stuttering: Meta-Analyses.

Reduced hemispheric asymmetries, as well as their behavioral manifestation in the form of atypical handedness (i.e., non-right, left-, or mixed-handedness), are linked to neurodevelopmental disorders, such as autism spectrum disorder, and several psychiatric disorders, such as schizophrenia. One neurodevelopmental disorder that is associated with reduced hemispheric asymmetries, but for which findings on behavioral laterality are conflicting, is stuttering. Here, we report a series of meta-analyses of studies that report handedness (assessed as hand preference) levels in individuals who stutter (otherwise healthy) compared to controls. For this purpose, articles were identified via a search in PubMed, Scopus, and PsycInfo (13 June 2023). On the basis of k = 52 identified studies totaling n = 2590 individuals who stutter and n = 17,148 controls, five random effects meta-analyses were conducted: four using the odds ratio [left-handers (forced choice); left-handers (extreme); mixed-handers; non-right-handers vs. total)] and one using the standardized difference in means as the effect size. We did not find evidence of a left (extreme)- or mixed-handedness difference or a difference in mean handedness scores, but evidence did emerge, when it came to left-handedness (forced-choice) and (inconclusively for) non-right-handedness. Risk-of-bias analysis was not deemed necessary in the context of these meta-analyses. Differences in hand skill or strength of handedness could not be assessed as no pertinent studies were located. Severity of stuttering could not be used s a moderator, as too few studies broke down their data according to severity. Our findings do not allow for firm conclusions to be drawn on whether stuttering is associated with reduced hemispheric asymmetries, at least when it comes to their behavioral manifestation.

A deep phenotyping approach to assess the association of handedness, early life factors and mental health.

The development of handedness and other form of functional asymmetries is not yet understood in its critical determinants. Early life factors (e.g., birth weight, birth order) have been discussed to contribute to individual manifestations of functional asymmetries. However, large-scale data such as the UK Biobank suggest that the variance in handedness that is explained by early life factors is minimal. Additionally, atypical handedness has been linked to clinical outcomes such as neurodevelopmental and psychiatric disorders. Against the background of this triad, the current study investigated associations between different forms of functional asymmetries and (a) early life factors as well as (b) clinical outcomes. Functional asymmetries were determined by means of a deep phenotyping approach which notably extends previous work. In our final sample of N = 598 healthy participants, the different variables were tested for associations by means of linear regression models and group comparisons (i.e., ANOVAs and Chi-squared tests). Confirming previous findings from larger cohorts with shallow phenotyping, we found that birth factors do not explain a substantial amount of variance in functional asymmetries. Likewise, functional asymmetries did not seem to have comprehensive predictive power concerning clinical outcomes in our healthy participants. Future studies may further investigate postulated relations in healthy and clinical samples while acknowledging deep phenotyping of laterality.

Handedness and anxiety: a review.

Handedness is a core phenotype in clinical laterality research and several different disorders such as schizophrenia and autism spectrum disorders have been linked to a higher prevalence of non-right-handedness. Moreover, subclinical personality traits like schizotypy have been linked to a higher prevalence of non-right-handedness. The association with handedness is poorly understood for generalized anxiety disorder and specific phobias, as well as for state and trait anxiety and fear of specific stimuli in nonclinical samples. Therefore, we performed a narrative review of studies investigating handedness in anxiety disorders patients and studies that compared anxiety scores between different handedness groups. Unlike schizophrenia and autism spectrum disorders, there seems to be no strong association between anxiety disorders and handedness in adult patients, except for specific phobias. Studies often had small sample sizes and therefore a high risk to report spurious findings. Similar findings were reported in most non-clinical studies. Importantly, familial handedness affects phobia risk and antenatal maternal anxiety increased the probability of mixed-handedness. This suggests that a transgenerational, developmental perspective is essential to better understand the complex interrelations between handedness and anxiety. Familial and especially maternal handedness and anxiety disorders should be integrated into future studies on handedness and anxiety whenever possible.

Walk the plank! Using mobile electroencephalography to investigate emotional lateralization of immersive fear in virtual reality.

Most studies on emotion processing induce emotions through images or films. However, this method lacks ecological validity, limiting generalization to real-life emotion processing. More realistic paradigms using virtual reality (VR) may be better suited to investigate authentic emotional states and their neuronal correlates. This pre-registered study examines the neuronal underpinnings of naturalistic fear, measured using mobile electroencephalography (EEG). Seventy-five healthy participants walked across a virtual plank which extended from the side of a skyscraper-either 80 storeys up (the negative condition) or at street level (the neutral condition). Subjective ratings showed that the negative condition induced feelings of fear. Following the VR experience, participants passively viewed negative and neutral images from the international affective picture system (IAPS) outside of VR. We compared frontal alpha asymmetry between the plank and IAPS task and across valence of the conditions. Asymmetry indices in the plank task revealed greater right-hemispheric lateralization during the negative VR condition, relative to the neutral VR condition and to IAPS viewing. Within the IAPS task, no significant asymmetries were detected. In summary, our findings indicate that immersive technologies such as VR can advance emotion research by providing more ecologically valid ways to induce emotion.

Monitoring Brain Activity in VR: EEG and Neuroimaging.

Virtual reality (VR) is increasingly used in neuroscientific research to increase ecological validity without sacrificing experimental control, to provide a richer visual and multisensory experience, and to foster immersion and presence in study participants, which leads to increased motivation and affective experience. But the use of VR, particularly when coupled with neuroimaging or neurostimulation techniques such as electroencephalography (EEG), functional magnetic resonance imaging (fMRI), or transcranial magnetic stimulation (TMS), also yields some challenges. These include intricacies of the technical setup, increased noise in the data due to movement, and a lack of standard protocols for data collection and analysis. This chapter examines current approaches to recording, pre-processing, and analyzing electrophysiological (stationary and mobile EEG), as well as neuroimaging data recorded during VR engagement. It also discusses approaches to synchronizing these data with other data streams. In general, previous research has used a range of different approaches to technical setup and data processing, and detailed reporting of procedures is urgently needed in future studies to ensure comparability and replicability. More support for open-source VR software as well as the development of consensus and best practice papers on issues such as the handling of movement artifacts in mobile EEG-VR will be essential steps in ensuring the continued success of this exciting and powerful technique in neuroscientific research.

Hemispheric asymmetries and brain size in mammals.

Hemispheric asymmetries differ considerably across species, but the neurophysiological base of this variation is unclear. It has been suggested that hemispheric asymmetries evolved to bypass interhemispheric conduction delay when performing time-critical tasks. This implies that large brains should be more asymmetric. We performed preregistered cross-species meta-regressions with brain mass and neuron number as predictors for limb preferences, a behavioral marker of hemispheric asymmetries, in mammals. Brain mass and neuron number showed positive associations with rightward limb preferences but negative associations with leftward limb preferences. No significant associations were found for ambilaterality. These results are only partly in line with the idea that conduction delay is the critical factor that drives the evolution of hemispheric asymmetries. They suggest that larger-brained species tend to shift towards more right-lateralized individuals. Therefore, the need for coordination of lateralized responses in social species needs to be considered in the context of the evolution of hemispheric asymmetries.

Ultra-high field imaging of the amygdala - A narrative review.

The amygdala is an evolutionarily conserved core structure in emotion processing and one of the key regions of interest in affective neuroscience. Results of neuroimaging studies focusing on the amygdala are, however, often heterogeneous since it is composed of functionally and neuroanatomically distinct subnuclei. Fortunately, ultra-high-field imaging offers several advances for amygdala research, most importantly more accurate representation of functional and structural properties of subnuclei and their connectivity. Most clinical studies using ultra-high-field imaging focused on major depression, suggesting either overall rightward amygdala atrophy or distinct bilateral patterns of subnuclear atrophy and hypertrophy. Other pathologies are only sparsely covered. Connectivity analyses identified widespread networks for learning and memory, stimulus processing, cognition, and social processes. They provide evidence for distinct roles of the central, basal, and basolateral nucleus, and the extended amygdala in fear and emotion processing. Amid largely sparse and ambiguous evidence, we propose theoretical and methodological considerations that will guide ultra-high-field imaging in comprehensive investigations to help disentangle the ambiguity of the amygdala's function, structure, connectivity, and clinical relevance.

A single dose of hydrocortisone does not alter interhemispheric transfer of information or transcallosal integration.

Stress has been suggested as a factor that may explain the link between altered functional lateralization and psychopathology. Modulation of the function of the corpus callosum via stress hormones may be crucial in this regard. Interestingly, there is evidence that interhemispheric integration and hemispheric asymmetries are modifiable by endocrinological influences. In previous studies, our group could show an enhancing effect of acute stress on interhemispheric integration. To investigate if this effect can be attributed to an increase in the stress hormone cortisol, 50 male participants received 20 mg hydrocortisone or a placebo in a double-blind crossover design. In each test session, we collected EEG data while participants completed a lexical decision task and a Poffenberger paradigm. In the lexical decision task, we found shorter latencies of the N1 ERP component for contralateral compared to ipsilateral presentation of lexical stimuli. Similarly, we replicated the classical Poffenberger effect with shorter ERP latencies for stimuli presented in the contralateral visual field compared to the ipsilateral visual field. However, no effect of cortisol on latency differences between hemispheres could be detected. These results suggest that a temporary increase in cortisol alone might not be enough to affect the interhemispheric transfer of information via the corpus callosum. Together with previous results from our group, this suggests that chronically elevated stress hormone levels play a more central role in the relationship between altered hemispheric asymmetries and a variety of mental disorders.

Structural architecture and brain network efficiency link polygenic scores to intelligence.

Intelligence is highly heritable. Genome-wide association studies (GWAS) have shown that thousands of alleles contribute to variation in intelligence with small effect sizes. Polygenic scores (PGS), which combine these effects into one genetic summary measure, are increasingly used to investigate polygenic effects in independent samples. Whereas PGS explain a considerable amount of variance in intelligence, it is largely unknown how brain structure and function mediate this relationship. Here, we show that individuals with higher PGS for educational attainment and intelligence had higher scores on cognitive tests, larger surface area, and more efficient fiber connectivity derived by graph theory. Fiber network efficiency as well as the surface of brain areas partly located in parieto-frontal regions were found to mediate the relationship between PGS and cognitive performance. These findings are a crucial step forward in decoding the neurogenetic underpinnings of intelligence, as they identify specific regional networks that link polygenic predisposition to intelligence.

Stress exposure, hand preference, and hand skill: A deep phenotyping approach.

ABSTRACTStress exposure and reactivity may show differential associations with handedness, but shallow phenotyping may influence the current knowledge. Importantly, different handedness measures do not necessarily show high correlations with each other and should not be used interchangeably as they may reflect different dimensions of laterality. Here, data on handedness from 599 participants in the population-based, longitudinal Dortmund Vital Study was used to determine various asymmetry indices. Hand preference was assessed with the Edinburgh Handedness Inventory (EHI) and the lateral preference inventory (LPI) measuring handedness, footedness, earedness, and eyedness. Hand performance was determined using the pegboard test. In addition, data on several dimensions of stress exposure and reactivity, including hair cortisol, and mental well-being was analysed to determine associations with handedness. All handedness measures correlated significantly with each other, with the strongest correlation between the EHI and the LPI handedness score. The EHI and LPI hand measures resulted in the highest effect sizes and most consistent correlations with stress or mental well-being. In contrast, the pegboard test only showed very little association with the stress and mental well-being measures. This highlights the importance of handedness phenotyping. Including preference measures is recommended to disentangle the link between handedness and mental health.