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.

Romantic partner embraces reduce cortisol release after acute stress induction in women but not in men.

Stress is omnipresent in our everyday lives. It is therefore critical to identify potential stress-buffering behaviors that can help to prevent the negative effects of acute stress in daily life. Massages, a form of social touch, are an effective buffer against both the endocrinological and sympathetic stress response in women. However, for other forms of social touch, potential stress-buffering effects have not been investigated in detail. Furthermore, the possible stress-buffering effects of social touch on men have not been researched so far. The present study focused on embracing, one of the most common forms of social touch across many cultures. We used a short-term embrace between romantic partners as a social touch intervention prior to the induction of acute stress via the Socially Evaluated Cold Pressor Test. Women who embraced their partner prior to being stressed showed a reduced cortisol response compared to a control group in which no embrace occurred. No stress-buffering effect could be observed in men. No differences between the embrace and control group were observed regarding sympathetic nervous system activation measured via blood pressure or subjective affect ratings. These findings suggest that in women, short-term embraces prior to stressful social situations such as examinations or stressful interviews can reduce the cortisol response in that situation.

Acute stress increases left hemispheric activity measured via changes in frontal alpha asymmetries.

Frontal EEG alpha band asymmetries have been linked to affective processing in healthy individuals and affective disorders. As stress provides a strong source of negative affect, the present study investigated how acute stress affects frontal EEG alpha asymmetries. Continuous EEG data were acquired from 51 healthy adult participants during stress induction with the Trier Social Stress Test. EEG data were also collected during a non-stressful control condition. Furthermore, EEG resting state data were acquired after both conditions. Under stress, participants showed stronger left hemispheric activation over frontal electrodes as well as reduced left-hemispheric activation over occipital electrodes compared to the control condition. Our results are in line with predictions of the asymmetric inhibition model which postulates that the left prefrontal cortex inhibits negative distractors. Moreover, the results support the capability model of emotional regulation which states that frontal asymmetries during emotional challenge are more pronounced compared to asymmetries during rest.

Ewww-Investigating the neural basis of disgust in response to naturalistic and pictorial nauseating stimuli.

Emotion induction in psychological and neuroscientific research has been mostly done by presenting participants with picture or film material. However, it is debatable whether this passive approach to emotion induction results in an affective state comparable to real-life emotions, and if the neural correlates of emotion processing are ecologically valid. To investigate the appropriateness of pictures for the induction of emotions, we presented 56 participants in a within-subjects design with naturalistic disgusting and neutral stimuli as well as with pictures of said stimulus material while recording continuous EEG data. We calculated asymmetry indices (AIs) for alpha power as an index of emotion processing and emotion regulation at the F3/4, F5/6, F7/8, and O1/2 electrode pairs. Participants reported higher disgust ratings for disgusting naturalistic compared to disgusting pictorial stimuli. Investigating changes in the EEG signal in participants with a pronounced disgust response (n = 38), we found smaller AIs for naturalistic stimuli compared to pictures. Moreover, in this disgusted sub-sample, there were smaller AIs in response to naturalistic disgusting stimuli compared to pictorial disgusting and neutral stimuli at the O1/2 electrode pair indicating stronger activation of the right relative to the left hemisphere by naturalistic stimuli. As the right hemisphere has been shown to display dominance in processing negative and withdrawal-associated emotions, this might indicate that naturalistic stimuli are more appropriate for the induction of emotions than picture stimuli. To improve the validity of results from emotion induction, future research should incorporate stimulus material that is as naturalistic as possible.

Improved interhemispheric connectivity after stress during lexical decision making.

Functional hemispheric asymmetries emerge as the left and the right hemisphere are dominant for different aspects of task processing. However, the hemispheres do not work independent of each other but share information through the corpus callosum. The integration of information across the corpus callosum is dependent on its structural integrity and functionality. Several hormones, like estradiol and progesterone, can influence this function. Since earlier work has demonstrated that long-term changes in stress hormone levels are accompanied by changes in hemispheric asymmetries in several mental disorders, the aim of the current study was to investigate whether acute stress and the associated changes in stress hormone levels also affect information transfer across the corpus callosum. For this purpose, we collected EEG data from 51 participants while completing a lexical decision task and a Poffenberger paradigm twice, once after stress induction with the Trier Social Stress Test and once after a control-condition. While there were no differences in interhemispheric transfer between the stress and the non-stress condition in the Poffenberger paradigm, we observed shorter latencies to stimuli in the left visual field in the left hemisphere at the CP3-CP4 electrode pair after stress. These results suggest that the transfer of lexical material from the right to the left hemisphere was quicker under stress. Stress may increase callosal excitability and lead to more efficient signal transfer across the corpus callosum between language related areas. Future studies using pharmacological intervention are needed to further examine cooperation of the hemispheres under stress in more detail.

Dichotic listening performance and interhemispheric integration after administration of hydrocortisone.

Chronic stress has been shown to have long-term effects on functional hemispheric asymmetries in both humans and non-human species. The short-term effects of acute stress exposure on functional hemispheric asymmetries are less well investigated. It has been suggested that acute stress can affect functional hemispheric asymmetries by modulating inhibitory function of the corpus callosum, the white matter pathway that connects the two hemispheres. On the molecular level, this modulation may be caused by a stress-related increase in cortisol, a major stress hormone. Therefore, it was the aim of the present study to investigate the acute effects of cortisol on functional hemispheric asymmetries. Overall, 60 participants were tested after administration of 20 mg hydrocortisone or a placebo tablet in a cross-over design. Both times, a verbal and an emotional dichotic listening task to assess language and emotional lateralization, as well as a Banich-Belger task to assess interhemispheric integration were applied. Lateralization quotients were determined for both reaction times and correctly identified syllables in both dichotic listening tasks. In the Banich-Belger task, across-field advantages were determined to quantify interhemispheric integration. While we could replicate previously reported findings for these tasks in the placebo session, we could not detect any differences in asymmetry between hydrocortisone and placebo treatment. This partially corroborates the results of a previous study we performed using social stress to induce cortisol increases. This suggests that an increase in cortisol does not influence dichotic listening performance on a behavioral level. As other studies reported an effect of stress hormones on functional hemispheric asymmetries on a neuro-functional level, future research using neuronal imaging methods would be helpful in the characterization of the relation of hemispheric asymmetries and stress hormones.

Handedness and depression: A meta-analysis across 87 studies.

Alterations in functional brain lateralization, often indicated by an increased prevalence of left- and/or mixed-handedness, have been demonstrated in several psychiatric and neurodevelopmental disorders like schizophrenia or autism spectrum disorder. For depression, however, this relationship is largely unclear. While a few studies found evidence that handedness and depression are associated, both the effect size and the direction of this association remain elusive. Here, we collected data from 87 studies totaling 35,501 individuals to provide a precise estimate of differences in left-, mixed- and non-right-handedness between depressed and healthy samples and computed odds ratios (ORs) between these groups. Here, an OR > 1 signifies higher rates of atypical handedness in depressed compared to healthy samples. We found no differences in left- (OR = 1.04, 95% CI = [0.95, 1.15], p = .384), mixed- (OR = 1.64, 95% CI = [0.98, 2.74], p = .060) or non-right-handedness (OR = 1.05, 95% CI = [0.96, 1.15], p = .309) between the two groups. We could thus find no link between handedness and depression on the meta-analytical level.

Laterality 2020: Response to the article commentaries.

In our recent opinion paper "Laterality 2020: entering the next decade", we highlighted trends that we thought are likely to shape laterality research in the 2020s. Our opinion paper inspired 11 commentaries by experts from several disciplines which discussed a wide range of topics complementing the 10 trends we identified in the opinion paper. In this reply, we summarize and discuss the 11 commentaries by clustering them into 3 different main topics. The topic that was covered by the largest number of commentaries was the role of comparative and evolutionary approaches in laterality research. Moreover, several comments focused on the ontogenesis of hemispheric asymmetries and the importance of reliability and validity in laterality research. Embracing the technical advances, research trends and controversies laid out in the commentaries will significantly improve our understanding of several of the core questions of laterality research.

Investigating real-life emotions in romantic couples: a mobile EEG study.

The neural basis of emotional processing has been largely investigated in constrained spatial environments such as stationary EEGs or fMRI scanners using highly artificial stimuli like standardized pictures depicting emotional scenes. Typically, such standardized experiments have low ecological validity and it remains unclear whether their results reflect neuronal processing in real-life affective situations at all. Critically, emotional situations do not only encompass the perception of emotions, but also behavioral components associated with them. In this study, we aimed to investigate real-life emotions by recording couples in their homes using mobile EEG technology during embracing, kissing and emotional speech. We focused on asymmetries in affective processing as emotions have been demonstrated to be strongly lateralized in the brain. We found higher alpha and beta power asymmetry during kissing and embracing on frontal electrodes during emotional kisses and speech compared to a neutral control condition indicative of stronger left-hemispheric activation. In contrast, we found lower alpha power asymmetry at parieto-occipital electrode sites in the emotional compared to the neutral condition indicative of stronger right-hemispheric activation. Our findings for alpha power asymmetries are in line with models of emotional lateralization that postulate a valence-specific processing over frontal cortices and right-hemispheric dominance in emotional processing in parieto-occipital regions. In contrast, beta power asymmetries pointed more towards valence-specific processing indicating that, while alpha and beta frequencies seem to be functionally associated, they are not reflecting identical cognitive processing.

The brain under stress-A systematic review and activation likelihood estimation meta-analysis of changes in BOLD signal associated with acute stress exposure.

Psychosocial stress is an omnipresent phenomenon whose neural correlates in humans are still poorly understood. Several paradigms have been developed to induce acute stress in fMRI settings, but it is unclear whether there is a global brain activation pattern related to psychosocial stress. To integrate the different neuronal activation patterns, we conducted an activation likelihood estimation analysis on 31 studies totaling 1279 participants. Studies used the ScanSTRESS, Montreal Imaging Stress Test, aversive viewing paradigm (AVP), Social-Evaluative Threat or Cyberball. The analysis revealed bilateral activation clusters comprising the claustrum, insula and inferior frontal gyrus. This indicates that exposure to psychosocial stress leads to activations in brain areas involved in affective processing and the endocrine stress response. Furthermore, in a systematic review, Cyberball and AVP presented themselves as outliers due to increased activation in motor areas and lack of induction of stress related activity changes, respectively. As different paradigms emphasize different dimensions of psychosocial stress such as social evaluation or performance pressure, future research is needed to identify differences between the paradigms.

Laterality 2020: entering the next decade.

In the 2010s, significant progress has been made in several key areas of laterality research, including neuroimaging, genetics and comparative research. In the present article, we discuss which trends are likely to shape laterality research in the 2020s. These include, but are not limited to: (1) Finding laterality-specific solutions to the replication crisis. (2) Integrating non-W.E.I.R.D. (Western, Educated, Industrialized, Rich, and Democratic) samples into laterality research to a larger extent. (3). Combining meta-analysis and large-scale databank studies to come to unbiased conclusions about true effects. (4) Understanding altered laterality in different psychiatric and neurodevelopmental disorders. (5) Exploring the relevance of laterality research for the treatment of psychiatric and neurodevelopmental disorders. (6) Investigating the molecular correlates of environmental factors that affect laterality. (7) Bridging the gap between laterality research in human subjects and non-human model species. (8) Utilizing "next-generation" neuroimaging in laterality research. (9) Integrating graph-theory and machine learning into laterality research. (10) Enhancing ecological validity in laterality research using mobile EEG and smartphone-based data collection. These trends will likely shape the next decade of laterality research by opening the way for novel questions, enhancing collaborations and boosting the reliability and validity of research findings in our field.

Dichotic listening performance and interhemispheric integration after stress exposure.

Functional hemispheric asymmetries (FHAs) have been thought to be relatively stable over time. However, past research has shown that FHAs are more plastic than initially thought. Endocrinological processes have been demonstrated to alter FHAs. As the product of the stress-activated hypothalamus-pituitary-adrenal axis, cortisol influences information processing at every level from stimulus perception to decision making and action. To investigate the influence of acute stress on FHAs, 60 participants performed a Banich-Belger task, as well as a verbal and an emotional dichotic listening task in two sessions. One session included a stress induction via the Trier Social Stress Test, the other session included a control procedure. We calculated across-field advantages (AFAs) in the Banich-Belger task and lateralization quotients for reaction times and responses per side in both dichotic listening tasks. There were no significant differences between the stress and control session in the dichotic listening tasks. In contrast, there was evidence for an influence of cortisol and sympathetic activation indicated by salivary alpha amylase changes on AFAs in the Banich-Belger task. This indicates that acute stress and the related increase in cortisol do not influence dichotic listening performance. However, stress does seem to affect interhemispheric integration of information. Future research using EEG, fMRI and pharmacological interventions is needed to further characterize the relation of hemispheric asymmetries and acute stress.

Four meta-analyses across 164 studies on atypical footedness prevalence and its relation to handedness.

Human lateral preferences, such as handedness and footedness, have interested researchers for decades due to their pronounced asymmetries at the population level. While there are good estimates on the prevalence of handedness in the population, there is no large-scale estimation on the prevalence of footedness. Furthermore, the relationship between footedness and handedness still remains elusive. Here, we conducted meta-analyses with four different classification systems for footedness on 145,135 individuals across 164 studies including new data from the ALSPAC cohort. The study aimed to determine a reliable point estimate of footedness, to study the association between footedness and handedness, and to investigate moderating factors influencing footedness. We showed that the prevalence of atypical footedness ranges between 12.10% using the most conservative criterion of left-footedness to 23.7% including all left- and mixed-footers as a single non-right category. As many as 60.1% of left-handers were left-footed whereas only 3.2% of right-handers were left-footed. Males were 4.1% more often non-right-footed compared to females. Individuals with psychiatric and neurodevelopmental disorders exhibited a higher prevalence of non-right-footedness. Furthermore, the presence of mixed-footedness was higher in children compared to adults and left-footedness was increased in athletes compared to the general population. Finally, we showed that footedness is only marginally influenced by cultural and social factors, which play a crucial role in the determination of handedness. Overall, this study provides new and useful reference data for laterality research. Furthermore, the data suggest that footedness is a valuable phenotype for the study of lateral motor biases, its underlying genetics and neurodevelopment.

Atypical lateralization in neurodevelopmental and psychiatric disorders: What is the role of stress?

Hemispheric asymmetries are a major organizational principle of the human brain. In different neurodevelopmental and psychiatric disorders, like schizophrenia, autism spectrum disorders, depression, dyslexia and posttraumatic stress disorder, functional and/or structural hemispheric asymmetries are altered compared to healthy controls. The question, why these disorders all share the common characteristic of altered hemispheric asymmetries despite vastly different etiologies and symptoms remains one of the unsolved mysteries of laterality research. This review is aimed at reviewing potential reasons for why atypical lateralization is so common in many neurodevelopmental and psychiatric disorders. To this end, we review the evidence for overlaps in the genetic and non-genetic factors involved in the ontogenesis of different disorders and hemispheric asymmetries. While there is evidence for genetic overlap between different disorders, only few asymmetry-related loci have also been linked to disorders and importantly, those effects are mostly specific to single disorders. However, there is evidence for shared non-genetic influences between disorders and hemispheric asymmetries. Most neurodevelopmental and psychiatric disorders show alterations in the hypothalamic-pituitary adrenocortical (HPA) axis and maternal as well as early life stress have been implicated in their etiology. Stress has also been suggested to affect hemispheric asymmetries. We propose a model in which early life stress as well as chronic stress not only increases the risk for psychiatric and neurodevelopmental disorders but also changes structural and functional hemispheric asymmetries leading to the aberrant lateralization patterns seen in these disorders. Thus, pathology-related changes in hemispheric asymmetries are not a factor causing disorders, but rather a different phenotype that is affected by partly overlapping ontogenetic factors, primarily stress.

Handedness and sex effects on lateral biases in human cradling: Three meta-analyses.

The earliest form of social contact for a newborn is being cradled by its mother. This important behavior has been found to be lateralized to the left side by many, but not all empirical studies. Factors that have been suggested to modulate cradling asymmetry are handedness and sex. However, these factors have not been demonstrated consistently, possibly due to low sample sizes and inconsistent experimental paradigms. To address this issue, we used a meta-analytical approach to (1) quantify the widely reported leftward bias in human cradling and (2) identify moderating factors of the cradling bias such as handedness and sex. Across forty studies, we observed a leftward cradling bias showing that this effect is robust and replicable. Furthermore, we found that left-handers demonstrate a significantly less pronounced leftward bias compared to right-handers and that males are less lateralized compared to females. In conclusion, we could verify that parental handedness and sex contribute to a cradling population bias. Future studies examining genetic factors could illuminate the mechanism supporting a cradling bias.

Structural Asymmetry in the Frontal and Temporal Lobes Is Associated with PCSK6 VNTR Polymorphism.

The nodal cascade influences the development of bodily asymmetries in humans and other vertebrates. The gene PCSK6 has shown a regulatory function during left-right axis formation and is therefore thought to influence bodily left-right asymmetries. However, it is not clear if variation in this gene is also associated with structural asymmetries in the brain. We genotyped an intronic 33bp PCSK6 variable number tandem repeat (VNTR) polymorphism that has been associated with handedness in a cohort of healthy adults. We acquired T1-weighted structural MRI images of 320 participants and defined cortical surface and thickness for each HCP region. The results demonstrate a significant association between PCSK6 VNTR genotypes and gray matter asymmetry in the superior temporal sulcus, which is involved in voice perception. Heterozygous individuals who carry a short (≤ 6 repeats) and a long (≥ 9 repeats) PCSK6 VNTR allele show stronger rightward asymmetry. Further associations were evident in the dorsolateral prefrontal cortex. Here, individuals homozygous for short alleles show a more pronounced asymmetry. This shows that PCSK6, a gene that has been implicated in the ontogenesis of bodily asymmetries by regulating the nodal cascade, is also relevant for structural asymmetries in the human brain.