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Obstructive sleep apnea (OSA) is considered one of the major causes of sleep disorders and psychological disorders in individuals. Brain asymmetry (BA) demonstrates individual hemispheric activity and psychological disorders. This study aimed to explore the characteristics of BA and psychology in OSA. Enrolment of patients for sleep assessment at the Sleep Medicine Center. Clinical characteristics, handedness, and psychological scales were prospectively collected from subjects. Subsequently, EEG power in alpha, beta, and theta bilaterally was calculated for the rest and sleep phases. A total of 152 OSA and 21 non-OSA subjects were included in the study. In the frontal, central and occipital regions, OSA exhibited increased interhemispheric asymmetry with increasing apnea-hypopnea index (AHI) during rest and sleep. Simultaneously, the results showed that greater activity in the right hemisphere was positively associated with anxiety and extraversion, while inversely with positive and lie scale. In addition, the results show that OSA contributes to abnormal BA fluctuations during sleep. Our results suggest that sleep disorders associated with apnea-hypopnea and arousal may contribute to increased BA during sleep. Such changes may persist into wakefulness with psychological traits. • The association between sleep apnea and brain asymmetry. • Pathological mechanisms involved in OSA psychological disorders. • The correlation of brain asymmetry during sleep and wakefulness. [ABSTRACT FROM AUTHOR]

The roles of brain asymmetry in Drosophila are diverse, encompassing the regulation of behavior, the creation of memory, neurodevelopment, and evolution. A comprehensive examination of the Drosophila brain has the potential to enhance our understanding of the functional significance of brain asymmetry in cognitive and behavioral processes, as well as its role in evolutionary perspectives. This study explores the influence of brain asymmetry on interval timing behaviors in Drosophila, with a specific focus on the asymmetric body (AB) structure. Despite being bilaterally symmetric, the AB exhibits functional asymmetry and is located within the central complex of the fly brain. Interval timing behaviors, such as rival-induced prolonged mating duration: longer mating duration behavior (LMD) and sexual experience-mediated shorter mating duration behavior (SMD), are essential for Drosophila. We utilize genetic manipulations to selectively activate or inhibit AB neurons and evaluates their impact on LMD and SMD behaviors. The results indicate that specific populations of AB neurons play unique roles in orchestrating these interval timing behaviors. Notably, inhibiting GAL4R38D01-labeled AB neurons disrupts both LMD and SMD, while GAL4R42C09 neuron inhibition affects only LMD. Moreover, hyperexcitation of GAL4R72A10-labeled AB neurons perturbs SMD. Our study identifies NetrinB (NetB) and Abdominal-B (Abd-B) are important genes for AB neurons in LMD and highlights the role of 5-HT1B neurons in generating LMD through peptidergic Pigment-dispersing factor (PDF) signaling. In summary, this study underscores the importance of AB neuron asymmetry in mediating interval timing behaviors and provides insights into the underlying mechanisms of memory formation and function in Drosophila. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diagnosis of Autism Spectrum Disorder (ASD) relies on the observation of difficulties in social communication and interaction, plus the presence of repetitive and restrictive behaviors. The identification of neurological correlates of these symptoms remains a high priority for clinical research, and has the potential to increase the validity of diagnosis of ASD as well as provide greater understanding of how the autistic brain functions. This study focused on two neurological phenomena that have been previously associated with psychiatric disorders (alpha- and theta-wave asymmetry across the frontal region of the brain), and tested for their association with the major diagnostic criteria for ASD. Methods: A total of 41 male autistic youth underwent assessment with the Autism Diagnostic Observation Schedule (ADOS-2) and 3 min of eyes-closed resting EEG to collect alpha- and theta-wave data from right and left frontal brain sites. Results: Different associations were found for theta versus alpha asymmetry and the ADOS-2 subscales, across different brain regions responsible for a varying range of cognitive functions. In general, theta asymmetry was associated with conversation with others, sharing of enjoyment, and making social overtures, whereas alpha asymmetry was linked with making eye contact, reporting events to others, and engaging in reciprocal social communication. Specific brain regions involved are identified, as well as implications for clinical practice. Conclusions: Specific autism symptoms may be associated with selected brain region activity, providing a neurological basis for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Previous research reported reversal of the prototypical brain torque in individuals with mirrored visceral topology (situs inversus totalis, SIT). Here, we investigate if typical asymmetry of the posterior intracranial venous system is also reversed in SIT and whether the direction and magnitude of this asymmetry is related to the direction and magnitude of the brain torque. Brain structural MRI images of 38 participants with SIT were compared with those of 38 matched control participants. Occipital and frontal petalia and bending were measured using a standardized procedure. In addition, representative sections of the left and right transverse sinuses were segmented, and their respective volumes determined. Participants with SIT showed general reversal of occipital and frontal petalia and occipital bending, as well as reversal of typical transverse sinus asymmetry. Transverse sinus volume was significantly correlated with several torque measures, such that the smaller transverse sinus was associated with a larger ipsilateral occipital petalia, contralateral occipital bending, and ipsilateral frontal bending. We propose an anatomical mechanism to explain occipital petalia and bending, and conclude that anatomical constraints imposed by the asymmetry of the posterior venous system provide and additional account to elucidate the formation of the human brain torque. [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the most common type of focal epilepsies. Hemispheric asymmetry is a feature of brain organization in both invertebrates and vertebrates and may be the key to some neurodegenerative diseases. In this context, we aimed to investigate the volumetric asymmetry difference in cerebral structures between TLE patients and the healthy control group, based on magnetic resonance imaging (MRI) data that may be used as a new neuroimaging marker for TLE cases. Patients and Methods: In this retrospective study the cranial MRIs of fourteen clinically manifesting, radiologically HS-identified, and diagnosed TLE patients and fourteen healthy individuals from the Radiology Department of Yeditepe University Hospital were evaluated. Volume measurements and asymmetry index (AI) calculations in the total brain, hippocampus, temporal lobe, amygdala, thalamus, nucleus accumbens (NAc), premotor cortex, primary and somatosensory cortices were performed using the medical NeuroQuant® software. A negative AI value represented asymmetry towards the right due to reduced left hemispheric volume; a positive AI value represented asymmetry towards the left due to reduced right hemispheric volume. Subsequently, differences in volume and asymmetric patterns were investigated among TLE subgroups (right and left-sided TLE) and controls. Results: The left-sided TLE patients showed significant bilateral total brain volume reduction compared to the control group. Significant ipsilateral volumetric declines were also detected in the premotor cortex, the temporal lobe, and NAc with remarkable asymmetry to the right side. No significant changes were detected in right-sided TLE patients compared to the other groups. Conclusion: Overall, findings suggest that TLE patients had volumetric alterations with symmetry changes beyond the mesial temporal structures. With further investigations, the asymmetry measures can provide additional knowledge for TLE diagnosis. [ABSTRACT FROM AUTHOR]

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Objective: Investigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability. Methods: Participants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition. Results: Participants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS

Introduction: Despite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of interhemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans. Methods: Super-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformationbased morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants' age and sex and using threshold-free cluster enhancement. Results: Fetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints. Discussion: While these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development. [ABSTRACT FROM AUTHOR]

The central role of the corpus callosum in integrating perception and cognition across the cerebral hemispheres makes it highly desirable for clinical and basic research to have a repertoire of experimental paradigms assessing callosal functioning. Here, the objective was to assess the validity of two such paradigms (Poffenberger, redundant-target paradigms) by conducting single-step meta-analyses on individual case data of callosotomy patients. Studies were identified by systematic literature search (source: Pubmed and WebOfKnowledge, date: 07.03.2022) and all studies were included that reported callosotomy case data for either paradigm. Twenty-two studies (38 unique cases) provided 116 observations of the crossed-uncrossed difference (CUD) for the Poffenberger paradigm, while ten studies (22 cases, 103 observations) provided bilateral redundancy gain (bRG) measures. Using linear-mixed models with "individual" and "experiment" as random-effects variable, the mean CUD was estimated at 60.6 ms (CI95%: 45.3; 75.9) for commissurotomy, 43.5 ms (26.7; 60.2) for complete callosotomy, and 8.8 ms (1.1; 16.6) for partial anterior-medial callosotomy patients. The estimates of commissurotomy/callosotomy patients differed significantly from patients with partial callosotomy and healthy controls. The mean bRGmin (minimum unilateral reference) was estimated at 42.8 ms (27.1;58.4) for patients with complete and 30.8 ms (16.8; 44.7) for patients with partial callosotomy, both differing significantly from controls. One limitation was that different formulas for bRG were used, making it necessary to split the sample and reducing test power of some analyses. Nevertheless, the present findings suggest that both paradigms assess interhemispheric callosal integration, confirming their construct validity, but likely test distinct callosal functions. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder is a common neurodevelopmental condition that manifests as a disruption in sensory and social skills. Although it has been shown that the brain morphology of individuals with autism is asymmetric, how this differentially affects the structural connectome organization of each hemisphere remains under-investigated. We studied whole-brain structural connectivity-based brain asymmetry in individuals with autism using diffusion magnetic resonance imaging obtained from the Autism Brain Imaging Data Exchange initiative. By leveraging dimensionality reduction techniques, we constructed low-dimensional representations of structural connectivity and calculated their asymmetry index. Comparing the asymmetry index between individuals with autism and neurotypical controls, we found atypical structural connectome asymmetry in the sensory and default-mode regions, particularly showing weaker asymmetry towards the right hemisphere in autism. Network communication provided topological underpinnings by demonstrating that the inferior temporal cortex and limbic and frontoparietal regions showed reduced global network communication efficiency and decreased send-receive network navigation in the inferior temporal and lateral visual cortices in individuals with autism. Finally, supervised machine learning revealed that structural connectome asymmetry could be used as a measure for predicting communication-related autistic symptoms and nonverbal intelligence. Our findings provide insights into macroscale structural connectome alterations in autism and their topological underpinnings.

Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

IntroductionDespite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans.MethodsSuper-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants’ age and sex and using threshold-free cluster enhancement.ResultsFetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints.DiscussionWhile these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development.

It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin–angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME. [ABSTRACT FROM AUTHOR]

An experimental investigation was conducted to elucidate the auditory characteristics of the older adult population. The study involved 24 older adult and 24 young participants, with the aim of exploring their horizontal lateralization ability. This was achieved by presenting 1-kHz pure tones to the participants' right and left ears while introducing interaural time differences (ITDs). We examined the impact of four rise times (2, 5, 20, and 50 ms) on the onset of the test sound. The findings revealed that older adult participants exhibited lower levels of lateralization than young participants. Moreover, both older adult and young participants demonstrated diminished recognition of the onset portion as the rise time increased. Of particular significance was the conspicuous presence of a right ear advantage (REA) among young participants as the rise time was extended (statistically significant between the left and right ears at the 1% level, considering an ITD of 0.8 ms and a rise time of 50 ms). In contrast, older adult participants did not exhibit REA, even with a prolonged rise time (not significant at the 5% level at the same condition). These results indicate that the REA is not only present in language, as previously observed, but also extends to a pure tone in young participants. The older adult participants exhibited reduced performance in both left-and right-ear sound recognition. The influence of hearing threshold and preferred ear on sound lateralization performance was minimal. Therefore, it can be inferred that factors other than hearing threshold or preferred ear contribute to the presence of REA in young participants or its decline with age. The central and/or corpus callosum functions may also contribute to this phenomenon. [ABSTRACT FROM AUTHOR]

Brain hemispheres develop rather symmetrically, except in the case of pathology or intense training. As school experience is a form of training, the current study tested the influence of pedagogy on morphological development through the cortical thickness (CTh) asymmetry index (AI). First, we compared the CTh AI of 111 students aged 4 to 18 with 77 adults aged > 20. Second, we investigated the CTh AI of the students as a function of schooling background (Montessori or traditional). At the whole-brain level, CTh AI was not different between the adult and student groups, even when controlling for age. However, pedagogical experience was found to impact CTh AI in the temporal lobe, within the parahippocampal (PHC) region. The PHC region has a functional lateralization, with the right PHC region having a stronger involvement in spatiotemporal context encoding, while the left PHC region is involved in semantic encoding. We observed CTh asymmetry toward the left PHC region for participants enrolled in Montessori schools and toward the right for participants enrolled in traditional schools. As these participants were matched on age, intelligence, home-life and socioeconomic conditions, we interpret this effect found in memory-related brain regions to reflect differences in learning strategies. Pedagogy modulates how new concepts are encoded, with possible long-term effects on knowledge transfer. [ABSTRACT FROM AUTHOR]

The human brain is generally anatomically symmetrical, boasting mirror-like brain regions in the left and right hemispheres. Despite this symmetry, fine-scale structural asymmetries are prevalent and are believed to be responsible for distinct functional divisions within the brain. Prior studies propose that these asymmetric structures are predominantly primate specific or even unique to humans, suggesting that the genes contributing to the structural asymmetry of the human brain might have evolved recently. In our study, we identified approximately 1,500 traits associated with human brain asymmetry by collecting paired brain magnetic resonance imaging features from the UK Biobank. Each trait is measured in a specific region of one hemisphere and mirrored in the corresponding region of the other hemisphere. Conducting genome-wide association studies on these traits, we identified over 1,000 quantitative trait loci. Around these index single nucleotide polymorphisms, we found approximately 200 genes that are enriched in brain-related Gene Ontology terms and are predominantly upregulated in brain tissues. Interestingly, most of these genes are evolutionarily old, originating just prior to the emergence of Bilateria (bilaterally symmetrical animals) and Euteleostomi (bony vertebrates with a brain), at a significantly higher ratio than expected. Further analyses of these genes reveal a brain-specific upregulation in humans relative to other mammalian species. This suggests that the structural asymmetry of the human brain has been shaped by evolutionarily ancient genes that have assumed new functions over time. [ABSTRACT FROM AUTHOR]

Hemispheric asymmetry or lateralization is a fundamental principle of brain organization. However, it is poorly understood to what extent the brain asymmetries across different levels of functional organizations are evident in health or altered in brain diseases. Here, we propose a framework that integrates three degrees of brain interactions (isolated nodes, node–node, and edge–edge) into a unified analysis pipeline to capture the sliding window-based asymmetry dynamics at both the node and hemisphere levels. We apply this framework to resting-state EEG in healthy and stroke populations and investigate the stroke-induced abnormal alterations in brain asymmetries and longitudinal asymmetry changes during poststroke rehabilitation. We observe that the mean asymmetry in patients was abnormally enhanced across different frequency bands and levels of brain interactions, with these abnormal patterns strongly associated with the side of the stroke lesion. Compared to healthy controls, patients displayed significant alterations in asymmetry fluctuations, disrupting and reconfiguring the balance of inter-hemispheric integration and segregation. Additionally, analyses reveal that specific abnormal asymmetry metrics in patients tend to move towards those observed in healthy controls after short-term brain-computer interface rehabilitation. Furthermore, preliminary evidence suggests that baseline clinical and asymmetry features can predict poststroke improvements in the Fugl-Meyer assessment of the lower extremity (mean absolute error of about 2). Overall, these findings advance our understanding of hemispheric asymmetry. Our framework offers new insights into the mechanisms underlying brain alterations and recovery after a brain lesion, may help identify prognostic biomarkers, and can be easily extended to different functional modalities.

Understanding the evolutionarily conserved feature of functional laterality in the habenula has been attracting attention due to its potential role in human cognition and neuropsychiatric disorders. Deciphering the structure of the human habenula remains to be challenging, which resulted in inconsistent findings for brain disorders. Here, we present a large‐scale meta‐analysis of the left–right differences in the habenular volume in the human brain to provide a clearer picture of the habenular asymmetry. We searched PubMed, Web of Science, and Google Scholar for articles that reported volume data of the bilateral habenula in the human brain, and assessed the left–right differences. We also assessed the potential effects of several moderating variables including the mean age of the participants, magnetic field strengths of the scanners and different disorders by using meta‐regression and subgroup analysis. In total 52 datasets (N = 1427) were identified and showed significant heterogeneity in the left–right differences and the unilateral volume per se. Moderator analyses suggested that such heterogeneity was mainly due to different MRI scanners and segmentation approaches used. While inversed asymmetry patterns were suggested in patients with depression (leftward) and schizophrenia (rightward), no significant disorder‐related differences relative to healthy controls were found in either the left–right asymmetry or the unilateral volume. This study provides useful data for future studies of brain imaging and methodological developments related to precision habenula measurements, and also helps to further understand potential roles of the habenula in various disorders. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated an asymmetry of left predominance for mean values of soluble leucine aminopeptidase (LeuAP) activity in the frontal cortex (FC) and hypothalamus of adult male rats, fluorimetrically analyzed by the hydrolysis of Leu-β-naphthylamide as a substrate. No asymmetries were observed in nine other left (L) and right (R) regions obtained from rostro-caudally sectioned coronal slices. Neither had inter-hemispheric differences observed for lactate dehydrogenase (LDH), analyzed simultaneously in the same brain regions (L and R) of the same animals. However, the level of intra-hemispheric or inter-hemispheric correlation of LeuAP or LDH between such brain regions has not been analyzed. In order to obtain additional suggestions on the functional heterogeneity between regions of LeuAP and LDH, in the present investigation, the level of intra-hemispheric and inter-hemispheric correlations of the frontal cortex with the rest of the regions studied is described: (A) between the left frontal cortex (LFC) and the rest of the left regions; (B) between the right frontal cortex (RFC) and the rest of the right regions; (C) between the left frontal cortex and all of the right regions; and (D) between the right frontal cortex and all of the left regions. All of the correlations obtained were positive. The intra-hemispheric analysis showed a greater heterogeneity of values in the correlations observed between RFC and the rest of the right regions than between LFC and the rest of the left regions. Greater heterogeneity is observed when comparing RFC correlations with left regions than when comparing LFC correlations with right regions. In conclusion, the greatest heterogeneity (suggesting a greater functional variability) was observed in the right intra-hemispheric analysis and in the inter-hemispheric analysis between the RFC and the left hemisphere. The results for LDH showed a great homogeneity between regions both in the intra- and inter-hemispheric studies. [ABSTRACT FROM AUTHOR]

Brain asymmetry, involving structural and functional differences between the two hemispheres, is a major organizational principle of the human brain. The structural and functional connectivity within each hemisphere defines the hemispheric network or connectome. Elucidating left-right differences of the hemispheric network provides opportunities for brain asymmetry exploration. This review examines the asymmetry in the hemispheric white matter and functional network to assess health and brain disorders. In this article, the brain asymmetry in structural and functional connectivity including network topologies of healthy individuals, involving brain cognitive systems and the development trend, is highlighted. Moreover, the abnormal asymmetry of the hemispheric network related to cognition changes in brain disorders, such as Alzheimer's disease, schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder, and bipolar disorder, is presented. This review suggests that the hemispheric network is highly conserved for measuring human brain asymmetries and has potential in the study of the cognitive system and brain disorders. [ABSTRACT FROM AUTHOR]

BackgroundLateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.MethodsWe studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.ResultsIn the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.ConclusionsThe results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

It is essential for neuroscience and clinic to estimate the influence of neuro-intervention after brain damage. Most related studies have used Mirrored Contralesional-Ipsilesional hemispheres (MCI) methods flipping the axial neuroimaging on the x-axis in prognosis prediction. But left-right hemispheric asymmetry in the brain has become a consensus. MCI confounds the intrinsic brain asymmetry with the asymmetry caused by unilateral damage, leading to questions about the reliability of the results and difficulties in physiological explanations. We proposed the Separated Left-Right hemiplegia (SLR) method to model left and right hemiplegia separately. Two pipelines have been designed in contradistinction to demonstrate the validity of the SLR method, including MCI and removing intrinsic asymmetry (RIA) pipelines. A patient dataset with 18 left-hemiplegic and 22 right-hemiplegic stroke patients and a healthy dataset with 40 subjects, age- and sex-matched with the patients, were selected in the experiment. Blood-Oxygen Level-Dependent MRI and Diffusion Tensor Imaging were used to build brain networks whose nodes were defined by the Automated Anatomical Labeling atlas. We applied the same statistical and machine learning framework for all pipelines, logistic regression, artificial neural network, and support vector machine for classifying the patients who are significant or non-significant responders to brain-computer interfaces assisted training and optimal subset regression, support vector regression for predicting post-intervention outcomes. The SLR pipeline showed 5-15% improvement in accuracy and at least 0.1 upgrades in $\text{R}^{{2}}$ , revealing common and unique recovery mechanisms after left and right strokes and helping clinicians make rehabilitation plans.

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. [ABSTRACT FROM AUTHOR]

Originating from a series of morphometric studies conducted in the 1980s, it appears a widely held belief in cognitive neuroscience that the corpus callosum is larger in left or mixed handers than in right handers (RH). However, a recent meta-analysis challenges this belief by not finding significant differences in corpus callosum size between handedness groups. Yet, relying on the available published data, the meta-analysis was not able to account for a series of factors potential influencing its outcome, such as confounding effects of brain size differences and a restricted spatial resolution of previous callosal segmentation strategies. To address these remaining questions, we here analysed N = 1057 participants' midsagittal corpus callosum of from the Human Connectome Project (HCP 1200 Young Adults) to compare handedness groups based on consistency (e.g., consistent RH vs. mixed handers, MH) and direction of hand preference (e.g., dominant RH vs. dominant left handers). A possible relevance of brain-size differences was addressed by analysing callosal variability by both using forebrain volume (FBV) as covariate and utilising relative area (callosal area/thickness divided by FBV) as a dependent variable. Callosal thickness was analysed at 100 measuring points along the structure to achieve high spatial resolution to detect subregional effects. However, neither of the conducted analyses was able to find significant handedness-related differences in the corpus callosum and the respective effect-sizes estimates were small. For example, comparing MH and consistent RH, the effect sizes for difference in callosal area were below a Cohen's d = 0.1 (irrespective of how FBV was included), and narrow confidence intervals allowed to exclude effects above |d| = 0.2. Analysing thickness, effect sizes were below d = 0.2 with confidence intervals not extending above |d| = 0.3. In this, the possible range of population effect sizes of hand preference on callosal morphology appears well below the effects commonly reported for factors like age, sex, or brain size. Effects on cognition or behaviour accordingly can be considered small, questioning the common practise to attribute performance differences between handedness groups to differences in callosal architecture.

This study was designed to determine whether there was an asymmetry of structure and neurochemical activity of the interhemispheric vestibular-cortical system between healthy individuals and patients with vestibular failure. Previous studies have identified differences in gray-matter-volume (GMV) and white-matter-volume (WMV) asymmetry in the central-vestibular system and in concentrations of brain metabolites in the parietal lobe 2 (PO2) between patients with vestibulopathy and healthy controls. However, a comparison of the left and right sides in the healthy controls has not been made conclusively. This study included 23 healthy right-handed volunteers, and was carried out between March 2016 and March 2020. A three-dimensional T1-weighted image was used to calculate the GMV and WMV of the central-vestibular network on both sides, and proton magnetic resonance spectroscopy (H1MRS) was employed to analyze the brain metabolites in the PO2 area. The relative ratios of N-acetylaspartate (NAA)/tCr, tNAA/tCr, glycerophosphocholine (GPC)/tCr, Glx/tCr, and myo-inositol/tCr were quantified from the proton-MRS data. GMV and WMV differed significantly between the right and left vestibular-cortical regions. The GMVs of the right PO2, caudate, insula, and precuneus were significantly higher than those of the same locations on the left side; however, in the Rolandic operculum, the GMV on the left was significantly higher than on the right. In the PO2, Rolandic operculum, thalamus, and insula, the WMV on the left side was higher than on the right side of the corresponding location. However, the right caudate and precuneus WMV were higher than the left at the same location. In the H1MRS study, the Glx/tCr and GPC/tCr ratios on the left side were significantly higher than on the right. In comparison, the NAA/tCr and tNAA/tCr ratios showed contrasting results. The NAA/tCr ratio (r = −0.478, p = 0.021), tNAA/tCr ratio (r = −0.537, p = 0.008), and Glx/tCr ratio (r = −0.514, p = 0.012) on the right side showed a significant negative correlation with the participants' age. There was no relationship between GMV and metabolites on either side. Brain structure and concentrations of brain metabolites related to the vestibular system may differ between the two hemispheres in healthy individuals. Therefore, the asymmetry of the central-vestibular system should be considered when performing imaging. [ABSTRACT FROM AUTHOR]

Volumetric analysis of hippocampal subfields and their asymmetry assessment recently has been useful biomarkers in neuroscience. In this study, hippocampal subfields atrophy and pattern of their asymmetry in the patient with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were evaluated. MRI images of 20 AD patients, 20 MCI patients, and 20 healthy control (HC) were selected. The volumes of hippocampal subfields were extracted automatically using Freesurfer toolkit. The subfields asymmetry index (AI) and laterality ( Δ R L ) were also evaluated. Analysis of covariance was used to compare the subfields volume between three patient groups (age and gender as covariates). We used ANOVA (P < 0.05) test for multiple comparisons with Bonferroni's post hoc correction method. Hippocampal subfields volume in AD patients were significantly lower than HC and MCI groups (P < 0.02); however, no significant difference was observed between MCI and HC groups. The asymmetry index (AI) in some subfields was significantly different between AD and MCI, as well as between AD and HC, while there was not any significant difference between MCI groups with HC. In all three patient groups, rightward laterality ( Δ R L ) was seen in several subfields except subiculum, presubiculum, and parasubiculum, while in AD patient, rightward lateralization slightly decrease. Hippocampal subfields asymmetry can be used as a quantitative biomarker in neurocognitive disorders. In this study, it was observed that the asymmetry index of some subfields in AD is significantly different from MCI. In AD, patient rightward laterality was less MCI an HC group. [ABSTRACT FROM AUTHOR]

Absence epilepsy is a specific generalized non-convulsive form occurring almost exclusively in children and adolescents. It is traditionally thought that the resulting seizure is completely generalized in the cortex of both hemispheres, as seen in humans on surface electroencephalograms and magnetoencephalograms. However, most studies were performed on animals, mainly rats—genetic (WAG/Rij and GAERS lines) and pharmacological models, since signals not only from the cortex, but also from subcortical structures such as the thalamus must be measured, what cannot be done on humans, who have no medical indications for intracranial surgery. In animals, measurements of local field potentials were almost always made from one hemisphere in order to cover the maximum number of brain structures involved. At the same time, the degree of synchrony of seizure onsets and terminations in different hemispheres in animals was practically not studied, and the markup itself in the vast majority of cases was done on the basis of one channel from motor or somato-sensory cortex. This work aims to reveal differences and similarities in the course of spike-wave discharges (the main encephalographic marker of absence seizures) in the cortex of the two hemispheres in a known pharmacological model of rats exposed to pentylenetetrazole. For discharge detection, a method of automatic discharge marking is proposed and its sensitivity and specificity are evaluated using records of nine animals. We used it to mark seizures in symmetrical cortical sites from both hemispheres separately. According to the results of the analysis of seizure duration it turned out that for five out of nine animals the distribution of discharges significantly differed between the hemispheres, and for the other four was equal. Consequently, in the rat model, spike-wave activity may be generalized both symmetrically and asymmetrically, which may be due to individual peculiarities or different discharge triggering scenarios. [ABSTRACT FROM AUTHOR]

Numerous studies have reported that long‐term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long‐term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion‐weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion‐related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience‐dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal‐related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long‐term musical training can strengthen or prune white matter connectivity networks in an experience‐dependent manner. [ABSTRACT FROM AUTHOR]

Birds are excellent model organisms to study perceptual categorization and concept formation. The renewed focus on avian neuroscience has sparked an explosion of new data in the field. At the same time, our understanding of sensory and particularly visual structures in the avian brain has shifted fundamentally. These recent discoveries have revealed how categorization is mediated in the avian brain and has generated a theoretical framework that goes beyond the realm of birds. We review the contribution of avian categorization research—at the methodical, behavioral, and neurobiological levels. To this end, we first introduce avian categorization from a behavioral perspective and the common elements model of categorization. Second, we describe the functional and structural organization of the avian visual system, followed by an overview of recent anatomical discoveries and the new perspective on the avian 'visual cortex'. Third, we focus on the neurocomputational basis of perceptual categorization in the bird's visual system. Fourth, an overview of the avian prefrontal cortex and the prefrontal contribution to perceptual categorization is provided. The fifth section outlines how asymmetries of the visual system contribute to categorization. Finally, we present a mechanistic view of the neural principles of avian visual categorization and its putative extension to concept learning. [ABSTRACT FROM AUTHOR]

Computer-aided diagnosis of health problems and pathological conditions has become a substantial part of medical, biomedical, and computer science research. This paper focuses on the diagnosis of early and progressive dementia, building on the potential of deep learning (DL) models. The proposed computational framework exploits a magnetic resonance imaging (MRI) brain asymmetry biomarker, which has been associated with early dementia, and employs DL architectures for MRI image classification. Identification of early dementia is accomplished by an eight-layered convolutional neural network (CNN) as well as transfer learning of pretrained CNNs from ImageNet. Different instantiations of the proposed CNN architecture are tested. These are equipped with Softmax, support vector machine (SVM), linear discriminant (LD), or k -nearest neighbor (KNN) classification layers, assembled as a separate classification module, which are attached to the core CNN architecture. The initial imaging data were obtained from the MRI directory of the Alzheimer's disease neuroimaging initiative 3 (ADNI3) database. The independent testing dataset was created using image preprocessing and segmentation algorithms applied to unseen patients' imaging data. The proposed approach demonstrates a 90.12% accuracy in distinguishing patients who are cognitively normal subjects from those who have Alzheimer's disease (AD), and an 86.40% accuracy in detecting early mild cognitive impairment (EMCI). [ABSTRACT FROM AUTHOR]

The purpose of this article is to supplement the discussion in the field of research and modeling of the process of cognition first with data from neuropsychology and interhemispheric asymmetry, and second with reflections on species’ (spontaneous) knowledge of Homo sapiens. I. The data of neuropsychology and interhemispheric asymmetry signify two differently directed and complementary ways of processing information and regulating the functions inherent in the brain. One of these methods is analytical computer-like information processing, which is necessary for voluntary learning, the other method provides holistic-simultaneous, imaginative, unconscious, and involuntary processing. The duality of cognitive strategies is clearly manifested in the psychological analysis of syndromes in the case of brain lesions, as well as various conditions in healthy people (for example, in the case of bilingualism). II. Biological existence, which is the basis for all other layers of life, is provided by species-specific behavior and knowledge. Presumably species knowledge manifests itself as 1 — Constant involuntary assessment of the surrounding world and adequate reactions to changes in the world: from ordinary reactions (step aside, add a step, etc.) to the ability to react without hesitation in dangerous situations. 2 — The ability to understand connections between phenomena without scientific calculations. The entire history of mankind speaks of the existence of such an ability. People survived without science and created science along the way. 3 — Deep knowledge (often without the ability to logically explain) of what is natural and useful for us as representatives of the Homo Sapiens species, and of what is unnatural and harmful. There are reasons to assume that species knowledge is the basis that determines the common behavior of people of different eras and cultures in everything related to the continuation of the family and the cultivation of a new generation. Species knowledge merges together in the process of development with the knowledge gained during training.

Handedness has traditionally been employed as a proxy of brain lateralization in research. Alzheimer's disease (AD) manifests as a neurodegenerative disorder characterized by impairments across various neuropsychological functions, including visuospatial and language, many of which exhibit lateralization in the human brain. While previous studies have investigated the relationship between AD and handedness, findings have been inconsistent. This article aims to provide an up-to-date overview of studies investigating hand preference in AD and the subtypes, specifically early- and late-onset AD. Through a synthesis of these studies, we conclude that handedness currently lacks utility as a diagnostic biomarker for AD and its subtypes, and this is further supported by the meta-analytic results based on data from over 10,000 AD patients. We emphasize the necessity for future research endeavors, particularly those leveraging advanced neuroimaging techniques to explore the role of brain asymmetry in AD. [ABSTRACT FROM AUTHOR]

It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin–angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration. The central and peripheral renin-angiotensin systems, particularly the aminopeptidases involved in its enzymatic cascade, play an important role in blood pressure control. In the present study, we report how these aminopeptidases from left and right cortico-limbic locations, plasma and systolic blood pressure interact among them in spontaneously hypertensive rats (SHR) unilaterally depleted of dopamine. The study comprises left and right sham and left and right lesioned (dopamine-depleted) rats as research groups. Results revealed important differences in the bilateral behavior comparing sham left versus sham right, lesioned left versus lesioned right, and sham versus lesioned animals. Results also suggest an important role for the asymmetrical functioning of the amygdala in cardiovascular control and an asymmetrical behavior in the interaction between the medial prefrontal cortex, hippocampus and amygdala with plasma, depending on the left or right depletion of dopamine. Compared with previous results of a similar study in Wistar-Kyoto (WKY) normotensive rats, the asymmetrical behaviors differ significantly between both WKY and SHR strains. [ABSTRACT FROM AUTHOR]

As some critics have stated, the term “developmental dyslexia” refers to a strictly human disorder, relating to a strictly human capacity – reading – so it cannot be modeled in experimental animals, much less so in lowly rodents. However, two endophenotypes associated with developmental dyslexia are eminently suitable for animal modeling: Cerebral Lateralization, as illustrated by the association between dyslexia and non-righthandedness, and Cerebrocortical Dysfunction, as illustrated by the described abnormal structural anatomy and/or physiology and functional imaging of the dyslexic cerebral cortex. This paper will provide a brief review of these two endophenotypes in human beings with developmental dyslexia and will describe the animal work done in my laboratory and that of others to try to shed light on the etiology of and neural mechanisms underlying developmental dyslexia. Some thought will also be given to future directions of the research.

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

Morphological left-right brain asymmetries are universal phenomena in animals. These features have been studied for decades, but the functional relevance is often unclear. Studies from the zebrafish dorsal diencephalon on the genetics underlying the establishment and function of brain asymmetries have uncovered genes associated with the development of functional brain asymmetries. To gain further insights, comparative studies help to investigate the emergence of asymmetries and underlying genetics in connection to functional adaptation. Evolutionarily distant isogenic medaka inbred lines, that show divergence of complex traits such as morphology, physiology and behavior, are a valuable resource to investigate intra-species variations in a given trait of interest. For a detailed study of asymmetry in the medaka diencephalon we generated molecular probes of ten medaka genes that are expressed asymmetrically in the zebrafish habenulae and pineal complex. We find expression of eight genes in the corresponding brain areas of medaka with differences in the extent of left-right asymmetry compared to zebrafish. Our marker gene analysis of the diverged medaka inbred strains revealed marked inter-strain size differences of the respective expression domains in the parapineal and the habenulae, which we hypothesize may result from strain-specific gene loss. Thus, our analysis reveals both inter-species differences but also intra-species plasticity of gene expression in the teleost dorsal diencephalon. These findings are a starting point showing the potential to identify the genetics underlying the emergence and modulations of asymmetries. They are also the prerequisite to examine whether variance in habenular gene expression may cause variation of behavioral traits.

Brain hemispheres develop rather symmetrically, except in the case of pathology or intense training. As school experience is a form of training, the current study tested the influence of pedagogy on morphological development through the cortical thickness (CTh) asymmetry index (AI). First, we compared the CTh AI of 111 students aged 4 to 18 with 77 adults aged > 20. Second, we investigated the CTh AI of the students as a function of schooling background (Montessori or traditional). At the whole-brain level, CTh AI was not different between the adult and student groups, even when controlling for age. However, pedagogical experience was found to impact CTh AI in the temporal lobe, within the parahippocampal (PHC) region. The PHC region has a functional lateralization, with the right PHC region having a stronger involvement in spatiotemporal context encoding, while the left PHC region is involved in semantic encoding. We observed CTh asymmetry toward the left PHC region for participants enrolled in Montessori schools and toward the right for participants enrolled in traditional schools. As these participants were matched on age, intelligence, home-life and socioeconomic conditions, we interpret this effect found in memory-related brain regions to reflect differences in learning strategies. Pedagogy modulates how new concepts are encoded, with possible long-term effects on knowledge transfer.