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The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been associated with altered or attenuated hemispheric asymmetries. However, the exact mechanism linking asymmetries and disorders is not known. Here, studies in animal models of mental disorders render important insights into the etiology and neuronal alterations associated with both disorders and atypical asymmetry. In this review, the current literature of animal studies in rats and mice focusing on anxiety and fear, anhedonia and despair, addiction or substance misuse, neurodegenerative disorders as well as stress exposure, and atypical hemispheric asymmetries is summarized. Results indicate overall increased right-hemispheric neuronal activity and a left-sided behavioral bias associated with symptoms of anxiety, fear, anhedonia, behavioral despair as well as stress exposure. Addiction behavior is associated with right-sided bias and transgenic models of Alzheimer's disease indicate an asymmetrical accumulation of fibrillar plaques. Most studies focused on changes in the bilateral amygdala and frontal cortex. Across studies, two crucial factors influencing atypical asymmetries arose independently of the disorder modeled: sex and developmental age. In conclusion, animal models of mental disorders demonstrate atypical hemispheric asymmetries similar to findings in patients. Particularly, increased left-sided behavior and greater right-hemispheric activity were found across models applying stress-based paradigms. However, sex- and age-dependent effects on atypical hemispheric asymmetries are present that require further investigation. Animal models enable the analysis of hemispheric changes on the molecular level which may be most effective to detect early alterations., (© 2023. The Author(s).)

EEG resting-state alpha asymmetry is one of the most widely investigated forms of functional hemispheric asymmetries in both basic and clinical neuroscience. However, studies yield inconsistent results. One crucial prerequisite to obtain reproducible results is the reliability of the index of interest. There is a body of research suggesting a moderate-to-good reliability of EEG resting-state alpha asymmetry, but unfortunately sample sizes in these studies are typically small. This study presents the first large-scale short-term reliability study of frontal and parietal EEG resting-state alpha asymmetry. We used the Dortmund Vital Study data set containing 370 participants. In each participant, EEG resting state was recorded eight times, twice with their eyes opened, twice with their eyes-closed, each on two different EEG systems. We found good reliability of EEG alpha power and alpha asymmetry on both systems for electrode pairs. We also found that alpha power asymmetry reliability is higher in the eyes-closed condition than in the eyes-open condition. The frontomedial electrode pair showed weaker reliability than the frontolateral and parietal electrode pairs. Interestingly, we found no population-level alpha asymmetry in frontal electrodes, one of the most investigated electrode sites in alpha asymmetry research. In conclusion, our results suggest that while EEG alpha asymmetry is an overall reliable measure, frontal alpha asymmetry should be assessed using multiple electrode pairs., (© 2021. The Author(s).)

Handedness is the most widely investigated motor preference in humans. The genetics of handedness and especially the link between genetic variation, brain structure, and right-left preference have not been investigated in detail. Recently, several well-powered genome-wide association studies (GWAS) on handedness have been published, significantly advancing the understanding of the genetic determinants of left and right-handedness. In the present study, we estimated polygenic scores (PGS) of handedness-based on the GWAS by de Kovel and Francks (Sci Rep 9: 5986, 2019) in an independent validation cohort (n = 296). PGS reflect the sum effect of trait-associated alleles across many genetic loci. For the first time, we could show that these GWAS-based PGS are significantly associated with individual handedness lateralization quotients in an independent validation cohort. Additionally, we investigated whether handedness-derived polygenic scores are associated with asymmetries in gray matter macrostructure across the whole brain determined using magnetic resonance imaging. None of these associations reached significance after correction for multiple comparisons. Our results implicate that PGS obtained from large-scale handedness GWAS are significantly associated with individual handedness in smaller validation samples with more detailed phenotypic assessment., (© 2021. The Author(s).)

Humans are highly social animals that show a wide variety of verbal and non-verbal behaviours to communicate social intent. One of the most frequently used non-verbal social behaviours is embracing, commonly used as an expression of love and affection. However, it can also occur in a large variety of social situations entailing negative (fear or sadness) or neutral emotionality (formal greetings). Embracing is also experienced from birth onwards in mother-infant interactions and is thus accompanying human social interaction across the whole lifespan. Despite the importance of embraces for human social interactions, their underlying neurophysiology is unknown. Here, we demonstrated in a well-powered sample of more than 2500 adults that humans show a significant rightward bias during embracing. Additionally, we showed that this general motor preference is strongly modulated by emotional contexts: the induction of positive or negative affect shifted the rightward bias significantly to the left, indicating a stronger involvement of right-hemispheric neural networks during emotional embraces. In a second laboratory study, we were able to replicate both of these findings and furthermore demonstrated that the motor preferences during embracing correlate with handedness. Our studies therefore not only show that embracing is controlled by an interaction of motor and affective networks, they also demonstrate that emotional factors seem to activate right-hemispheric systems in valence-invariant ways.

The corpus callosum is the brain's largest commissural fiber tract and is crucial for interhemispheric integration of neural information. Despite the high relevance of the corpus callosum for several cognitive systems, the molecular determinants of callosal microstructure are largely unknown. Recently, it was shown that genetic variations in the myelin-related proteolipid 1 gene PLP1 and the axon guidance related contactin 1 gene CNTN1 were associated with differences in interhemispheric integration at the behavioral level. Here, we used an innovative new diffusion neuroimaging technique called neurite orientation dispersion and density imaging (NODDI) to quantify axonal morphology in subsections of the corpus callosum and link them to genetic variation in PLP1 and CNTN1. In a cohort of 263 healthy human adults, we found that polymorphisms in both PLP1 and CNTN1 were significantly associated with callosal microstructure. Importantly, we found a double dissociation between gene function and neuroimaging variables. Our results suggest that genetic variation in the myelin-related gene PLP1 impacts white matter microstructure in the corpus callosum, possibly by affecting myelin structure. In contrast, genetic variation in the axon guidance related gene CNTN1 impacts axon density in the corpus callosum. These findings suggest that PLP1 and CNTN1 gene variations modulate specific aspects of callosal microstructure that are in line with their gene function.

Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization.

Next to neurogenic inflammation and pathological sympathetic-afferent coupling, functional imaging studies have shown the crucial role of maladaptive cortical reorgansation in the pathophysiology of CRPS. Bilateral neuroplastic alterations in the somatosensory cortex seem to play a substantial role in the dysfunctional sensory processing of stimuli. The aim was to investigate the multimodal integration of sensory and visual stimuli into the body scheme and the influence of higher cognitive body representation in the integration of multimodal schema, body relevant stimuli in patients with CRPS. The investigated sample included 24 patients suffering from CRPS of the upper extremities, 21 patients with chronic hand pain of other origins and 24 healthy probands. The rubber hand illusion was carried out for the first time in patients with complex regional pain syndrome (CRPS). The reprentations show that the patients can integrate a rubber hand in their body representation to the same degree as healthy patients. The intact experience of the rubber hand illusion by CRPS patients indicates that the integration of congruent visual and tactile stimuli in CRPS is intact.

The lateralized visual systems of pigeons and chickens are excellent models to study neural asymmetries at the functional and anatomical level. The aim of the current study was to reveal why these two species closely resemble each other with respect to left-right differences in behavior but not with respect to the pathways involved: While pigeons show an asymmetrically organized tectofugal system, only transient lateralizations of the thalamofugal system have been observed in chickens. Four possible explanations are conceivable. (1) Adult pigeons might also show a hitherto undiscovered thalamofugal asymmetry like chickens. (2) The thalamofugal asymmetry might be transient in both species. (3) Prehatch light stimulation could differentially affect the two visual pathways of chickens and pigeons that mature with different speeds. (4) Tecto- and thalamofugal asymmetries represent species differences, independent of developmental factors. To test these explanations, we injected retrograde tracers into the Wulst of adult pigeons, of hatchlings, and of dark reared pigeons which were monocularly deprived on their left or right eye for one week after hatch. Subsequently we counted labeled cells within the ipsi- and contralateral n. geniculatus lateralis pars dorsalis in search for possible lateralizations of ascending pathways. None of the experimental groups displayed significant differences in the thalamofugal projection pattern. This indicates that visual lateralization in pigeons and chickens depends on tectofugal and thalamofugal asymmetries, respectively. Thus, in different species a highly similar pattern of behavioral asymmetries can be subserved by diverse neural systems.

The aim of the present study was to analyze if the left hemisphere preferentially controls flexion responses toward positive stimuli, while the right hemisphere is specialized toward extensor responses to negative pictures. To this end, right-handed subjects had to pull or push a joystick subsequent to seeing a positive or a negative stimulus in their left or right hemifield. Flexion responses were faster for positive stimuli, while negative stimuli were associated with faster extensions responses. Overall, performance was fastest when emotional stimuli were presented to the left visual hemifield. This right hemisphere superiority was especially clear for negative stimuli, while reaction times toward positive pictures showed no hemispheric difference. We did not find any interaction between hemifield and response type. Neither was there a triple interaction between valence, hemifield and response type. We suppose that response dichotomies in humans are not as tightly linked to a hemisphere- and valence-bound reaction type as previously assumed.

In patients with complex regional pain syndrome (CRPS) a disruption of the body schema has been shown in an altered cortical representation of the hand and in delayed reaction times (RT) in the hand laterality recognition task. However, the role of attentional processes or the effect of isolated limb laterality training has not yet been clarified. The performance of healthy subjects (n = 38), CRPS patients (n = 12) and phantom limb pain (PLP) patients (n = 12) in a test battery of attentional performance (TAP) and in a limb laterality recognition task was compared and the effect of limb laterality training in CRPS patients and healthy subjects evaluated. The RTs of both CRPS and PLP patients were significantly slower than those of healthy subjects despite normal TAP values. The CRPS and PLP patients showed bilaterally delayed RTs. Through training RTs improved significantly but the RTs of CRPS patients remained slower than those of healthy subjects. In this study an equal disruption of the body schema was found in both CRPS and PLP patients which cannot be accounted for by attentional processes. For CRPS patients this disorder cannot be fully reversed by isolated limb laterality recognition training.

The stereotype of women's limited parking skills is deeply anchored in modern culture. Although laboratory tests prove men's average superiority in visuospatial tasks and parking requires complex, spatial skills, underlying mechanisms remain unexplored. Here, we investigated performance of beginners (nine women, eight men) and more experienced drivers (21 women, 27 men) at different parking manoeuvres. Furthermore, subjects conducted the mental rotation test and self-assessed their parking skills. We show that men park more accurately and especially faster than women. Performance is related to mental rotation skills and self-assessment in beginners, but only to self-assessment in more experienced drivers. We assume that, due to differential feedback, self-assessment incrementally replaces the controlling influence of mental rotation, as parking is trained with increasing experience. Results suggest that sex differences in spatial cognition persist in real-life situations, but that socio-psychological factors modulate the biological causes of sex differences.