BackgroundThe interhemispheric transfer deficit theory proposes that individuals with dyslexia have impaired interhemispheric transfer, particularly affecting the integration of visual information from the left and right visual fields. This study aimed to evaluate this hypothesis by examining interhemispheric transfer in dyslexia using visual half-field tasks targeting both linguistic and visuospatial processing.MethodsWe examined interhemispheric transfer in dyslexia using two visual half-field tasks: a lexical decision task to assess written word processing, and a symmetry decision task to examine visuospatial processing. We compared reaction times and accuracy in 90 Dutch-speaking participants (45 with dyslexia, 45 controls) across left, right, and bilateral stimulus presentations.ResultsWhile both tasks successfully captured expected visual half-field differences in the control group, favoring the right visual field in the lexical decision task and the left visual field in the symmetry detection task, we did not observe that the dyslexia group showed increased differences between the two fields, as predicted by the interhemispheric transfer deficit theory. Furthermore, the dyslexia group benefited just as much as controls from stimuli presented simultaneously to both visual fields. Thus, no evidence of interhemispheric transfer deficits related to dyslexia was found in either task.ConclusionsThese findings challenge the broad applicability of the interhemispheric transfer deficit theory in dyslexia, suggesting that such impairments may be task-dependent rather than domain-general. Future studies should further explore the conditions under which interhemispheric transfer deficits might occur in dyslexia.

Various aspects of brain organization differ between the left and right hemispheres. Clues to the developmental origins of these asymmetries may be gained through associations with situs inversus totalis (SIT), a rare condition in which visceral organs are reversed on the left-right axis. In the largest previous brain imaging analyses of SIT (38 cases, 38 controls from Belgium), typical functional asymmetries such as left-hemisphere language dominance were mostly unaltered, but various aspects of asymmetrical cerebral structure - petalia, bending, and posterior venous anatomy - were often reversed in this condition. SIT can be a monogenic trait that arises from rare genetic variants, usually affecting motile cilia which help to create the embryonic left-right body axis. However, most SIT cases do not have obvious genetic causes and may arise from environmental or random effects during embryogenesis. We sequenced the genomes of 23 SIT cases and 23 controls from the Belgian brain imaging dataset and pooled with prior data from 15 cases and 15 controls. We aimed to discover whether there are altered brain asymmetries in SIT cases with disruptive DNA variants in ciliary genes, or in other types of genes, as compared to genetically unsolved cases. In total, 19 cases had likely causal variants affecting ciliary function, while 19 cases remained genetically unsolved. Functional and structural brain asymmetries were not significantly different in genetically solved versus unsolved SIT cases. Therefore, functional brain asymmetries seem largely independent of known mechanisms of visceral situs formation, while structural brain torque is altered in SIT regardless of the presence or absence of overt genetic causes.

Situs inversus totalis (SIT), a rare condition involving the complete reversal of thoracic and abdominal organ placement, provides a unique model for investigating potential relationships between visceral and cerebral asymmetries. In this study, we examined whether white matter asymmetries are altered in a group of 21 SIT participants compared with 21 matched situs solitus (SO) controls. This sample represents the largest cohort of SIT individuals studied to date. Using fixel-based analysis, an advanced diffusion magnetic resonance imaging framework, we compared micro- and macrostructural white matter asymmetries across the whole brain between the two groups, specifically assessing fiber density and cross-section (FDC). Both groups showed extensive yet comparable patterns of white matter asymmetry, with no significant group differences. These asymmetry patterns were consistent with those reported in previous fixel-based studies. These results suggest that white matter lateralization is preserved despite complete visceral reversal. The observed divergence between brain and visceral asymmetry patterns suggests that symmetry breaking in visceral laterality relies on distinct mechanisms.

Hemispheric lateralization has been central to developmental dyslexia research for over a century, yet its role in the etiology of reading and language deficits remains elusive. While altered asymmetries have long been implicated, evidence is inconsistent, with limited consideration given to individual variability in lateralization patterns. This study investigated hemispheric lateralization in 35 adults with dyslexia and 35 matched controls using functional MRI across three language tasks: word generation, rhyming decision, and lexical decision. Laterality indices were calculated to comprehensively assess the strength, direction, and consistency of activation across global and regional task-specific brain areas. Significant group differences were not found in the absolute strength of lateralization for global measures or any regional measures, except in the fusiform gyrus, where people with dyslexia showed lower asymmetry. Directional asymmetry was similar across the two groups, except in the fusiform gyrus during the reading task, where dyslexic individuals showed a higher prevalence of right-hemisphere lateralization compared to controls. Interestingly, we found that dyslexic participants demonstrated greater inconsistency in regional lateralization during reading and rhyming tasks. Among individuals with dyslexia, those with inconsistent lateralization in the reading task had weaker fusiform lateralization, although fusiform lateralization strength itself did not predict reading outcomes. Our findings suggest that dyslexia is characterized by inconsistent, rather than universally weaker, lateralization patterns. Inconsistencies in task-related and regional lateralization may disrupt the efficiency of language networks, contributing to observed reading deficits. By highlighting the role of regional and task-specific inconsistencies, this study provides new insights into the neural mechanisms underlying dyslexia and underscores the importance of considering individual variability in hemispheric lateralization when investigating language disorders.

Several core cognitive networks in the human brain show marked left–right differences in their functional organization. While these asymmetries are well described at the level of individual functions, overarching patterns of variability in hemispheric functional organization across multiple domains have not been mapped in a representative sample. To address this gap, we conducted a large-scale neuroimaging study with 200 participants (100 left-handers and 100 right-handers) to map hemispheric phenotypes across four distinct cognitive domains: language, tool use, spatial attention, and face perception. We challenge the traditional one-size-fits-all view of hemispheric organization by showing that deviations from the typical pattern of functional segregation are more prevalent than generally assumed, in both left- and right-handers. As predicted, variation in asymmetry was more pronounced in the left-handed sample. Critically, we found no evidence that the prototypical, “textbook”, pattern of brain organization confers any advantage in general cognitive ability or IQ. These results challenge the assumption of a single optimal brain organization and demonstrate that hemispheric functional segregation in humans is much more variable than anticipated. ### Competing Interest Statement The authors have declared no competing interest. BOF, BOF/24J/2021/172

Although word production is considered a strongly left hemispheric lateralized function, its cerebral asymmetry varies among individuals. The most popular way of determining hemisphere dominance is to calculate a laterality index (LI) by comparing brain activity between the two hemispheres. Large LIs can readily be classified as left or right dominant, but there is no consensus on how to treat bilateral LIs indicating (near) symmetrical activity. The problem with interpreting very small LIs is perpetuated by a lack of reliability, stemming from the challenge of systematically investigating these uncommon cases (usually ≤ 10% of a sample). To address this gap, we performed two studies that investigated the reliability and across-methods generalizability of bilateral LIs obtained from functional transcranial Doppler sonography (fTCDS)-an ultrasound-based approach that measures cerebral blood flow velocity. In Study 1, we compared reproducibility of bilateral LIs (n=35) and clearly lateralized LIs (n=32) during a letter verbal fluency fTCDS task across two sessions. While left-lateralized classifications were highly replicable (97% reproduced), poorer reproducibility was observed for bilateral classifications (51% reproduced). In fact, dichotomous left-right categorization yielded more reliable outcomes than assigning participants with bilateral LIs to a separate category (80% reproduced). Study 2 assessed whether small fTCDS asymmetry extended to other instruments for determining cerebral laterality (visual half-field method and fMRI). Participants consistently classified as bilateral by fTCDS (n=18) also exhibited reduced group-level asymmetry in these other methods. Based on these results, we suggest that LIs reflect a combination of idiosyncratic cerebral asymmetry, state-dependent fluctuations, and measurement noise. Our findings also indicate that a subset of the population has a neural system for word production that is inherently weakly lateralized, although true hemispheric equivalence is likely extremely rare. Finally, we offer recommendations for classifying asymmetry in clinical and research contexts.

This review examines the relationship between visceral and brain asymmetry and explores whether their alignment observed in some vertebrate species also exists in humans. While the development of visceral and brain asymmetry may have occurred for different reasons, it is possible that the basic mechanisms for left-right differentiation of the visceral system were duplicated in the brain. We describe the main phenotypical anomalies and the general mechanism of left-right differentiation in vertebrates, followed by a systematic review of available human studies on behavioral and brain asymmetry in individuals with reversed visceral organization. The available evidence shows no direct link between human visceral and brain laterality. Most individuals with situs inversus totalis (SIT) show typical population biases for handedness and brain functional asymmetry, although an increased prevalence of atypical hemispheric segregation may be present. Perisylvian brain structural asymmetries also reveal the expected population bias in participants with SIT. However, several independent studies indicate that SIT is associated with a general reversal of the gross morphologic asymmetry of brain torque. Potential differences in brain structural and functional asymmetries between subtypes of situs inversus with ciliary and nonciliary causes remain to be determined.

No two human brains are alike, and with the rise of precision medicine in neurology, we are seeing an increased emphasis on understanding the individual variability in brain structure and function that renders every brain unique. Functional and structural brain asymmetries are a fundamental principle of brain organization, and recent research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. In this Review, we provide an overview of brain asymmetries, variations in such asymmetries and their relevance in the clinical context. We review recent findings on brain asymmetries in neuropsychiatric and neurodevelopmental disorders, as well as in specific learning disabilities, with an emphasis on large-scale database studies and meta-analyses. We also highlight the relevance of asymmetries for disease symptom onset in neurodegenerative diseases and their implications for lateralized treatments, including brain stimulation. We conclude that alterations in brain asymmetry are not sufficiently specific to act as diagnostic biomarkers but can serve as meaningful symptom or treatment response biomarkers in certain contexts. On the basis of these insights, we provide several recommendations for neurological clinical practice. Functional and structural brain asymmetries are a fundamental principle of brain organization, and research suggests substantial individual variability in these asymmetries that needs to be considered in clinical practice. This Review provides an overview of brain asymmetries, variations in such asymmetries and their relevance in the context of clinical neurology. Brain asymmetries - that is, structural and functional differences between the left and the right hemispheres - are a major source of interindividual brain variability.The substantial interindividual variability in brain asymmetry currently precludes its use as a diagnostic biomarker.Individual variability in brain asymmetry needs to be considered in the assessment of symptoms and treatment of various disorders.Altered brain asymmetries are observed in a number of neurological, neuropsychiatric and neurodevelopmental disorders.Brain asymmetries can act as meaningful symptom or treatment response biomarkers in a range of neurological contexts.Advancement of patient-tailored medicine will require clinical trials to elucidate how individual brain asymmetry influences the efficacy of lateralized interventions.

Background: COVID-19 acute respiratory distress syndrome (C-ARDS) survivors suffer from long-term physical complications. However, at the time of this study limited data are available on possible long-term cognitive impairment. Objectives: We hypothesized that COVID-19 ICU patients perform worse on cognitive tasks 6 months after admission, in comparison to reference values of a healthy population. Design: Two-center cohort study with a six months’ time horizon. Patients: Patients admitted to the ICU for COVID-19 associated respiratory failure between March and June 2020. Setting: Post-ICU follow up. Methods and main outcome measures: The primary measure was the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) score (with lower values indicating worse global cognition). The secondary outcome measure was the Trail Making Test (TMT) Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive functions). The Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE, on a scale from 1.0 to 5.0, with 5.0 indicating severe cognitive impairment) was taken for not patients not fluent in Dutch. Results: 117 COVID-19 patients were admitted to the ICU, of whom 32 patients (27%) died within 6 months. 67/85 (79%) patients participated in the cohort study. COVID-19 survivors had lower total RBANS cognition scores than the age-adjusted population norms (n=45). Fifteen (33%) patients had a global cognition score 1.5 SD below the population means. RBANS-subscale performance showed that both memory (immediate and delayed recall) and attention were at minus 1 SD below normative means, while language and visuospatial cognition were unaffected. Median TMT B score was 40 (IQR 10-65) (n=45). There were elevated scores of the short form IQCODE (mean 3.4 (SD 0.4). Conclusions: Our results suggests that COVID-19 ARDS negatively affects long-term cognitive function. Trial registration: ClinicalTrials.gov NCT04593069.

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.

Situs inversus totalis (SIT) is a rare congenital anomaly in which the arrangement of the visceral organs is completely left-right mirrored. A previous study by our lab suggests that SIT (N = 15) pairs with more heterogeneous asymmetrical brain organization and increased left-handedness. In addition, visceral reversal paired with poorer cognitive performance, especially when hemisphere organization was atypical. The current study sought to replicate these findings in a larger sample. We scanned 23 volunteers with SIT as well as an equal number of controls with usual organ arrangement, and determined their hemisphere dominance for two left hemisphere functions (language and manual praxis) and two right hemisphere functions (spatial attention and face recognition). Effects of situs inversus etiology were explored by pooling data from the original cohort with the replication sample. Our results reveal the expected population dominance for each of the cognitive functions in SIT, albeit they were less pronounced – but not significantly so – compared to controls. Unusual patterns of hemispheric crowding and mirror-reversal of functional brain organization was observed more often in SIT (48%) than in the controls (30%), but this difference also did not reach statistical significance. However, left-handedness was found to be significantly more common in SIT (24%) than in the overall population (10.6%). Finally, cognitive ability was not associated with organ situs or hemisphere organization. Taken together, our data adds to the growing evidence that the determinants of visceral and neural asymmetries are largely independent from one another and that complete situs inversus does not co-occur with an obligatory transposition of the brain’s functional architecture. There nevertheless might be instances in which (genetic) factors simultaneously cause complete visceral reversal and atypical brain laterality, particularly in asyndromal cases of situs inversus.

Laterality indices (LIs) quantify the left-right asymmetry of brain and behavioural variables and provide a measure that is statistically convenient and seemingly easy to interpret. Substantial variability in how structural and functional asymmetries are recorded, calculated, and reported, however, suggest little agreement on the conditions required for its valid assessment. The present study aimed for consensus on general aspects in this context of laterality research, and more specifically within a particular method or technique (i.e., dichotic listening, visual half-field technique, performance asymmetries, preference bias reports, electrophysiological recording, functional MRI, structural MRI, and functional transcranial Doppler sonography). Experts in laterality research were invited to participate in an online Delphi survey to evaluate consensus and stimulate discussion. In Round 0, 106 experts generated 453 statements on what they considered good practice in their field of expertise. Statements were organised into a 295-statement survey that the experts then were asked, in Round 1, to independently assess for importance and support, which further reduced the survey to 241 statements that were presented again to the experts in Round 2. Based on the Round 2 input, we present a set of critically reviewed key recommendations to record, assess, and report laterality research for various methods.

Language is the most commonly described lateralised cognitive function, relying more on the left hemisphere compared to the right hemisphere in over 90% of the population. Most research examining the structure-function relationship of language lateralisation only included people showing a left language hemisphere dominance. In this work, we applied a state-of-the-art "fixel-based" analysis approach, allowing statistical analysis of white matter micro- and macrostructure on a fibre-specific level in a sample of participants with left and right language dominance (LLD and RLD). Both groups showed a similar extensive pattern of white matter lateralisation including a comparable leftwards lateralisation of the arcuate fasciculus, regardless of their functional language lateralisation. These results suggest that lateralisation of language functioning and the arcuate fasciculus are driven by independent biases. Finally, a significant group difference of lateralisation was detected in the forceps minor, with a leftwards lateralisation in LLD and rightwards lateralisation for the RLD group.

Functional and anatomical hemispheric asymmetries abound in the neural language system, yet the relationship between them remains elusive. One attractive proposal is that structural interhemispheric differences reflect or even drive functional language laterality. However, studies on structure–function couplings either find that left and right language dominant individuals display similar leftward structural asymmetry or yield inconsistent results. The current study aimed to replicate and extend prior work by comparing structural asymmetries between neurologically healthy left-handers with right hemispheric language dominance (N = 24) and typically lateralized left-handed controls (N = 39). Based on structural MRI data, anatomical measures of six ‘language-related’ perisylvian structures were derived, including the surface area of five gray matter regions with known language functions and the FDC (combined fiber density and fiber-bundle cross-sectional area) of the arcuate fasciculus. Only the surface area of the pars triangularis and the anterior insula differed significantly between participant groups, being on average leftward asymmetric in those with typical dominance, but right lateralized in volunteers with atypical language specialization. However, these findings did not survive multiple testing correction and the asymmetry of these structures demonstrated much inter-individual variability in either subgroup. By integrating our findings with those reported previously we conclude that while some perisylvian anatomical asymmetries may differ subtly between typical and atypical speech dominants at the group level, they serve as poor participant-specific predictors of hemispheric language specialization.

AIM:To assess the impact of neonatal brachial plexus palsy (NBPP) on higher-order hand representation.METHOD:Eighty-two left-handed children and adolescents with and without right-sided NBPP were recruited. Thirty-one participants with NBPP (mean age [SD] 11y 4mo [4y 4mo]; age range 6y 2mo-21y 0mo; 15 females; C5-6, n=4, C5-7, n=12, C5-T1, n=11, C5-T1 with Horner sign, n=4) were assessed along with 30 controls (mean age 11y 5mo [4y 4mo]; age range 6y 7mo-21y 7mo; 14 females). Participants' estimated hand size and shape on measure of implicit and explicit hand representation was assessed. A linear mixed model (LMM) was used to investigate the effect of condition, sensorimotor impairment, and age.RESULTS:Individuals with NBPP showed a significant difference in implicit hand representation between affected and non-affected hands. LMM confirmed a significant influence of the severity of sensorimotor injury. Only the estimated implicit hand representation was associated with age, with a significant difference between 6- to 8-year-olds and 9- to 10-year-olds.INTERPRETATION:The effect of sensorimotor impairment on central hand representation in individuals with NBPP is specific due to its implicit component and is characterized by finger length underestimation in the affected hand compared to the characteristic underestimation in the unaffected hand. Neither NBPP nor age impacted the explicit hand estimate. This study confirms the importance of sensorimotor contribution to the development of implicit hand representation.

The alignment of visceral and brain asymmetry observed in some vertebrate species raises the question of whether this association also exists in humans. While the visceral and brain systems may have developed asymmetry for different reasons, basic visceral left–right differentiation mechanisms could have been duplicated to establish brain asymmetry. We describe the main phenotypical anomalies and the general mechanism of left–right differentiation of vertebrate visceral and brain laterality. Next, we systematically review the available human studies that explored the prevalence of atypical behavioral and brain asymmetry in visceral situs anomalies, which almost exclusively involved participants with the mirrored visceral organization (situs inversus). The data show no direct link between human visceral and brain functional laterality as most participants with situs inversus show the typical population bias for handedness and brain functional asymmetry, although an increased prevalence of functional crowding may be present. At the same time, several independent studies present evidence for a possible relation between situs inversus and the gross morphological asymmetry of the brain torque with potential differences between subtypes of situs inversus with ciliary and non-ciliary etiologies.

OBJECTIVE:A significant proportion of adjuvant-treated breast cancer patients experience cognitive decline, challenging the person's ability to return to normal activities after treatment. However, not every patient experiences cognitive problems, and even in patients with impairments, determining clinically important cognitive decline remains challenging. Our objective was to explore differences in neuropsychological performance following adjuvant chemotherapy (CT) in patients with breast cancer.METHOD:We conducted a prospective observational study in an Oncology Breast Clinic and assessed neuropsychological performance before and after adjuvant CT and in non-CT-treated women with breast cancer and healthy controls (HCs). Standardised between-group differences and regression-based change scores were calculated.RESULTS:CT-treated patients (n = 66) performed significantly different from non-CT-treated patients (n = 39) and HCs (n = 56). There was a significant effect on verbal fluency (p = .0013). CT performed significantly worse than non-CT and HC [effect size (ES) = .89, p < .001 and ES = .61, p ≤ .001, respectively] and from HCs with regard to proactive interference (ES = .62, p ≤ .001). Regression-based scores revealed more severe cognitive decline in the CT-treated group [24.24% (16/66)] than in the non-CT-treated group [15.20% (6/39)] and HC group [7.14% (4/56)]. Patients who underwent CT and showed cognitive decline were less educated and older, with significantly lower baseline scores.CONCLUSIONS:CT-treated patients showed more vulnerability on cognitive control and monitoring than non-CT-treated breast cancer patients and HCs. Older patients with less education and lower baseline cognitive performance represent a group at risk for cognitive decline following CT. Identification of patients at risk for decline could improve targeted support and rehabilitation.

Whereas we experience our body as a coherent volumetric object, the brain appears to maintain highly fragmented representations of individual body parts. Little is known about how body representations of hand size and shape are built and evolve during infancy and young adulthood. This study aimed to investigate the effect of hand side, handedness, and age on the development of central hand size representation. The observational study with comparison groups was conducted with 90 typically developing Belgian school children and young adults (48 male and 42 female; age range = 5. 0-23.0 years; 49 left-handed and 41 right-handed). Participants estimated their hand size and shape using two different tasks. In the localization task, participants were verbally cued to judge the locations of 10 anatomical landmarks of an occluded hand. An implicit hand size map was constructed and compared with actual hand dimensions. In the template selection task, the explicit hand shape was measured with a depictive method. Hand shape indexes were calculated and compared for the actual, implicit, and explicit conditions. Participants were divided into four age groups (5-8 years, 9-10 years, 11-16 years, and 17-23 years). Implicit hand maps featured underestimation of finger length and overestimation of hand width, which is already present in the youngest children. Linear mixed modeling revealed no influence of hand side on finger length underestimation; nonetheless, a significant main effect of age (p = .001) was exposed. Sinistrals aged 11 to 16 years showed significantly less underestimation (p = .03) than dextrals of the same age. As for the hand shape, the implicit condition differed significantly with the actual and explicit conditions (p < .001). Again, the implicit shape index was subjected to handedness and age effects, with significant differences being found between sinistrals and dextrals in the age groups of 9 and 10 years (p = .029) and 11 to 16 years (p < .001). In conclusion, the implicit metric component of the hand representation in children and young adults is misperceived, featuring shortened fingers and broadened hands since a very young age. Crucially, the finger length underestimation increases with age and shows a different developmental trajectory for sinistrals and dextrals. In contrast, the explicit hand shape is approximately veridical and seems immune from age and handedness effects. This study confirms the dual character of somatoperception and establishes a point of reference for children and young adults. (C) 2020 Elsevier Inc. All rights reserved.