Functional Lateralization Research Articles

Handedness and the control of human technology and language

The impact of handedness on neural substrates of common tool processing and tool use skills as proxies to the mechanisms underlying modern reciprocal relationships among humans and their brains, the tools they create and use, and technologies they implement and utilise, has only recently started to be elucidated. Yet, as most of the reports on lateralisation of such processing or skills focused on a single task, and sharp divisions of participants into right-, left-, and mixed-handed, or non-righthanded for the latter two groups combined, little is known about interrelationships between the neuronal underpinnings of different skilled manual actions—e.g., manual praxis skills in the form of disparate hand-tool interactions, including their most common neural phenotypes in the population at large. Here, in 62 individuals with different handedness status, we studied the laterality of two praxic abilities involving common tools. Even though their neural substrates were expected to be closely linked, we identified numerous cases (in 7/28 righthanders [RH] – 25%, and in 6/21 lefthanders [LH] – 29% of participants) with hemispheric dissociations in the underlying mechanisms. They involved both right-lateralised functional grasp planning vs. left-lateralised visual tool use (8% of all tested cases, 3/28 RH: ~11%, and 2/21 LH: ~10%), and vice versa (13% of all cases, 4/28 RH: ~14%, and 4/21 LH: ~19% of participants). The laterality/organisation of these praxic skills was also compared to the laterality/organisation of productive language, with only few cases of dissociations identified. The observed phenotypes are discussed in the context of coevolutionary hypotheses linking ancient toolmaking and tool use skills, the associated cultural evolution, technological innovations, and language to the cortical expansion and functional lateralisation in human evolution.

Amphipods (Gammarus pseudolimnaeus) do not demonstrate a left-right preference in a 3-D printed aquatic T-maze

Crustaceans are increasingly used as research subjects in experiments investigating learning in invertebrates. While many of these species may be useful models it is essential to document the presence or absence of behavioral laterality, especially considering the long-held belief that functional lateralization was unique to humans or other vertebrate species. Neglecting this fundamental step weakens the applicability of results and may unnecessarily complicate experimental design. Amphipods (Gammarus pseudolimnaeus) may be a useful invertebrate for studying simple discriminations or escape behavior, but research on their potential behavioral laterality is absent. The current study investigated whether amphipods demonstrate a left-right bias when navigating an aquatic T-maze by placing them in the maze and recording their choices across multiple trials. Our results suggested that amphipods do not show a strong left-right bias during initial navigation of an aquatic T-maze. These findings may encourage other researchers to test invertebrates for behavioral laterality, utilize amphipods in studies of simple forms of learning, and potentially simplify future experimental design.

Abnormal functional lateralization and cooperation in bipolar disorder are associated with neurotransmitter and cellular profiles

BackgroundHemispheric lateralization and cooperation are essential for efficient brain function, and aberrations in both have been found in psychiatric disorders such as schizophrenia. This study investigated alterations in hemispheric lateralization and cooperation among patients with bipolar disorder (BD) and associations with neurotransmitter and cell-type density distributions to identify potential molecular and cellular pathomechanisms. MethodsSixty-seven BD patients and 127 healthy controls (HCs) were examined by resting-state functional MRI (rs-fMRI). Whole-brain maps of the autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) were constructed to reveal BD-specific changes in brain functional lateralization and interhemispheric cooperation, respectively. Spatial associations of regional AI and CFH abnormalities with neurotransmitter and cell-type density distributions were examined by correlation analyses. ResultsBipolar disorder patients exhibited higher AI values in left superior parietal gyrus, cerebellar right Crus I, and cerebellar right Crus II, and these regional abnormalities were associated with the relative densities (proportions) of oligodendrocyte precursor cells and microglia. Patients also exhibited lower CFH values in right inferior parietal gyrus, bilateral middle occipital gyrus, left postcentral gyrus, and bilateral cerebellar crus II, and these regional abnormalities were associated with the densities of serotonin 1A and dopamine D2 receptors, oligodendrocyte precursor cells, astrocytes, and neurons. ConclusionsThese findings indicate that abnormal functional lateralization and cooperation in BD with potential molecular and cellular basis.

Individual variation in the functional lateralization of human ventral temporal cortex: Local competition and long-range coupling.

The ventral temporal cortex (VTC) of the human cerebrum is critically engaged in computations related to high-level vision. One intriguing aspect of this region is its asymmetric organization and functional lateralization. Notably, in the VTC, neural responses to words are stronger in the left hemisphere, whereas neural responses to faces are stronger in the right hemisphere. Converging evidence has suggested that left-lateralized word responses emerge to couple efficiently with left-lateralized frontotemporal language regions, but evidence is more mixed regarding the sources of the right-lateralization for face perception. Here, we use individual differences as a tool to adjudicate between three theories of VTC organization arising from: 1) local competition between words and faces, 2) local competition between faces and other categories, 3) long-range coupling with VTC and frontotemporal areas subject to their own local competition. First, in an in-house functional MRI experiment, we demonstrated that individual differences in laterality are both substantial and reliable within a right-handed population of young adults. We found no (anti-)correlation in the laterality of word and face selectivity relative to object responses, and a positive correlation when using selectivity relative to a fixation baseline, challenging ideas of local competition between words and faces. We next examined broader local competition with faces using the large-scale Human Connectome Project (HCP) dataset. Face and tool laterality were significantly anti-correlated, while face and body laterality were positively correlated, consistent with the idea that generic local representational competition and cooperation may shape face lateralization. Last, we assessed the role of long-range coupling in the development of VTC laterality. Within our in-house experiment, substantial correlation was evident between VTC text laterality and several other nodes of a distributed text-processing circuit. In the HCP data, VTC face laterality was both negatively correlated with frontotemporal language laterality, and positively correlated with social perception laterality in the same areas, consistent with a long-range coupling effect between face and social processing representations, driven by local competition between language and social processing. We conclude that both local and long-range interactions shape the heterogeneous hemispheric specializations in high-level visual cortex.

Rest2Task: Modeling task-specific components in resting-state functional connectivity and applications

The networks observed in the brain during resting-state activity are not entirely “task-free.” Instead, they hint at a hierarchical structure prepared for adaptive cognitive functions. Recent studies have increasingly demonstrated the potential of resting-state fMRI to predict local activations or global connectomes during task performance. However, uncertainties remain regarding the unique and shared task-specific components within resting-state brain networks, elucidating local activations and global connectome patterns. A coherent framework is also required to integrate these task-specific components to predict local activations and global connectome patterns. In this work, we introduce the Rest2Task model based on the partial least squares-based multivariate regression algorithm, which effectively integrates mappings from resting-state connectivity to local activations and global connectome patterns. By analyzing the coefficients of the regression model, we extracted task-specific resting-state components corresponding to brain local activation or global connectome of various tasks and applied them to the brain lateralization prediction and psychiatric disorders diagnostic. Our model effectively substitutes traditional whole-brain functional connectivity (FC) in predicting functional lateralization and diagnosing brain disorders. Our research represents the inaugural effort to quantify the contribution of patterns (components) within resting-state FC to different tasks, endowing these components with specific task-related contextual information. The task-specific resting-state components offer new insights into brain lateralization processing and disease diagnosis, potentially providing fresh perspectives on the adaptive transformation of brain networks in response to tasks.

The relationship between white matter architecture and language lateralisation in the healthy brain.

Interhemispheric anatomical differences have long been thought to be related to language lateralisation. Previous studies have explored whether asymmetries in the diffusion characteristics of white matter language tracts are consistent with language lateralisation. These studies, typically with smaller cohorts, yielded mixed results. This study investigated whether connectomic analysis of quantitative anisotropy (QA) and shape features of white matter tracts across the whole brain are associated with language lateralisation. We analysed 1040 healthy individuals (562 females) from the Human Connectome Project database. Hemispheric language dominance for each participant was quantified using a laterality quotient (LQ) derived from fMRI activation in regions of interest (ROIs) associated with a language comprehension task compared against a math task. A linear regression model was used to examine the relationship between structural asymmetry and functional lateralisation. Connectometry revealed a significant negative correlation between LQs and QA of corpus callosum tracts, indicating that higher QA in these regions is associated with bilateral and right-hemisphere language representation in frontal and temporal regions, respectively. Left language laterality in temporal lobe was significantly associated with longer right inferior fronto-occipital fasciculus (IFOF) and forceps minor tracts. These results suggest that diffusion measures of microstructural architecture as well as geometrical features of reconstructed white matter tracts play a role in language lateralisation. People with increased dependence on right or both frontal hemispheres for language processing may have more developed commissural fibres, which may support more efficient interhemispheric communication.Significance statement The left cerebral hemisphere is dominant for language functions in most people. In some healthy people, language functions are lateralised to the right hemisphere or distributed across both hemispheres. The anatomy underlying patterns of hemispheric language dominance are not well established. Emerging evidence suggests that white matter connectivity and architecture is an important feature of cortical functional organisation. In this work, we report that people who have language functions distributed across both hemispheres have greater inter-hemispheric connectivity compared to lateralised people. Our findings provide further insights into the anatomical basis of language function and may have wider clinical implications.

A meta-analysis of cognitive flexibility in aging: Perspective from functional network and lateralization.

Cognitive flexibility, the ability to switch between mental processes to generate appropriate behavioral responses, is reduced with typical aging. Previous studies have found that age-related declines in cognitive flexibility are often accompanied by variations in the activation of multiple regions. However, no meta-analyses have examined the relationship between cognitive flexibility in aging and age-related variations in activation within large-scale networks. Here, we conducted a meta-analysis employing multilevel kernel density analysis to identify regions with different activity patterns between age groups, and determined how these regions fall into functional networks. We also employed lateralization analysis to explore the spatial distribution of regions exhibiting group differences in activation. The permutation tests based on Monte Carlo simulation were used to determine the significance of the activation and lateralization results. The results showed that cognitive flexibility in aging was associated with both decreased and increased activation in several functional networks. Compared to young adults, older adults exhibited increased activation in the default mode, dorsal attention, ventral attention, and somatomotor networks, while displayed decreased activation in the visual network. Moreover, we found a global-level left lateralization for regions with decreased activation, but no lateralization for regions with higher activation in older adults. At the network level, the regions with decreased activation were left-lateralized, while the regions with increased activation showed varying lateralization patterns within different networks. To sum up, we found that networks that support various mental functions contribute to age-related variations in cognitive flexibility. Additionally, the aging brain exhibited network-dependent activation and lateralization patterns in response to tasks involving cognitive flexibility. We highlighted that the comprehensive meta-analysis in this study offered new insights into understanding cognitive flexibility in aging from a network perspective.

A hierarchical atlas of the human cerebellum for functional precision mapping

The human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from seven large-scale datasets, outperforming existing group atlases. The atlas has three further advantages. First, the atlas allows for precision mapping in individuals: the integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across three levels, allowing analyses at the appropriate level of granularity. Overall, the present atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.

Lateralization of activation within the superior temporal gyrus during speech perception in sleeping infants is associated with subsequent language skills in kindergarten: A passive listening task-fMRI study

Brain asymmetries are hypothesized to reduce functional duplication and thus have evolutionary advantages. The goal of this study was to examine whether early brain lateralization contributes to skill development within the speech-language domain. To achieve this goal, 25 infants (2–13 months old) underwent behavioral language examination and fMRI during sleep while listening to forward and backward speech, and then were assessed on various language skills at 55–69 months old. We observed that infant functional lateralization of the superior temporal gyrus (STG) for forward > backward speech was associated with phonological, vocabulary, and expressive language skills 4 to 5 years later. However, we failed to observe that infant language skills or the anatomical lateralization of STG were related to subsequent language skills. Overall, our findings suggest that infant functional lateralization of STG for speech perception may scaffold subsequent language acquisition, supporting the hypothesis that functional hemisphere asymmetries are advantageous.

Hemispheric asymmetries in borderline personality disorder: a systematic review.

Borderline personality disorder (BPD) is characterized by increased mood reactivity and affective instability. Since core structures involved in emotion processing, such as the amygdala, demonstrate strong lateralization, BPD is an interesting target for laterality research. So far, a systematic integration of findings on lateralization in BPD is missing. Therefore, we systematically reviewed studies published until February 2024 in PubMed, Web of Science, and PsycInfo databases that measured hemispheric asymmetries and behavioral lateralization in patients with BPD. Inclusion criteria were (a) diagnosis of BPD and (b) results on hemispheric or behavioral asymmetries. Specifically for neuroimaging studies, hemispheres need to be assessed separately. Review articles and studies with disorders other than BPD were excluded. Risk of bias was assessed with the Newcastle Ottawa Scale for non-randomized, non-comparative intervention studies. A total of 21 studies met the inclusion criteria. Thirteen studies investigated structural hemispheric asymmetries, five functional hemispheric asymmetries, two examined handedness, and one studied hemispheric asymmetry in visuospatial attention. Overall, studies examining structural asymmetries in BPD report bilateral volume reduction in the amygdala and hippocampus but a right-sided reduction in the orbitofrontal cortex. For functional lateralization, asymmetrical de/activation patterns in the default mode network in BPD and reduced right-frontal asymmetry were evident. Also, studies indicate a trend towards increased non-right-handedness in BPD. Risk factors for BPD, such as childhood abuse, may play a crucial role in the development of structural and functional alterations. However, the generalization of results may be limited by small sample sizes and varying study designs.

Using the online version of the Trier Social Stress Test to investigate the effect of acute stress on functional lateralization

How stress affects functional hemispheric asymmetries is relevant because stress represents a risk factor for the development of mental disorders and various mental disorders are associated with atypical lateralization. Using three lateralization tasks, we investigated whether functional hemispheric asymmetries in the form of hemispheric dominance for language (verbal dichotic listening task), emotion processing (emotional dichotic listening task), and visuo-spatial attention (line bisection task) were affected by acute stress in healthy adults. One hundred twenty right-handed men and women performed these lateralization tasks in randomized order after exposure to a mild online stressor (i.e., an online variant of the Trier Social Stress Test (TSST), TSST-OL) and a non-stressful online control task (friendly TSST-OL, fTSST-OL) in a within-subjects design. Importantly, the verbal and the emotional dichotic listening tasks were presented online whereas the line bisection task was completed in paper–pencil form. During these tasks, we found the expected hemispheric asymmetries, indicating that online versions of both the verbal and the emotional dichotic listening task can be used to measure functional hemispheric asymmetries in language and emotion processing remotely. Even though subjective and physiological markers confirmed the success of the online stress manipulation, replicating previous studies, we found no stress-induced effect on functional hemispheric asymmetries. Thus, in healthy participants, functional hemispheric asymmetries do not seem to change flexibly in response to acute stress.

Differential Effects of Continuous Theta Burst Stimulation over the Bilateral and Unilateral Cerebellum on Working Memory.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Intrahemispheric White Matter Asymmetries and Interhemispheric Connections Underlying the Lateralization of Language Production and Spatial Attention in Left-Handers

ABSTRACT Leftward language production and rightward spatial attention are salient features of functional organization in most humans, but their anatomical basis remains unclear. Interhemispheric connections and intrahemispheric white matter asymmetries have been proposed as important factors underlying functional lateralization. To investigate the role of white matter connectivity in functional lateralization, we first identified 96 left-handers using visual half field naming tasks. They were then divided into atypical and typical functional dominance based on the lateralization of brain activation in a word generation task (for language production) and a landmark task (for spatial attention). Using a novel fixel-based framework, we obtained fiber-specific properties of white matter pathways. Results showed, first, that differences between two language dominance groups occurred in the asymmetry of the superior longitudinal fasciculus-III (SLF-III), whereas differences between two spatial attention dominance groups occurred in the rostrum and rostral body of the corpus callosum. However, the directions of functional lateralization were not associated with the directions of white matter asymmetries. Second, the degree of language lateralization was predicted by SLF-III asymmetry and the rostral body of the corpus callosum, whereas the degree of spatial attention lateralization was predicted by the rostrum of the corpus callosum. Notably, the degree of each functional lateralization was positively correlated with the anterior and middle callosal connections, supporting the excitatory model of the corpus callosum. The results suggest that language lateralization is shaped by a combined effect of intra- and interhemispheric connections, whereas spatial attention lateralization relies more on interhemispheric connections.

Reduced lateralization of the language network in the blind and its relationship with white matter tract neuroanatomy.

Several previous studies reported reduced leftward lateralization in blind participants' samples compared to the sighted population. The origins of this difference remain unknown. Here, we tested whether functional lateralization is connected with the structural characteristics of white matter tracts [corpus callosum (CC), uncinate fasciculus (UF), and superior longitudinal fasciculus (SLF)], as suggested by previous studies conducted in the typical sighted population. Twenty-three blind and 21 sighted adult participants were tested during fMRI with a semantic decision paradigm presented both auditorily and in the modality appropriate for reading (tactually for the blind and visually for the sighted). Lateralization indices (LI) were calculated based on the activations. The fractional anisotropy (FA) measure was extracted from the white matter tracts of interest. Correlation analyses testing the relationship between FA and LI were conducted. The reduced leftward lateralization of both speech processing and reading-related activations was replicated. Nevertheless, the relationship between the structural integrity of the CC and LI and between the asymmetry of the intrahemispheric tracts and LI was not confirmed, possibly due to the lack of power. The sources of the reduced lateralization of the language network in the sensory-deprived population remain unknown. Further studies should account for environmental variables (e.g., the frequency of contact with written language) and the complexity of the factors that may influence the functional lateralization of the human brain.

Dysfunction of the magnocellular subdivision of the visual thalamus in developmental dyslexia.

Developmental dyslexia (DD) is one of the most common learning disorders, affecting millions of children and adults worldwide. To date, scientific research has attempted to explain DD primarily based on pathophysiological alterations in the cerebral cortex. In contrast, several decades ago, pioneering research on five post-mortem human brains suggested that a core characteristic of DD might be morphological alterations in a specific subdivision of the visual thalamus - the magnocellular LGN (M-LGN). However, due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans, this finding was never confirmed in-vivo, and its relevance for DD pathology remained highly controversial. Here, we leveraged recent advances in high-resolution magnetic resonance imaging (MRI) at high field strength (7 Tesla) to investigate the M-LGN in DD in-vivo. Using a case-control design, we acquired data from a large sample of young adults with DD (n = 26; age 28 ± 7 years; 13 females) and matched control participants (n = 28; age 27 ± 6 years; 15 females). Each participant completed a comprehensive diagnostic behavioral test battery and participated in two MRI sessions, including three functional MRI experiments and one structural MRI acquisition. We measured blood-oxygen-level-dependent responses and longitudinal relaxation rates to compare both groups on LGN subdivision function and myelination. Based on previous research, we hypothesized that the M-LGN is altered in DD and that these alterations are associated with a key DD diagnostic score, i.e., rapid letter and number naming (RANln). The results showed aberrant responses of the M-LGN in DD compared to controls, which was reflected in a different functional lateralization of this subdivision between groups. These alterations were associated with RANln performance, specifically in male DD. We also found lateralization differences in the longitudinal relaxation rates of the M-LGN in DD relative to controls. Conversely, the other main subdivision of the LGN, the parvocellular LGN (P-LGN), showed comparable blood-oxygen-level-dependent responses and longitudinal relaxation rates between groups. The present study is the first to unequivocally show that M-LGN alterations are a hallmark of DD, affecting both the function and microstructure of this subdivision. It further provides a first functional interpretation of M-LGN alterations and a basis for a better understanding of sex-specific differences in DD with implications for prospective diagnostic and treatment strategies.

Flight patterns of monocularly occluded homing pigeons further reveal a left eye/right cerebral hemispheric advantage in the visual processing of familiar landscape/landmark features

Studying pigeons during homing has offered an opportunity to investigate visual–functional brain lateralization in the context of free flying and long distance navigation. In the current study we examine at a high scale of spatial resolution the flight paths of pigeons, which vary with respect to monocular and binocular treatment, as they familiarise themselves with landscape and landmark features during repeated flights home from two locations. The analysis of the flight paths of monocularly occluded pigeons revealed that pigeons using the right eye/left hemisphere visual system were more likely to display more tortuous paths over tracts of 500 m along the flight path home compared to both pigeons using the left eye/right hemisphere visual system and control birds. Accompanying this finding was the observation that pigeons using the right eye/left hemisphere system were more likely to perform flight “loops”, suggesting that, without right hemispheric visual processing, pigeons are more motivated to seek out visual input, behaviourally expanding the now monocularly reduced visual field. Taken together, the data are consistent with a more important role of the left eye/right hemisphere system in processing visual features of the landscape, which may contribute to the construction of the familiar landmark-based map used for navigation. More broadly, our data are consistent with the hypothesis that the right cerebral hemisphere of the avian brain plays a more important role in memorising and using the relational properties of visual stimuli to guide performance on spatial tasks.

Hemispheric dominance in reading system alters contribution to face processing lateralization across development

Face processing dominates the right hemisphere. This lateralization can be affected by co-lateralization within the same system and influence between different systems, such as neural competition from reading acquisition. Yet, how the relationship pattern changes through development remains unknown. This study examined the lateralization of core face processing and word processing in different age groups. By comparing fMRI data from 36 school-aged children and 40 young adults, we investigated whether there are age and regional effects on lateralization, and how relationships between lateralization within and between systems change across development. Our results showed significant right hemispheric lateralization in the core face system and left hemispheric lateralization in reading-related areas for both age groups when viewing faces and texts passively. While all participants showed stronger lateralization in brain regions of higher functional hierarchy when viewing faces, only adults exhibited this lateralization when viewing texts. In both age cohorts, there was intra-system co-lateralization for face processing, whereas an inter-system relationship was only found in adults. Specifically, functional lateralization of Broca’s area during reading negatively predicted functional asymmetry in the FFA during face perception. This study initially provides neuroimaging evidence for the reading-induced neural competition theory from a maturational perspective in Chinese cohorts.

Evolutionary Strategies Enable Systematic and Reliable Uncertainty Quantification: A Proof-of-Concept Pilot Study on Resting-State Functional MRI Language Lateralization.

Reliable and trustworthy artificial intelligence (AI), particularly in high-stake medical diagnoses, necessitates effective uncertainty quantification (UQ). Existing UQ methods using model ensembles often introduce invalid variability or computational complexity, rendering them impractical and ineffective in clinical workflow. We propose a UQ approach based on deep neuroevolution (DNE), a data-efficient optimization strategy. Our goal is to replicate trends observed in expert-based UQ. We focused on language lateralization maps from resting-state functional MRI (rs-fMRI). Fifty rs-fMRI maps were divided into training/testing (30:20) sets, representing two labels: "left-dominant" and "co-dominant." DNE facilitated acquiring an ensemble of 100 models with high training and testing set accuracy. Model uncertainty was derived from distribution entropies over the 100 model predictions. Expert reviewers provided user-based uncertainties for comparison. Model (epistemic) and user-based (aleatoric) uncertainties were consistent in the independently and identically distributed (IID) testing set, mainly indicating low uncertainty. In a mostly out-of-distribution (OOD) holdout set, both model and user-based entropies correlated but displayed a bimodal distribution, with one peak representing low and another high uncertainty. We also found a statistically significant positive correlation between epistemic and aleatoric uncertainties. DNE-based UQ effectively mirrored user-based uncertainties, particularly highlighting increased uncertainty in OOD images. We conclude thatDNE-based UQ correlates with expert assessments, making it reliable for our use case and potentially for other radiology applications.

Symmetry in Frontal But Not Motor and Somatosensory Cortical Projections.

The neocortex and striatum are topographically organized for sensory and motor functions. While sensory and motor areas are lateralized for touch and motor control, respectively, frontal areas are involved in decision-making, where lateralization of function may be less important. This study contrasted the topographic precision of cell-type-specific ipsilateral and contralateral cortical projections while varying the injection site location in transgenic mice of both sexes. While sensory cortical areas had strongly topographic outputs to the ipsilateral cortex and striatum, they were weaker and not as topographically precise to contralateral targets. The motor cortex had somewhat stronger projections but still relatively weak contralateral topography. In contrast, frontal cortical areas had high degrees of topographic similarity for both ipsilateral and contralateral projections to the cortex and striatum. Corticothalamic organization is mainly ipsilateral, with weaker, more medial contralateral projections. Corticostriatal computations might integrate input outside closed basal ganglia loops using contralateral projections, enabling the two hemispheres to act as a unit to converge on one result in motor planning and decision-making.

The relationship between interhemispheric homotopic functional connectivity and left-right difference of intrahemispheric functional integration in the human brain

Abstract The brain comprises left and right hemispheres, with notable distinctions in intrahemispheric functional integration observed between homotopic regions of each hemisphere. Previous studies have shown these left-right differences may be induced by interhemispheric connectivity between homotopic regions. However, no research has comprehensively investigated the relationship between lateralization of intrahemispheric functional integration and interhemispheric homotopic functional connectivity in the resting state. Based on resting-state functional connectivity, we identified two brain functional organization properties named lateralization of intrahemispheric functional integration (LI) and interhemispheric homotopic functional connectivity (HoFC), hypothesizing the former was modulated by the latter in healthy individuals. Results showed a widespread significant negative correlation between LI and HoFC among the whole brain, which could be affected by age and task state presenting a still negative pattern but with weaker strength, especially in heteromodal regions. Furthermore, two mediation models showed that HoFC significantly mediated the age and brain state effect on LI, suggesting age and task state might influence lateralization of intrahemispheric functional integration via interhemispheric homotopic functional connectivity in adults. Lastly, these two intrinsic organization properties with different heritability together correlated with the general intelligence factor in an antagonistic manner. In summary, our findings offer important and valuable insight into functional lateralization, functional homotopy, and their relationship from the perspective of intrinsic functional architecture, together with influential factors such as age and task state. These results provide direct evidence to further understand the link between the left and right hemispheres of the human brain, along with the relation to cognitive functions.