Jaeseung Jeong

Partitioned-heritability studies have shown which tissues carry the heritability of complex traits, but whether the regulatory layer whose annotations are most informative for heritability within a tissue differs between traits has not been tested, because measured annotations for different layers come from different sets of biosamples. Sequence-to-function models predict the allelic effect of every variant on several regulatory layers with a single model, so that layers can be compared on the same variants within the same tissues. We grouped AlphaGenome Atlas predictions into 12 lineages and six regulatory layers and partitioned the heritability of 11 complex traits with stratified LD score regression. Traits localized largely to the expected lineages, and within these lineages the most informative predicted layer differed between traits ( P = 3.6 × 10 ^-8 ). Predicted chromatin-accessibility (DNase) effects were the most informative for height and bone mineral density, whereas predicted transcription-initiation (CAGE) effects were the most informative for Alzheimer’s disease, most brain traits and cholesterol levels. The difference persisted across sensitivity analyses, and the predicted contrast held for three related traits whose layers had been predicted in advance ( P = 2 × 10 ^-7 ). Predicted CAGE effects also remained informative after conditioning on fine-mapped eQTLs and measured regulatory annotations. These results identify differences across traits in the heritability information captured by predicted regulatory layers and offer testable hypotheses for investigating the regulatory basis of complex traits.

Gossip is central to social exchange, yet how adolescents select what to share and with whom remains unclear. Across two endent samples aged 10–18 years (behavioural, n = 98; fMRI, n = 101 scanned), adolescents read information about absent third parties, chose whether and with whom to share it, and rated interest, usefulness and emotional response. Sharing frequency showed no detectable age association. The association between interest ratings and sharing strengthened with age in both samples; usefulness showed a smaller age interaction. Adolescents selected close friends more often with age when sharing. During scenario reading, before participants reported choices, BOLD responses in a left inferior frontal cluster tracked subsequent interest ratings more strongly with age (n = 92), also within regions defined by a mental-state judgment localizer. Together, these findings link age in adolescence to stronger valuation-to-decision coupling for interest and a greater proportion of sharing directed to close friends.

Sequence models predict the molecular effects of genetic variation, yet their contribution to interpreting Alzheimer’s disease (AD) association signals remains uncertain. Here we analysed AlphaGenome Atlas predictions for 111,446 common variants across 75 regions from a European-ancestry genome-wide association study (GWAS) of AD and related dementias. Predicted expression effects modestly tracked association within loci (mean partial Spearman ρ = 0.018, P = 0.003) and were higher in variants with the highest posterior inclusion probability than in correlated variants outside credible sets (mean difference, 0.044 percentile units; P = 0.005). This relationship remained after adjustment for genic position (ρ = 0.011, P = 0.026). Predicted splicing effects also tracked association, but this relationship was attenuated after the adjustment. Expression and splicing scores were associated with the corresponding Genotype-Tissue Expression (GTEx) quantitative trait locus (QTL) status, although these analyses did not establish colocalization or agreement in allelic direction. Across 50 loci with multiple fine-mapping candidates, predicted cellular labels were no more concentrated than in position-matched comparisons, and expression direction profiles showed no detectable excess concordance with lead variants. These findings support expression predictions as complementary evidence for interpreting AD risk variants, while showing that the assignment of cellular context must account for fine-mapping uncertainty.

Bilateral organization is a prominent feature of the C. elegans nervous system, yet bilateral neuron pairs differ substantially in their individual left–right connections. Whether, and how, such pairs nonetheless come to occupy similar roles in the network is not fully understood. Here we analyze the adult hermaphrodite and male C. elegans connectomes to examine bilateral redundancy using three complementary graph‐theoretic measures: connectivity similarity, which captures overlap in shared in‐ and out‐neighbours; motif‐fingerprint difference, which captures the difference in local motif participation (with lower differences indicating greater overlap); and path compensation, which quantifies the extent to which paired neurons make overlapping contributions to global communication. Across measures, bilateral pairs showed elevated redundancy relative to other neuron pairs. Null‐model comparisons further supported this finding, demonstrating that these patterns cannot arise from preserving symmetry alone: e.g., for connectivity similarity, randomizing the asymmetric edges while holding the symmetric ones reduced bilateral similarity, suggesting that bilateral asymmetry is itself what enables paired neurons to share neighbours and converge on similar network roles. Redundancy was not uniform across the nervous system: in the hermaphrodite it was more pronounced among interneurons than among sensory neurons across all three measures, while in the male this gradient was only significant for path compensation. Together, these results show that bilateral redundancy is a systematic multiscale principle of the C. elegans connectome, one that cannot be explained by bilateral symmetry alone.

A growing body of neuroscience evidence indicates that perceiving everyday objects and environments triggers mental simulations of potential actions, preparing the brain for movement even before any motion occurs. Although previous research on navigation has demonstrated how the spatial configuration of corridors and doorways guide locomotion, it remains unclear whether architectural elements (e.g., doors, windows, stairs) that require direct interaction evoke distinct, action-specific representations in the brain. Thus, the aim of this study is to investigate whether the passive perception of such elements (viewed without any intention to act) spontaneously recruits motor-related brain networks and whether these activations are specific to the actions implied by each element. fMRI data were collected from 31 participants during passive viewing of each architectural element followed by imagery of four actions: one reflecting the element's primary function, one representing manipulation, and two corresponding to peripheral actions. Using multi-voxel pattern analysis, we created classification ratio maps to identify action–architectural element associations. Our analyses revealed that passive perception significantly elicits neural patterns aligned with the elements' primary function while also encoding sensorimotor representations of the required interactions. Furthermore, our results show that this anticipatory process activates motor-related regions, including premotor cortex and the dorsal visual pathway. These results underscore the crucial role of action simulation in architectural perception and demonstrate the brain's readiness to engage with environmental affordances at the sensorimotor level. Consequently, we propose possibilities for a neuroscience-informed design, suggesting that architecture can be optimized to align with the embodied nature of human cognition.

Choi YH, et al. J Clin Neurol. 2026 ;22:e31. https://doi.org/10.3988/jcn.2025.0552

Connectome network analysis across multiple species should help identify principles of brain function. Here, we examined three fundamental properties—global efficiency, global betweenness centrality, and global clustering—in the mesoscale tract‐tracing data of the mouse connectome; and conducted vulnerability analysis to identify the critical regions and connections based on the loss in network function when each brain region (213) and connection (16,594) was removed. Robustness tests examining noise effects were also conducted. There were five key findings. First, we identified eight critical regions and 38 critical connections, with more central, limbic regions dominant; and with robustness analysis showing (a) the importance of connection strength; and (b) the findings being robust to noise. Second, although critical regions and connections were significantly based on their local network properties, global influences sometimes deviated from local ones (e.g., critical globally but with lower local scores), thereby revealing global‐level interactions. Third, the critical components organized into two main pathways (one from piriform cortex to globus pallidus; the other, entorhinal cortex to the amygdala), and two main clusters (centred on caudoputamen and entorhinal cortex). Fourth, for brain function, all main categories from perception to action were represented: e.g., olfaction (piriform cortex), learning and memory (entorhinal cortex), affect (amygdala and caudoputamen), and cognitive and motor processing (caudoputamen, globus pallidus). Finally, the claustrum was intriguingly identified as critical, perhaps for information integration and motor translation. Vulnerability analysis provides a unique approach to characterizing the fundamental structure of nervous systems.

Jung YJ, et al. J Clin Neurol. 2025 Jul;21:e26. https://doi.org/10.3988/jcn.2025.0053

Understanding the balance between symmetry and asymmetry in animal nervous systems is crucial for unraveling the complexities of neural architectures and their functions. Previous studies have primarily focused on morphological symmetry, such as neuron placement, leaving the symmetry in the functional architecture largely unexplored. The current study investigates this aspect within the Caenorhabditis elegans connectomes by introducing a graph-theoretic approach. By defining a ‘mirror-symmetry index,’ we quantitatively assess the symmetry in these connectomes, revealing a significant level of bilateral symmetry alongside notable asymmetry. Our approach also incorporates measures including connectivity similarity, motif-fingerprint differences, and path-compensation index to evaluate the network’s functional redundancy and its capacity to compensate for unilateral disturbances. Here we show the C. elegans connectomes’ robust bilateral symmetry, which not only facilitates similar functions across neuron pairs but also ensures resilience against disruptions. This redundancy is not confined to symmetrical connections; it also includes asymmetric ones, adding to the neural network’s complexity. An in-depth analysis into different neuron types shows varied redundancy levels: high in interneurons, moderate in motor neurons, and low in sensory neurons. This pattern suggests a strategic neural design where diverse inputs from sensory neurons, coupled with the stable integration by interneurons, lead to coordinated actions through motor neurons. This study advances our understanding of neural connectomes, offering insights into the intricate balance of symmetry and asymmetry in neural systems and their implications for complex, adaptive behaviors.