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Fan, L.

Publications and source records attributed to Fan, L..

At least 55 records · Page 3Linked to original sources

Visual Regularities Underlie Hierarchical Object Representations in the Human Brain and Self-supervised DNN

NeuroAI develops the interplay of neuroscience and artificial intelligence, especially on visual processing. Human visual system organizes objects based on a representational hierarchy. However, it remains unclear whether this hierarchy arises from visual or semantic information. One hypothesis posits that the visual system is structured around statistical regularities of visual information. Here, we test this hypothesis using the THINGS datasets and pure-visual deep neural networks (DNN). We constructed a low-dimensional object space based on multiple abstract object properties, reflecting statistical patterns of visual regularities. By applying voxelwise encoding models, we identified clusters in the higher visual cortex based on their property tuning, and they were found to support specific object categories. These clusters serve as the middle level to reveal a property-cluster-object hierarchical organization. Subsequently, we investigated whether this hierarchical structure could be captured by a self-supervised DNN. Through activity similarity analysis, we mapped the brain clusters onto the DNN and independently found that the DNNs clusters exhibited distinct property tuning and influenced the classification accuracy of corresponding object categories, mirroring the effects observed in the human brain. Our results demonstrate similar hierarchical structures in the human brain and self-supervised DNN, suggesting that the visual regularities shape neural architecture of visual system. This study highlights the great potential of neural computational model in neuroscience study. Index Terms Visual Processing, Abstract Property, Hierarchical Representation, Self-supervised Visual DNN

neuroscience↗

Multifunctional Injectable GelMA Hydrogels with MSN-Mediated Spatiotemporal Icariin Release for Enhanced Osseointegration in Bone Defects

The repair of bone defects is faced with the dual challenges of limited autograft donors and single function of artificial materials. The development of new materials with mechanical adaptability, drug-controlled release and osteogenic induction has become a research hotspot in bone tissue engineering. Here, we developed an injectable photocrosslinkable hydrogel by integrating icariin (ICA)-loaded mesoporous silica nanoparticles (MSN) into gelatin methacryloyl (GelMA). The amino-functionalized MSN enhanced compressive modulus by 1.5-fold (p < 0.05) and enabled pH-responsive ICA release (91.2{+/-}4.2% cumulative release over 15 days). Our in vitro findings revealed the composite hydrogel promoted BMSC proliferation was 1.43{+/-}0.04 times that of GelMA group. And express excellent osteogenic differentiation ability (ALP activity: 3.25-fold; Mineralization: 5.01-fold). In vivo study, Micro-CT revealed significantly higher bone volume fraction (BV/TV) in rat calvarial defects at 12 weeks, with histology confirming mature trabecular bone formation. This MSN-mediated spatiotemporal delivery system synchronizes immunomodulation and osteogenesis, offering a promising strategy for non-load-bearing osseointegration.

bioengineering↗

Identification of cellular and molecular risk signatures for progression to late-stage age-related macular degeneration using the 9-step Minnesota Grading System

Age-related macular degeneration (AMD) is a complex multifactorial disease, and the molecular mechanisms underpinning the progression of intermediate AMD to geographic atrophy are not fully understood. To better understand mechanisms driving progression, we performed bulk RNA sequencing on dissected macular and peripheral RPE/choroid and neural retina tissue from postmortem human eyes graded using the 9-step Minnesota Grading System (MGS). Binning of intermediate AMD cases into three distinct groups (AMD3L, AMD3M, AMD3H) based on the 5-year risk of progression enabled identification of distinct gene and pathway changes associated with progression to late-stage disease. Identified changes in gene expression were validated using ELISA or histological methods. RPE-specific genes and lipid metabolic pathways showed a transient increase in AMD3L followed by a pronounced decrease in AMD3H. In AMD3H, immune response genes such as C3, TREM2, and OLR1 were upregulated when compared to AMD3L samples, as well as genes specific to Muller glia/astrocytes (NGFR, SPP1, GPX3). Our findings support complement inhibition as a promising therapeutic option for slowing conversion to advanced AMD and identify macrophage and Muller/astrocyte genes as potential cell types to target in AMD. Further, we demonstrate the value of combining emerging, outcomes-based, clinically relevant grading systems with profiling technologies to generate new insights into ocular diseases. HighlightsO_LIIntermediate AMD (AMD3) can be further divided into 3 stages - AMD3L (low risk), AMD3M (intermediate risk), AMD3H (high risk) - using the MGS9 grading system based on the risk of disease progression to late AMD. C_LIO_LIRNA sequencing of the macular RPE/choroid shows opposing changes in gene expression of multiple biological pathways for both RPE and immune cells between AMD3L and AMD3H stages. C_LIO_LIIn the macular neural retina, most biological pathways were downregulated in AMD2 (early AMD) but upregulated in AMD4 (late AMD) compared to AMD1 (non-AMD control). C_LIO_LIMolecular and cellular signatures associated with a high risk of progression to AMD4 include activation of complement C3, two subtypes of macrophages expressing either TREM2 or OLR1, and Muller glia/astrocytes as evidenced by the upregulation of GFAP and NGFR. C_LIO_LIUnderstanding the roles of these high-risk associated genes in AMD progression will facilitate the development of new treatments that prevent or delay the irreversible central vision loss in AMD patients. C_LI

neuroscience↗

Pp6-Pfkfb1 axis modulates intracellular bacterial proliferation by orchestrating host-pathogen metabolic crosstalk

Intracellular bacterial pathogens exhibit heterogeneous replication rates within host macrophages, but the mechanisms by which they manipulate host factors for survival remain incompletely understood. Using a fluorescence-dilution reporter system in Salmonella typhimurium (Salmonella)-infected macrophages, we found that Protein Phosphatase 6 (Pp6) was downregulated in macrophages harboring growing bacteria. Conditional knockout of Pp6 elevated host susceptibility to Salmonella-mediated lethality due to compromised antimicrobial defenses. MicroRNA-31 (miR-31) was identified as a negative regulator of Pp6, and its conditional ablation enhanced bacterial clearance. Yeast two-hybrid screening identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 (Pfkfb1), a metabolic regulator, as a substrate of Pp6. Pp6 deficiency resulted in significantly elevated expression of Pfkfb1, which was highly expressed in macrophages containing replicating Salmonella. Pfkfb1 deletion restricted bacterial proliferation by promoting nitric oxide (NO) production while concurrently suppressing arginase-1 (Arg-1) expression and impairing arginine metabolism in macrophages. Collectively, these results establish the Pp6-Pfkfb1 axis as a key regulator of host metabolic adaptation and intracellular bacterial survival, offering potential therapeutic targets against multidrug-resistant pathogens. Author summaryIntracellular pathogens secrete effector proteins that intercept and modify host cells to usurp host defenses and establish habitable intracellular niches, yet the host factors they manipulate for survival and virulence are not fully understood. Using a fluorescence-dilution reporter system in Salmonella typhimurium (Salmonella)-infected macrophages, we found Protein Phosphatase 6 (Pp6) was significantly decreased in macrophages harboring replicating Salmonella and its deficiency indulged bacterial growth in macrophages. However, the deletion of microRNA-31 (miR-31), a negative regulator of Pp6, enhanced Salmonella clearance. Furthermore, through yeast two- hybrid screening, we identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 (Pfkfb1) is a substrate of Pp6. And we demonstrated Pfkfb1, abundantly expressed in macrophages containing growing bacteria, is crucial for Salmonella proliferation by regulating nitric oxide (NO) levels, arginase-1 (Arg-1) expression and arginine metabolism. Overall, the molecular changes in Pp6-Pfkfb1 axis drive host metabolic adaptations that enable intracellular bacterial survival.

microbiology↗

Arcuate Fasciculus: Evolutionary Convergence in Marmosets and Humans

The marmoset is a highly vocal platyrrhine monkey that shares key anatomical and functional features with humans, offering insights into the evolution of brain connectivity. Although similarities in vocalization features with humans have been reported, it remains unclear whether marmosets possess an arcuate fasciculus (af) homolog. This study delineated white matter tracts in marmosets, establishing homologies with those observed in other primates, including macaques, chimpanzees, and humans. The presence of an af homolog in marmosets was confirmed by tracer and ultra-high-resolution diffusion magnetic resonance imaging datasets. We compared cortical connectivity patterns across these species and found the af in marmosets terminates in the ventral frontal cortex, with greater similarity to humans than macaques. Furthermore, we linked af connectivity with vocalization-related brain activation in both marmosets and humans. Collectively, our findings suggest that a dorsal pathway, which emerged early in marmoset evolution, has evolved convergently with humans, despite their distant phylogenetic kinship.

neuroscience↗

Mapping the coupling between tract reachability and cortical geometry of the human brain

The study of cortical geometry and connectivity is prevalent in research on the human brain. However, these two aspects of brain structure are usually examined separately, leaving the essential connections between the brains folding patterns and white matter connectivity unexplored. In this study, we aimed to elucidate fundamental links between cortical geometry and white matter tract connectivity. We developed the concept of tract-geometry coupling (TGC) by optimizing the alignment between tract connectivity to the cortex and multiscale cortical geometry. Specifically, spectral analyses of the cortical surface yielded a set of geometrical eigenmodes, which were then used to explain the locations on the cortical surface reached by specific white matter tracts, referred to as tract reachability. In two independent datasets, we confirmed that tract reachability was well characterized by cortical geometry. We further observed that TGC had high test-retest ability and was specific to each individual. Interestingly, low-frequency TGC was found to be heritable and more informative than the high-frequency components in behavior prediction. Finally, we found that TGC could reproduce task-evoked cortical activation patterns. Collectively, our study provides a new approach to mapping coupling between cortical geometry and connectivity, highlighting how these two aspects jointly shape the connected brain.

neuroscience↗

TP53 Inactivation Confers Resistance to the Menin Inhibitor Revumenib in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous cancer that is associated with poor outcomes. Revumenib and other menin inhibitors have shown promising activity against AMLs with KMT2A-rearrangements or NPM1 mutations. However, mechanisms of de novo resistance have not yet been elucidated. We analyzed a panel of cell lines and generated an isogenic model to assess the impact of TP53 mutations on the response of AML cells to revumenib. TP53 mutations are associated with de novo resistance to revumenib, impaired induction of TP53 transcriptional targets, and deregulated expression of the BH3 proteins BCL-2 and MCL-1. The MCL-1 inhibitor MIK665, but not venetoclax, preferentially sensitized TP53-mutant AML cells to revumenib. These data identify mutant TP53 as a potential biomarker for de novo resistance to revumenib, and provide a rationale to evaluate MCL-1 and menin inhibitor combinations in patients KMT2A-rearranged leukemias with TP53 mutations.

cancer biology↗

SHINE: SERS-based Hepatotoxicity detection using Inference from Nanoscale Extracellular vesicle content

Extracellular vesicles (EV) are becoming crucial tools in liquid biopsy, diagnostics, and therapeutic applications, yet their nanoscale characterization remains challenging. In this context, the detection of drug-induced liver injury, i.e., hepatotoxicity, through extracellular vesicle molecular content remains an unexplored frontier. To this end, we present a label-free surface-enhanced Raman (SERS) spectroscopy approach, which provides rapid EV content analysis under ten minutes and requires only 1.3 microliters of sample. Using hepatic cultures as a model, our platform captures distinct and reproducible EV molecular changes in response to acetaminophen-induced hepatoxicity. Our platform achieves exceptional accuracy with root mean squared error values as low as 3.80%, establishing strong correlations between EV spectra and conventional toxicity biomarkers. Unlike previous EV-SERS studies limited to vesicle identification and disease markers, this approach reveals EV drug-response signatures strongly correlated with conventional toxicity markers. These findings establish EVs as dynamic reporters of cellular drug responses and demonstrate use of SERS-based EV detection of hepatotoxicity.

biophysics↗

Mapping Early Brain Maturation: Anatomical Substrates of Cortical Connectivity Shifts in Neonates

Understanding the early development of brain connectivity is essential for unraveling the mechanisms of brain maturation. In this study, we utilized diffusion MRI data from 242 term neonates to chart the developmental trajectory of cortical connectivity in infants. We quantified interareal variations in connectivity and identified three distinct global connectopies (GCs) along the rostrocaudal, dorsoventral, and mediolateral axes by using gradient mapping techniques. A pivotal age-dependent shift between the dorsoventral and mediolateral GCs occurred at 40 postmenstrual weeks. This shift was diminished by virtual thalamic fiber lesions, underscoring the critical role of thalamic projections. A longitudinal analysis disclosed a delayed structural connectivity pattern development in preterm infants who failed to exhibit the anticipated shift. This research helps to clarify the topographic principles that shape infant brain organization and emphasizes the influence of thalamic connectivity on early brain development. Our findings elucidate the anatomical underpinnings of early brain development, providing critical insights into the formation of cortical hierarchies and highlighting the influence of thalamic connectivity on developmental trajectories. These findings are essential for understanding typical brain growth and the pathogenesis of neurodevelopmental disorders.

neuroscience↗

Photoaffinity enabled transcriptome-wide identification of splice modulating small molecule-RNA binding events in native cells

Splice modulating small molecules have been developed to promote the U1 snRNP to engage with pre-mRNAs with strong and altered sequence preference. Transcriptomic profiling of bulk RNA from compound treated cells enables detection of RNAs impacted; however, it is difficult to delineate whether transcriptional changes are a consequence of direct compound treatment or trans-acting effects. To identify RNA targets that bind directly with splice modulating compounds, we deployed a photoaffinity labeling (PAL)-based Chem-CLIP approach. Through this workflow, we identify the telomerase lncRNA (TERC) as a previously unknown target of this class of clinically relevant small molecules. Using cellular {Delta} SHAPE-MaP, we orthogonally validate and further define the compound binding site as likely to be the conserved CR4/5 domain. Additionally, a thorough analysis of the PAL-based Chem-CLIP data reveals that considering competed RNAs, irrespective of magnitude of enrichment, adds a rich dimension of hit calling. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/623654v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1ef467eorg.highwire.dtl.DTLVardef@1fd201dorg.highwire.dtl.DTLVardef@1478f83org.highwire.dtl.DTLVardef@11ef59a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

A regulator controls both DNA damage response and anti-phage defense networks in Moraxellaceae

DNA damage chemicals, including many antibiotics, often induce prophage induction and phage outbreaks in microbial communities, a major threat to bacterial survival. Moraxellaceae contains clinically highly relevant strains with outstanding antibiotic and radio resistance, yet their cellular-level regulation in DNA damage response and anti-phage defense is largely unknown. Here, we identified a WYL family protein that had replaced the ubiquitous SOS system in evolution and directly regulated a transcriptional network of both DNA repair genes and anti-phage defense genes under DNA damage stress. This study depicts a mechanism that how bacteria maintain immunity to phages without compromising on antibiotic resistance, and sheds light on controlling the resistance of Moraxellaceae strains in clinical practice.

microbiology↗

Global patterns, drivers and impacts of metabolic traits across amniotes

Metabolism and climate are thought to influence species richness and diversification, yet few studies have examined whether global patterns of metabolic traits are linked to climate and diversification rate. Here we investigate the drivers of global metabolic rates and their impacts on biodiversity across 2,633 amniote vertebrates. We found consistent distribution patterns of metabolic rates in terrestrial amniotes and marine birds, with metabolic rates increasing with distance from the equator across latitudes. Temperature is a primary climatic variable affecting metabolic rates in birds and mammals, whereas precipitation dominates in terrestrial reptiles. Furthermore, elevated metabolic rates promote diversification rates and reduce extinction risks in birds and terrestrial mammals. Conversely, high metabolic rates decrease diversification rates and increase extinction risks in reptiles. Our results show that global patterns of metabolic rates are driven by various climate variables and may shape diversification and extinction patterns among amniotes in the context of climate change.

ecology↗

Uncovering Individualized Cerebellar Atrophy Pattern and Behavioral Links in Children with Brainstem Tumor

Background and PurposeBrainstem tumors are rare but cause enduring behavioral issues, challenging patients and surgeons. Research on cerebellar changes in these patients limited, despite symptoms similar to cerebellar injuries. This study aims to investigate cerebellar damage pattern resulting from brainstem tumors and its association with behavioral disorders. MethodsIn this study, a U-Net-based segmentation algorithm was used to divide the cerebellum into 26 lobules, which were then used to build a normative model for assessing individual structural deviations. Furthermore, a behavior prediction model was developed using the total outlier count (tOC) index and brain volume as predictive features. ResultsMost patients were found to have negative deviations in cerebellar regions, particularly in anterior lobules like Left V. Higher tOC was significantly associated with severe social problems (r = 0.31, p = 0.001) and withdrawal behavior (r = 0.28, p = 0.001). Smaller size of cerebellar regions strongly correlated with more pronounced social problems (r = 0.27, p = 0.007) and withdrawal behavior (r = 0.25, p = 0.015). Notably, lobules Right X, V, IV, VIIB, Left IX, VIII, and X influenced social problems, while Left V, Right IV, Vermis VI, and VIII impacted withdrawal behavior. ConclusionsOur study revealed cerebellar damage patterns in patients with brainstem tumors, emphasizing the role of both anterior and posterior cerebellar lobes in social problems and withdrawal behavior. This research sheds light on the brain mechanisms underlying complex behavioral disorders in brainstem tumor patients.

neuroscience↗

Normative Growth Modeling of Cortical Thickness Identify Neuroanatomical Variability and Distinct Subtypes in Brainstem Tumor Patients

BackgroundBrainstem tumors can cause structural brain changes, but the resulting heterogeneity within wholebrain structure is not well-studied. This study examines cortical thickness to identify patterns of structural alterations and explore underlying biological subtypes and their associations with clinical factors. Materials and MethodsThis study involved 124 pediatric brainstem tumor patients, aged 4-18 years. Cortical thickness was measured using CAT12 segmentation of 3D T1-weighted structural MRI. A normative model was established using data from 849 healthy children. Deviations in cortical thickness were estimated, and patients were classified into two subtypes using spectral clustering. Clinical statistical analyses were conducted with SPSS 26.0. ResultsThe normative model revealed significant heterogeneity in cortical thickness deviations, which correlated with tumor size and growth patterns. Focal tumors primarily caused negative deviations (t = 3.14, p = 0.02). There was a significant positive correlation between extreme positive deviations and tumor volume (r = 0.214, p = 0.010), and between extreme negative deviations and progression-free survival (r = 0.39, p = 0.008). Two subtypes were identified: Subtype 1, consisting of diffuse tumors with extreme positive deviations, and Subtype 2, consisting of focal tumors with extreme negative deviations. Subtype and tumor growth pattern significantly influenced duration (p < 0.01). The Kaplan-Meier survival curves for Subtype 1 and Subtype 2 demonstrated a significant difference in survival probabilities over time (p = 0.03). ConclusionOverall, this study identifies two major patterns of cortical thickness changes in brainstem tumor patients, enhancing our understanding of their relationship with cortical morphology. The findings suggest that cortical thickness alterations could serve as valuable biomarkers for predicting progression-free survival, which is crucial for clinical assessment and personalized treatment strategies. This research provides new insights into the physiological mechanisms by which brainstem tumors affect brain structure, supporting more precise clinical interventions and efficacy monitoring in the future.

neuroscience↗

Genetic diversity and evolution of rice centromeres

AbstractUnderstanding the mechanisms driving centromere evolution is crucial for deciphering eukaryotic evolution and speciation processes. Despite their widely recognized characteristics of conserved function in cell division, the centromeres have showed high diversity in composition and structure between species. The mechanism underlying this paradox remain poorly understood. Here, we assembled 67 high-quality rice genomes from Oryza AA group, encompassing both Asian and African rice species, and conducted an extensive analysis of over 800 nearly complete centromeres. Through de novo annotation of satellite sequences and employing a progressive compression strategy, we quantified the local homogenization and multi-layer nested structures of rice centromeres and found that genetic innovations in rice centromeres primarily arise from internal structural variations and retrotransposon insertions, along with a certain number of non-canonical satellite repeats (sati). Despite these rapid structural alterations, the single-base substitution rate in rice centromeres appears relatively lower compared to the chromosome arms. Contrary to the KARMA model for Arabidopsis centromere evolution, our model (RICE) suggests that centrophilic LTRs contribute to the decline of progenitor centromeres composed of satellite repeats, and facilitate the formation of evolutionary neo-centromeres, which are enriched with extended CENH3 binding regions beyond the native satellite arrays in plant genomes. In summary, this study provides novel insights into genomic divergence and reproductive barriers among rice species and subspecies, and advances our understanding of plant centromere evolution.

genetics↗

tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

genetics↗

A spontaneous mutation in ADIPOR1 causes retinal degeneration in mice

Adiponectin receptor 1 (ADIPOR1) is a transmembrane protein necessary for normal anatomy and physiology in the retina. In a recent study of complement factor H knockout mice (Cfh-/-), our lab discovered a flecked retina phenotype and retinal thinning by fundus imaging and optical coherence tomography (OCT), respectively. The phenotype was observed in a subset (50%) of Cfh-/- mice. The thinning observed in vivo is due to an early degeneration of rod photoreceptors. This phenotype has not been reported in published studies of Cfh-/- mice. AdipoR1 knockout mice (AdipoR1-/-) and mice deficient in Membrane Frizzled Related Protein (MFRP) exhibit this phenotype, suggesting an involvement in the emergence of the retinal degeneration observed in a subset of Cfh-/- mice. Cfh and AdipoR1 are located in close proximity on mouse Chromosome 1 (Chr1) and a complementation cross between Cfh and AdipoR1 mice with retinal degeneration produced 100% progeny with retinal degeneration. Sequencing of the Cfh-/- mice revealed a c.841 C > T mutation in AdipoR1. Furthermore, one Cfh wildtype (of Cfh+/+) and 2 heterozygous (of Cfh+/-) mice exhibited retinal degeneration and were homozygous for the point mutation. The c.841 C > T mutation results in a proline to serine conversion at position 281 (P281S) in ADIPOR1. This residue is critical for ADIPOR1 open and closed conformations in the membrane. In silico modeling of candidate ADIPOR1 ligands, 11-cis-retinaldehyde and docosahexaenoic acid (DHA), that are deficient in AdipoR1-/-, suggests that ADIPOR1 is involved in trafficking retinoids and fatty acids and their combined deficiency in the ADIPOR1 mutant retinas might explain the retinal degeneration phenotype.

neuroscience↗

Comparative Analysis of Human-Chimpanzee Divergence in Brain Connectivity and its Genetic Underpinnings

Chimpanzees (Pan troglodytes) are humans closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

neuroscience↗