Brain Structure and Function

Prior studies have reported inconsistent results for neuroanatomical differences between early bilinguals and monolinguals. These studies primarily measured gray matter volume (GMV), involved small samples, and prioritized adults. Few studies of early bilinguals have measured cortical thickness (CT), which offers more anatomical specificity. It remains unclear whether results derived from differing metrics and approaches (e.g., vertex-versus parcel-wise analyses) converge. Using data from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, we compared neuroanatomy between large groups of early cultural Spanish-English bilingual and English monolingual children (N = 1,209) matched on age, pubertal status, sex, handedness, socioeconomic status (SES), and nonverbal reasoning. Whole-brain voxel-based morphometry revealed areas of greater and of lesser GMV in bilinguals than monolinguals across all lobes. Vertex-wise CT analyses similarly identified widespread differences, with bilinguals showing areas of both thicker and thinner cortex. We contextualized these findings with parcel-wise CT analyses (average CT values), utilizing two atlases of differing spatial granularity. Parcel-wise results showed good correspondence with vertex-wise findings when implementing the more fine-grained atlas (Destrieux), but use of the coarser atlas (Desikan-Killiany) provided results that led to different conclusions. Finally, we tested for interaction effects between bilingualism and SES on CT and found several regions where differences between bilinguals and monolinguals in CT were modulated by SES. Together, these findings indicate that early bilingualism is associated with extensive neuroanatomical differences relative to monolinguals during childhood, and that these results can vary as a function of neuroanatomical metric, analysis approach, atlas granularity, and SES. Research HighlightsEarly Spanish-English bilingual and monolingual children differ in gray matter volume and cortical thickness across multiple brain regions. Cortical thickness differences between bilinguals and monolinguals cannot be firmly attributed to adaptations associated with language or executive control. Socioeconomic status modulates cortical differences between early bilinguals and monolinguals, revealing unique thickness patterns for those with lower versus higher SES backgrounds. Parcel-wise between-group cortical thickness results are affected by atlas choice and can influence the interpretation of the findings.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

Prior studies in bilinguals have reported relationships between brain structure and the dimensions of (i) language proficiency or (ii) language balance (the discrepancy between a bilinguals two proficiencies), but rarely both, even though they are highly related. These studies were often conducted in late bilinguals and the analyses limited to regions of interest. Here, we tested for relationships between brain structure and these two dimensions in 46 early cultural Spanish-English bilinguals (mean age = 16.7 years) at the level of the whole brain for gray matter volume (GMV) and cortical thickness (CT). Results revealed a positive association between GMV and proficiency in the weaker language in the right angular gyrus (AG; BA 39) extending into the superior temporal gyrus (BA 22). More balanced bilingualism was also associated with more GMV in the AG (BA 39), in addition to less GMV in left postcentral gyrus (BA 1), right cerebellum lobule IX and right superior occipital gyrus (BA 18). However, these relationships between GMV and balance disappeared after controlling for language proficiency. No significant associations were observed for CT and these two dimensions of language. Our findings suggest that relationships between GMV and balance are driven by language proficiency, and that the relationship between GMV and language proficiency likely does not involve language-specific mechanisms, given the location of the association is in the right inferior parietal cortex. Together, this study separates the neuroanatomical bases of these two language dimensions and places them in brain regions outside those usually targeted in prior studies. HighlightsO_LINeuroanatomy was correlated with proficiencies in early Spanish-English bilinguals C_LIO_LIRight angular gyrus gray matter volume (GMV) was positively related to proficiency C_LIO_LIGMV was positively related to balance, but not after controlling for proficiency C_LIO_LIRelations with these language dimensions are located outside of language cortex C_LIO_LINo significant associations were observed for cortical thickness C_LI

3.The fusiform face area (FFA) preferentially responds to faces within the first months of life. One hypothesis is that higher-order social responses in middle medial prefrontal cortex (MMPFC) or face responses in superior temporal sulcus (STS) drive the development of face-selective responses in FFA, with right-hemisphere dominance in FFA eventually arising from lateralised connections to these regions. Another hypothesis proposes an innate face template in the amygdala guides attention to face-like shapes. This study opportunistically examined the development of the FFA, MMPFC, STS, and amygdala in childhood using an open cross-sectional movie-viewing fMRI dataset with 3-12-year-olds (N=117, M=6.77 years) and adults (N=33, M=24.77 years). We tested for correlations between FFA development and development in MMPFC, STS, and amygdala on the premise that associations between these regions may be observable even in children, and such associations could constrain hypotheses and analytic approaches in future studies with infants. First, we measured functional maturity-how similar each childs response to the movie was to an adult average response timecourse. In all regions, older childrens responses were more adult-like. Next, we tested whether FFA maturity correlated with functional connectivity with, or functional maturity of, MMPFC, STS, or amygdala. Children with more mature right FFA responses showed stronger right FFA-right MMPFC connectivity. Children with more mature FFA responses also had more mature STS responses, bilaterally. This study provides preliminary evidence that FFA co-develops with higher-order social brain regions and specific metrics to take forward in future research with infants. HighlightsO_LIWhat drives face selective responses in FFA is the subject of recent debate. C_LIO_LI117 children aged 3 to 12 years watched a short movie while undergoing fMRI. C_LIO_LIRight FFA development correlated with functional connectivity to right MMPFC C_LIO_LIFFA development correlated with STS development, bilaterally. C_LIO_LIFFA codevelops with higher-order social brain regions (controlling for age). C_LI

Previous studies exploring the connection between early language development and brain anatomy have shown that cortical areas relating to individual differences in language skills are diverse and vary depending on the age of child. However, due to lack of large longitudinal samples, current literature is limited in answering the extent to which individual differences in language development prior to school age are reflected in areas of the cortex. To fill this gap, we compared gray matter density between participants that belonged to different longitudinally defined language profiles from 14 months to five years of age in a large population-based sample. Participants were 166 children from the FinnBrain Birth Cohort Study who had longitudinal language data from 14 months to five years of age and magnetic resonance imaging data at five years of age. Three groups of language development were used as per our prior study: persistent low, stable average, and stable high. Voxel-based morphometry metrics were calculated using SPM12 and the three language profile groups were compared to one another. Covariates included sex and age at brain scan. The statistics were thresholded at p < 0.01 and false discovery rate corrected at the cluster level. Of the three longitudinal language profiles, the stable high group had higher gray matter density than the persistent low group in the right superior frontal gyrus. No differences were found between the stable average and stable high groups, nor persistent low and stable average groups. The identified superior frontal cortical area belongs to executive functions neural network. This finding adds to the cumulating evidence that individual differences in language development are reflected in growth of gray matter supporting general processing ability rather than specialized language regions. The results suggest that cognitive development and early language development are linked through shared principles of neural growth, identifiable already at age five. Key pointsO_LIAn association between early language development from 14 months to five years of age and gray matter density differences of the right superior frontal gyrus was found at the age of five years. Children following the strongest language trajectory were more likely to exhibit higher gray matter density of the right superior frontal gyrus than children following the weakest trajectory. C_LIO_LIAs the superior frontal gyrus is part of executive functions network, we propose that individual differences in early language development are more defined by general learning mechanisms supported by those networks, rather than language specific pathways. C_LI

Hippocampal area CA2 has recently emerged as a critical region for social recognition memory. Furthermore, this understudied region has been implicated in psychiatric diseases and neurodegenerative diseases. There has been accumulating evidence indicating that the pyramidal neurons (PNs) in area CA2 exhibit functional specializations that correlate with somatic position in stratum pyramidale (sp). In this study, we investigated the morphological differences in dendritic architecture of CA2 PNs with a focus on the radial gradient, i.e., along the deep-superficial axis of the sp. We conducted a comprehensive morphological analysis including Sholl intersection profiles, branching order distributions, root angle distributions, and dendritic cable lengths. We found that CA2 PNs have fewer oblique dendrites and a larger number of tuft-like dendrites as compared to CA1 PNs. Furthermore, within the CA2 population, we found that many of the dendritic structural features gradually changed along the radial axis from deep to superficial somatic location, indicating a continuum of dendritic morphology rather than two sharply defined subtypes of pyramidal neurons. This morphological characterization may serve as a starting point to better understand the corresponding functional organization of CA2. The gradual difference between deeper and superficial CA2 PNs suggests a continuum of their computational capabilities beyond two binary functional classes. In briefUsing several methods, we examine the dendritic morphology of over 130 CA2 and CA1 pyramidal neurons and find that many properties such as the cable length and terminal numbers of the dendritic arbors vary as a with the location of the soma in the pyramidal layer. HighlightsO_LIWe use scholl analysis, graph theory and machine learning techniques to quantify the different dendritic morphologies of CA2 pyramidal neurons. C_LIO_LIMany properties of CA2 pyramidal neuron apical dendrites vary as a function of somatic location in the pyramidal layer. C_LIO_LIMore superficial CA2 pyramidal neurons have longer oblique apical dendrites, and shorter tuft dendrites. C_LI

Abstract: BACKGROUND: Perivascular spaces (PVS), visible on brain MRI, contribute to the brain clearance system and are associated with age and neurodegenerative disorders. While lower volumes of PVS in the forebrains white matter and basal ganglia have been also demonstrated in preterm-born neonates, the long-term trajectory of PVS after premature birth remains unclear. This study tests for altered PVS volumes in very preterm/very low birthweight-born (VP/VLBW) adults compared to full-term controls and explores potential associations with cognitive performance. METHODS: PVS were assessed on T2-weighted MRI from 97 VP/VLBW and 89 full-term (FT) subjects at 26 years from the prospective, population-based Bavarian Longitudinal Study. PVS volume and count was based on automated nnU-Net-based segmentation. Regional PVS volumes were normalized by corresponding regional parenchyma volumes. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale. MANCOVA was used for PVS group comparisons, Spearman rank correlations for testing PVS relationships with birth variables and cognitive scores. RESULTS: VP/VLBW-born adults showed significantly higher normalized PVS volumes in bilateral basal ganglia (p < 0.001, partial eta-squared = 0.096) and insula-related white matter (p = 0.001, partial eta-squared = 0.057). In the basal ganglia, higher PVS volumes were negatively correlated with gestational age (rho = -0.223, p = 0.030) and positively correlated with the Intensity of Neonatal Treatment Index (rho = 0.222, p = 0.030) in the VP/VLBW group. PVS volume was not associated with IQ scores. CONCLUSION: We demonstrate region-specific alterations of perivascular spaces in VP/VLBW-born adults. Data suggest that prematurity has lasting impact on the PVS.

Elite athletes exhibit sport-specific neural adaptations, yet it remains unclear whether such changes reflect general effects of training or the unique demands of individual sports. Skiing requires postural control and whole-body coordination under dynamically unstable environments, placing high demands on somatosensory processing and sensorimotor integration. The present study aimed to identify structural brain characteristics specific to elite skiers by comparing them with athletes from other sports disciplines and non-athletes. T1-weighted MRI data were analyzed using voxel-based morphometry in 13 skiers, 23 non-ski control athletes and 25 non-athletes. Whole-brain analysis comparing skiers with non-ski athletes revealed a significant cluster showing greater gray matter volume in skiers compared with non-ski athletes in the left postcentral gyrus, extending into the superior parietal lobule. The identified cluster primarily encompassed cytoarchitectonic Areas 2 and 5L. These regions are involved in higher-order somatosensory processing and multisensory integration. Importantly, region-of-interest analysis demonstrated that gray matter volume within this cluster was greater in skiers compared with non-ski athletes and non-athletes, with no difference between non-ski athletes and non-athletes. These findings highlight the relative prominence of structural adaptations within somatosensory-parietal networks, reflecting the unique integration of proprioceptive and other sensory information required for elite skiing. Overall, these findings provide evidence for sport-specific structural brain differences in elite athletes and highlight the importance of somatosensory and parietal regions in sensorimotor integration relevant to skiing. These findings may have implications for understanding neural markers of expertise and may inform future approaches to training and performance evaluation in skiing.

IntroductionWhile global topological properties of brain networks reach relative maturity early in development, functional reconfigurations at the regional level continue throughout adolescence to support cognitive maturation. However, regional age and sex-specific developmental patterns of functional reconfiguration remain incompletely understood. MethodsWe analyzed resting-state fMRI data from 528 participants aged 5-21 years from the Human Connectome Project in Development. Three regional graph-theory metrics (betweenness centrality, hub score, and local efficiency) were computed for each individuals functional network. Cognition was measured using NIH toolbox. Parallel factor analysis was employed to decompose an individual x region x metric array into factors representing distinct developmental properties in the full sample and separately for males and females. Brain-cognition associations were examined in developmental subgroups (<13, 13-18, >18 years). ResultsThree factors emerged, characterizing visual, multimodal integration, and higher-order factors. Across development, metrics capturing network integration (betweenness centrality and hubness) showed general stability, while metrics capturing segregation (local efficiency) presented distinct peaks, particularly in the visual factor. Females showed earlier peaks and declines in higher-order factor, while males exhibited greater variability and protracted maturation in multimodal and higher-order factors. Brain-cognition associations were modest with early childhood and crystallized cognition composites showed small negative correlations with hub score in entire sample (r=-0.212) and local efficiency in males aged <13 years (r=-0.215). ConclusionFindings highlight nonlinear, sex-specific functional reconfiguration at region-level during childhood and adolescence, underscoring the importance of sex-stratified analyses in developmental and providing a crucial foundation for future investigations of developmental disorders.

PurposeCerebral glucose metabolism and cortical morphology are known to undergo significant changes across the lifespan, yet their network-level coordination remains poorly understood. This study aimed to investigate whether individual-level metabolic connectivity (MC) reflects underlying inter-areal morphometric similarity, and to determine how this metabolic-morphometric coupling evolves across the adult lifespan. MethodsDynamic [18F]FDG-PET and structural MRI data were acquired from 67 healthy adults (age range: 38-86 years). Individual MC networks were estimated based on the similarity between regional time-activity curves. Corresponding structural similarity networks were generated using the morphometric inverse divergence (MIND) framework, which integrates multiple vertex-wise features of cortical morphology. The correspondence between metabolic and structural networks was quantified at both global and local scales using Spearman correlations. General linear models were employed to assess age-related effects on MC-MIND similarity. ResultsMC demonstrated a robust positive association with cortical morphometric similarity ({rho} = 0.32, p < 0.0001), an association that persisted after distance correction and was replicated at the individual level. Regional coupling followed a topographic gradient, peaking in heteromodal association cortices and reaching its minimum in paralimbic areas. Crucially, morphology-metabolism alignment systematically strengthened with age at the global level ({beta} = 0.59, p < 0.001). Local age-related increases were spatially heterogeneous, predominantly affecting visual, dorsal parietal, and premotor cortices alongside adjacent multimodal regions. ConclusionIndividual-level MC captures the morphometric organisation of the brain. The age-related increase in morphology-metabolism coupling indicates that metabolic coordination becomes progressively more aligned with cortical architecture, consistent with reduced neuroenergetic flexibility in the ageing brain.

Low statistical power remains a persistent concern in functional magnetic resonance imaging (fMRI) research, largely due to small sample sizes. Although prior work has documented gradual increases in sample size over time, it remains unclear whether structural factors in the publication process are associated with study design characteristics such as sample size. This review addresses this gap by analyzing a large sample of fMRI studies to assess how institutional prestige, journal impact factor, and journal review practices are associated with sample size. We analyzed articles published in 2021-2024 reporting new fMRI data collection in adult humans and including a measure of memory. We found studies with specialized populations, such as patient populations, had smaller sample sizes, as did studies with task-based designs compared to resting-state designs. We also found larger sample sizes were associated with journals with a double-blind review process. Institutional prestige was positively associated with sample size such that more highly ranked institutions tended to have larger samples, but there was no interaction between review type (single-vs. double-blind) and prestige, indicating this difference is not likely due to reviewer bias. Journal impact factor was not associated with sample size, however institutional prestige score predicted journal impact factor. These results suggest structural factors at the institutional level likely have a stronger influence on published study sample size than reviewer practices or biases.

IntroductionThe thalamic nuclei play a crucial role in regulating information flow to the cortex and supports diverse cognitive functions. Although previous studies have linked thalamic structural and functional characteristics to cognition, these measures do not fully capture the thalamuss role in dynamic control, which is essential for complex cognitive processes. Moreover, it remains unclear how these different metrics relate to each other in the way they account for cognition. MethodsT1-weighted MRI, diffusion MRI, resting-state fMRI, and neuropsychological data were obtained from 419 unrelated participants in the Human Connectome Project. We measured grey matter volume, white matter integrity, and functional controllability of each thalamic nucleus to examine their associations with cognitive performance across domains identified through clustering analysis of the neuropsychological data. We also assessed the relationships among these structural and functional metrics and evaluated their individual and combined contributions in capturing covariance with performance in various cognitive domains. ResultsSignificant correlations were observed between thalamic grey matter volume and white matter integrity; however, thalamic functional controllability showed no significant association with either structural metric. White matter integrity demonstrated the strongest association with sequence working memory and language processing. In contrast, thalamic controllability metrics accounted more for performance in executive function, reasoning and encoding, visuospatial processing, and impulse control, outperforming the combination of grey and white matter structural metrics. ConclusionThis study highlights the critical role of the thalamus from a dynamic control perspective, demonstrating that thalamic structural and functional metrics provide complementary rather than redundant information related to cognitive performance. These findings underscore a promising new direction for understanding the complex and dynamic contributions of the thalamus to human cognition.

The thalamus is essential for learning, dynamically engaging with other subcortical and cerebral cortex regions throughout the learning process. Here, the thalamus serves as a critical connector hub and synchroniser within the thalamocortical system of the brain. However, whilst higher order thalamic nuclei are known to be particularly important for this process, the exact contributions of individual higher order and first order thalamic nuclei, alongside their individual involvement with cortical networks and subcortical regions, remains unexplored within the initial phase of learning. In light of this, we analysed fMRI data obtained within a paradigm which is designed to examine initial learning processes within feedback-driven stimulus-response learning, in order to explore thalamic contributions. We investigated dynamic learning-related functional connectivity alterations between various thalamic nuclei with other subcortical regions and cortical networks. Our results show that the initial phase of learning was associated with: (1) decreasing functional connectivity between thalamic nuclei and frontoparietal and cingulo-opercular networks, (2) increasing functional connectivity between thalamic nuclei with default mode and salience networks, (3) decreasing functional connectivity between thalamic nuclei and the putamen, and (4) decreasing functional connectivity amongst higher order thalamic nuclei. Furthermore (5) these dynamic alterations were associated primarily by mediodorsal thalamus. Altogether, these results indicate that higher order thalamic nuclei play a crucial role within initial learning and in the generation of novel goal-directed behaviour. This was demonstrated through enhanced functional connectivity with selected cortical networks which drive goal-directed behaviour, alongside decreased functional connectivity with striatal regions which drive motor selectivity.

Heschls gyrus (HG), which contains the primary auditory cortex, shows marked individual variability in its folding pattern, ranging from a single gyrus to partial or complete duplication. Greater HG duplication has been reported in expert musicians, often interpreted as evidence that auditory experience can shape cortical morphology. However, these structural differences might alternatively indicate a bias for musical careers in individuals whose anatomical predispositions facilitate expertise. Here, we examined HG morphology in blind individuals--a population with extensive auditory experience but without selection based on auditory ability. T1-weighted MRI data from 100 human participants (48 females, 42 males, 10 unknown) across blind and sighted groups were analyzed. HG was manually defined in each hemisphere, and folding was measured using both categorical morphology classification and continuous surface-based metrics. Across all analyses, blindness did not increase HG folding. These results suggest that the morphology of HG is largely predetermined. Significance statementIncreased anatomical folding in the auditory cortex has been reported in professional musicians. Is this structural variability due to experience-dependent plasticity, or is it that individuals with increased anatomical folding are more likely to become musicians? We examined Heschls gyrus (HG), which contains the primary auditory cortex, in blind individuals who rely heavily on auditory input. Despite extensive auditory experience, blindness did not alter HG folding. This finding suggests that the morphology of HG is not strongly influenced by auditory experience.

Early childhood development is scaffolded by rapid maturation of brain white matter structure, believed to support the emergence of cognitive and socioemotional functions. Previous whole-tract studies have suggested patterns of white matter development occurring along posterior-anterior, deep-superficial and inferior-superior axes. However, little is known as to whether these patterns are evident within tracts. Using longitudinal diffusion imaging data from 133 children (4-8 years; 76 females), the present work characterizes along-tract patterns of white matter development across association, commissural and projection bundles using fixel-based analyses of microstructure and macrostructure. Within long range association bundles, faster age-related changes were observed for segments adjacent to the visual cortices relative to segments located near association regions, supporting a sensorimotor-association axis of brain development. An inferior-superior pattern was found for projection tracts, with faster age-effects observed for segments near the brainstem. Lastly, while several association and commissural bundles exhibited faster maturation within central segments; indicative of a deep-superficial axis, effects were mixed between micro- and macrostructure, underscoring the unique developmental timing of these different fiber properties. Our findings provide evidence that within-tract white matter maturation unfolds along key spatiotemporal axes and suggests that increased spatial precision can advance our understanding of early childhood brain development.

Brain banks provide small tissue samples fixed in neutral-buffered-formalin (NBF), but human anatomy teaching laboratories could provide full brains fixed with solutions that are more appropriate for gross anatomy such as a saturated salt solution (SSS) or an alcohol-formaldehyde solution (AFS). Advanced aging and prolonged exposure to aldehydes are known to enhance brain tissue autofluorescence (AF), limiting the efficacy of immunofluorescence (IF) procedures. We have previously shown by IF staining the antigenicity preservation in mouse brains fixed with the three solutions. We now aimed to compare the quality of IF staining in human brains fixed with SSS, AFS and NBF. In addition, we compared the efficiency of AF quenching methods, namely the application of SudanBlackB (SBB) and the treatment of sections with sodium borohydride (NaBH4). Blocks of neocortex were extracted from 18 brains (NBF=6, SSS=6, AFS=6) and cut into 40{micro}m sections. Neurons (anti-NeuN, AlexaFluor-488) and astrocytes (anti-GFAP, AlexaFluor-555) were revealed with IF after an antigen retrieval protocol, while two treatments (SBB or NaBH4) were used to quench AF. We then assessed the degree of AF (criteria: background or cell AF) and the immunostaining quality with excitation wavelengths of 488nm, 555nm and 647nm. Brains fixed with all three solutions showed well-labeled astrocytes, whereas neurons werent always stained, but this was not associated to the fixative solution. The overall AF intensity was similar in sections from brains fixed with all three solutions. Finally, the SBB treatment was the most effective at reducing AF in all specimens. Given the similarity in AF and antigenicity assessment across the three solutions, we conclude that brains fixed with SSS and AFS could be good alternatives for NBF-fixed specimens in the context of IF experiments processed with a SBB protocol. Highlights- Immunofluorescence staining is feasible in brains fixed with anatomy labs solutions - GFAP is less affected by fixation than NeuN - Autofluorescence can be reduced by Sudan Black treatment

Two decades of research have provided evidence for gray matter volume (GMV) differences in developmental dyslexia (or reading disability, RD) in the left perisylvian cortex. However, there are concerns about result inconsistencies, likely attributable to small sample sizes, lenient statistical thresholds, and insufficient accounting for demographic variables and global GMV (Ramus et al., 2018). To address these concerns, we conducted a Discovery and Replication Study (N=262) using data from the Adolescent Brain Cognitive Development Study. We found GMV differences between the RD and Control Groups did not replicate across the Discovery and Replication Studies using voxel-based morphometry (VBM) in Statistical Parametric Mapping (SPM), and that a more conservative threshold yielded far fewer results. We then conducted Reproducibility Studies and first found that when using surface-based morphometry in FreeSurfer instead of VBM, the Discovery and the Replication Study results again failed to converge. Second, we combined all groups in a factorial VBM/SPM analysis and the interaction analysis provided quantitative confirmation for diverging between-group difference results across the two studies. Third, we tested for the role of covariates of no interest and found that when total GMV is not controlled for, this divergence dissipates and group differences in RD (main effect of Reading Ability) are amplified. In conclusion, replication of GMV differences in RD is low, even when using large, well-matched groups, and analyses approaches play a modulating role. As such, results from prior studies using lenient statistical thresholds and not accounting for total GMV should therefore be viewed with caution.

Despite substantial progress in understanding how visual features of food are processed in the brain, it remains unclear how subjective and nutritional properties, such as perceived palatability, caloric content, and health value, are reflected in neural representational structure. Using functional MRI and representational similarity analysis (RSA), we examined how visual, subjective, and nutritional food properties are encoded in ventral visual cortex. Univariate analyses revealed reliable activation differences between high- and low-calorie foods in lateral occipitotemporal cortex (LOTC) and fusiform gyrus. RSA further revealed a functional dissociation within the ventral stream: LOTC showed systematic correspondence with both visual and subjective dimensions, whereas fusiform cortex exhibited a selective association with perceived caloric content, with both effects persisting after controlling for visual similarity. These results suggest that food-related dimensions not fully captured by the tested visual models are reflected within visual representational spaces, and that LOTC and fusiform cortex show dissociable representational profiles with respect to subjective and perceived nutritional food dimensions.

Apuschkin et al. (2024) proposed a GPCR-based transcriptomic atlas for midbrain dopamine (DA) neuron subpopulations, including candidates such as Nmur1, Cckar, and Ffar4. To guide genetic targeting, these markers must reflect functional expression in adult DA neurons. Using in situ hybridization, Cre-dependent reporter lines, and both intracranial and systemic viral approaches, we find no evidence of adult Nmur1-mediated recombination in DA neurons, while Cckar-driven recombination is consistent with developmental expression only. Notably, Ffar4 expression overlaps extensively with Ntsr1 midbrain populations, indicating that it does not define a distinct DA neuron class. Furthermore, analysis of independent spatial transcriptomic datasets together with our MERFISH data shows that many proposed GPCR markers are not detectably expressed in adult DA neurons. These findings demonstrate that transcriptomic enrichment does not always yield reliable adult markers and highlight the need for functional validation prior to use in circuit targeting.

Fiber-tracts exhibit distinct projection patterns along the anterior-posterior axis of the hippocampus, promoting a specialization in function. This specialization becomes increasingly pronounced throughout child development, with important implications for neurocognitive outcomes. Developmental changes in fiber-tract properties, including intra-axonal cross-sectional area and myelin content, may contribute to this anterior-posterior functional specialization. To test this, we developed a diffusion-MRI tractography pipeline to identify hippocampal fiber-tracts in single subjects, then examined whether age-related differences in total intra-axonal cross-sectional area and myelin content (T1w/T2w) could predict functional specialization in a large cross-sectional sample (N=539, aged 5-21 years). With age, we found that the cross-sectional area of short-range medial-temporal tracts, which primarily target the anterior/body of the hippocampus, exhibited rapid growth. Concomitantly, the cross-sectional area of long-range occipito-parietal tracts, which primarily target the posterior hippocampus, exhibited a modest pruning. Increases in myelin content were relatively homogenous across fiber-tracts. In support of our hypothesis, we found that the cross-sectional area of fiber-tracts significantly predicts the surface-area of an fMRI-defined posterior system; a sensitive marker of functional specialization in the hippocampus. Tracts targeting early visual cortex (V2, V3, V4) showed the strongest association, with statistical modeling indicating a mediating effect of early-visual tract development on the relation between age and functional specialization. These findings provide evidence consistent with a mechanism whereby anatomical neurodevelopment contributes to functional specialization in the human hippocampus.