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Brain Structure and Function

Springer Science and Business Media LLC

Preprints posted in the last 90 days, ranked by how well they match Brain Structure and Function's content profile, based on 83 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Replication Challenges in Linking Personality to Resting-State Functional Connectomics

Jajcay, N.; Tomecek, D.; Fajnerova, I.; Rydlo, J.; Tintera, J.; Horacek, J.; Lukavsky, J.; Hlinka, J.

2026-01-21 neuroscience 10.64898/2026.01.19.700331 medRxiv
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An increasing number of studies are currently focusing on personality neuroscience, a term denoting the research aimed at neuroimaging correlates of inter-individual temperament and character variability. Among other methods, a graph theoretical analysis of the functional connectivity in resting-state functional magnetic resonance imaging data was applied in a study by Gao et al. (2013), reporting novel functional connectivity correlates of personality traits. The current paper presents a conceptual replication of the results of this study and discusses the related challenges, including an extension of the original statistical methods in order to illustrate the effect of the multiple comparison problem. Five personality dimensions were obtained using the revised Big Five Personality Inventory, including scores of Extraversion and Neuroticism covered in the original paper. Using a larger sample (84 subjects) with adequate statistical power (ranging from 0.75 to 0.95 across analyses), we failed to replicate any of the nine specific neuroimaging correlates of personality presented by Gao et al. While acknowledging differences in the experimental procedures, we discuss that the lack of replication might be caused by the relatively liberal control of false positives in the original study. Indeed, the original testing scheme leads to an expected count of about 10 false positive observations among all tests; applying this scheme to our data we observed a similar number of positive tests, albeit for different relations. No significant correlations were found in our data when standard family-wise error control was applied. These results illustrate the importance of combining exploration with independent validation, use of large datasets, as well as appropriate control of multiple comparison problem in order to prevent false alarms in research into neural substrates of personality differences. Importantly, our findings do not disprove the existence of a link between personality and the brains intrinsic functional architecture; but rather suggest that such a link might be even more subtle and elusive than previously reported.

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Population receptive field properties of the human visual claustrum zone

Pizka, C. A.; Linhardt, D.; Coates, A.; Zuschlag, D.; Windischberger, C.; Zaretskaya, N.

2026-02-04 neuroscience 10.64898/2026.02.02.703259 medRxiv
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The claustrum is a thin, bilateral sheet of grey matter between the insula and putamen that stands out by its high interconnectivity with almost the entire cortex. Despite continuing research in humans and animals, its functional role remains largely unknown. In the present study, we explored the topographic organization of the recently described human visual claustrum zone. We performed a population receptive field (pRF) analysis on the 7T retinotopy dataset of the Young Adult Human Connectome Project (N = 181, 109 female) comparing the visual claustrum with established visual field properties of the lateral geniculate nucleus, the primary visual cortex, and higher-level topographic maps of the dorsal and the ventral stream. Our results demonstrate for the first time that the human visual claustrum showed several topographic properties typical for visual areas, including a representational bias towards the contralateral visual field, and a pRF size increase with increasing eccentricity. At the same time, the claustrum also exhibited a positive eccentricity gradient along the posterior-anterior axis, an extended representation of the visual periphery compared to other areas and a lack of horizontal meridian bias. These latter two properties highlight the claustrums role as a higher-level nucleus which is less dependent on sensory input. This study is the first to characterize the topographic organization of the visual claustrum zone in humans, highlighting its uniqueness among the known visually responsive regions. Significance StatementThe claustrum is a thin subcortical brain region whose function is still largely unknown. Previous animal studies showing unimodal sensory zones within the nucleus suggest an involvement in sensory processing. The present study focuses on the visual claustrum zone and is the first to characterize its topographic organization in humans. We used population receptive field mapping for functional Magnetic Resonance Imaging on the 7T retinotopy dataset of the human connectome project. We could demonstrate similarities to other visually responsive areas and characteristics that distinguish the visual claustrum. Our study yields important information on the claustrums visuotopic organization that can guide further investigation of its role in visual processing and cognition.

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The in-vivo microstructural profile of human hippocampal subfield CA1 and its relation to memory performance

Hoepker Fernandes, J.; Hayek, D.; Vockert, N.; Garcia-Garcia, B.; Mattern, H.; Behrenbruch, N.; Fischer, L.; Kalyania, A.; Doehler, J.; Haemmerer, D.; Yi, Y.-Y.; Schreiber, S.; Maass, A.; Kuehn, E.

2026-04-01 neuroscience 10.64898/2026.03.30.714764 medRxiv
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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.

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Cerebellar Gray Matter Volume Changes Across Development: Posterolateral and Vermal Transient Increases during Adolescence

Gil-Paterna, P.; M. Hoppe, J.; Timmann, D.; Apps, R.; Widegren, E.; Frick, M. A.; Fallmar, D.; Gingnell, M.; Frick, A.

2026-01-27 neuroscience 10.64898/2026.01.27.701939 medRxiv
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The cerebellum undergoes substantial maturation with regionally distinct developmental trajectories. This study examined cerebellar gray matter volume (GMV) in healthy children, adolescents, and adults, using voxel-based morphometry, the ACAPULCO algorithm, and the SUIT toolbox for cerebellum-optimized analyses. A total of 104 typically developing children (n=31, 6-9 years), adolescents (n=35, 13-17 years), and adults (n=38, 30-40 years) were included. We hypothesized age group differences in cerebellar GMV, with adolescents showing the greatest volume, specifically in posterolateral regions. Results revealed significant group differences in GMV. We observed region-specific volumetric patterns, with some areas (e.g., Crus II, lobule X) increasing from childhood to adolescence followed by stabilization, whereas other areas (e.g., lobules I-IV and VI, Crus I, vermis VI and VIIb) exhibited peak GMV during adolescence, with lower volumes in both children and adults. These patterns were partly consistent with our hypothesis. Notably, no regions had greater GMV in adults than adolescents, suggesting that cerebellar growth peaks in adolescence before stabilizing. Our findings indicate differential developmental patterns both between and within lobules of the cerebellum, and highlight adolescence as a peak period of cerebellar growth, with potential implications for the development of cerebellar-supported cognitive and emotional functions that undergo significant changes during this period.

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Fusiform face area development correlates with development in higher-order social brain regions

Jimenez-Sanchez, L.; Thye, M.; Richardson, H.

2026-03-11 neuroscience 10.64898/2026.03.10.710863 medRxiv
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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

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The methodological foundations of lesion network mapping remain sound

Siddiqi, S. H.; Horn, A.; Schaper, F. L.; Khosravani, S.; Cohen, A. L.; Joutsa, J.; Rolston, J. D.; Ferguson, M. A.; Snider, S. B.; Winkler, A. M.; Akram, H.; Smith, S.; Nichols, T. E.; Friston, K.; Boes, A. D.; Fox, M. D.

2026-02-26 neuroscience 10.64898/2026.02.24.707529 medRxiv
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Lesion network mapping (LNM) and related techniques have been used in over 200 studies, primarily to test whether anatomically distributed lesions that cause the same symptom fall within a common brain network. A recent article1 challenges the specificity and validity of this technique, suggesting that lesion network maps primarily reflect intrinsic properties of the normative connectome rather than lesion-symptom relationships. However, the data and procedures in van den Heuvel et al. do not reflect those used in most LNM studies. Further, the main conclusions were based on similarity between maps, but similarity does not imply the absence of meaningful differences. In contrast, LNM provides evidence for meaningful differences using specificity testing. Exemplary analyses of 1090 lesion locations from 34 prior LNM studies do not support van den Heuvels concerns and confirm the lesion-deficit specificity of LNM. While we encourage further methodological investigation, the analyses of van den Heuvel et al. do not invalidate prior LNM findings or future applications.

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Cortical gray matter density at age five associated with preceding early longitudinal language profiles: A Voxel-based morphometry analysis of the FinnBrain Birth Cohort Study

Saloranta, E.; Tuulari, J. J.; Pulli, E. P.; Audah, H. K.; Barron, A.; Jolly, A.; Rosberg, A.; Mariani Wigley, I. L. C.; Kurila, K.; Yada, A.; Yli-Savola, A.; Savo, S.; Eskola, E.; Fernandes, M.; Korja, R.; Merisaari, H.; Saukko, E.; Kumpulainen, V.; Copeland, A.; Silver, E.; Karlsson, H.; Karlsson, L.; Mainela-Arnold, E.

2026-03-27 neuroscience 10.64898/2026.03.27.714719 medRxiv
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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

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Hippocampal Projections to the Striatal Compartments, Striosome and Matrix, are Spatially Segregated in CA1

Tieu, A. N.; Sadi, A.; Waugh, J. L.

2026-01-30 neuroscience 10.64898/2026.01.27.702163 medRxiv
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The hippocampus routes information to the striatum through at least four polysynaptic circuits. Striatal projection neurons are organized into two tissue compartments, the matrix and striosome, which differ in their embryologic origins, relative abundance, intra-striate location, and afferent and efferent connectivity. These compartments are embedded in distinct functional networks and are activated by different tasks. Consequently, hippocampal inputs that route preferentially through the striosome may underpin different functions and engage with different remote networks than inputs that route through the matrix. It was unknown whether striosome-bound and matrix-bound projections from the hippocampus followed different polysynaptic circuits. We assessed hippocampo-striate projections in living humans using probabilistic diffusion tractography by first parcellating the striatum into voxels with striosome-like and matrix-like structural connectivity. We then quantified structural connectivity between hippocampal efferents (CA1) to each set of compartment-like voxels. CA1 projections to striosome-like voxels in the dorsal striatum (caudate and putamen) were 3.1-fold more abundant than those to matrix-like voxels, particularly in caudo-lateral CA1. This striosome-favoring bias was similar in three segregated hippocampo-striate circuits, in streamlines routing through the subiculum, lateral septum, or medial prefrontal cortex. However, a small region in rostro-medial CA1 preferentially targeted matrix-like voxels. Functional connectivity between CA1 and compartment-like voxels matched this segregated pattern: CA1 activation was correlated with striosome-like voxels but anti-correlated with matrix-like voxels. Additionally, streamlines from CA1 to nucleus accumbens exhibited hemispheric asymmetries, with the left hemisphere biased towards matrix and the right towards striosome. These findings suggest that hippocampo-striate projections are spatially segregated into compartment-specific circuits.

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Resting-state Compensatory Remapping in Patients with Brain Tumour Before and After Surgery

Manso-Ortega, L.; Diez, I.; Amoruso, L.; Bermudez, G.; Gil-Robles, S.; Pomposo, I.; Carreiras, M.; Quinones, I.

2026-02-20 neuroscience 10.64898/2026.02.19.706837 medRxiv
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Brain tumours invade neural tissue, disrupting the functional organisation of neural networks. This disruption can trigger compensatory neuroplastic mechanisms that help preserve cognitive function despite pathological burden. Resting-state functional connectivity (rs-FC) provides a valuable approach for examining these alterations, yet the scope and trajectory of network-level changes remain unclear. In this study, we used rs-FC to characterise compensatory responses induced by left-hemisphere brain tumours affecting the integrity of the language network. The comparison of connectivity patterns at diagnosis and after surgery allowed us to track the temporal progression of these patterns. Relative to healthy participants, patients showed significant deviations in pre-surgical rs-FC, with widespread changes involving the dorsal attention, sensorimotor, frontoparietal, default mode, and cerebellar networks. These differences persisted post-surgically, with no significant longitudinal modifications. Network-level alterations also influenced topological properties: patients showed increased segregation while preserving global integration relative to controls. These properties changed significantly from pre- to postoperative period, with a postoperative increase in segregation and integration towards a pattern more closely resembling that of healthy controls. Furthermore, preoperative network segregation was identified as a predictor of postoperative cognitive recovery. These findings suggest that brain tumours induce network remapping, affecting functional connectivity far beyond the regions strictly related to the affected region. The observed changes in network topological organisation likely reflect the adaptive role of domain-general networks in facilitating homeostatic processes. Surgical strategies aimed at preserving these changes seem to promote sustained cognitive function, regardless of malignancy grade or lesion extent. Key pointsO_LIPresurgical patients show widespread inter- and intrahemispheric rs-FC alterations, reflecting tumour-driven network remapping. C_LIO_LINetwork integration and segregation show longitudinal recovery, approaching neurotypical topology four months post-surgery. C_LIO_LIPreoperative network segregation predicts postoperative cognitive recovery. C_LI Importance of the StudyBrain tumours disrupt large-scale brain networks, yet the extent, temporal dynamics, and cognitive relevance of these alterations remain poorly understood. Using resting-state functional connectivity, this study provides a longitudinal, network-level characterisation of tumour-induced neuroplasticity in patients with left-hemisphere lesions affecting language-related regions. Compared with prior work focused on local effects or single networks, our results demonstrate widespread inter- and intrahemispheric connectivity changes involving multiple domain-general resting-state networks, highlighting extensive network remapping beyond lesion boundaries. Importantly, we show that postoperative recovery is accompanied by a rebalancing of network integration and segregation toward a neurotypical configuration. Critically, preoperative network segregation emerges as a predictor of postoperative cognitive recovery, identifying a potential biomarker of resilience. These findings have direct translational relevance, suggesting that preserving and supporting large-scale network organisation during surgical planning may promote cognitive outcomes independently of tumour grade or lesion extent.

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Individual-level metabolic connectivity captures cortical morphology and their coupling strengthens with age

Facca, M.; Tarricone, C.; Ridolfo, A.; Corbetta, M.; Vlassenko, A. G.; Goyal, M. S.; Bertoldo, A.

2026-03-04 neuroscience 10.64898/2026.03.03.709267 medRxiv
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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.

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How the brain represents a romantic partner: dissociable roles of the nucleus accumbens and anterior insula

Fujisaki, K.; Ueda, R.; Nakai, R.; Abe, N.

2026-03-02 neuroscience 10.64898/2026.02.16.706085 medRxiv
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Humans form selective and enduring pair bonds with romantic partners, a principal feature of human sociality. Neuroimaging studies have shown that romantic partners are differentially represented from other individuals in the nucleus accumbens (NAcc) and anterior insula (aINS), and that the specificity of partner representations in the NAcc diminishes as relationships mature. However, it remains unclear whether such differentiation reflects partner-specific coding or mere differences in familiarity with others, and whether these regions play different roles in romantic bonding. To address these questions, we applied multiple regression representational similarity analysis to fMRI data from 51 heterosexual male participants in early romantic relationships. The data were acquired during a social incentive delay task, in which participants anticipated social approval from their female romantic partner, a female friend, or an unfamiliar female individual. This approach allowed us to dissociate partner-specific representations from familiarity-related effects in the NAcc and aINS. We found that both regions exhibited partner-specific representations that could not be explained by familiarity. Consistent with previous findings, partner specificity in the NAcc was negatively associated with relationship duration, indicating that partner-specific coding in this region is established early in romantic relationships and diminishes as relationships progress. Moreover, greater partner specificity in the aINS was associated with more frequent intrusive thoughts about the partner. Together, these findings demonstrate that romantic partners are represented in the NAcc and aINS in a qualitatively distinct manner from other individuals, and that these regions support dissociable aspects of romantic bonding. Key PointsO_LIMultiple regression representational similarity analysis revealed partner-specific representations in the nucleus accumbens and anterior insula that cannot be explained by familiarity. C_LIO_LIIndividuals in longer relationships showed reduced partner specificity in the nucleus accumbens, consistent with prior findings. C_LIO_LIIndividuals exhibiting greater partner specificity in the anterior insula reported more frequent intrusive thoughts about their partner, indicating dissociable psychological functions across regions. C_LI

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Selective reorganization of face-processing lateralization in participants with right-lateralized language network

Zargar, P.; Rajimehr, R.

2026-02-17 neuroscience 10.64898/2026.02.17.706260 medRxiv
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A well-known feature of cortical organization is the lateralization of the language network (LN) to the left hemisphere (LH). Although atypical LN lateralization to the right hemisphere (RH) is well documented, its consequences for other lateralized functions remain poorly understood. Face processing and other category-selective visual areas, which are typically RH-biased, provide key test cases for examining whether atypical LN lateralization is associated with reorganization in other networks. Using functional magnetic resonance imaging (fMRI) data from the Human Connectome Project (HCP), we identified participants with right-hemisphere language dominance (RHLD) and examined whether category-selective visual areas exhibit reorganized hemispheric biases in these participants relative to those with typical left-hemisphere language dominance (LHLD). The results demonstrated selective reorganization within the face-selective areas: some regions showed a leftward shift in hemispheric bias in RHLD participants, whereas others preserved the canonical RH preference. This pattern indicates that cortical reorganization associated with atypical LN lateralization is region-specific rather than global, consistent with a flexible neural architecture in which hemispheric specialization can be selectively reconfigured. These results clarify how atypical LN lateralization impacts the hemispheric organization of face-selective areas and provide evidence for altered network-level specialization in the cerebral cortex.

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Spatiotemporal Variation in White-Matter Development Across Early Childhood

Singh, M.; Dimond, D.; Dewey, D.; Lebel, C.; Bray, S.

2026-03-25 neuroscience 10.64898/2026.03.24.713971 medRxiv
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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.

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Immunofluorescence quality of human brain tissue fixed with solutions used in gross anatomy laboratories

Frigon, E.-M.; Perreault, V.; Gerin-Lajoie, A.; Boire, D.; Maranzano, J.

2026-03-06 neuroscience 10.64898/2026.03.04.709624 medRxiv
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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

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Distributed representational encoding of food attributes in ventral visual cortex

Marrazzo, G.; Pimpini, L.; Kochs, S.; De Martino, F.; Valente, G.; Roefs, A.

2026-04-02 neuroscience 10.64898/2026.03.31.715483 medRxiv
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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.

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Calcium-binding protein expression alone is insufficient to identify and classify GABAergic neurons in macaque cortex

Brigande, A. M.; Krueger, J.; Park, C.; Disney, A. A.

2026-01-28 neuroscience 10.64898/2026.01.26.701495 medRxiv
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Understanding neuron subclasses and their functional consequences can contribute to understanding brain circuits. A scheme long used to classify GABAergic neurons in the neocortex is based on expression of three calcium-binding proteins (CBPs): parvalbumin (PV), calbindin D-28K (CB), and calretinin (CR). Because CB and CR are frequently co-expressed by individual neurons in rodents, this scheme has been replaced by one based on PV and two signaling peptides: somatostatin (SST) and vasoactive intestinal peptide (VIP). In macaques, however, CBPs are generally not co-expressed, and so their use has persisted despite suggestions that the underlying populations are not, in fact, entirely GABAergic. We set out to quantitatively evaluate CBPs as a classification scheme for GABAergic neurons in early and mid-level visual regions in macaque cortex. Combining immunohistochemistry and in situ hybridization, we find that up to half of neurons expressing CBPs are likely not GABAergic. Furthermore, contrary to what has been previously suggested, the GABAergic subpopulations cannot be distinguished based on staining intensity. Thus, the CBP-based classification scheme is not valid, at least as it has traditionally been used. Instead, we find support for co-labeling CB and CR neurons with SST and VIP, an approach that can identify GABAergic subpopulations within the CBP classes; or simply adopting the PV/SST/VIP scheme. We discuss the functional implications of expressing these various cell type markers, and how consideration of marker functions can support proper selection of a classification scheme for a given experimental purpose.

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A 3.5-minute-long reading-based fMRI localizer for the language network

Tuckute, G.; Lee, E. J.; Sathe, A.; Fedorenko, E.

2026-02-15 neuroscience 10.1101/2024.07.02.601683 medRxiv
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The field of human cognitive neuroscience is increasingly acknowledging inter-individual differences in the precise locations of functional areas and the corresponding need for individual-level analyses in fMRI studies. One approach to identifying functional areas and networks within individual brains is based on robust and extensively validated localizer paradigms--contrasts of conditions that aim to isolate some mental process of interest. Here, we present a new version of a localizer for the fronto-temporal language-selective network. This localizer is similar to a commonly-used localizer based on the reading of sentences and nonword sequences (Fedorenko et al., 2010) but uses speeded presentation (200ms per word/nonword). Based on a direct comparison between the standard version (450ms per word/nonword) and the speeded versions of the language localizer in 24 participants, we show that a single run of the speeded localizer (3.5 min) is highly effective at identifying the language-selective areas: indeed, it is more effective than the standard localizer given that it leads to an increased response to the critical (sentence) condition and a decreased response to the control (nonwords) condition. This localizer may therefore become the version of choice for identifying the language network in neurotypical adults or special populations (as long as they are proficient readers), especially when time is of essence.

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Modular functional brain network organization contributes to training-related changes in task switching in children

Schwarze, S. A.; Lindenberger, U.; Bunge, S.; Fandakova, Y.

2026-02-26 neuroscience 10.64898/2026.02.26.708262 medRxiv
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Cognitive training often aims to improve cognitive skills, but outcomes have been variable in terms of their success. One factor that has been found to predict training outcomes is the degree of modularity of functional brain networks, defined as the extent to which brain regions are more strongly connected to regions within the same functional subnetwork than to regions outside of the subnetwork. Specifically, more modular organization of functional brain networks at baseline has been associated with greater benefits from cognitive training in adults. During childhood, cognitive development is marked by a slow progression towards network integration and segregation, which together contribute to increasing modularity. Thus, network modularity might also be an important predictor of training outcomes in children. To investigate whether individual differences in network modularity predict training outcomes in children, we examined 84 children aged 8 to 11 years who completed nine weeks of either high-intensity task-switching training or high-intensity single-task training. Prior to training, children showed lower network modularity than adults, in line with previously reported developmental changes in network configuration. With training, performance improved, especially in the high-intensity task-switching group. More modular organization of functional brain networks before training was associated with faster improvements in task-switching performance, especially at the beginning of training. These results suggest that more modular functional networks might allow for faster adaptation to training demands in children and thus faster improvements with training. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/708262v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@ac568aorg.highwire.dtl.DTLVardef@658bb4org.highwire.dtl.DTLVardef@b6eb24org.highwire.dtl.DTLVardef@1079a4a_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- Intensive training improved task-switching performance in children. - Children showed less modular network organization than adults. - More modular networks before training were associated with faster training gains. - Children with more modular networks adapted more quickly to training demands.

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Where is God? A comparison of the neural correlates of mystical and religious praying

Rubia, K.; Hernandez, S. E.; Perez-Diaz, O.; Gonzalez Mora, J. L.; Barros Loscertales, A. R.

2026-02-25 neuroscience 10.64898/2026.02.22.707337 medRxiv
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The perception of God can be as a transcendent entity that is infinite and outside of human beings, typical for religious traditions, or as an immanent entity that is outside and inside of human beings, typical for mystical traditions. These different perceptions of God may be associated with different neural correlates depending on which God we pray to. To elucidate the neural correlates of these different perceptions of the divine, we compared fMRI activation during praying between 18 Christians and 16 practitioners of Sahaja Yoga Meditation, characterised by transcendent and immanent perceptions of God, respectively. The thalamus was deactivated during praying in Meditators relative to Christians. Due to the sensory relay function of thalamus, the thalamic deactivation in meditators presumably reflects a reduction in the perception of external stimuli in order to focus on the internal perception of an immanent God, while the activation of the thalamus in Christian prayers could be associated with the dialogue with an externally perceived transcendent God.

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Paw Preference in Rats Across Tests, Strains, Sex, and Age: A PRISMA-Compliant Systematic Review and Meta-Analysis

Pokharel, D.; Swain, C. C.; Beligala, D. H.; Reddy, M. V. S. R. R.; Subramanian, T.

2026-02-10 neuroscience 10.64898/2026.02.08.704684 medRxiv
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Paw preference in rats is widely used to study hemispheric lateralization, but many individual studies are underpowered and employ inconsistent methods, leading to conflicting reports of population-level bias. We conducted a PRISMA-compliant systematic review and meta-analysis to determine whether rats consistently display paw preference at the individual and population levels, and to evaluate the influence of behavioral test type, strain, sex, and age. Studies published between 1930 and 2025 were identified through PubMed, Google Scholar, and ScienceDirect. Data were extracted on strain, age, sex, behavioral paradigm, and paw-preference classification. Random-effects models were used to estimate pooled prevalence, with subgroup analyses for key variables. Forty studies (n = 1,609 rats) met inclusion criteria. At the individual level, 84% of rats displayed consistent paw preference (95% CI: 78-89%, p < 0.0001), demonstrating robust individual-level lateralization. However, population-level analyses showed no universal directional bias, right paw use occurred in 48% of rats (95% CI: 43-54%) and left paw use in 39% (95% CI: 34-44%). Ambidextrous classification thresholds were standardized across studies to ensure comparability. Subgroup analyses indicated modest strain- and test-dependent effects, with Sprague Dawley rats tending toward balanced paw use, while other strains showed slight rightward bias. Skilled-reaching tasks produced slightly stronger asymmetry than the Collins test. Sex- and age-related differences were subtle and inconsistent. Overall, rats exhibit reliable individual-level paw preference without species-wide directional asymmetry, distinguishing them from humans. Standardized testing protocols and balanced cohort designs will enhance reproducibility and translational relevance in lateralization research.