Brain maturation during childhood and adolescence involves complex structural changes that vary among individuals. Characterizing these trajectories is essential for understanding normative development and identifying deviations associated with neurological conditions.

The medial habenula (MHb), a medial subdivision of the habenula located in the dorsal diencephalon, sends axons towards the interpeduncular nucleus (IPN) through the fasciculus retroflexus. Upon reaching the IPN, MHb axons cross the midline multiple times. Although heparan sulfate proteoglycans have previously been shown to play a role in MHb axon guidance, the role of heparan sulfate 6-O-endosulfatases, Sulfatase 1 (Sulf1) and Sulfatase 2 (Sulf2), has to date not been investigated. We thus examined MHb axon trajectories in Sulf1 and Sulf2 knockout mice and found that Sulf1/2 double knockout (DKO) mice showed several types of pathfinding errors after reaching the ventral surface of the brain. The abnormalities included aberrant anterior extension into the mammillary body, abnormal lateral projection on the brain surface, and reduced midline crossing within the IPN. Furthermore, the DKO mice exhibited altered outcomes in social conflict in a tube test assay: they showed a higher win rate against wild-type mice. This behavioral phenotype may reflect functional impairment of the MHb-IPN circuit resulting from its developmental abnormalities. Taken together, these findings suggest that Sulf1/2 are required for proper MHb-IPN circuit formation during development, which is in turn critical for its normal function in adulthood.

This review outlines the development of thalamic atlases from early post-mortem 2D histological maps to modern 3D multimodal atlases used in neuroscience and clinical practice. Given the central role of the thalamus in sensory processing, movement, and cognition, accurate anatomical mapping has been essential for both research and neurosurgical targeting. By synthesizing historical and modern approaches, we highlight the methodological advances, such as the development of thalamus-specific MRI sequences, that have improved the precision of thalamic nuclei delineation. We focus on open-source atlases that support reproducible research and clinical applications. Future developments will likely focus on integrating multi-scale data; combining cytoarchitectonic, with quantitative MRI and computational models to improve thalamic parcellation and accurate localization in vivo.

When thinking about the beginning of modern anatomical drawings that reflect topography in detail, our thoughts often turn to the more than 200 woodcuts included in Andreas Vesalius's "De humani corporis fabrica libri septem." However, Leonardo da Vinci also produced detailed anatomical sketches before the publication of the Fabrica, including drawings that addressed the cerebral ventricular system. The goal of this narrative historical review is to examine how medical knowledge of the ventricular system evolved from antiquity, represented by Galen of Pergamon and Hippocrates of Kos, toward post-Galenic anatomy. This analysis is based on four sketches created between approximately 1487 and 1509, held in the collections of the Royal Library at Windsor, England, and the Schlossmuseum in Weimar, Germany. Although medical literature frequently references Leonardo's anatomical work, relatively few studies have focused specifically on the morphology of the ventricular system while also considering the physiology and philosophy of the turn of the 15th and 16th centuries. This study therefore analyzes Leonardo's ventricular drawings as an important transitional episode in the visual history of neuroanatomy. At the same time, it acknowledges that Leonardo's anatomical studies were largely unpublished during his lifetime, that their influence on later anatomists remains uncertain, and that retrospective interpretation of historical drawings requires caution.

To avoid image blurring, the vestibulo-ocular (VOR) and the optokinetic (OKR) reflexes stabilize gaze. In all vertebrates, the VOR is mediated via direct projections from the vestibular nuclei to the motor nuclei that control the extraocular muscles. Lampreys show three vestibular nuclei that are well characterized in terms of their projections and sensory inputs, but much less is known about their inputs from other brain regions and the connectivity between them.

Donald O. Hebb was born in Chester Nova Scotia on 22 July 1904, attended the Chester school and the Halifax County Academy, and obtained a BA in English and Philosophy from Dalhousie University in 1925. After obtaining a teacher's certificate he taught in his old school in Chester for a year and then in Montreal while attending McGill University to obtain his MA in Psychology as a part-time student. He moved to Chicago to work with Karl Lashley and then completed his PhD with Lashley at Harvard in 1936. He was an instructor for a year at Harvard (1936-37) and then received a Fellowship to work at the Montreal Neurological Institute (1937-39), conducting neuropsychological tests on the patients of Dr. Wilder Penfield. From 1939 to 1942 he was a professor at Queen's University in Kingston, Ontario and then a Research Associate of Professor Lashley, studying emotionality in chimpanzees at the Yerkes Primate Center in Florida (1942-1947). It was there that he began to write his influential book, The Organization of Behavior. This book introduced the concepts of synaptic change, cell assemblies, and phase sequences to account for the neural events underlying behavior. Hebb's work revolutionized the study of brain and behavior by establishing a biological basis for psychological phenomena. Hebb became a professor of Psychology at McGill University in 1947 and head of this department in 1948, completing his book at McGill in 1949. The crucial element in Hebb's theory was the concept of reverberatory circuits of Lorente de Nó, based on Cajal's concept of closed circuits. This paper examines the unpublished notes and papers written by Hebb between 1932 and 1947 as he developed his theory of neuropsychological function based on the concept of closed or reverberatory circuits and how this theory was used in psychology, neuroscience and the computer modeling of brain functions.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone involved in glucose homeostasis, appetite regulation, and energy balance. Beyond its peripheral metabolic actions, growing evidence indicates that GLP-1 signalling within the central nervous system modulates reward-related processes. The nucleus accumbens (NAc), a key component of the mesolimbic reward pathway, represents a critical site where metabolic and motivational signals converge. However, the role of GLP-1 signalling within the human NAc remains incompletely understood. This systematic review aimed to synthesize current human evidence on GLP-1 expression and receptor signalling in the NAc and their role in reward and metabolic regulation.

The superior clinical utility of 7T magnetic resonance imaging (MRI) is constrained by high acquisition costs and limited scanner availability. While deep learning-based 3T-to-7T synthesis offers a potential solution, prevailing models typically rely on heavy parameterization, which increases computational redundancy and risk of overfitting on restricted medical datasets. In this paper, we focus on model efficiency and propose LiteMamba-Synth, an architecturally streamlined state space framework designed for high-fidelity MRI translation with minimal resource requirements.

Combining diffusion tract descriptors with structural connectome descriptors may help characterize athlete-related brain imaging patterns; however, this approach is challenging in small-sample studies, where flexible learned models can easily overfit. In such settings, simple linear classifiers often serve as strong baselines, although they do not explicitly encode the anatomical correspondence between tract-level microstructural descriptors and connectome-level organization. To address this gap, we introduce Tensor Connectome Consistency Residual (TC2-Res), a lightweight structured fusion framework that combines pair-aware tract representations, global modality branches, family-level encoders, and a tract-connectome consistency regularizer that encourages matched anatomical families to align in a shared latent space. In a small cohort of collegiate athletes, TC2-Res achieved a slightly higher mean balanced accuracy compared to a matched naive learned fusion baseline on the primary football-vs.-others task, whereas a classical linear support vector machine (SVM) remained the strongest overall classifier. The observed performance gain was modest and inconsistent across folds, and evidence of improvement specifically attributable to the consistency term was limited. These results suggest that anatomically structured fusion represents a plausible lightweight design direction for learned multimodal classification in limited-data settings while also highlighting the continued strength of classical linear baselines in this regime.

The nuclear ubiquitin proteasome system (UPS) is fundamental to maintaining proteostasis and ensuring the quality control of nuclear proteins. Within the nucleus, proteasomes are distributed throughout the nucleoplasm and can aggregate into nuclear bodies. In 2002, our group provided the first description in mammalian cells of a specific subtype of nuclear body highly enriched in: (i) ubiquitin conjugates, (ii) the proteolytically active 20S and 19S regulatory complexes of the 26S proteasome, (iii) the molecular chaperone Hsp70, and (iv) proteasome substrates. We coined the term clastosome to define this nuclear proteolytic center of the UPS. Clastosomes exhibit dynamic behavior, and their formation is transiently and robustly induced in mammalian neurons during osmotic stress, coinciding with enhanced proteasomal activity. Subsequent studies have confirmed and mechanistically expanded our understanding of these nuclear proteolytic centers, which are now recognized as nuclear condensates formed via liquid-liquid phase separation mechanisms. Notably, PML nuclear bodies can establish interactions with clastosomes, thereby linking the PML protein and the SUMOylation pathway with UPS-mediated protein degradation. The association between PML nuclear bodies and clastosomes has been implicated in the clearance of toxic mutant proteins associated with certain neurodegenerative diseases. This review examines the structure, composition, and dynamic regulation of clastosomes, focusing on their modulation during stress responses and neurodegeneration. Given the essential role of nuclear proteolytic centers in proteostasis regulation, a better understanding of mechanisms that modulate their assembly may offer therapeutic strategies for neurodegenerative proteinopathies and other pathologies.

The evolutionary expansion of the primate prefrontal cortex (PFC) presents a profound biological enigma: how does this region achieve a highly ordered, modular architecture in the absence of direct dense sensory templates that govern primary sensory areas? In this review, we synthesize classical neuroanatomical frameworks with recent advances in spatial transcriptomics and connectomics to delineate a model of intrinsic elaboration. We propose that PFC modularity emerges from a developmental program facilitated by expansion of the outer subventricular zone (OSVZ) and the legacy of whole-genome duplication (2R-WGD). Central to this proposal is a "Dual-Control Model" of circuit assembly, inferred by integrating anatomical tracer data with spatial and spatiotemporal transcriptomic datasets. This framework suggests that long-range connectivity is established through pre-target axon bundling (fasciculation), governed by a high-dimensional navigation code (e.g., ephrin/Eph, PCDH11X, PCDH17, ROBO2), while these bundles are anchored onto vertical columnar scaffolds through synaptic docking mechanisms (e.g., CBLN2, cadherins). By contrasting the PFC with the map-driven visual system, point-driven olfactory system, and layer-driven hippocampus, we argue that PFC uniqueness lies not in novel genes but in a combinatorial logic of a shared molecular toolkit, which can be understood as intrinsic elaboration. This framework may facilitate the emergence of a cognitive scaffold under relatively weak external sensory constraints. These molecular systems are considered to operate in concert with activity-dependent developmental refinement rather than independently of neural activity.

The transcription factor 4 (TCF4) gene is essential for brain development, and its disruption causes Pitt-Hopkins syndrome. Common genetic variants in TCF4 also confer risk for schizophrenia and related psychiatric disorders. While the developmental roles of TCF4 are well established, its postnatal functions remain poorly defined, particularly during the prolonged maturation of the primate neocortex, when many neuropsychiatric symptoms first emerge. Here, we mapped cell-type-specific TCF4 expression across postnatal development in rhesus macaque neocortex using immunofluorescence, and in situ hybridization. We also re-analyzed public bulk-tissue and single-nucleus transcriptomic datasets spanning 16 brain regions in both humans and macaques. TCF4 was predominantly neuronal, with minimal expression in microglia, oligodendrocytes, and astrocytes. In late gestation, TCF4 was broadly expressed in excitatory and inhibitory neurons, but expression declined with maturation and became selectively enriched in inhibitory populations. By young adulthood, nuclear TCF4 levels were highest in somatostatin-positive and vasoactive intestinal peptide-positive interneurons, intermediate in parvalbumin interneurons (~6-fold above non-GABAergic cells), and lowest in cholecystokinin interneurons (~4-fold above non-GABAergic cells). This interneuron-subtype hierarchy was independently reproduced by single-nucleus RNA sequencing across all neocortical regions. Together, these findings position mature GABAergic interneurons as the principal site of TCF4 function in the primate neocortex, providing a cellular framework for linking TCF4 dysfunction to cortical circuit imbalance in Pitt-Hopkins syndrome and psychiatric disease.