Brain Structure and Function

Economic choices are believed to depend on the orbitofrontal cortex (OFC). Work in primates and rodents indicates that neurons in OFC participate in computing and comparing subjective values, suggesting that different groups of cells constitute the building blocks of a decision circuit. In a recent study (Livi et al., 2025), we examined the laminar organization of this circuit in mice. We found that different decision variables were differentially represented in layer 2/3 (L2/3) and layer 5 (L5). Furthermore, the temporal dynamics of decision signals indicated a combination of feed-forward and feed-back across layers, and pointed to L5 as the locus for winner-take-all value comparison. Importantly, these results were obtained under the constraint that each neuron encoded a single variable. Here, we tested whether our results on laminar organization depended on the categorical framework. We applied LASSO regression to identify a minimal set of variables explaining each neurons activity. Even with approximately half of all neurons representing two or more variables, the layer specificity of decision variables was preserved. In addition, Granger Causality Analysis and activity profiles reached similar conclusions as for analyses conducted under the single-variable constraint. We conclude that the decision circuit in OFC exhibits a laminar architecture, independently of whether the representation of decision variables in this area is categorical or mixed.

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.

The lateral septum (LS) integrates afferents from multiple brain regions, including the raphe nuclei. The organization of these inputs contributes to the regionalization of LS functions, for example spatial coding in dorsal LS and emotional regulation in ventral LS. Raphe-LS projections include glutamatergic axons expressing the vesicular glutamate transporter type 3 (VGLUT3), which often form pericellular baskets around LS neurons. This study provides an anatomical characterization of the organization and origins of VGLUT3-positive (VGLUT3+) raphe inputs to the LS. We mapped VGLUT3+ axon terminal density across the rostro-caudal extent of the LS and quantified colocalization with serotonin (5-HT) using immunohistochemistry. Our results showed that VGLUT3 density was highest in the ventral LS, whereas VGLUT3/5-HT colocalization was strongest in the dorsal LS. Retrograde viral vector-mediated tracing identified predominant inputs from the median raphe and B9 neuron group. Interestingly, the ventral hippocampus, a functionally related region which is known to also receive raphe VGLUT3 inputs, showed collaterals with the LS. Additional VGLUT3+ inputs to the LS arose from the interpeduncular nucleus, bed nucleus of the stria terminalis, nucleus incertus and pontine central gray. Anterograde tracing revealed that inputs from these brain regions target distinct and largely non-overlapping domains in the LS. Our findings highlight multiple sources of VGLUT3+ inputs to the LS, beyond the raphe nuclei, and suggest that distinct VGLUT3 circuits could contribute to LS functional specialization.

The superficial white matter (SWM), the region of white matter immediately beneath the gray matter-white matter (GM-WM) border, contains short cortico-cortical association fibers that interconnect neighboring cortical regions. The SWM is estimated to comprise the majority of axons in the cerebral white matter and is thus thought to play a major role in cortical information processing. Despite this prominence, and growing attention in the diffusion MRI field, the connectional organization of the SWM remains poorly defined. A major component of the SWM is U-shaped fiber bundles, classically depicted in brain dissections as bundles beneath sulci that interconnect adjacent gyri. The prevailing view, from both brain dissection and diffusion MRI, considers U-fibers to be ubiquitous elements of the SWM that form symmetric connections between corresponding portions of adjacent gyri beneath all sulci, and they are routinely reconstructed in tractography as a layer of short association connections. However, their actual prevalence and organization in the primate brain have never been systematically evaluated with experimental tract tracing. To address this gap, we analyzed 28 archival macaque tract-tracing cases in which anterograde tracers were injected on gyri adjacent to major cortical sulci (intraparietal, central, principal, superior temporal), all of which have clear anatomical correspondences to sulci in the human cerebral cortex. Several organizational principles emerged. First, although short association fibers were present in every case, U-fibers - operationally defined as labeled fibers that left the injection site, passed beneath a sulcus, and terminated on the adjacent gyrus - were only observed in a minority of cases. Second, U-fiber incidence was sulcus-dependent: U-fibers were consistently present beneath the principal and central sulci, but uncommon beneath the intraparietal and superior temporal sulci. Third, when present, U-fibers did not follow a uniform trajectory - some took a course symmetric and orthogonal to the sulcus, whereas others followed oblique trajectories to more distant regions. In addition to U-fibers, we identified shorter association fiber bundles that terminated on the sulcal bank proximal to the injection, or on the opposing bank after they crossed the fundus of the sulcus, evidence that the SWM contains multiple classes of short association fiber bundles rather than a single canonical U-fiber system. We further identified a consistent 200-300 {micro}m band of white matter beneath cortical layer 6 that contained exclusively short association fibers on approach to their cortical terminations and was selectively avoided by deeper long cortico-cortical pathways. This band was present across all examined sulci, suggesting that it is a conserved feature of the cortical white matter. Notably, U-fibers were found both within this band and in the white matter below. We also identified deeper fiber bundles that adopted a U-shaped course beneath a sulcus but did not interconnect adjacent gyri. Thus, a U-shaped trajectory alone does not define a U-fiber. Together, these findings constitute the first systematic connectional study of cortical U-fibers in major sulci of the non-human primate brain and indicate that the white matter beneath the cortex is a highly complex system in which short association fiber bundle organization reflects the selective connectivity of the cortical areas separated by a sulcus, rather than a uniform U-fiber architecture imposed by the geometry of the overlying sulcus. These results have potential consequences for dMRI and anatomical studies of white matter and provide an anatomically grounded basis to better define SWM organization in anatomy and tractography.

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.

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

The paraventricular nucleus (PVN) plays a central role in neuroendocrine and autonomic regulation, including male sexual behavior. Dopaminergic and nitrergic signaling within the PVN are functionally linked, but their cellular relationship remains unclear. We examined the colocalization of dopamine D1 and D2 receptors with neuronal nitric oxide synthase (nNOS) in adult male rats using double-label immunohistochemistry. nNOS-immunoreactive neurons were widely distributed in PVN, with subsets co-expressing D1R or D2R. Approximately 45% of nNOS-positive neurons expressed dopaminergic receptors. These findings provide structural evidence for dopaminergic-nitrergic interaction in the PVN and support the possibility of direct dopaminergic modulation of nitrergic neurons.

A substantial body of research suggests that the left and right cerebral hemispheres play differential roles in shaping human behavior. However, due to methodological considerations, most studies in this field have relied primarily on psychological methods. Here, we present exploratory neurobiological evidence suggesting that brain volume across numerous cortical and non-cortical homotopic regions may display consistent directional asymmetry in relation to a wide range of behavioral measures. Of particular note, such asymmetry recurred between contralateral homotopic areas across many behavioral parameters. The asymmetric behavioral directionality is distributed across most regions of the human brain, especially in the frontal and temporal cortices, which are particularly developed in humans. This may add a new dimension to previously described aspects of hemispheric asymmetry. In addition, it may help to understand why a marked functional asymmetry can be observed even when structural asymmetry is subtle. Moreover, these findings may shed light on how the brain modulates behavior in health and disease and may contribute to understanding processes involved in neurological and psychiatric disorders.

Post-stroke semantic aphasia is characterised by multimodal semantic deficits and reflects disruption of a distributed brain network spanning frontal and temporal regions. Connectivity gradients, which capture key dimensions of whole-brain variation in functional connectivity, offer a promising framework for understanding the global impact of stroke on brain function. This study investigated whether changes in connectivity gradients following stroke can explain semantic aphasia deficits. First, we evaluated whether lesion-location and lesion-load information from structural MRI could predict the gradient changes observed in resting-state fMRI, as a proof-of-principle analysis. Second, we tested whether simulated gradient changes predict the severity of semantic impairment. Results show that post-stroke gradient changes simulated from structural MRI are correlated with actual changes in resting-state fMRI, particularly for the principal gradient that separates unimodal and heteromodal regions. Semantic deficits were related to simulated connectivity changes along this gradient: left prefrontal areas involved in controlled semantic retrieval exhibited stronger connectivity to unimodal cortex in patients with more severe deficits. Semantic deficits also correlated with changes in the second gradient, which distinguishes visual and motor cortex. Particularly, the right parahippocampal gyrus, typically visually biased--showed reduced visual connectivity in more impaired patients. These results help explain controlled semantic retrieval deficits in semantic aphasia. More broadly, the findings suggest that functional connectivity gradients capture post-stroke reorganisation of global brain networks linked to cognitive impairment, and that these changes can be estimated from structural MRI alone, enhancing clinical utility of gradient-based approaches. HighlightsO_LIFunctional connectivity gradients explain the multimodal impairments in semantic aphasia from a dimensional perspective, using the unimodal-transmodal and motor-visual axes. C_LIO_LIPost-stroke functional changes are explored through alterations in connectivity gradient patterns. C_LIO_LICortical lesion information from structural MRI can be used to simulate changes in connectivity gradients, offering potential clinical relevance. C_LI

Verbal fluency is a behavioral task that requires the generation of words from a semantic category (category fluency) or words beginning with a specific letter (letter fluency). Although word production engages a frontal-temporal-parietal network, no studies have tested how lesions to temporal and parietal lobe areas that represent semantic and phonological knowledge dampen neural responses in the left pars triangularis and the left pars opercularis, two adjacent regions in the left inferior frontal gyrus implicated in word search and retrieval. Here, 52 patients with temporal lobe lesions underwent clinical functional MRI while performing the category and letter fluency tasks. We investigated where lesion presence was inversely related to the magnitude of task-specific neural responses in pars triangularis and pars opercularis using a technique referred to as voxel-based lesion activity mapping (VLAM). We found that lesions to the left anterior superior temporal gyrus, left temporal pole, left hippocampus, left insula, and underlying inferior fronto-occipital fasciculus were associated with reduced neural responses in the left pars triangularis during the category fluency task. Lesion damage to the right hippocampus was associated with reduced neural responses in the left pars opercularis during category fluency. By contrast, lesions to the left posterior superior temporal gyrus, left supramarginal gyrus, left parietal operculum, and the inferior fronto-occipital fasciculus and left arcuate fasciculus were associated with reduced neural responses in the left pars triangularis and the left pars opercularis during the letter fluency task. These results suggest that anatomically dissociable brain networks interact with the left inferior frontal gyrus when different search strategies constrain the retrieval of word representations.

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.

Purpose: To investigate sex differences in cerebral blood flow through densely parcellated cortical and subcortical regions using explainable artificial intelligence methods and identify neurobiologically interpretable perfusion biomarkers. Methods: High-resolution pseudo-continuous arterial spin labelling (1.875 mm x 1.875 mm x 3 mm) and structural MRI data were curated from 215 healthy young adults (150 females, 95 males; age 18-30 years) from the publicly available I See your Brains (ISYB) dataset. Cerebral blood flow was quantified using atlas-based regional analysis with the Brainnetome Atlas (246 regions) and optimized registration procedures. Sex classification employed diverse machine learning paradigms including linear classifiers, ensemble methods, and kernel-based approaches for regional CBF features, with deep convolutional neural networks (CNN) applied to whole-brain 3D imaging data. Model interpretability was achieved using SHapley Additive exPlanations (SHAP), computed over an ensemble of 500 logistic regression models (100 iterations x 5-fold cross-validation). Regions appearing among the top 20% of discriminative features more than 289 times were considered statistically significant using binomial testing. GradCAM was used to obtain class-specific attribution maps from the CNN model. Results: Perfusion-based features demonstrated superior sex classification performance compared to structural morphometry. Regional CBF analysis using logistic regression achieved 91 +/- 2% balanced accuracy and 0.95 +/- 0.05 ROC-AUC, substantially outperforming morphometric features (85 +/- 8% balanced accuracy, 0.88 +/- 0.06 ROC-AUC). Deep learning classification of 3D CBF maps achieved a performance of 92 +/- 5% balanced accuracy, 0.92 +/- 0.05 ROC-AUC. SHAP analysis identified 30 statistically significant aggregation-agnostic CBF-based biomarker regions using regional CBF, predominantly involving frontoparietal control networks (27%) and default mode networks (17%). Grad-CAM revealed that the 3D CNN model primarily focused on regions within the frontal lobe. Morphometry-based analysis identified 28 discriminative regions with markedly different anatomical distribution (r = 0.21) emphasizing visual (32%) and default mode (14%) networks. Conclusion: Cerebral blood flow patterns provide highly sensitive and biologically interpretable markers of sex differences in young adult brain. The identification of robust perfusion biomarkers through explainable AI demonstrates the clinical potential of ASL imaging for precision medicine applications in neuroscience. We establish a methodological framework for investigating sex-specific brain physiology using non-invasive neuroimaging.

Background and Objectives: Are some brain regions intrinsically more vulnerable to metastatic colonization? We sought to characterize the spatial distribution of brain metastases and determine whether regional patterns vary according to primary tumor origin. Methods: We analyzed baseline MRI scans and expert tumor segmentations from 906 patients with 3,492 brain metastases treated with stereotactic radiosurgery. Lesions were normalized to MNI152 standard space and superimposed to generate probabilistic atlases of metastatic occurrence. Regional metastatic burden was quantified using anatomical and vascular atlases. Spatial distributions were additionally compared between lung cancer and melanoma metastases. Results: Metastatic burden was distributed nonuniformly throughout the brain. The cerebellum demonstrated the strongest enrichment relative to its anatomical volume (fold change 1.61, p < 0.001), accompanied by overrepresentation of the vertebrobasilar circulation (fold change 1.49, p < 0.001). Spatial distribution also varied by primary tumor type. Lung cancer metastases demonstrated greater infratentorial involvement than melanoma metastases (16.6% vs. 8.7%, p < 0.05), with a corresponding increase in cerebellar burden (14.8% vs. 6.8%, p < 0.05), whereas melanoma metastases were relatively concentrated within the frontal lobe (37.7% vs. 24.6%, p < 0.01). Infratentorial enrichment was observed across all carcinoma subgroups, with the greatest enrichment seen in gastrointestinal metastases (32.9% infratentorial). Conclusion: Brain metastases exhibit nonrandom spatial distributions, with preferential involvement of posterior and infratentorial structures. Regional patterns vary according to primary tumor origin, supporting the existence of region-specific vulnerability to metastatic disease.

The human brainstem is a complex division of the brain comprised of more than 200 nuclei and fiber tracts. The brainstem is essential for the functioning of the entire body. We introduce here the most detailed human brainstem Atlas across the human lifespan: fetus, child, adult. ANCHOR, the Atlas of Neurochemical Characterization of the Human Brainstem, is an online platform that includes more than 800 serial histological sections, stained for Nissl and seven immunochemical (IHC) markers, from the human brainstem of three ages: 25 fetal gestational weeks (GW), 9 years old, and 54 years old. This makes ANCHOR the most comprehensive human brainstem Atlas to date. In these three brainstems, we identified and manually annotated over 200 structures. We further characterized these structures with the seven IHC markers. We specifically describe the catecholaminergic groups in the human brainstem across all three age groups. In addition, we identified the protoplasmic commissural dendrites of the hypoglossal nucleus and we describe the pretectal nuclei in the Nissl-stained fetal 25 GW brainstem. ANCHOR includes an online viewer that integrates multimodal data, from magnetic resonance imaging and block face imaging to Nissl- and IHC-stained serial sections and 3D reconstruction of the entire brainstem. For the 9-year-old specimen, the online viewer allows simultaneous navigation of annotated sections with corresponding IHC, for viewing the specific region-wise cellular features accessible at https://anchor.humanbrain.in/.

The thalamic reticular nucleus (TRN) is a thin, inhibitory shell surrounding the thalamus. It regulates the thalamocortical information flow, and thereby plays a central role in attention, task switching, and the sleep-wake cycle. Despite its importance, the TRN remains poorly studied in the human brain. This is largely because its small size and deep anatomical location limit its visibility with conventional non-invasive neuroimaging techniques. Here, we assessed whether the human TRN can be reliably visualised and segmented in vivo using ultra-high field (UHF) magnetic resonance imaging (MRI) at 7 Tesla. High resolution (0.35 mm isotropic) partial-brain T2* and T1 scans were acquired from healthy individuals, followed by manual delineation of the TRN. These in vivo segmentations were compared with TRN estimates obtained from two high-quality postmortem datasets serving as an anatomical reference. In vivo segmentations of TRN volume and thickness closely matched measurements derived from the postmortem reference datasets, and quantitative comparisons showed high consistency in TRN shape and location across individuals while also capturing meaningful inter-individual variability. Using these segmentations, we constructed a publicly available probabilistic atlas of the human TRN. This atlas provides a new resource for incorporating TRN anatomy into functional, structural, and clinical neuroimaging studies. Our findings demonstrate that the human TRN can be robustly mapped in vivo at 7T and establish a foundation for future investigations into its structure and function.

The rostral nucleus of the solitary tract (rNST) is the initial central site for taste processing. This nucleus has a complex circuitry and multiple cell types with different response properties, connectivity, and morphology (Travers and Travers 2018). However, unlike its visceral counterpart, the caudal NST, neurochemical phenotypes in rNST are poorly defined. Recent studies have begun to probe this gap. Based on fiber photometry, optogenetics, and cell-type specific deletion. For example, one group proposed that somatostatin (SST) rNST neurons, neither calbindin or dynorphin cells, responded specifically to bitter stimuli and that these neurons were necessary for suppression of quinine-induced licking (Jin, Fishman et al. 2021) (Zhang, Jin et al. 2019). The present study employed in situ hybridization, optotagging, and chemogenetic suppression in male and female mice to demonstrate that SST neuron function is more complex. Although most SST neurons responded optimally to bitter stimuli, many others were activated by different qualities and some non-SST neurons responded to bitter tastants. Moreover, roughly equal proportions of SST neurons expressed excitatory (VGLUT2) or inhibitory (VGAT) markers. Suppressing SST neural activity with DREADDS enhanced licking to both quinine and sucrose suggesting that neural activity elicited by the aversive bitter stimulus was suppressed whereas licking elicited by the sweet, preferred stimulus was increased. We hypothesize that these effects arise from suppressing excitatory quinine-responsive SST neurons but that a separate population of inhibitory SST neurons synapse on sucrose-responsive cells. Significance StatementRecent studies have revealed molecular heterogeneity of gustatory system neurons. However, it is unclear whether molecularly-distinct cells are associated with specific roles. The current study investigated somatostatin (SST) neurons in rNST, the first central hub for taste processing. Well over half were inhibitory, expressing VGAT, but a substantial proportion were excitatory, expressing VGLUT2. A narrow majority responded optimally to the bitter quality and none to NaCl, but other SST cells responded most vigorously to sweet, umami, or sour stimuli. Subsets of neurons not expressing SST responded best to each quality, including bitter. Suppressing activity in SST neurons dampened behavioral avoidance to quinine but enhanced consummatory responses to sucrose. Thus, SST rNST neurons exhibited varied functional characteristics but also clear distinctiveness.

Reconciling the anatomical observation that the human brain comprises two asymmetrical halves with the phenomenal unity of the mind is a puzzle that has challenged neuroscientists since the dawn of research in the field. White-matter commissural fibres of the corpus callosum constitute a critical anatomical substrate for the functional resolution of this anatomical duality. However, the extent of the functional involvement of the callosum in different domains of cognition represents, to this day, a mostly uncharted territory. Here we present a probabilistic characterization of callosal involvement in a set of cognitive functions. In particular, we estimated structural callosal connections by means of the Disconnectome approach applied to a reference sample of healthy participants while using the macro-anatomical cortical areas contained in the Harvard-Oxford template as seeds. By multiplying structural connectivity by the involvement of each cortical area in a set of cognitive functions (as derived from Neurosynth meta-analyses), we produced a voxel-wise characterization of the corpus callosum in different functional domains. We were able to highlight greater involvement of posterior callosal regions in vision and episodic memory, greater involvement of more anterior callosal regions in decision making and working memory, with somatosensory and motor functions more related to the central dorsal portion of the callosum.

The addictive properties of opioids are due in part to these drugs ability to alter ventral tegmental area (VTA) activity via activation of mu opioid receptors (MORs) on local and distal inputs. Prior studies have identified numerous opioid-modulated afferents to the VTA, some of which show differing levels of functional modulation by opioids, but the degree to which this parallels differences in receptor expression is not known. Hence, we used retrograde labeling combined with RNAscope to examine oprm1 mRNA expression in VTA-projecting afferents arising from a variety of distal brain regions. Because opioids are thought to be particularly influential on GABAergic afferents to the VTA, we also examined colocalization of oprm1 with GABAergic markers in VTA-projecting neurons. Interestingly, we found that oprm1 mRNA is present in both GABAergic and non-GABAergic VTA-projecting neurons. However, many (though not all) GABAergic afferents expressed higher levels of oprm1 compared to most non-GABAergic afferents (especially those arising from the cortex). These results complement previous anatomical studies that had examined oprm1 expression in these regions but in a non-quantitative way and without regard to their efferent targets. Our findings encourage future work to examine the functional implications of MOR sensitivity within these afferent pathways.

The Dorsal Vagal Complex (DVC) is a critical brainstem relay for visceral sensory information, sympathetic regulation, and gut-brain communication. Current weight-reducing pharmacotherapies are reported to target this brainstem region to elicit their main satiety actions. Despite its importance, no published step-by-step protocol exists for stereotaxic targeting of this region in rodents. Here, we present a detailed protocol for bilateral administration of substances into the DVC of mice using the atlanto-occipital membrane approach. We describe the surgical access, obex-referenced coordinate system, injection parameters, and we provide a histological validation. This protocol is useful for the study of DVC cells and efferent and afferent neuronal DVC circuits using common neuroscience tools such as tracings, optogenetics or chemogenetics. For complete details on the use and execution of this protocol, please refer to Martinez de Morentin et al.(Martinez De Morentin et al., 2024)

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.