Brain Structure and Function

BackgroundThe medial cerebral cortex contains several sulci of high anatomical and clinical relevance, including the cingulate, paracingulate, calcarine, parieto-occipital, callosal, Rostral, supra-rostral and subparietal sulci. These structures serve as essential neuroanatomical landmarks and surgical corridors in microneurosurgical procedures, yet they exhibit considerable morphological variability. Although numerous studies have examined these sulci, no comprehensive synthesis exists focusing exclusively on cadaveric morphological and morphometric data, which remain critical for accurate neuroanatomical understanding. MethodsThis scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology and reported following the PRISMA-ScR checklist. A comprehensive literature search identified 4,440 records, of which 60 duplicates were removed. Screening of titles and abstracts excluded 3911 records, leaving 469 for full-text review. After applying eligibility criteria, eight cadaveric studies were included. Data were extracted on sample characteristics, morphological classification, and quantitative morphometry for the medial sulci. Findings were synthesized narratively and tabulated by sulcus type. ResultsThe included studies analyzed a total of 422 hemispheres from formalin-fixed cadaveric brains. The cingulate sulcus was consistently present in all examined specimens, whereas the paracingulate sulcus displayed marked variability. The calcarine sulcus demonstrated relatively stable morphometry, with mean anterior and posterior segment lengths ranging from 2.3 to 3.5 cm, yet exhibited variable bifurcation patterns and lunate sulcus connections. The parieto-occipital sulcus was a reliable boundary between the cuneus and precuneus, with mean lengths around 4.0 cm. The subparietal sulcus was described less frequently, highlighting a gap in detailed morphometric literature. ConclusionCadaveric evidence confirms both consistent and highly variable features in the medial cerebral sulci. These variations have direct implications for surgical planning, particularly in interhemispheric approaches. The paucity of detailed morphometric descriptions for certain sulci, especially the subparietal, callosal, rostral and supra-rostral sulcus, underscores the need for further targeted anatomical research.

Segmenting the magnocellular (M) and parvocellular (P) divisions of the human lateral geniculate nucleus (LGN) has been challenging yet remains an important goal because the LGN is the only place in the brain where these two information streams are spatially disjoint and can be studied independently. Previous research used the amplitude of responses to different types of stimuli to separate M and P regions (Denison et al., 2014; Zhang et al., 2015). However, this method is confounded because the hilum region of the LGN exhibits greater response amplitudes to all stimuli and can be mistaken for the M subdivision (DeSimone & Schneider, 2019). Therefore, we have employed two independent methodologies that do not rely upon the functional response properties of the M and P neurons to segment the M and P regions: 1) structural quantitative MRI (qMRI) at 3T to measure the T1 relaxation time, and 2) monocular and dichoptic functional MRI (fMRI) procedures to measure eye-specific responses. Our qMRI results agreed with the anatomical expectations, identifying M regions on the ventromedial surface of the LGN. The monocular fMRI procedure was better than the dichoptic condition to identify the eye-dominance signals. Both procedures revealed significant right eye bias, and neither could reliably identify the first M layer of the LGN. These findings indicated that the qMRI methods are promising whereas the functional identification of contralateral layers requires further refinement. HighlightsO_LIT1 parameter in qMRI segregates M and P regions of LGN in individual subjects at 3T. C_LIO_LIEye-specific voxels in LGN respond more strongly to monocular than dichoptic viewing. C_LIO_LIClusters of eye-specific regions but not layers can be separated at 1.5 mm resolution. C_LI

Despite advances in neuromelanin-sensitive brain imaging and a plethora of manual labelling, atlas- and signal intensity-based software solutions, the reliable non-invasive delineation of the locus coeruleus (LC) in the human brain stem remains challenging. We sought to evaluate the spatial accuracy and consistency of atlas-and probabilistic spatial prior-based LC delineation. We acquired neuromelanin-sensitive magnetic resonance imaging data in healthy volunteers (n = 24; mean age 40.0 {+/-} 16.8 years; 42% females). Manual labelling by 9 raters performed twice provided the basis for individual- and group-level comparisons with the automated delineation methods. For the atlas-based labelling, we separately tested seven open-access LC atlases, the averaged output of the manual labelling, and a consensus reference representing the atlases overlap. Each one of the atlases served as spatial prior for automated LC delineation in a probabilistic segmentation framework. Manual labelling showed moderate inter-rater agreement (mean Dice = 0.7), with higher delineation variability in the rostral and caudal LC. For the atlas-based labelling we observed a low spatial concordance for all open-access atlases (Dice = 0.2-0.4) with inconsistent boundary accuracy and volume similarity indices relative to the consensus reference. In the same comparison, the averaged manual labelling atlas showed higher spatial overlap (Dice = 0.6). Probabilistic delineation using spatial priors showed the strongest voxel-wise similarity with manual labelling (correlation coefficient r = 0.3) when the averaged manual labelling atlas was used as prior. Principal component analysis confirmed the greater spatial compactness for atlas-based labelling in comparison with spatial prior-based delineation, underscoring method-dependent differences in anatomical organization. Our results highlight the potential advantage of atlas-based labelling for robust and spatially reliable LC identification. The observed variability across methods and atlases calls for harmonised validation strategies and context-sensitive approaches that improve reliability.

The right inferior frontal gyrus (rIFG) has most strongly, although not exclusively, been associated with response inhibition, not least based on covariations of behavioral performance measures and local grey matter characteristics. However, the white matter microstructure of the rIFG as well as its connectivity has been less in focus, especially when it comes to the consideration of potential subdivisions within this area. The present study reconstructed the structural connections of the three main subregions of the rIFG (i.e. pars opercularis, pars triangularis and pars orbitalis) using diffusion tensor imaging, and further assessed their associations with behavioral measures of inhibitory control. The results revealed a marked heterogeneity of the three subregions with respect to the pattern and extent of their connections, with the pars orbitalis showing the most widespread inter-regional connectivity, while the pars opercularis showed the least amount of connections. When relating behavioral performance measures of a stop signal task to brain structure, the data indicated a differential association of dorsal and ventral opercular connectivity with the go reaction time and the stopping accuracy, respectively.

There remains little consensus about the relationship between sex and brain structure, particularly in childhood. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest - many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years-old (N=7693). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. The model with sex, but not gender diversity, was the best-fitting model in 75% of gray matter regions and 79% of white matter regions examined. The addition of gender to the sex model explained significantly more variance than sex alone with regard to bilateral cerebellum volume, left precentral cortical thickness, as well as gyrification in the right superior frontal gyrus, right parahippocampal gyrus, and several regions in the left parietal lobe. For mean diffusivity in the left uncinate fasciculus, the model with sex, gender, and their interaction captured the most variance. Nonetheless, the magnitude of variance accounted for by sex was small in all cases and felt-gender score was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years-old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity. HighlightsO_LISex-related variance in regional human brain structure is widespread at ages 9-11 C_LIO_LITogether, sex and gender diversity accounted for more variance in only a few regions C_LIO_LIFelt-gender diversity itself was not significantly related to any outcome at ages 9-11 C_LIO_LIEffect sizes for sex and felt-gender estimates were small C_LI

INTRODUCTIONCushings disease is a condition of hypercortisolaemia caused by a functional adrenocorti-cotropic hormone secreting pituitary adenoma. Surgical management is the first line of treatment for Cushings disease, but remains challenging in some cases. Various imaging modalities have been tried in an attempt to improve surgical remission rates. However, the sizes and certainties of any effect, in comparison to standard preoperative MRI imaging, remain unclear. METHODSThis protocol has been developed according to the PRISMA-P 2015 standards. Searches of PubMed and Embase were conducted on 21 May 2020, and abstract screening commenced. The eligibility criteria, items for data extraction, and the analysis plan are laid out in this protocol, and uploaded prior to commencement of formal data extraction. DISCUSSIONThe results of this review will inform decision-making and priority-setting at the clinical, organisational and research levels. The results will be disseminated throughout the international neurosurgical community through presentations and publications.

Perivascular spaces (PVS) surrounding cerebral blood vessels play an important role in the blood-brain barrier and glymphatic system. Although it was once thought that PVS were either absent or too small to be seen or quantified during healthy development with MRI, recent studies have found visible, quantifiable PVS exist throughout the white matter of the cerebrum in childhood and adolescence. As a result, researchers have begun to explore individual differences, including potential sex-based variations in developing PVS. Meta-analyses in adults have shown that PVS are larger on average in males than in females, and several studies have shown a similar relationship in children. In contrast, no studies to date have examined the association between gender and PVS at any age. This cross-sectional study examined 6,538 youths from a large, nationwide sample of 9- to 11-year-olds in the U.S. to examine the relationship between sex, felt-gender, and PVS count and volume. Using a model-building approach, we conducted a series of linear mixed-effects models to determine the maximum variance explained in PVS count and volume, including age, pubertal development status, race, parent education, BMI z-score, and regional white matter volume, while also adjusting for MRI scanner and site. BMI z-score, age, and parent education were significant predictors of both PVS volume and count. Adding sex to the model improved model fit in all regions, and the further addition of felt-gender significantly improved model fit for PVS count in 5/6 regions of interest. Moreover, we found increases in PVS volume and count were associated with reduced executive function, learning, and memory. As the first study to report an association between felt-gender and PVS, our findings demonstrate the importance of considering gender in addition to sex as a potential source of structural variance in PVS in adolescents.

Face processing is mediated by a distributed neural network commonly divided into a \"core system\" and an \"extended system\". The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area) and the FFA for common neural resources.\n\nThe goal of the present pilot study was to prepare the basis for a larger follow-up study assessing the ontogenetic development of the lateralization of the face processing network. More specifically, we aimed on the one hand to establish a functional magnetic resonance imaging (fMRI) paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level, and on the other hand to calculate the necessary group size for the planned follow-up study.\n\nTwelve children aged 7-9 years, and ten adults were measured with a face localizer task that was specifically adapted for children. Our results showed that it is possible to localize the core systems brain regions in children even at the single subject level. We further found a (albeit non-significant) trend for increased right-hemispheric lateralization of all three regions in adults compared to children, with the largest effect for the FFA (estimated effect size d=0.78, indicating medium to large effects). Using these results as basis for an informed power analysis, we estimated that an adequately powered (sensitivity 0.8) follow-up study testing developmental changes of FFA lateralization would require the inclusion of 18 children and 26 adults.

Contemporary neuroscientific accounts suggest that ventral anterior temporal lobe (ATL) regions act as a bilateral heteromodal semantic hub. However, research also shows graded functional differences between the hemispheres relating to linguistic versus non-linguistic semantic tasks and to knowledge of objects versus people. Individual differences in connectivity from bilateral ATL and between left and right ATL might therefore give rise to differences in function within this system. We investigated whether the relative strength of intrinsic connectivity from left and right ATL would relate to differences in performance on semantic tasks. We examined resting-state fMRI in 74 individuals and, in a separate session, examined semantic categorisation, manipulating stimulus type (famous faces versus landmarks) and modality of presentation (visual versus verbal). We found that people with greater connectivity between left and right ATL were more efficient at categorising landmarks, especially when these were presented visually. In addition, participants who showed stronger connectivity from right than left ATL to medial occipital cortex showed more efficient semantic categorisation of landmarks regardless of modality of presentation. These findings show that individual differences in the intrinsic connectivity of left and right ATL are associated with effects of category and modality in semantic categorisation. The results can be interpreted in terms of graded differences in the strengths of inputs from spoke regions, such as regions of visual cortex, to a bilateral yet partially segregated semantic hub, encompassing left and right ATL.

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.

With advancing age, the distinctiveness of neural representations of information declines. While the finding of this so-called age-related neural dedifferentiation in category-selective neural regions is well-described, how neural dedifferentiation manifests at the level of large-scale functional networks is less understood. Furthermore, the relationship between age-related changes in network organization and dedifferentiation is unknown. Here, we investigated age-related neural dedifferentiation of category-selective regions as well as whole-brain functional networks. We additionally examined age differences in connectivity of category-selective regions to the rest of the brain. Younger and older adults viewed blocks of face and house stimuli while performing memory encoding and retrieval in the fMRI scanner. We found an age-related decline in neural distinctiveness for faces in the fusiform gyrus (FG) and for houses in the parahippocampal gyrus (PHG). Functional connectivity analyses revealed age-related dedifferentiation of global network structure as well as age differences in the connectivity profiles to category-selective regions. Together, our findings suggest that age-related neural dedifferentiation manifests both in regional categorical representations as well as in whole- brain functional networks. HighlightsO_LICategory representations are less distinctive, or dedifferentiated, in older adults C_LIO_LIFunctional networks are less segregated in older adults C_LIO_LIOlder adults reveal less connectivity between fusiform gyrus and visual cortices C_LI

Heschls gyrus (HG) can occur as a single gyrus or with a completely duplicated posterior HG that has been related to a variety of abilities and disorders. Voxel-based studies typically involve the normalization of these qualitatively different HG types, thus making it difficult to evaluate the contribution of sulcal/gyral variability to voxel-based effects and perhaps obscuring some effects. To examine the structural covariance of single and duplicated HG, templates were created for the left single and duplicated HG. Structural covariance analysis with a Jacobian measure of volumetric displacement demonstrated consistent spatial covariance with homologous structure in the right hemisphere across qualitatively different HG morphology. These results suggest that HG duplication is aptly named with respect to cortical structure variation and demonstrate a multi-template approach for studying qualitatively unique brain function and structure linked to perceptual and cognitive functions. HighlightsQualitatively unique sulcal/gyral features can affect voxel-based analyses. Heschls gyrus is highly variable across people. Morphology-specific templates were created to study Heschls gyrus structural covariance. Single and duplicated Heschls gyrus exhibited a similar pattern of covariance.

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.

IntroductionSex differences in autonomic control may contribute to physiological sex differences in cardiovascular disease, thermoregulation, and the experience of pain. We previously showed sex differences in functional mapping of autonomic responses across the insula, a central autonomic control region. Anterior insula response patterns to sympathetic activation (Valsalva) and parasympathetic withdrawal (handgrip) differed between men and women. We here assessed sex differences in autonomic insula gyrus responses to a cold pressor challenge, which involves temperature and pain regulation. MethodsFunctional MRI (fMRI) involved a 1-minute right-foot cold pressor challenge in 22 women (age; mean{+/-}std: 50{+/-}4 yrs), and 39 men (45{+/-}3 yrs). Regions of interest (ROI) comprised left and right anterior short gyrus (ASG), middle short gyrus (MSG), posterior short gyrus (PSG), anterior long gyrus (ALG), and posterior long gyrus (PLG). Two-second time intervals of fMRI signal responses per ROI and concurrently recorded heart rate and blood oxygen saturation (SaO2) were tested for within- and between-group effects over time (repeated measures ANOVA P[≤]0.05). We tested sex differences in 1) each ROI; 2) lateralization effects; and 3) posterior-to-anterior gradients in responses. ResultsNo sex differences emerged in heart rate or SaO2. Women showed larger signal changes in several gyri than men after cold pressor onset and offset. Most consistently, women showed a greater right-over-left hemisphere dominance in cold pressor response compared to men in the MSG, PSG and ALG. Greater right-over-left hemisphere anterior-to-posterior dominance was more pronounced in men. ConclusionsThe findings confirm anterior and right-hemispheric dominance of insular responses during sympathetic activation that includes pain and cold. Although distinct transient male-female differences in fMRI responses appeared during the cold pressor, unlike the Valsalva and handgrip, no sex differences in ASG lateralization emerged, suggesting that the previously found sex differences may not solely relate to regulating blood pressure responses.

To better understand the cortical connections and organization of visual areas in galagos, we examined the interconnections among cortical visual fields and their relationships with posterior parietal cortex (PPC) and temporal regions associated with dorsal and ventral streams of visual processing. In five galagos, two to four distinguishable tracers were injected into different visual areas, allowing direct comparison of connection patterns within the same cases. To reveal distributions of labeled neurons for each injection, labeled cells were plotted from serial brain sections cut parallel to the flattened cortical surface and summed across sections to generate surface reconstructions. Alternate sections processed for cytoarchitectonic features were used to identify cortical borders, especially those of V1 and middle temporal visual area (MT). Overall, our results support the conclusion that regions of V2 and V3 represent the contralateral visual hemifield in parallel with V1 and with each other. However, dorsal V3, representing the lower visual hemifield, includes at least one discontinuity where representations of the upper visual field extend to the dorsal border of V2. This portion of V3 appears to belong to the dorsomedial visual area (DM), which extends rostrally from V2 into PPC. The dorsal part of the DL-V4 region receives projections from other parts of dorsolateral visual area (DL), central V1, V2 and V3, inferotemporal (IT) cortex, the MT complex, and PPC regions surrounding the intraparietal sulcus (IPS). More central portions of DL-V4 receive inputs from central representations of V1, V2, and V3, as well as from PPC regions lateral to the IPS, the MT complex, and upper IT cortex. The ventral part of DL receives projections from central V2, caudal PPC adjoining DM and ventral PPC, and from IT cortex. These patterns indicate that the DL-V4 region serves as a major node linking dorsal and ventral streams and likely includes more than one functionally distinct visual area. In addition, areas MT and DM show strong reciprocal connections with PPC, while the connections of IT cortex indicate that much of this region is visual in nature having strong connections with higher order visual areas and it is composed of multiple functionally specialized visual domains. Key pointsO_LIOrganization of the visual cortex in galagos is much like that in New World and Old Word monkeys. C_LIO_LIPatterns of cortical connections of early visual areas V1 and V2 support the view that dorsal V3 has a gap in the representation of the lower visual field that is occupied by the proposed dorsomedial visual area (DM). C_LIO_LIVisual areas DM and middle temporal visual area (MT) provide the major visual inputs to posterior parietal cortex (PPC) of the dorsal stream of visual processing for actions. C_LI

Much is known regarding the major white matter pathways connecting the right and left temporal lobes, which project through the posterior corpus callosum, the anterior commissure, and the dorsal hippocampal commissure. However, details about the spatial location of these tracts are unclear, including their exact course and proximity to cortical and subcortical structures, the spatial relations between corpus callosum and anterior commissure projections, and the caudal extent of transcallosal connections within the splenium. We present an atlas of these tracts derived from high angular resolution diffusion tractography maps, providing improved visualization of the spatial relationships of these tracts. The data show several new details, including branching of the transcallosal pathway into medial and lateral divisions, projections of the transcallosal pathway into the external capsule and claustrum, complex patterns of overlap and interdigitation of the transcallosal and anterior commissure tracts, distinct dorsal and ventral regions of the splenium with high tract densities, and absence of temporal lobe projections in the caudal third of the splenium. Intersection of individual tract probability maps with individual cortical surfaces were used to identify likely regions with relatively higher cortical termination densities. These data should be useful for planning surgical approaches involving the temporal lobe and for developing functional-anatomical models of processes that depend on interhemispheric temporal lobe integration, including speech perception, semantic memory, and social cognition. HighlightsO_LIInterhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography. C_LIO_LIResults are displayed on serial orthogonal sections to reveal detailed spatial relationships. C_LIO_LICorpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium. C_LIO_LIThe transcallosal pathway consists of distinct medial and lateral divisions. C_LIO_LIThe results reveal projections to the external capsule and claustrum not previously described. C_LIO_LITranscallosal and anterior commissural pathways show complex patterns of overlap and interdigitation. C_LIO_LISurface mapping revealed areas with relatively high density of projections to the cortical surface. C_LI

The functional organization of first (L1) and second (L2) language processing in bilinguals remains a topic of great interest to the neurolinguistics community. Functional magnetic resonance imaging (fMRI) studies report meaningful differences in the location and extent of hemodynamic changes between tasks performed in the L1 and L2, yet there is no consensus on whether these networks can be considered truly distinct. In part, this may be due to the multiplicity of task designs implemented in such studies, which complicates the interpretation of their findings. This paper compares the results of previous bilingual meta-analyses to a new ALE meta-analysis that categorizes neuroimaging studies by task design. Factors such as the age of L2 acquisition (AoA) and the L2 language proficiency level of participants are also considered. The findings support previous accounts of the effect of participant characteristics on linguistic processing, while at the same time revealing dissociable differences in fMRI activation for L1 and L2 networks within and across tasks that appear independent of these external factors.

The hypothalamus and pituitary regulate, amongst other functions, third order endocrine systems, and their volumes have been associated with normal and pathological outcomes. Yet, there are very few studies that examine their combined structural variations in vivo. This is due, in part, to their small size and a lack of comprehensive image segmentation protocols. In the current project we acquired high-resolution T1- (1mm isotropic) and T2-weighted (0.4mm in plane resolution) 3T magnetic resonance images (MRI) of the hypothalamus and pituitary gland, as well as salivary estradiol and testosterone from 31 (17M, 14F) young healthy adults. Women reported oral contraceptive use. Image preprocessing included non-uniformity correction, signal intensity normalization and standard stereotaxic space registration. We applied a comprehensive manual segmentation protocol of the whole hypothalamus, with detailed segmentation of the pituitary stalk, the anterior and posterior pituitary gland, and the posterior bright spot. We also propose a novel medial-lateral hypothalamic parcellation into medial preoptic, periventricular (PVN), and lateral hypothalamic regions. The protocol yielded good inter- (range: 0.78-0.92) and intra-rater (range: 0.79-0.94) Dice kappa overlap coefficients. We detected sex differences of the whole hypothalamus and each hemisphere, and a trend for the right preoptic region to be larger in males than in females, with a moderate effect size. Sex differences were maintained or enhanced when covarying for estradiol, but not when covarying for testosterone. In addition, testosterone was associated with the volume of the PVN, but only in women. In summary, these results suggest that there are morphometric differences at the level of the pituitary and hypothalamus that are likely driven by central regulation of gonadal hormones. The here described protocol allows the structural investigation of neuroendocrine effects in the central nervous system.

BackgroundVariations in regional cortical folds across individuals have been examined using computationally-derived morphological measures, or by manual characterization procedures that map distinct variants of a regional fold to a set of human-interpretable shapes. Although manual mapping approaches have proven useful for identifying morphological differences of clinical relevance, such procedures are subjective and not amenable to scaling. New MethodWe propose a 3-step pipeline to develop computational models of manual mapping. The steps are: represent regional folds as feature vectors, manually map each feature vector to a shape-variant that the underlying fold represents, and train classifiers to learn the mapping. ResultsFor demonstration, we chose a 2D-problem of detecting within slice discontinuity of medial and lateral sulci of orbitofrontal cortex (OFC); the discontinuity may be visualized as a broken H-shaped pattern, and is fundamental to OFC-type-characterization. The classifiers predicted discontinuities with 86-95% test-accuracy. Comparison with Existing MethodsThere is no existing pipeline that automates a manual characterization process. For the current demonstration problem, we conduct multiple analyses using existing softwares to explain our design decisions, and present guidelines for using the pipeline to examine other regional folds using conventional or non-conventional morphometric measures. ConclusionWe show that this pipeline can be useful for determining axial-slice discontinuity of sulci in the OFC and can learn structural-features that human-raters may rely on during manual-characterization.The pipeline can be used for examining other regional folds and may facilitate discovery of various statistically-reliable 2D or 3D human-interpretable shapes that are embedded throughout the brain.

Sexual stimuli processing is a key element in the repertoire of human affective and motivational states. Previous neuroimaging studies of sexual stimulus processing have revealed a complicated mosaic of activated regions, leaving unresolved questions about their sensitivity and specificity to sexual stimuli per se, generalizability across individuals, and potential utility as neuromarkers for sexual stimulus processing. In this study, data on sexual, negative, non-sexual positive, and neutral images from Wehrum et al. (2013) (N = 100) were re-analyzed with multivariate Support Vector Machine models to create the Brain Activation-based Sexual Image Classifier (BASIC) model. This model was tested for sensitivity, specificity, and generalizability in cross-validation (N = 100) and an independent test cohort (N = 18; Kragel et al. 2019). The BASIC model showed highly accurate performance (94-100%) in classifying sexual versus neutral or nonsexual affective images in both datasets. Virtual lesions and test of individual large-scale networks (e.g., visual or attention networks) show that these individual networks are neither necessary nor sufficient to capture sexual stimulus processing. These findings suggest that brain responses to sexual stimuli constitute a category of mental event that is distinct from general affect and involves multiple brain networks. It is, however, largely conserved across individuals, permitting the development of neuromarkers for sexual processing in individual persons. Future studies could assess performance of BASIC to a broader array of affective/motivational stimuli and link brain responses with physiological and subjective measures of sexual arousal.