Degeneration in Nucleus basalis of Meynert signals earliest stage of Alzheimer's disease progression.

Nucleus Basalis of Meynert (NbM), a crucial source of cholinergic projection to the entorhinal cortex (EC) and hippocampus (HC), has shown sensitivity to neurofibrillary degeneration in the early stages of Alzheimer's Disease. Using deformation-based morphometry (DBM) on up-sampled MRI scans from 1447 Alzheimer's Disease Neuroimaging Initiative participants, we aimed to quantify NbM degeneration along the disease trajectory. Results from cross-sectional analysis revealed significant differences of NbM volume between cognitively normal and early mild cognitive impairment cohorts, confirming recent studies suggesting that NbM degeneration happens before degeneration in the EC or HC. Longitudinal linear mixed-effect models were then used to compare trajectories of volume change after realigning all participants into a common timeline based on their cognitive decline. Results indicated the earliest deviations in NbM volumes from the cognitively healthy trajectory, challenging the prevailing idea that Alzheimer's originates in the EC. Converging evidence from cross-sectional and longitudinal models suggest that the NbM may be a focal target of early AD progression, which is often obscured by normal age-related decline.

Atypical co-development of the thalamus and cortex in autism: Evidence from age-related white-gray contrast change.

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a group of individuals with biallelic variants in DENND5A and determine that variant type is correlated with disease severity. We demonstrate that DENND5A interacts with MUPP1 and PALS1, components of the Crumbs apical polarity complex, which is required for both neural progenitor cell identity and the ability of these stem cells to divide symmetrically. Induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division during neural induction and have an inherent propensity to differentiate into neurons, and transgenic DENND5A mice, with phenotypes like the human syndrome, have an increased number of neurons in the adult subventricular zone. Disruption of symmetric cell division following loss of DENND5A results from misalignment of the mitotic spindle in apical neural progenitors. A subset of DENND5A is localized to centrosomes, which define the spindle poles during mitosis. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state and ultimately shortening the period of neurogenesis. This study provides a mechanism behind DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Bloody noise: The impact of blood-flow artifacts on registration.

Blood-flow artifacts present a serious challenge for most, if not all, volumetric analytical approaches. We utilize T1-weighted data with prominent blood-flow artifacts from the Autism Brain Imaging Data Exchange (ABIDE) multisite agglomerative dataset to assess the impact that such blood-flow artifacts have on registration of T1-weighted data to a template. We use a heuristic approach to identify the blood-flow artifacts in these data; we use the resulting blood masks to turn the underlying voxels to the intensity of the cerebro-spinal fluid, thus mimicking the effect of blood suppression. We then register both the original data and the deblooded data to a common T1-weighted template, and compare the quality of those registrations to the template in terms of similarity to the template. The registrations to the template based on the deblooded data yield significantly higher similarity values compared with those based on the original data. Additionally, we measure the nonlinear deformations needed to transform the data from the position achieved by registering the original data to the template to the position achieved by registering the deblooded data to the template. The results indicate that blood-flow artifacts may seriously impact data processing that depends on registration to a template, that is, most all data processing.

A dataset of multi-contrast unbiased average MRI templates of a Parkinson's disease population.

Parkinson's disease (PD) is a complex neurodegenerative disorder affecting regions such as the substantia nigra (SN), red nucleus (RN) and locus coeruleus (LC). Processing MRI data from patients with PD requires anatomical structural references for spatial normalization and structural segmentation. Extending our previous work, we present multi-contrast unbiased MRI templates using nine 3T MRI modalities: T1w, T2*w, T1-T2* fusion, R2*, T2w, PDw, fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging, and neuromelanin-sensitive MRI (NM). One mm isotropic voxel size templates were created, along with 0.5 mm isotropic whole brain templates and 0.3 mm isotropic templates of the midbrain. All templates were created from 126 PD patients (44 female; ages=40-87), and 17 healthy controls (13 female; ages=39-84), except the NM template, which was created from 85 PD patients and 13 controls, respectively. The dataset is available on the NIST MNI Repository via the following link: http://nist.mni.mcgill.ca/multi-contrast-pd126-and-ctrl17-templates/. The data is also available on NITRC at the following link: https://www.nitrc.org/projects/pd126/.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system.

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

Dynamic Amyloid and Metabolic Signatures of Delayed Recall Performance within the Clinical Spectrum of Alzheimer's Disease.

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer's disease (AD). In this study, we assessed patients' scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer's Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [18F]florbetapir and [18F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [18F]FDG uptake, and RAVLT30 scores positively associated with [18F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake in the right frontal lobe. For the AD group, [18F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [18F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Increased brain volumetric measurement precision from multi-site 3D T1-weighted 3 T magnetic resonance imaging by correcting geometric distortions.

PURPOSE: Magnetic resonance imaging (MRI) scanner-specific geometric distortions may contribute to scanner induced variability and decrease volumetric measurement precision for multi-site studies. The purpose of this study was to determine whether geometric distortion correction increases the precision of brain volumetric measurements in a multi-site multi-scanner study. METHODS: Geometric distortion variation was quantified over a one-year period at 10 sites using the distortion fields estimated from monthly 3D T1-weighted MRI geometrical phantom scans. The variability of volume and distance measurements were quantified using synthetic volumes and a standard quantitative MRI (qMRI) phantom. The effects of geometric distortion corrections on MRI derived volumetric measurements of the human brain were assessed in two subjects scanned on each of the 10 MRI scanners and in 150 subjects with cerebrovascaular disease (CVD) acquired across imaging sites. RESULTS: Geometric distortions were found to vary substantially between different MRI scanners but were relatively stable on each scanner over a one-year interval. Geometric distortions varied spatially, increasing in severity with distance from the magnet isocenter. In measurements made with the qMRI phantom, the geometric distortion correction decreased the standard deviation of volumetric assessments by 35% and distance measurements by 42%. The average coefficient of variance decreased by 16% in gray matter and white matter volume estimates in the two subjects scanned on the 10 MRI scanners. CONCLUSION: Geometric distortion correction using an up-to-date correction field is recommended to increase precision in volumetric measurements made from MRI images.

DARQ: Deep learning of quality control for stereotaxic registration of human brain MRI to the T1w MNI-ICBM 152 template.

Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the subsequent image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none have a 100% success rate. Manual assessment of the registration is commonly used as part of quality control. To reduce the burden of this time-consuming step, we propose Deep Automated Registration Qc (DARQ), a fully automatic quality control method based on deep learning that can replace the human rater and accurately perform quality control assessment for stereotaxic registration of T1w brain scans. In a recently published study from our group comparing linear registration methods, we used a database of 9325 MRI scans and 64476 registrations from several publicly available datasets and applied seven linear registration tools to them. In this study, the resulting images that were assessed and labeled by a human rater are used to train a deep neural network to detect cases when registration failed. We further validated the results on an independent dataset of patients with multiple sclerosis, with manual QC labels available (n=1200). In terms of agreement with a manual rater, our automated QC method was able to achieve 89% accuracy and 85% true negative rate (equivalently 15% false positive rate) in detecting scans that should pass quality control in a balanced cross-validation experiments, and 96.1% accuracy and 95.5% true negative rate (or 4.5% FPR) when evaluated in a balanced independent sample, similar to manual QC rater (test-retest accuracy of 93%). The results show that DARQ is robust, fast, accurate, and generalizable in detecting failure in linear stereotaxic registrations and can substantially reduce QC time (by a factor of 20 or more) when processing large datasets.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study.

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

Subcortical Brain Development in Autism and Fragile X Syndrome: Evidence for Dynamic, Age- and Disorder-Specific Trajectories in Infancy.

OBJECTIVE: Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown. METHODS: Longitudinal MRIs were acquired at 6-24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans). RESULTS: Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen's d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors. CONCLUSIONS: This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome-related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.

Regional Cerebellar Volume Loss Predicts Future Disability in Multiple Sclerosis Patients.

Cerebellar symptoms in multiple sclerosis (MS) are well described; however, the exact contribution of cerebellar damage to MS disability has not been fully explored. Longer-term observational periods are necessary to better understand the dynamics of pathological changes within the cerebellum and their clinical consequences. Cerebellar lobe and single lobule volumes were automatically segmented on 664 3D-T1-weighted MPRAGE scans (acquired at a single 1.5 T scanner) of 163 MS patients (111 women; mean age: 47.1 years; 125 relapsing-remitting (RR) and 38 secondary progressive (SP) MS, median EDSS: 3.0) imaged annually over 4 years. Clinical scores (EDSS, 9HPT, 25FWT, PASAT, SDMT) were determined per patient per year with a maximum clinical follow-up of 11 years. Linear mixed-effect models were applied to assess the association between cerebellar volumes and clinical scores and whether cerebellar atrophy measures may predict future disability progression. SPMS patients exhibited faster posterior superior lobe volume loss over time compared to RRMS, which was related to increase of EDSS over time. In RRMS, cerebellar volumes were significant predictors of motor scores (e.g. average EDSS, T25FWT and 9HPT) and SDMT. Atrophy of motor-associated lobules (IV-VI + VIII) was a significant predictor of future deterioration of the 9HPT of the non-dominant hand. In SPMS, the atrophy rate of the posterior superior lobe (VI + Crus I) was a significant predictor of future PASAT performance deterioration. Regional cerebellar volume reduction is associated with motor and cognitive disability in MS and may serve as a predictor for future disease progression, especially of dexterity and impaired processing speed.

A sub+cortical fMRI-based surface parcellation.

Both cortical and subcortical structures are organized into a large number of distinct areas reflecting functional and cytoarchitectonic differences. Mapping these areas is of fundamental importance to neuroscience. A central obstacle to this task is the inaccuracy associated with bringing results from individuals into a common space. The vast individual differences in morphology pose a serious problem for volumetric registration. Surface-based approaches fare substantially better, but have thus far been used only for cortical parcellation, leaving subcortical parcellation in volumetric space. We extend the surface-based approach to include also the subcortical deep gray-matter structures, thus achieving a uniform representation across both cortex and subcortex, suitable for use with surface-based metrics that span these structures, for example, white/gray contrast. Using data from the Enhanced Nathan Klein Institute-Rockland Sample, limited to individuals between 19 and 69 years of age, we generate a functional parcellation of both the cortical and subcortical surfaces. To assess this extended parcellation, we show that (a) our parcellation provides greater homogeneity of functional connectivity patterns than do arbitrary parcellations matching in the number and size of parcels; (b) our parcels align with known cortical and subcortical architecture; and (c) our extended functional parcellation provides an improved fit to the complexity of life-span (6-85 years) changes in white/gray contrast data compared to arbitrary parcellations matching in the number and size of parcels, supporting its use with surface-based measures. We provide our extended functional parcellation for the use of the neuroimaging community.

MNI-FTD templates, unbiased average templates of frontotemporal dementia variants.

Standard templates are widely used in human neuroimaging processing pipelines to facilitate group-level analyses and comparisons across subjects/populations. MNI-ICBM152 template is the most commonly used standard template, representing an average of 152 healthy young adult brains. However, in patients with neurodegenerative diseases such as frontotemporal dementia (FTD), high atrophy levels lead to significant differences between individuals' brain shapes and MNI-ICBM152 template. Such differences might inevitably lead to registration errors or subtle biases in downstream analyses and results. Disease-specific templates are therefore desirable to reflect the anatomical characteristics of the populations of interest and reduce potential registration errors. Here, we present MNI-FTD136, MNI-bvFTD70, MNI-svFTD36, and MNI-pnfaFTD30, four unbiased average templates of 136 FTD patients, 70 behavioural variant (bv), 36 semantic variant (sv), and 30 progressive nonfluent aphasia (pnfa) variant FTD patients and a corresponding age-matched template of 133 controls (MNI-CN133), along with probabilistic tissue maps for each template. Public availability of these templates will facilitate analyses of FTD cohorts and enable comparisons between different studies in an appropriate common standardized space.

MRI of Capn15 Knockout Mice and Analysis of Capn 15 Distribution Reveal Possible Roles in Brain Development and Plasticity.

The Small Optic Lobe (SOL) family of calpains are intracellular cysteine proteases that are expressed in the nervous system and play an important role in neuronal development in both Drosophila, where loss of this calpain leads to the eponymous small optic lobes, and in mouse and human, where loss of this calpain leads to eye anomalies. Some human individuals with biallelic variants in CAPN15 also have developmental delay and autism. However, neither the specific effect of the loss of the Capn15 protein on brain development nor the brain regions where this calpain is expressed in the adult is known. Here we show using small animal MRI that mice with the complete loss of Capn15 have smaller brains overall with larger decreases in the thalamus and subregions of the hippocampus. These losses are not seen in Capn15 conditional knockout (KO) mice where Capn15 is knocked out only in excitatory neurons in the adult. Based on ß-galactosidase expression in an insert strain where lacZ is expressed under the control of the Capn15 promoter, we show that Capn15 is expressed in adult mice, particularly in neurons involved in plasticity such as the hippocampus, lateral amygdala and Purkinje neurons, and partially in other non-characterized cell types. The regions of the brain in the adult where Capn15 is expressed do not correspond well to the regions of the brain most affected by the complete knockout suggesting distinct roles of Capn15 in brain development and adult brain function.

Neonatal amygdala volumes and the development of self-regulation from early infancy to toddlerhood.

Objective: At the broadest level, self-regulation (SR) refers to a range of separate, but interrelated, processes (e.g., working memory, inhibition, and emotion regulation) central for the regulation of cognition, emotion, and behavior that contribute to a plethora of health and mental health outcomes. SR skills develop rapidly in early childhood, but their neurobiological underpinnings are not yet well understood. The amygdala is one key structure in negative emotion generation that may disrupt SR. In the current study, we investigated the associations between neonatal amygdala volumes and mother-reported and observed child SR during the first 3 years of life. We expected that larger neonatal amygdala volumes would be related to poorer SR in children. Method: We measured amygdala volumes from magnetic resonance imaging (MRI) performed at age M = 3.7 ± 1.0. We examined the associations between the amygdala volumes corrected for intracranial volume (ICV) and (a) parent-reported indicators of SR at 6, 12, and 24 months (N = 102) and (b) observed task-based indicators of SR (working memory and inhibitory control) at 30 months of age in a smaller subset of participants (N = 80). Results: Bilateral neonatal amygdala volumes predicted poorer working memory at 30 months in girls, whereas no association was detected between amygdalae and inhibitory control or parent-reported SR. The left amygdala by sex interaction survived correction for multiple comparisons. Conclusions: Neonatal amygdala volume is associated with working memory, particularly among girls, and the association is observed earlier than in prior studies. Moreover, our findings suggest that the neural correlates for parent-reported, compared to observed early life SR, may differ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder.

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.

Creating a Comprehensive Research Platform for Surgical Technique and Operative Outcome in Primary Brain Tumor Neurosurgery.

BACKGROUND: The operative environment poses many challenges to studying the relationship between surgical acts and patient outcomes in intracranial oncological neurosurgery. We sought to develop a framework in which neurosurgical performance and extent of resection could be precisely quantified in a controlled setting. METHODS: The stiffness of an alginate hydrogel-based tumor was modified with differing concentrations of the cross-linking agent calcium sulfate until biomechanical properties similar to those of human primary brain tumors measured at resection were achieved. The artificial tumor was subsequently incorporated into an ex-vivo animal brain as a final model. Magnetic resonance imaging enhancement and ultraviolet fluorescence was achieved by incorporating gadolinium and fluorescein solution, respectively. Video recordings from the operative microscope, ceiling cameras, and instrument-mounted fiducial markers within a surgical suite environment captured operative performance. RESULTS: A total of 24 rheometer measurements were conducted on alginate hydrogels containing 10-, 11-, and 12-mM concentrations of calcium sulfate. Sixty-eight stiffness measurements were conducted on eight patient tumor samples. No differences were found between the alginate and brain tumor stiffness values [Kruskal-Wallis χ2(4) = 9.187; P = 0.057]. Tumor was identified using ultraviolet fluorescence and ultrasonography. The volume and location of the resected white and gray matter and residual tumor could be quantified in 0.003-mm3 increments using a 7T magnetic resonance imaging coil. Ultrasonic aspirator and bipolar electrocautery movement data were successfully transformed into performance metrics. CONCLUSION: The developed framework can offer clinicians, learners, and researchers the ability to perform operative rehearsal, teaching, and studies involving brain tumor surgery in a controlled laboratory environment and represents a crucial step in the understanding and training of expertise in neurosurgery.