This study aims to investigate the early change in cortical thickness and surface area in early-stage depressed PD (dPD) patients, and its associations with severity of depression.

59 patients with dPD, 27 patients with non-depressed PD (ndPD), and 43 healthy controls (HC) were recruited. The dPD patients were subclassified into mild-depressed PD (mi-dPD, n = 24), moderate-depressed PD (mo-dPD, n = 21) and severe-depressed PD (se-dPD, n = 14) subgroups. Structural MRI and surface-based morphometry analysis were applied to compare differences in cortical thickness and surface area among groups, and their correlations with Beck Depression Inventory (BDI) scores were analyzed.

Compared with ndPD, dPD exhibited cortical thinning in the dorsolateral prefrontal cortex (dlPFC, mainly involving the left superior frontal and bilateral middle frontal gyri), the right pars opercularis and bilateral lateral occipital gyri. The mean cortical thickness values within these regions negatively correlated with BDI scores. Subgroup analysis revealed that patients with mi-dPD had cortical thinning only in the right middle frontal gyrus, while se-dPD showed cortical thinning more extensively involving the right fusiform gyrus, posterior cingulate gyrus, and pars opercularis. There was no significant change in cortical surface area in either the dPD or its subgroups.

Our findings indicated that PD-related depression was associated with decrease of cortical thickness, instead of surface area, of which the patterns correlated with the severity of depression. Cortical thinning in dlPFC, mainly involving the left middle frontal gyrus, may serve as a potential neuroimaging indicator for early recognition of depression in PD patients.

Surface-based analysis of the cerebral cortex is ubiquitous in human neuroimaging with MRI. It is crucial for tasks like cortical registration, parcellation, and thickness estimation. Traditionally, such analyses require high-resolution, isotropic scans with good gray-white matter contrast, typically a T1-weighted scan with 1 mm resolution. This requirement precludes application of these techniques to most MRI scans acquired for clinical purposes, since they are often anisotropic and lack the required T1-weighted contrast. To overcome this limitation and enable large-scale neuroimaging studies using vast amounts of existing clinical data, we introduce recon-all-clinical, a novel methodology for cortical reconstruction, registration, parcellation, and thickness estimation for clinical brain MRI scans of any resolution and contrast. Our approach employs a hybrid analysis method that combines a convolutional neural network (CNN) trained with domain randomization to predict signed distance functions (SDFs), and classical geometry processing for accurate surface placement while maintaining topological and geometric constraints. The method does not require retraining for different acquisitions, thus simplifying the analysis of heterogeneous clinical datasets. We evaluated recon-all-clinical on multiple public datasets like ADNI, HCP, AIBL, OASIS and including a large clinical dataset of over 9,500 scans. The results indicate that our method produces geometrically precise cortical reconstructions across different MRI contrasts and resolutions, consistently achieving high accuracy in parcellation. Cortical thickness estimates are precise enough to capture aging effects, independently of MRI contrast, even though accuracy varies with slice thickness. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/recon-all-clinical, enabling researchers to perform detailed cortical analysis on the huge amounts of already existing clinical MRI scans. This advancement may be particularly valuable for studying rare diseases and underrepresented populations where research-grade MRI data is scarce.

To understand the role of neuroinflammation in Alzheimer's disease (AD), we characterized immune-related proteins in central and peripheral biofluids.

Selection of participants from the Translational Biomarker of Aging and Dementia (TRIAD) cohort with available translocator protein (TSPO) positron emission tomography (PET), cerebrospinal fluid (CSF) (n = 97), and plasma (n = 165). Biofluid samples analyzed with Olink technology (368 inflammation proteins).

Elevated proteins levels in CSF of TSPO-positive individuals were identified. Functional enrichment analysis of CSF proteins revealed processes implicated in AD (MAPK, ERK cascades, cytokine, and leukocyte signaling). Selected candidates (CXCL1 and TNFRSF11B) showed high correlation with each other in CSF and with TSPO PET signal, but weaker associations with amyloid and tau PET. No significantly changed proteins in plasma between TSPO groups were found.

This explorative study identified two potential targets in CSF showing correlations with TSPO, amyloid and tau PET, suggesting a direct link between neuroinflammation, expression of these proteins and their potential implication in AD.

Several proteins are elevated in CSF of TSPO PET-positive individuals, linking them to neuroinflammation. Elevated CSF proteins were enriched in pathways such as MAPK, ERK, and cytokine signaling, linking them to the AD pathophysiology. Candidate proteins (CXCL1 and TNFRSF11B) correlated strongly with TSPO PET, particularly in brain regions known to be affected in AD. Although none of the plasma proteins remained significant after multiple comparisons correction when comparing their expression between TSPO groups, as done for CSF, candidate CSF proteins were found to correlate with plasmatic proteins, highlighting the complexity of the immune system.

The Developing Human Connectome Project (dHCP) aims to explore developmental patterns of the human brain during the perinatal period. An automated processing pipeline has been developed to extract high-quality cortical surfaces from structural brain magnetic resonance (MR) images for the dHCP neonatal dataset. However, the current implementation of the pipeline requires more than 6.5 h to process a single MRI scan, making it expensive for large-scale neuroimaging studies. In this paper, we propose a fast deep learning (DL) based pipeline for dHCP neonatal cortical surface reconstruction, incorporating DL-based brain extraction, cortical surface reconstruction and spherical projection, as well as GPU-accelerated cortical surface inflation and cortical feature estimation. We introduce a multiscale deformation network to learn diffeomorphic cortical surface reconstruction end-to-end from T2-weighted brain MRI. A fast unsupervised spherical mapping approach is integrated to minimize metric distortions between cortical surfaces and projected spheres. The entire workflow of our DL-based dHCP pipeline completes within only 24 s on a modern GPU, which is nearly 1000 times faster than the original dHCP pipeline. The qualitative assessment demonstrates that for 82.5% of the test samples, the cortical surfaces reconstructed by our DL-based pipeline achieve superior (54.2%) or equal (28.3%) surface quality compared to the original dHCP pipeline.

Stroke leads to complex chronic structural and functional brain changes that specifically affect motor outcomes. The brain-predicted age difference (brain-PAD) has emerged as a sensitive biomarker. Our previous study showed higher global brain-PAD associated with poorer motor function post-stroke. However, the relationship between local stroke lesion load, regional brain age, and motor impairment remains unclear.

We studied 501 individuals with chronic unilateral stroke (>180 days post-stroke) from the ENIGMA Stroke Recovery Working Group dataset (34 cohorts). Structural T1-weighted MRI scans were used to estimate regional brain-PAD in 18 predefined functional subregions via a graph convolutional network algorithm. Lesion load for each region was calculated based on lesion overlap. Linear mixed-effects models assessed associations between lesion size, local lesion load, and regional brain-PAD. Machine learning classifiers predicted motor outcomes using lesion loads and regional brain-PADs. Structural equation modeling examined directional relationships among corticospinal tract lesion load (CST-LL), ipsilesional brain-PAD, motor outcomes, and contralesional brain-PAD.

Larger total lesion size was positively associated with higher ipsilesional regional brain-PADs (older brain age) across most regions (p < 0.05), and with lower contralesional brain-PAD, notably in the ventral attention-language network (p < 0.05). Higher local lesion loads showed similar patterns. Specifically, lesion load in the salience network significantly influenced regional brain-PADs across both hemispheres. Machine learning models identified CST-LL, salience network lesion load, and regional brain-PAD in the contralesional frontoparietal network as the top three predictors of motor outcomes. Structural equation modeling revealed that larger stroke damage was associated with poorer motor outcomes (β = -0.355, p < 0.001), which were further linked to younger contralesional brain age (β = 0.204, p < 0.001), suggesting that severe motor impairment is linked to compensatory decreases in contralesional brain age.

Our findings reveal that larger stroke lesions are associated with accelerated aging in the ipsilesional hemisphere and paradoxically decelerated brain aging in the contralesional hemisphere, suggesting compensatory neural mechanisms. Assessing regional brain age may serve as a biomarker for neuroplasticity and inform targeted interventions to enhance motor recovery after stroke.

Micheal J Fox Foundation, National Institutes of Health, Canadian Institutes of Health Research, National Health and Medical Research Council, Australian Brain Foundation, Wicking Trust, Collie Trust, and Sidney and Fiona Myer Family Foundation, National Heart Foundation, Hospital Israelita Albert Einstein, Australian Research Council Future Fellowship, Wellcome Trust, National Institute for Health Research Imperial Biomedical Research Centre, European Research Council, Deutsche Forschungsgemeinschaft, REACT Pilot, National Resource Center, Research Council of Norway, South-Eastern Norway Regional Health Authority, Norwegian Extra Foundation for Health and Rehabilitation, Sunnaas Rehabilitation Hospital HT, University of Oslo, and VA Rehabilitation Research and Development.

Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value <0.0001) increases in network strength as measured by average clustering coefficient and assortativity. We then identify genes from the Allen Human Brain Atlas with similar co-expression patterns to genetically-mediated structural covariation in children. This set was enriched for genes involved in potassium transport and dendrite formation. Genetically-mediated CT-CT covariance was also strongly correlated with expression patterns for genes located in cells of neuronal origin.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction.

We recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aβ negative (-) and Aβ positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs.

We identified SNPs related to cortical thickness using SCCA in Aβ negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aβ uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes.

Our findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.

With brain structure and function undergoing complex changes throughout childhood and adolescence, age is a critical consideration in neuroimaging studies, particularly for those of individuals with neurodevelopmental conditions. However, despite the increasing use of large, consortium-based datasets to examine brain structure and function in neurotypical and neurodivergent populations, it is unclear whether age-related changes are consistent between datasets and whether inconsistencies related to differences in sample characteristics, such as demographics and phenotypic features, exist. To address this, we built models of age-related changes of brain structure (regional cortical thickness and regional surface area; N = 1218) and function (resting-state functional connectivity strength; N = 1254) in two neurodiverse datasets: the Province of Ontario Neurodevelopmental Network and the Healthy Brain Network. We examined whether deviations from these models differed between the datasets, and explored whether these deviations were associated with demographic and clinical variables. We found significant differences between the two datasets for measures of cortical surface area and functional connectivity strength throughout the brain. For regional measures of cortical surface area, the patterns of differences were associated with race/ethnicity, while for functional connectivity strength, positive associations were observed with head motion. Our findings highlight that patterns of age-related changes in the brain may be influenced by demographic and phenotypic characteristics, and thus future studies should consider these when examining or controlling for age effects in analyses.

Cognitive functioning is increasingly considered when making treatment decisions for patients with a brain tumor in view of a personalized onco-functional balance. Ideally, one can predict cognitive functioning of individual patients to make treatment decisions considering this balance. To make accurate predictions, an informative representation of tumor location is pivotal, yet comparisons of representations are lacking. Therefore, this study compares brain atlases and principal component analysis (PCA) to represent voxel-wise tumor location. Pre-operative cognitive functioning was predicted for 246 patients with a high-grade glioma across eight cognitive tests while using different representations of voxel-wise tumor location as predictors. Voxel-wise tumor location was represented using 13 different frequently-used population average atlases, 13 randomly generated atlases, and 13 representations based on PCA. ElasticNet predictions were compared between representations and against a model solely using tumor volume. Preoperative cognitive functioning could only partly be predicted from tumor location. Performances of different representations were largely similar. Population average atlases did not result in better predictions compared to random atlases. PCA-based representation did not clearly outperform other representations, although summary metrics indicated that PCA-based representations performed somewhat better in our sample. Representations with more regions or components resulted in less accurate predictions. Population average atlases possibly cannot distinguish between functionally distinct areas when applied to patients with a glioma. This stresses the need to develop and validate methods for individual parcellations in the presence of lesions. Future studies may test if the observed small advantage of PCA-based representations generalizes to other data.

Although functional changes of the frontal and (para)limbic area for emotional hyper-reactivity and emotional dysregulation are well documented in social anxiety disorder (SAD), prior studies on structural changes have shown mixed results. This study aimed to identify differences in cortical thickness between SAD and healthy controls (CON). Thirty-five patients with SAD and forty-two matched CON underwent structural magnetic resonance imaging. A vertex-based whole brain and regional analyses were conducted for between-group comparison. The whole-brain analysis revealed increased cortical thickness in the left insula, left superior parietal lobule, left superior temporal gyrus, and left frontopolar cortex in patients with SAD compared to CON, as well as decreased thickness in the left superior/middle frontal gyrus and left fusiform gyrus in patients (after multiple-correction). The results from the ROI analysis did not align with these findings at the statistically significant level after multiple corrections. Changes in cortical thickness were not correlated with social anxiety symptoms. While consistent results were not obtained from different analysis methods, the results from the whole-brain analysis suggest that patients with SAD exhibit distinct neural deficits in areas involved in salience, attention, and socioemotional processing.

To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms.

In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time.

None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified.

Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

Peri-lead edema (PLE) is a poorly understood complication of deep brain stimulation (DBS), which has been described in patients presenting occasionally with profound and often delayed symptoms with an incidence ranging from 0.4% up to even 100%. Therefore, our study aims to investigate the association of brain and brain compartment volumes on magnetic resonance imaging (MRI) with the occurrence of PLE in Parkinson's disease (PD) patients after DBS implantation in subthalamic nuclei (STN).

This retrospective study included 125 consecutive PD patients who underwent STN DBS at the Department of Neurosurgery, Dubrava University Hospital from 2010 to 2022. Qualitative analysis was done on postoperative MRI T2-weighted sequence by two independent observers, marking PLE on midbrain, thalamus, and subcortical levels as mild, moderate, or severe. Quantitative volumetric analysis of brain and brain compartment volumes was conducted using an automated CIVET processing pipeline on preoperative MRI T1 MPRAGE sequences. In addition, observed PLE on individual hemispheres was delineated manually and measured using Analyze 14.0 software.

In our cohort, PLE was observed in 32.17%, mostly bilaterally. Mild PLE was observed in the majority of patients, regardless of the level observed. Age, sex, diabetes, hypertension, vascular disease, and the use of anticoagulant/antiplatelet therapy showed no significant association with the occurrence of PLE. Total grey matter volume showed a significant association with the PLE occurrence (r = -0.22, p = 0.04), as well as cortex volume (r = -0.32, p = 0.0005). Cortical volumes of hemispheres, overall hemisphere volumes, as well as hemisphere/total intracranial volume ratio showed significant association with the PLE occurrence. Furthermore, the volume of the cortex and total grey volume represent moderate indicators, while hemisphere volumes, cortical volumes of hemispheres, and hemisphere/total intracranial volume ratio represent mild to moderate indicators of possible PLE occurrence.

The results of our study suggest that the morphometric MRI measurements, as a useful tool, can provide relevant information about the structural status of the brain in patients with PD and represent moderate indicators of possible PLE occurrence. Identifying patients with greater brain atrophy, especially regarding grey matter before DBS implantation, will allow us to estimate the possible postoperative symptoms and intervene in a timely manner. Further studies are needed to confirm our findings and to investigate other potential predictors and risk factors of PLE occurrence.

The laminar microstructure of the cerebral cortex has distinct anatomical characteristics of the development, function, connectivity, and even various pathologies of the brain. In recent years, multiple neuroimaging studies have utilized magnetic resonance imaging (MRI) relaxometry to visualize and explore this intricate microstructure, successfully delineating the cortical laminar components. Despite this progress, T1 is still primarily considered a direct measure of myeloarchitecture (myelin content), rather than a probe of tissue cytoarchitecture (cellular composition). This study aims to offer a robust, whole-brain validation of T1 imaging as a practical and effective tool for exploring the laminar composition of the cortex. To do so, we cluster complex microstructural cortical datasets of both human (N = 30) and macaque (N = 1) brains using an adaptation of an algorithm for clustering cell omics profiles. The resulting cluster patterns are then compared to established atlases of cytoarchitectonic features, exhibiting significant correspondence in both species. Lastly, we demonstrate the expanded applicability of T1 imaging by exploring some of the cytoarchitectonic features behind various unique skillsets, such as musicality and athleticism.

Multiple Sclerosis (MS) is an autoimmune disease that combines chronic inflammatory and neurodegenerative processes underlying different clinical forms of evolution, such as relapsing-remitting, secondary progressive, or primary progressive MS. This identification is usually performed by clinical evaluation at the diagnosis or during the course of the disease for the secondary progressive phase. In parallel, magnetic resonance imaging (MRI) analysis is a mandatory diagnostic complement. Identifying the clinical form from MR images is therefore a helpful and challenging task. Here, we propose a new approach for the automatic classification of MS forms based on conventional MRI (i.e., T1-weighted images) that are commonly used in clinical context. For this purpose, we investigated the morphological connectome features using graph based convolutional neural network. Our results obtained from the longitudinal study of 91 MS patients highlight the performance (F1-score) of this approach that is better than state-of-the-art as 3D convolutional neural networks. These results open the way for clinical applications such as disability correlation only using T1-weighted images.

The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve homologous points between two hippocampi with grossly different morphologies. Here, we present a surface-based registration method that solves this issue in a contrast-agnostic, topology-preserving manner. Specifically, the entire hippocampus is first analytically unfolded, and then samples are registered in 2D unfolded space based on thickness, curvature, and gyrification. We demonstrate this method in seven 3D histology samples and show superior alignment with respect to subfields using this method over more conventional registration approaches.

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.

Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated.

In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated.

Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes.

These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

Autism has been associated with differences in the developmental trajectories of multiple neuroanatomical features, including cortical thickness, surface area, cortical volume, measures of gyrification, and the gray-white matter tissue contrast. These neuroimaging features have been proposed as intermediate phenotypes on the gradient from genomic variation to behavioral symptoms. Hence, examining what these proxy markers represent, i.e., disentangling their associated molecular and genomic underpinnings, could provide crucial insights into the etiology and pathophysiology of autism. In line with this, an increasing number of studies are exploring the association between neuroanatomical, cellular/molecular, and (epi)genetic variation in autism, both indirectly and directly in vivo and across age. In this review, we aim to summarize the existing literature in autism (and neurotypicals) to chart a putative pathway from (i) imaging-derived neuroanatomical cortical phenotypes to (ii) underlying (neuropathological) biological processes, and (iii) associated genomic variation.

Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.

Brain maturation studies typically examine relationships linking a single morphometric feature with cognition, behavior, age, or other demographic characteristics. However, the coordinated spatiotemporal arrangement of morphological features across development and their associations with behavior are unclear. Here, we examine covariation across multiple cortical features (cortical thickness [CT], surface area [SA], local gyrification index [GI], and mean curvature [MC]) using magnetic resonance images from the NIMH developmental cohort (ages 5-25). Neuroanatomical covariance was examined using non-negative matrix factorization (NMF), which decomposes covariance resulting in a parts-based representation. Cross-sectionally, we identified six components of covariation which demonstrate differential contributions of CT, GI, and SA in hetero- vs. unimodal areas. Using this technique to examine covariance in rates of change to identify longitudinal sources of covariance highlighted preserved SA in unimodal areas and changes in CT and GI in heteromodal areas. Using behavioral partial least squares (PLS), we identified a single latent variable (LV) that recapitulated patterns of reduced CT, GI, and SA related to older age, with limited contributions of IQ and SES. Longitudinally, PLS revealed three LVs that demonstrated a nuanced developmental pattern that highlighted a higher rate of maturational change in SA and CT in higher IQ and SES females. Finally, we situated the components in the changing architecture of cortical gradients. This novel characterization of brain maturation provides an important understanding of the interdependencies between morphological measures, their coordinated development, and their relationship to biological sex, cognitive ability, and the resources of the local environment.

Alzheimer's disease (AD) is an irreversible neurodegenerative brain disorder that degrades the memory and cognitive ability in elderly people. The main reason for memory loss and reduction in cognitive ability is the structural changes in the brain that occur due to neuronal loss. These structural changes are most conspicuous in the hippocampus, cortex, and grey matter and can be assessed by using neuroimaging techniques viz. Positron Emission Tomography (PET), structural Magnetic Resonance Imaging (MRI) and functional MRI (fMRI), etc. Out of these neuroimaging techniques, structural MRI has evolved as the best technique as it indicates the best soft tissue contrast and high spatial resolution which is important for AD detection. Currently, the focus of researchers is on predicting the conversion of Mild Cognitive Impairment (MCI) into AD. MCI represents the transition state between expected cognitive changes with normal aging and Alzheimer's disease. Not every MCI patient progresses into Alzheimer's disease. MCI can develop into stable MCI (sMCI, patients are called non-converters) or into progressive MCI (pMCI, patients are diagnosed as MCI converters). This paper discusses the prognosis of MCI to AD conversion and presents a review of structural MRI-based studies for AD detection. AD detection framework includes feature extraction, feature selection, and classification process. This paper reviews the studies for AD detection based on different feature extraction methods and machine learning algorithms for classification. The performance of various feature extraction methods has been compared and it has been observed that the wavelet transform-based feature extraction method would give promising results for AD classification. The present study indicates that researchers are successful in classifying AD from Normal Controls (N_rmC) but, it still requires a lot of work to be done for MCI/ N_rmC and MCI/AD, which would help in detecting AD at its early stage.

Multimodal imaging studies targeting preschoolers and low-functioning autism spectrum disorder (ASD) patients are scarce. We applied machine learning classifiers to parameters from T1-weighted MRI and DTI data of 58 children with ASD (age 3-6 years) and 48 typically developing controls (TDC). Classification performance reached an accuracy, sensitivity, and specificity of 88.8%, 93.0%, and 83.8%, respectively. The most prominent features were the cortical thickness of the right inferior occipital gyrus, mean diffusivity of the middle cerebellar peduncle, and nodal efficiency of the left posterior cingulate gyrus. Machine learning-based analysis of MRI data was useful in distinguishing low-functioning ASD preschoolers from TDCs. Combination of T1 and DTI improved classification accuracy about 10%, and large-scale multi-modal MRI studies are warranted for external validation.

This study aimed to investigate the effects of phenylalanine on the growth, digestive capacity, antioxidant capability, and intestinal health of triploid rainbow trout (Oncorhynchus mykiss) fed a low fish meal diet (15%). Five isonitrogenous and isoenergetic diets with different dietary phenylalanine levels (1.82, 2.03, 2.29, 2.64, and 3.01%) were fed to triplicate groups of 20 fish (initial mean body weight of 36.76 ± 3.13 g). The weight gain rate and specific growth rate were significantly lower (p < 0.05) in the 3.01% group. The trypsin activity in the 2.03% group was significantly higher than that in the control group (p < 0.05). Amylase activity peaked in the 2.64% treatment group. Serum superoxide dismutase, catalase, and lysozyme had the highest values in the 2.03% treatment group. Liver superoxide dismutase and catalase reached their maximum values in the 2.03% treatment group, and lysozyme had the highest value in the 2.29% treatment group. Malondialdehyde levels in both the liver and serum were at their lowest in the 2.29% treatment group. Interleukin factors IL-1β and IL-6 both reached a minimum in the 2.03% group and were significantly lower than in the control group, while IL-10 reached a maximum in the 2.03% group (p < 0.05). The tight junction protein-related genes occludin, claudin-1, and ZO-1 all attained their highest levels in the 2.03% treatment group and were significantly higher compared to the control group (p < 0.05). The intestinal villi length and muscle layer thickness were also improved in the 2.03% group (p < 0.05). In conclusion, dietary phenylalanine effectively improved the growth, digestion, absorption capacity, antioxidant capacity, and intestinal health of O. mykiss. Using a quadratic curve model analysis based on WGR, the dietary phenylalanine requirement of triploid O. mykiss fed a low fish meal diet (15%) was 2.13%.

Medical images are providing vital information to aid physicians in diagnosing a disease afflicting the organ of a human body. Magnetic resonance imaging is an important imaging modality in capturing the soft tissues of the brain. Segmenting and extracting the brain is essential in studying the structure and pathological condition of brain. There are several methods that are developed for this purpose. Researchers in brain extraction or segmentation need to know the current status of the work that have been done. Such an information is also important for improving the existing method to get more accurate results or to reduce the complexity of the algorithm. In this paper we review the classical methods and convolutional neural network-based deep learning brain extraction methods.

The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically.

High-resolution 3T magnetic resonance imaging was acquired in 79 individuals with 22q11DS and 70 typically developing control subjects (N = 149). Lobar and lobule-level cerebellar volumes were estimated using validated automated segmentation algorithms, and subsequently group differences were compared. Hierarchical clustering, principal component analysis, and graph theoretical models were used to explore intercerebellar relationships. Cerebrocerebellar structural connectivity with cortical thickness was examined via linear regression models.

Individuals with 22q11DS had, on average, 17.3% smaller total cerebellar volumes relative to typically developing subjects (p < .0001). The lobules of the superior posterior cerebellum (e.g., VII and VIII) were particularly affected in 22q11DS. However, all cerebellar lobules were significantly smaller, even after adjusting for total brain volumes (all cerebellar lobules p < .0002). The superior posterior lobule was disproportionately associated with cortical thickness in the frontal lobes and cingulate cortex, brain regions known be affected in 22q11DS. Exploratory analyses suggested that the superior posterior lobule, particularly Crus I, may be associated with psychotic symptoms in 22q11DS.

The cerebellum is a critical but understudied component of the 22q11DS neuroendophenotype.

Sleep architecture and microstructures alter with aging and sleep disorder-led accelerated aging. We proposed a sleep EEG based brain age prediction model using convolutional neural networks. We then associated the estimated brain age index with brain structural aging features, sleep disorders and various sleep parameters. Our model also showed a higher BAI (predicted brain age minus chronological age) is associated with cortical thinning in various functional areas. We found a higher BAI for sleep disorder groups compared to healthy sleepers, as well as significant differences in the spectral pattern of EEG among different sleep disorders (lower power in slow and ϑ waves for sleep apnea vs. higher power in β and σ for insomnia), suggesting sleep disorder-dependent pathomechanisms of aging. Our results demonstrate that the new EEG-BAI can be a biomarker reflecting brain health in normal and various sleep disorder subjects, and may be used to assess treatment efficacy.

Purpose: The main goal of this study is to investigate the discrimination power of Grey Matter (GM) thickness connectome data between Multiple Sclerosis (MS) clinical profiles using statistical and Machine Learning (ML) methods. Materials and Methods: A dataset composed of 90 MS patients acquired at the MS clinic of Lyon Neurological Hospital was used for the analysis. Four MS profiles were considered, corresponding to Clinical Isolated Syndrome (CIS), Relapsing-Remitting MS (RRMS), Secondary Progressive MS (SPMS), and Primary Progressive MS (PPMS). Each patient was classified in one of these profiles by our neurologist and underwent longitudinal MRI examinations including T1-weighted image acquisition at each examination, from which the GM tissue was segmented and the cortical GM thickness measured. Following the GM parcellation using two different atlases (FSAverage and Glasser 2016), the morphological connectome was built and six global metrics (Betweenness Centrality (BC), Assortativity (r), Transitivity (T), Efficiency (E g ), Modularity (Q) and Density (D)) were extracted. Based on their connectivity metrics, MS profiles were first statistically compared and second, classified using four different learning machines (Logistic Regression, Random Forest, Support Vector Machine and AdaBoost), combined in a higher level ensemble model by majority voting. Finally, the impact of the GM spatial resolution on the MS clinical profiles classification was analyzed. Results: Using binary comparisons between the four MS clinical profiles, statistical differences and classification performances higher than 0.7 were observed. Good performances were obtained when comparing the two early clinical forms, RRMS and PPMS (F1 score of 0.86), and the two neurodegenerative profiles, PPMS and SPMS (F1 score of 0.72). When comparing the two atlases, slightly better performances were obtained with the Glasser 2016 atlas, especially between RRMS with PPMS (F1 score of 0.83), compared to the FSAverage atlas (F1 score of 0.69). Also, the thresholding value for graph binarization was investigated suggesting more informative graph properties in the percentile range between 0.6 and 0.8. Conclusion: An automated pipeline was proposed for the classification of MS clinical profiles using six global graph metrics extracted from the GM morphological connectome of MS patients. This work demonstrated that GM morphological connectivity data could provide good classification performances by combining four simple ML models, without the cost of long and complex MR techniques, such as MR diffusion, and/or deep learning architectures.

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase ¹⁸ F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent ¹⁸ F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

Although the term sulcus is known for almost four centuries, its formal, precise, consistent, constructive, and quantitative definition is practically lacking. As the cerebral sulci (and gyri) are vital in cortical anatomy which, in turn, is central in neuroeducation and neuroimage processing, a new sulcus definition is needed. The contribution of this work is threefold, namely to (1) propose a new, morphology-based definition of the term sulcus (and consequently that of gyrus), (2) formulate a constructive method for sulcus calculation, and (3) provide a novel way for the presentation of sulci. The sulcus is defined here as a volumetric region on the cortical mantle between adjacent gyri separated from them at the levels of their gyral white matter crest lines. Consequently, the sulcal inner surface is demarcated by the crest lines of the gyral white matter of its adjacent gyri. Correspondingly, the gyrus is defined as a volumetric region on the cortical mantle separated from its adjacent sulci at the level of its gyral white matter crest line. This volumetric sulcus definition is conceptually simple, anatomy-based, educationally friendly, quantitative, and constructive. Considering the sulcus as a volumetric object is a major differentiation from other works. Based on the introduced sulcus definition, a method for volumetric sulcus construction is proposed in two, conceptually straightforward, steps, namely, sulcal intersection formation followed by its propagation which steps are to be repeated for every sulcal segment. These sulcal and gyral constructions can be automated by applying existing methods and public tools. As a volumetric sulcus forms an imprint into the white matter, this enables prominent sulcus presentation. Since this type of presentation is novel yet unfamiliar to the reader, also a dual surface presentation was proposed here by employing the spatially co-registered white matter and cortical surfaces. The results were presented as dual surface labeled sulci on eight standard orthogonal views, anterior, left lateral, posterior, right lateral, superior, inferior, medial left, and medial right by using a 3D brain atlas. Moreover, additional 108 labeled images were created with sulcus-oriented views for 27 individual left and right sulci forming 54 dual white matter-cortical surface images strengthening in this way the educational value of the proposed approach. These images were included for public use in the NOWinBRAIN neuroimage repository with over 7700 3D images available at www.nowinbrain.org. The results demonstrated the superiority of white matter surface sulci presentation over the standard cortical surface and cross-sectional presentations in terms of sulcal course, continuity, size, shape, width, depth, side branches, and pattern. To my best knowledge, this is the first work ever presenting the labeling of sulci on all cerebral white matter surfaces as well as on dual white matter-cortical surfaces. Additionally to neuroeducation, three other applications of the proposed approach were discussed, sulcal reference maps, sulcus quantification in terms of new parameters introduced here (sulcal volume, wall skewness, and the number of white matter basins), and an atlas-assisted tool for exploration and studying of cerebral sulci and gyri .

In the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on cortical thickness, brain volume, and the serum brain-derived neurotrophic factor (BDNF). Totally, 152 participants, aged 60-79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 controls) underwent brain MRI at baseline and 24 weeks. We compared changes in global/regional mean cortical thickness at the region-of-interest (ROI) between the intervention and control groups. The changes in the total cortical gray matter volume and global mean cortical thickness were compared using analysis of covariance with age, sex, and education as covariates. ComBat site harmonization was applied for cortical thickness values across the scanners. ROI-based analysis was controlled for multiple comparisons, with a false discovery rate threshold of p < 0.05. Serum BDNF levels were significantly higher in the FMI group than in the control group (p = 0.029). Compared with the control group, the mean global cortical thickness increased in the FMI group (0.033 ± 0.070 vs. - 0.003 ± 0.040, p = 0.013); particularly, cortical thickness of the bilateral frontotemporal lobes, cingulate gyri, and insula increased. The increase in cortical thickness and serum BDNF in the FMI group suggests that group preventive strategies at the facility may be beneficial through structural neuroplastic changes in brain areas, which facilitates learning and neurotrophic factors.