Publications by authors named "Svenja Caspers"

83 Publications

The MRI posterior drawer test to assess posterior cruciate ligament functionality and knee joint laxity.

Sci Rep 2021 Oct 4;11(1):19687. Epub 2021 Oct 4.

Department of Diagnostic and Interventional Radiology, Medical Faculty, University Dusseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.

Clinical Magnetic Resonance Imaging (MRI) of joints is limited to mere morphologic evaluation and fails to directly visualize joint or ligament function. In this controlled laboratory study, we show that knee joint functionality may be quantified in situ and as a function of graded posterior cruciate ligament (PCL)-deficiency by combining MRI and standardized loading. 11 human knee joints underwent MRI under standardized posterior loading in the unloaded and loaded (147 N) configurations and in the intact, partially, and completely PCL-injured conditions. For each specimen, configuration, and condition, 3D joint models were implemented to analyse joint kinematics based on 3D Euclidean vectors and their projections on the Cartesian planes. Manual 2D measurements served as reference. With increasing PCL deficiency, vector projections increased significantly in the anteroposterior dimension under loading and manual measurements demonstrated similar patterns of change. Consequently, if combined with advanced image post-processing, stress MRI is a powerful diagnostic adjunct to evaluate ligament functionality and joint laxity in multiple dimensions and may have a role in differentiating PCL injury patterns, therapeutic decision-making, and treatment monitoring.
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http://dx.doi.org/10.1038/s41598-021-99216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490383PMC
October 2021

Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients.

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52428 Juelich, Germany.

Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, -(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1-214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.
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http://dx.doi.org/10.3390/cancers13102373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156090PMC
May 2021

The Effects of Domestication on the Brain and Behavior of the Chicken in the Light of Evolution.

Brain Behav Evol 2020 27;95(6):287-301. Epub 2021 May 27.

Institute for Anatomy I, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

The avian class is characterized by particularly strong variability in their domesticated species. With more than 250 breeds and highly efficient commercial lines, domestic chickens represent the outcome of a really long period of artificial selection. One characteristic of domestication is the alterations in brain size and brain composition. The influence of domestication on brain morphology has been reviewed in the past, but mostly with a focus on mammals. Studies on avian species have seldom been taken into account. In this review, we would like to give an overview about the changes and variations in (brain) morphology and behavior in the domestic chicken, taking into consideration the constraints of evolutionary theory and the sense or nonsense of excessive artificial selection.
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http://dx.doi.org/10.1159/000516787DOI Listing
May 2021

Generalizing Longitudinal Age Effects on Brain Structure - A Two-Study Comparison Approach.

Front Hum Neurosci 2021 16;15:635687. Epub 2021 Apr 16.

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.

Cross-sectional studies indicate that normal aging is accompanied by decreases in brain structure. Longitudinal studies, however, are relatively rare and inconsistent regarding their outcomes. Particularly the heterogeneity of methods, sample characteristics and the high inter-individual variability in older adults prevent the deduction of general trends. Therefore, the current study aimed to compare longitudinal age-related changes in brain structure (measured through cortical thickness) in two large independent samples of healthy older adults ( = 161 each); the Longitudinal Healthy Aging Brain (LHAB) database project at the University of Zurich, Switzerland, and 1000BRAINS at the Research Center Juelich, Germany. Annual percentage changes in the two samples revealed stable to slight decreases in cortical thickness over time. After correction for major covariates, i.e., baseline age, sex, education, and image quality, sample differences were only marginally present. Results suggest that general trends across time might be generalizable over independent samples, assuming the same methodology is used, and similar sample characteristics are present.
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http://dx.doi.org/10.3389/fnhum.2021.635687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085300PMC
April 2021

Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate.

Neuroimage 2021 07 2;235:118006. Epub 2021 Apr 2.

Institute of Neuroscience and Medicine (INM-7), Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute of Systems Neuroscience, Research Centre Jülich, Jülich, Germany. Electronic address:

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214073PMC
July 2021

Occipital Intralobar fasciculi: a description, through tractography, of three forgotten tracts.

Commun Biol 2021 03 30;4(1):433. Epub 2021 Mar 30.

Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, The University of Malta, Msida, Malta.

Diffusion MRI paired with tractography has facilitated a non-invasive exploration of many association, projection, and commissural fiber tracts. However, there is still a scarcity of research studies related to intralobar association fibers. The Dejerines' (two of the most notable neurologists of 19 century France) gave an in-depth description of the intralobar fibers of the occipital lobe. Unfortunately, their exquisite work has since been sparsely cited in the modern literature. This work gives a modern description of many of the occipital intralobar lobe fibers described by the Dejerines. We perform a virtual dissection and reconstruct the tracts using diffusion MRI tractography. The dissection is guided by the Dejerines' treatise, Anatomie des Centres Nerveux. As an accompaniment to this article, we provided a French-to-English translation of the treatise portion concerning five intra-occipital tracts, namely: the stratum calcarinum, the stratum proprium cunei, the vertical occipital fasciculus of Wernicke, the transverse fasciculus of the cuneus and the transverse fasciculus of the lingual lobule of Vialet. It was possible to reconstruct all but one of these tracts. For completeness, the recently described sledge runner fasciculus, although not one of the Dejerines' tracts, was identified and successfully reconstructed.
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http://dx.doi.org/10.1038/s42003-021-01935-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010026PMC
March 2021

Genetic factors influencing a neurobiological substrate for psychiatric disorders.

Transl Psychiatry 2021 03 29;11(1):192. Epub 2021 Mar 29.

Institute of Neuroscience and Medicine (INM-1, INM-7), Research Centre Jülich, Jülich, Germany.

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex-areas that constitute hub nodes of the salience network-represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk.
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http://dx.doi.org/10.1038/s41398-021-01317-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007575PMC
March 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 03 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

Vitamin D and white matter hyperintensities: results of the population-based Heinz Nixdorf Recall Study and 1000BRAINS.

Eur J Neurol 2021 06 31;28(6):1849-1858. Epub 2021 Mar 31.

Institute for Urban Public Health, University Hospital of University Duisburg-Essen, Essen, Germany.

Background And Purpose: Cross-sectional studies showed an inverse association between serum 25-hydroxyvitamin D (25OHD) and white matter hyperintensities (WMHs) whereas the few longitudinal studies did not. The association between baseline 25OHD and WMHs at 10-year follow-up in the Heinz Nixdorf Recall Study plus 1000BRAINS was investigated.

Methods: Data of 505 participants (49% women, 56.2 ± 6.6 years) with 25OHD at baseline (2000-2003) and WMH volume and grade of WMHs using the Fazekas classification at 10-year follow-up were analysed. The association between deseasonalized 25OHD and the base-10 logarithm of WMH volume was evaluated by multiple linear regression, adjusted for age, sex, education, smoking, alcohol consumption, sports, diabetes mellitus, systolic blood pressure and total cholesterol. β-estimators were transformed back (10 ). Using multiple logistic regression, odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the association between deseasonalized 25OHD and Fazekas grades (0, absence and 1, punctate foci vs. 2, beginning and 3, large confluence).

Results: Mean 25OHD was 17.0 ± 8.2 ng/ml, and mean deseasonalized 25OHD was 16.9 ± 7.5 ng/ml. Mean WMH volume was 16.6 ± 17.4 ml, range 1-132 ml. Most grade 2-3 WMHs were found to be periventricular (39% of the participants), parietal (32%) and frontal (31%) (temporal 6%, occipital 3%). The linear regression showed an inverse association between 25OHD and WMH volume. On average, a 25OHD increase of 1 ng/ml was associated with a reduced WMH volume by a factor of 0.99 (95% CI 0.98; 1.00) (fully adjusted). There was also some indication for an inverse association between 25OHD and extent of periventricular (OR 0.98 [95% CI 0.96; 1.01]), frontal (0.99 [0.97; 1.02]) and parietal (0.98 [0.95; 1.00]) WMHs according to the Fazekas classification.

Conclusions: Lower 25OHD may be a risk factor for the occurrence of WMHs.
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http://dx.doi.org/10.1111/ene.14810DOI Listing
June 2021

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Hum Brain Mapp 2021 Feb 21. Epub 2021 Feb 21.

Center for Neuroimaging, Genetics and Genomics, School of Psychology, NUI Galway, Galway, Ireland.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
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http://dx.doi.org/10.1002/hbm.25354DOI Listing
February 2021

The role of thickness inhomogeneities in hierarchical cortical folding.

Neuroimage 2021 05 4;231:117779. Epub 2021 Feb 4.

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. Electronic address:

The mammalian brain cortex is highly folded, with several developmental disorders affecting folding. On the extremes, lissencephaly, a lack of folds in humans, and polymicrogyria, an overly folded brain, can lead to severe mental retardation, short life expectancy, epileptic seizures, and tetraplegia. Not only a specific degree of folding, but also stereotyped patterns, are required for normal brain function. A quantitative model on how and why these folds appear during the development of the brain is the first step in understanding the cause of these conditions. In recent years, there have been various attempts to understand and model the mechanisms of brain folding. Previous works have shown that mechanical instabilities play a crucial role in the formation of brain folds, and that the geometry of the fetal brain is one of the main factors in dictating its folding characteristics. However, modeling higher-order folding, one of the main characteristics of the highly gyrencephalic brain, has not been fully tackled. The simulations presented in this work are used to study the effects of thickness inhomogeneity in the gyrogenesis of the mammalian brain in silico. Finite-element simulations of rectangular slabs are performed. These slabs are divided into two distinct regions, where the outer region mimicks the gray matter, and the inner region the underlying white matter. Differential growth is introduced by growing the top region tangentially, while keeping the underlying region untouched. The brain tissue is modeled as a neo-Hookean hyperelastic material. Simulations are performed with both homogeneous and inhomogeneous cortical thicknesses. Our results show that the homogeneous cortex folds into a single wavelength, as is common for bilayered materials, while the inhomogeneous cortex folds into more complex conformations. In the early stages of development of the inhomogeneous cortex, structures reminiscent of the deep sulci in the brain are obtained. As the cortex continues to develop, secondary undulations, which are shallower and more variable than the structures obtained in earlier gyrification stage emerge, reproducing well-known characteristics of higher-order folding in the mammalian, and particularly the human, brain.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117779DOI Listing
May 2021

When your brain looks older than expected: combined lifestyle risk and BrainAGE.

Brain Struct Funct 2021 Apr 10;226(3):621-645. Epub 2021 Jan 10.

Institute for Anatomy I, Medical Faculty, Heinrich-Heine University Düsseldorf, Universitätstr. 1, 40225, Düsseldorf, Germany.

Lifestyle may be one source of unexplained variance in the great interindividual variability of the brain in age-related structural differences. While physical and social activity may protect against structural decline, other lifestyle behaviors may be accelerating factors. We examined whether riskier lifestyle correlates with accelerated brain aging using the BrainAGE score in 622 older adults from the 1000BRAINS cohort. Lifestyle was measured using a combined lifestyle risk score, composed of risk (smoking, alcohol intake) and protective variables (social integration and physical activity). We estimated individual BrainAGE from T1-weighted MRI data indicating accelerated brain atrophy by higher values. Then, the effect of combined lifestyle risk and individual lifestyle variables was regressed against BrainAGE. One unit increase in combined lifestyle risk predicted 5.04 months of additional BrainAGE. This prediction was driven by smoking (0.6 additional months of BrainAGE per pack-year) and physical activity (0.55 less months in BrainAGE per metabolic equivalent). Stratification by sex revealed a stronger association between physical activity and BrainAGE in males than females. Overall, our observations may be helpful with regard to lifestyle-related tailored prevention measures that slow changes in brain structure in older adults.
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http://dx.doi.org/10.1007/s00429-020-02184-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981332PMC
April 2021

White Matter Microstructure Underlies the Effects of Sleep Quality and Life Stress on Depression Symptomatology in Older Adults.

Front Aging Neurosci 2020 13;12:578037. Epub 2020 Nov 13.

Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany.

Sleep complaints are the most prevalent syndromes in older adults, particularly in women. Moreover, they are frequently accompanied with a high level of depression and stress. Although several diffusion tensor imaging (DTI) studies reported associations between sleep quality and brain white matter (WM) microstructure, it is still unclear whether gender impacts the effect of sleep quality on structural alterations, and whether these alterations mediate the effects of sleep quality on emotional regulation. We included 389 older participants (176 females, age = 65.5 ± 5.5 years) from the 1000BRAINS project. Neuropsychological examinations covered the assessments of sleep quality, depressive symptomatology, current stress level, visual working memory, and selective attention ability. Based on the DTI dataset, the diffusion parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated and normalized to a population-specific FA template. According to the global Pittsburgh Sleep Quality Index (PSQI), 119 poor sleepers (PSQI: 10∼17) and 120 good sleepers (PSQI: 3∼6) were identified. We conducted a two by two (good sleepers/poor sleepers) × (males/females) analysis of variance by using tract-based spatial statistics (TBSS) and JHU-ICBM WM atlas-based comparisons. Moreover, we performed a voxel-wise correlation analysis of brain WM microstructure with the neuropsychological tests. Finally, we applied a mediation analysis to explore if the brain WM microstructure mediates the relationship between sleep quality and emotional regulation. No significant differences in brain WM microstructure were detected on the main effect of sleep quality. However, the MD, AD, and RD of pontine crossing tract and bilateral inferior cerebellar peduncle were significant lower in the males than females. Voxel-wise correlation analysis revealed that FA and RD values in the corpus callosum were positively related with depressive symptomatology and negatively related with current stress levels. Additionally, we found a significantly positive association between higher FA values in visual-related WM tracts and better outcomes in a visual pattern recognition test. Furthermore, a mediation analysis suggested that diffusion metrics within the corpus callosum partially mediated the associations between poor sleep quality/high stress and depressive symptomatology.
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http://dx.doi.org/10.3389/fnagi.2020.578037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691589PMC
November 2020

Chimpanzee brain morphometry utilizing standardized MRI preprocessing and macroanatomical annotations.

Elife 2020 11 23;9. Epub 2020 Nov 23.

Institute of Systems Neuroscience, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.

Chimpanzees are among the closest living relatives to humans and, as such, provide a crucial comparative model for investigating primate brain evolution. In recent years, human brain mapping has strongly benefited from enhanced computational models and image processing pipelines that could also improve data analyses in animals by using species-specific templates. In this study, we use structural MRI data from the National Chimpanzee Brain Resource (NCBR) to develop the chimpanzee brain reference template Juna.Chimp for spatial registration and the macro-anatomical brain parcellation Davi130 for standardized whole-brain analysis. Additionally, we introduce a ready-to-use image processing pipeline built upon the CAT12 toolbox in SPM12, implementing a standard human image preprocessing framework in chimpanzees. Applying this approach to data from 194 subjects, we find strong evidence for human-like age-related gray matter atrophy in multiple regions of the chimpanzee brain, as well as, a general rightward asymmetry in brain regions.
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http://dx.doi.org/10.7554/eLife.60136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723405PMC
November 2020

Hippocampus co-atrophy pattern in dementia deviates from covariance patterns across the lifespan.

Brain 2020 09;143(9):2788-2802

Institute of Neuroscience and Medicine (INM-1, INM-7), Research Centre Jülich, Jülich, Germany.

The hippocampus is a plastic region and highly susceptible to ageing and dementia. Previous studies explicitly imposed a priori models of hippocampus when investigating ageing and dementia-specific atrophy but led to inconsistent results. Consequently, the basic question of whether macrostructural changes follow a cytoarchitectonic or functional organization across the adult lifespan and in age-related neurodegenerative disease remained open. The aim of this cross-sectional study was to identify the spatial pattern of hippocampus differentiation based on structural covariance with a data-driven approach across structural MRI data of large cohorts (n = 2594). We examined the pattern of structural covariance of hippocampus voxels in young, middle-aged, elderly, mild cognitive impairment and dementia disease samples by applying a clustering algorithm revealing differentiation in structural covariance within the hippocampus. In all the healthy and in the mild cognitive impaired participants, the hippocampus was robustly divided into anterior, lateral and medial subregions reminiscent of cytoarchitectonic division. In contrast, in dementia patients, the pattern of subdivision was closer to known functional differentiation into an anterior, body and tail subregions. These results not only contribute to a better understanding of co-plasticity and co-atrophy in the hippocampus across the lifespan and in dementia, but also provide robust data-driven spatial representations (i.e. maps) for structural studies.
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http://dx.doi.org/10.1093/brain/awaa222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523701PMC
September 2020

Joint Multi-modal Parcellation of the Human Striatum: Functions and Clinical Relevance.

Neurosci Bull 2020 Oct 23;36(10):1123-1136. Epub 2020 Jul 23.

Institute of Neuroscience and Medicine (INM-7, Brain and Behaviour), Research Centre Jülich, Jülich, Germany.

The human striatum is essential for both low- and high-level functions and has been implicated in the pathophysiology of various prevalent disorders, including Parkinson's disease (PD) and schizophrenia (SCZ). It is known to consist of structurally and functionally divergent subdivisions. However, previous parcellations are based on a single neuroimaging modality, leaving the extent of the multi-modal organization of the striatum unknown. Here, we investigated the organization of the striatum across three modalities-resting-state functional connectivity, probabilistic diffusion tractography, and structural covariance-to provide a holistic convergent view of its structure and function. We found convergent clusters in the dorsal, dorsolateral, rostral, ventral, and caudal striatum. Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions, while the caudal striatum was related to action execution. Interestingly, significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ, but atrophy in the dorsolateral striatum was specifically attributable to PD. Our study revealed a cross-modal convergent organization of the striatum, representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.
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http://dx.doi.org/10.1007/s12264-020-00543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532244PMC
October 2020

A tutorial and tool for exploring feature similarity gradients with MRI data.

Neuroimage 2020 11 7;221:117140. Epub 2020 Jul 7.

Division of Neuroscience & Experimental Psychology, School of Biological Sciences, The University of Manchester, UK.

There has been an increasing interest in examining organisational principles of the cerebral cortex (and subcortical regions) using different MRI features such as structural or functional connectivity. Despite the widespread interest, introductory tutorials on the underlying technique targeted for the novice neuroimager are sparse in the literature. Articles that investigate various "neural gradients" (for example based on region studied "cortical gradients," "cerebellar gradients," "hippocampal gradients" etc … or feature of interest "functional gradients," "cytoarchitectural gradients," "myeloarchitectural gradients" etc …) have increased in popularity. Thus, we believe that it is opportune to discuss what is generally meant by "gradient analysis". We introduce basics concepts in graph theory, such as graphs themselves, the degree matrix, and the adjacency matrix. We discuss how one can think about gradients of feature similarity (the similarity between timeseries in fMRI, or streamline in tractography) using graph theory and we extend this to explore such gradients across the whole MRI scale; from the voxel level to the whole brain level. We proceed to introduce a measure for quantifying the level of similarity in regions of interest. We propose the term "the Vogt-Bailey index" for such quantification to pay homage to our history as a brain mapping community. We run through the techniques on sample datasets including a brain MRI as an example of the application of the techniques on real data and we provide several appendices that expand upon details. To maximise intuition, the appendices contain a didactic example describing how one could use these techniques to solve a particularly pernicious problem that one may encounter at a wedding. Accompanying the article is a tool, available in both MATLAB and Python, that enables readers to perform the analysis described in this article on their own data. We refer readers to the graphical abstract as an overview of the analysis pipeline presented in this work.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116330PMC
November 2020

Somatosensory area 3b is selectively unaffected in corticobasal syndrome: combining MRI and histology.

Neurobiol Aging 2020 10 21;94:89-100. Epub 2020 May 21.

Institute for Anatomy I, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; JARA-BRAIN, Jülich-Aachen Research Alliance, Research Centre Jülich, Jülich, Germany. Electronic address:

An increasing number of neuroimaging studies addressing patients with corticobasal syndrome use macroscopic definitions of brain regions. As a closer link to functionally relevant units, we aimed at identifying magnetic resonance-based atrophy patterns in regions defined by probability maps of cortical microstructure. For this purpose, three analyses were conducted: (1) Whole-brain cortical thickness was compared between 36 patients with corticobasal syndrome and 24 controls. A pattern of pericentral atrophy was found, covering primary motor area 4, premotor area 6, and primary somatosensory areas 1, 2, and 3a. Within the central region, only area 3b was without atrophy. (2) In 18 patients, longitudinal measures with follow-ups of up to 59 months (mean 21.3 ± 15.4) were analyzed. Areas 1, 2, and 6 showed significantly faster atrophy rates than primary somatosensory area 3b. (3) In an individual autopsy case, longitudinal in vivo morphometry and postmortem pathohistology were conducted. The rate of magnetic resonance-based atrophy was significantly correlated with tufted-astrocyte load in those cytoarchitectonically defined regions also seen in the group study, with area 3b being selectively unaffected.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.009DOI Listing
October 2020

Role of the default mode resting-state network for cognitive functioning in malignant glioma patients following multimodal treatment.

Neuroimage Clin 2020 26;27:102287. Epub 2020 May 26.

Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.

Background: Progressive cognitive decline following multimodal neurooncological treatment is a common observation in patients suffering from malignant glioma. Alterations of the default-mode network (DMN) represent a possible source of impaired neurocognitive functioning and were analyzed in these patients.

Methods: Eighty patients (median age, 51 years) with glioma (WHO grade IV glioblastoma, n = 57; WHO grade III anaplastic astrocytoma, n = 13; WHO grade III anaplastic oligodendroglioma, n = 10) and ECOG performance score 0-1 underwent resting-state functional MRI (rs-fMRI) and neuropsychological testing at a median interval of 13 months (range, 1-114 months) after initiation of therapy. For evaluation of structural and metabolic changes after treatment, anatomical MRI and amino acid PET using O-(2-[F]fluoroethyl)-L-tyrosine (FET) were simultaneously acquired to rs-fMRI on a hybrid MR/PET scanner. A cohort of 80 healthy subjects matched for gender, age, and educational status served as controls.

Results: The connectivity pattern within the DMN (12 nodes) of the glioma patients differed significantly from that of the healthy subjects but did not depend on age, tumor grade, time since treatment initiation, presence of residual/recurrent tumor, number of chemotherapy cycles received, or anticonvulsive medication. Small changes in the connectivity pattern were observed in patients who had more than one series of radiotherapy. In contrast, structural tissue changes located at or near the tumor site (including resection cavities, white matter lesions, edema, and tumor tissue) had a strong negative impact on the functional connectivity of the adjacent DMN nodes, resulting in a marked dependence of the connectivity pattern on tumor location. In the majority of neurocognitive domains, glioma patients performed significantly worse than healthy subjects. Correlation analysis revealed that reduced connectivity in the left temporal and parietal DMN nodes was associated with low performance in language processing and verbal working memory. Furthermore, connectivity of the left parietal DMN node also correlated with processing speed, executive function, and verbal as well as visual working memory. Overall DMN connectivity loss and cognitive decline were less pronounced in patients with higher education.

Conclusion: Personalized treatment strategies for malignant glioma patients should consider the left parietal and temporal DMN nodes as vulnerable regions concerning neurocognitive outcome.
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http://dx.doi.org/10.1016/j.nicl.2020.102287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298724PMC
March 2021

Associations of Air Pollution and Noise with Local Brain Structure in a Cohort of Older Adults.

Environ Health Perspect 2020 06 15;128(6):67012. Epub 2020 Jun 15.

Environmental Epidemiology Group, Institute of Occupational, Social and Environmental Medicine, Centre for Health and Society, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Background: Despite the importance of understanding associations of air pollution and noise exposure with loss of neurocognitive performance, studies investigating these exposures and local brain structure are limited.

Objective: We estimated associations of residential air pollution and noise exposures with neurocognitive test performance and the local gyrification index (lGI), a marker for local brain atrophy, among older adults.

Methods: For participants from the population-based 1000BRAINS study, based on the German Heinz Nixdorf Recall study, we assessed residential exposures to particulate matter (, , ), accumulation mode particle number (), and nitrogen oxides (, ), using land-use regression and chemistry transport models. Weighted 24-h and nighttime noise were modeled according to the European noise directive. We evaluated associations of air pollution and noise exposure at the participants' 2006-2008 residential addresses with neurocognitive test performance and region-specific lGI values () from magnetic resonance imaging, both assessed in 2011-2015, using linear regression and adjusting for demographic and personal characteristics.

Results: Air pollution and noise were associated with language and short-term/working memory and with local atrophy of the fronto-parietal network (FPN), a functional resting-state network associated with these cognitive processes. For example, per , local brain atrophy was more pronounced in the posterior brain regions of the FPN, with a [95% confidence interval (CI): , 0.00] lower lGI. In contrast, in the anterior regions of the FPN, weighted 24-h and nighttime noise were associated with less local brain atrophy [e.g., 0.02 (95% CI: 0.00, 0.04) for (A) 24-h noise].

Conclusions: Air pollution and noise exposures were associated in opposite directions with markers of local atrophy of the FPN in the right brain hemisphere in older adults, suggesting that both chronic air pollution and noise exposure may influence the physiological aging process of the brain. https://doi.org/10.1289/EHP5859.
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http://dx.doi.org/10.1289/EHP5859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295241PMC
June 2020

Prevalence and psychosocial correlates of subjectively perceived decline in five cognitive domains: Results from a population-based cohort study in Germany.

Int J Geriatr Psychiatry 2020 10 2;35(10):1219-1227. Epub 2020 Jul 2.

Department of Psychiatry and Psychotherapy, University Clinic Bonn, Bonn, Germany.

Objective: Subjective cognitive decline (SCD) was frequently investigated for memory in healthy aging or in relation to diseases like dementia. It was found to be related to sociodemographic and psychological variables as well as cognitive abilities. The prevalence of SCD in other cognitive domains and their relation to these variables is largely unknown to date. The present study aimed to fill this gap.

Methods: A total of 807 subjects (18-85 years of age, M = 57.8 years, female: 43%) completed the Juelich Questionnaire on Subjective Cognitive Decline, to investigate SCD in memory, attention, language, motor, and executive functions. Logistic regression analyses were used to estimate association of depressive symptomatology, emotionality, and general cognitive performance as well as age, gender, and educational attainment with domain-specific SCD.

Results: The highest prevalence rate was obtained for the memory domain (65.9%), followed by the attention (54.6%), motor (52.9%), executive (39.7%), and language domain (31.5%). Of the psychosocial factors, only age, depressive symptomatology and emotionality were consistently and strongly associated with domain-specific SCD prevalence.

Conclusions: SCD is prevalent not only in the memory domain, but also in other major cognitive domains. Our results also suggest that the suspicion from previous research, that subjective memory decline might be more strongly associated with depressive symptomatology and emotionality than with actual decline of cognitive performance, might also apply to the attention, motor, executive, and language domain. Further investigations using neuropsychological testing for specific cognitive functions and employing longitudinal designs are required for substantiating this suspicion.
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http://dx.doi.org/10.1002/gps.5359DOI Listing
October 2020

Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study.

Front Psychiatry 2020 4;11:342. Epub 2020 May 4.

Institute of Neurodegenerative Diseases (IMN), CNRS, CEA, Bordeaux, France.

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.
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http://dx.doi.org/10.3389/fpsyt.2020.00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212692PMC
May 2020

Functional network reorganization in older adults: Graph-theoretical analyses of age, cognition and sex.

Neuroimage 2020 07 19;214:116756. Epub 2020 Mar 19.

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany; Institute for Anatomy I, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. Electronic address:

Healthy aging has been associated with a decrease in functional network specialization. Importantly, variability of alterations of functional connectivity is especially high across older adults. Whole-brain functional network reorganization, though, and its impact on cognitive performance within particularly the older generation is still a matter of debate. We assessed resting state functional connectivity (RSFC) in 772 older adults (55-85 years, 421 males) using a graph-theoretical approach. Results show overall age-related increases of between- and decreases of within-network RSFC. With similar phenomena observed in young to middle-aged adults, i.e. that RSFC reorganizes towards more pronounced functional network integration, the current results amend such evidence for the old age. The results furthermore indicate that RSFC reorganization in older adults particularly pertain to early sensory networks (e.g. visual and sensorimotor network). Importantly, RSFC differences of these early sensory networks were found to be a relevant mediator in terms of the age-related cognitive performance differences. Further, we found systematic sex-related network differences with females showing patterns of more segregation (i.e. default mode and ventral attention network) and males showing a higher integrated network system (particularly for the sensorimotor network). These findings underpin the notion of sex-related connectivity differences, possibly facilitating sex-related behavioral functioning.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116756DOI Listing
July 2020

The genetic architecture of the human cerebral cortex.

Science 2020 03;367(6484)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
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http://dx.doi.org/10.1126/science.aay6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295264PMC
March 2020

Cytoarchitectonic Characterization and Functional Decoding of Four New Areas in the Human Lateral Orbitofrontal Cortex.

Front Neuroanat 2020 5;14. Epub 2020 Feb 5.

Cécile and Oskar Vogt-Institute for Brain Research, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

A comprehensive concept of the biological basis of reward, social and emotional behavior, and language requires a deeper understanding of the microstructure and connectivity of the underlying brain regions. Such understanding could provide deeper insights into their role in functional networks, and form the anatomical basis of the functional segregation of this region as shown in recent imaging studies. Here, we investigated the cytoarchitecture of the lateral orbitofrontal cortex (lateral OFC) in serial histological sections of 10 human postmortem brains by image analysis and a statistically reproducible approach to detect borders between cortical areas. Profiles of the volume fraction of cell bodies were therefore extracted from digitized histological images, describing laminar changes from the layer I/layer II boundary to the white matter. As a result, four new areas, Fo4-7, were identified. Area Fo4 was mainly found in the anterior orbital gyrus (AOG), Fo5 anteriorly in the inferior frontal gyrus (IFG), Fo6 in the lateral orbital gyrus (LOG), and Fo7 in the lateral orbital sulcus. Areas differed in cortical thickness, abundance and size of pyramidal cells in layer III and degree of granularity in layer IV. A hierarchical cluster analysis was used to quantify cytoarchitectonic differences between them. The 3D-reconstructed areas were transformed into the single-subject template of the Montreal Neurological Institute (MNI), where probabilistic maps and a maximum probability map (MPM) were calculated as part of the JuBrain Cytoarchitectonic Atlas. These maps served as reference data to study the functional properties of the areas using the BrainMap database. The type of behavioral tasks that activated them was analyzed to get first insights of co-activation patterns of the lateral OFC and its contribution to cognitive networks. Meta-analytic connectivity modeling (MACM) showed that functional decoding revealed activation in gustatory perception in Fo4; reward and somesthetic perception in Fo5; semantic processing and pain perception in Fo6; and emotional processing and covert reading in Fo7. Together with existing maps of the JuBrain Cytoarchitectonic Atlas, the new maps can now be used as an open-source reference for neuroimaging studies, allowing to further decode brain function.
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http://dx.doi.org/10.3389/fnana.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014920PMC
February 2020

Functional Characterization of Atrophy Patterns Related to Cognitive Impairment.

Front Neurol 2020 24;11:18. Epub 2020 Jan 24.

Department of Neurology, RWTH Aachen University, Aachen, Germany.

Mild cognitive impairment (MCI) is a heterogenous syndrome considered as a risk factor for developing dementia. Previous work examining morphological brain changes in MCI has identified a temporo-parietal atrophy pattern that suggests a common neuroanatomical denominator of cognitive impairment. Using functional connectivity analyses of structurally affected regions in MCI, we aimed to investigate and characterize functional networks formed by these regions that appear to be particularly vulnerable to disease-related disruptions. Areas of convergent atrophy in MCI were derived from a quantitative meta-analysis and encompassed left and right medial temporal (i.e., hippocampus, amygdala), as well as parietal regions (precuneus), which were defined as seed regions for connectivity analyses. Both task-based meta-analytical connectivity modeling (MACM) based on the BrainMap database and task-free resting-state functional MRI in a large cohort of older adults from the 1000BRAINS study were applied. We additionally assessed behavioral characteristics associated with the seed regions using BrainMap meta-data and investigated correlations of resting-state connectivity with age. The left temporal seed showed stronger associations with a fronto-temporal network, whereas the right temporal atrophy cluster was more linked to cortico-striatal regions. In accordance with this, behavioral analysis indicated an emphasis of the left temporal seed on language generation, and the right temporal seed was associated with the domains of emotion and attention. Task-independent co-activation was more pronounced in the parietal seed, which demonstrated stronger connectivity with a frontoparietal network and associations with introspection and social cognition. Correlation analysis revealed both decreasing and increasing functional connectivity with higher age that may add to pathological processes but also indicates compensatory mechanisms of functional reorganization with increasing age. Our findings provide an important pathophysiological link between morphological changes and the clinical relevance of major structural damage in MCI. Multimodal analysis of functional networks related to areas of MCI-typical atrophy may help to explain cognitive decline and behavioral alterations not tractable by a mere anatomical interpretation and therefore contribute to prognostic evaluations.
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http://dx.doi.org/10.3389/fneur.2020.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993791PMC
January 2020

Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.

JAMA Psychiatry 2020 04;77(4):420-430

Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.

Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.

Design, Setting, And Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.

Main Outcomes And Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.

Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.

Conclusions And Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.3779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096PMC
April 2020

Pathway-Specific Genetic Risk for Alzheimer's Disease Differentiates Regional Patterns of Cortical Atrophy in Older Adults.

Cereb Cortex 2020 03;30(2):801-811

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, D-52428 Jülich, Germany.

Brain aging is highly variable and represents a challenge to delimit aging from disease processes. Moreover, genetic factors may influence both aging and disease. Here we focused on this issue and investigated effects of multiple genetic loci previously identified to be associated with late-onset Alzheimer's disease (AD) on brain structure of older adults from a population sample. We calculated a genetic risk score (GRS) using genome-wide significant single-nucleotide polymorphisms from genome-wide association studies of AD and tested its effect on cortical thickness (CT). We observed a common pattern of cortical thinning (right inferior frontal, left posterior temporal, medial occipital cortex). To identify CT changes by specific biological processes, we subdivided the GRS effect according to AD-associated pathways and performed follow-up analyses. The common pattern from the main analysis was further differentiated by pathway-specific effects yielding a more bilateral pattern. Further findings were located in the superior parietal and mid/anterior cingulate regions representing 2 unique pathway-specific patterns. All patterns, except the superior parietal pattern, were influenced by apolipoprotein E. Our step-wise approach revealed atrophy patterns that partially resembled imaging findings in early stages of AD. Our study provides evidence that genetic burden for AD contributes to structural brain variability in normal aging.
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http://dx.doi.org/10.1093/cercor/bhz127DOI Listing
March 2020

Bilingualism and "brain reserve": a matter of age.

Neurobiol Aging 2019 09 5;81:157-165. Epub 2019 Jun 5.

Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; C. & O. Vogt Institute for Brain Research, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany.

There is a lively debate whether bilingualism as a state of permanent cognitive control contributes to so-called brain reserve, thus delaying the onset of symptoms associated with neurodegeneration by up to 5 years. Here, we address this question in a large-scale (n = 399) population-based study. We compared the gray matter volume of monolinguals versus bilinguals in the left inferior frontal gyrus and inferior parietal lobule cortex and its modulation by biological age. Three core findings emerged: (1) Brain volume was systematically higher in bilinguals than monolinguals. (2) This difference disappeared at higher ages, and the slope of decline was steeper for bilinguals than monolinguals. (3) The volume difference between age groups disappeared in the inferior frontal gyrus at earlier ages than in the inferior parietal lobule. Thus, bilingualism might indeed contribute to brain reserve in older age, with posterior regions showing a particular resilience to atrophy and thus less necessity for functions to shift to anterior control regions.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.05.021DOI Listing
September 2019
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