| 1. |
- Lindeberg, Tony, 1964-, et al.
(author)
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Analysis of brain activation patterns using a 3-D scale-space primal sketch
- 1999
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In: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 7:3, s. 166-94
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Journal article (peer-reviewed)abstract
- A fundamental problem in brain imaging concerns how to define functional areas consisting of neurons that are activated together as populations. We propose that this issue can be ideally addressed by a computer vision tool referred to as the scale-space primal sketch. This concept has the attractive properties that it allows for automatic and simultaneous extraction of the spatial extent and the significance of regions with locally high activity. In addition, a hierarchical nested tree structure of activated regions and subregions is obtained. The subject in this article is to show how the scale-space primal sketch can be used for automatic determination of the spatial extent and the significance of rCBF changes. Experiments show the result of applying this approach to functional PET data, including a preliminary comparison with two more traditional clustering techniques. Compared to previous approaches, the method overcomes the limitations of performing the analysis at a single scale or assuming specific models of the data.
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| 2. |
- Abe, C., et al.
(author)
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Cross-sex shifts in two brain imaging phenotypes and their relation to polygenic scores for same-sex sexual behavior: A study of 18,645 individuals from the UK Biobank
- 2021
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 42:7, s. 2292-2304
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Journal article (peer-reviewed)abstract
- Genetic and hormonal factors have been suggested to influence human sexual orientation. Previous studied proposed brain differences related to sexual orientation and that these follow cross-sex shifted patterns. However, the neurobiological correlates of sexual orientation and how genetic factors relate to brain structural variation remains largely unexplored. Using the largest neuroimaging-genetics dataset available on same-sex sexual behavior (SSB) (n = 18,645), we employed a data-driven multivariate classification algorithm (PLS) on magnetic resonance imaging data from two imaging modalities to extract brain covariance patterns related to sex. Through analyses of latent variables, we tested for SSB-related cross-sex shifts in such patterns. Using genotype data, polygenic scores reflecting the genetic predisposition for SSB were computed and tested for associations with neuroimaging outcomes. Patterns important for classifying between males and females were less pronounced in non-heterosexuals. Predominantly in non-heterosexual females, multivariate brain patterns as represented by latent variables were shifted toward the opposite sex. Complementary univariate analyses revealed region specific SSB-related differences in both males and females. Polygenic scores for SSB were associated with volume of lateral occipital and temporo-occipital cortices. The present large-scale study demonstrates multivariate neuroanatomical correlates of SSB, and tentatively suggests that genetic factors related to SSB may contribute to structural variation in certain brain structures. These findings support a neurobiological basis to the differences in human sexuality.
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| 3. |
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| 4. |
- Aghajani, Moji, et al.
(author)
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Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders
- 2016
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In: Human Brain Mapping. - Hoboken, USA : Wiley-Blackwell. - 1065-9471 .- 1097-0193. ; 37:11, s. 4017-4033
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Journal article (peer-reviewed)abstract
- Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Bas-Hoogendam, Janna Marie, et al.
(author)
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ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders
- 2022
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 83-112
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Research review (peer-reviewed)abstract
- Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
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| 10. |
- Beck, Dani, et al.
(author)
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Dissecting unique and common variance across body and brain health indicators using age prediction
- 2024
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In: Human Brain Mapping. - : WILEY. - 1065-9471 .- 1097-0193. ; 45:6
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Journal article (peer-reviewed)abstract
- Ageing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter-individual heterogeneity in the multisystem ageing process. Using machine-learning regression models on the UK Biobank data set (N = 32,593, age range 44.6-82.3, mean age 64.1 years), we first estimated tissue-specific brain age for white and gray matter based on diffusion and T1-weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict 'body age'. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion-based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle-fat infiltration were related to older-appearing body age compared to brain age. Conversely, higher hand-grip strength and muscle volume were related to a younger-appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals. A 'body age' model trained on health traits demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. Health traits may differentially influence age predictions beyond what is captured by the brain imaging data, revealing a degree of unique variance in brain and bodily ageing processes. image
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| 11. |
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| 12. |
- Bonkhoff, Anna K, et al.
(author)
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The relevance of rich club regions for functional outcome post-stroke is enhanced in women.
- 2023
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In: Human brain mapping. - : Wiley. - 1097-0193 .- 1065-9471. ; 44:4, s. 1579-1592
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Journal article (peer-reviewed)abstract
- This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS>2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.
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| 13. |
- Burke, Sarah M., et al.
(author)
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Sex differences in own and other body perception
- 2019
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:2, s. 474-488
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Journal article (peer-reviewed)abstract
- Own body perception, and differentiating and comparing one's body to another person's body, are common cognitive functions that have relevance for self-identity and social interactions. In several psychiatric conditions, including anorexia nervosa, body dysmorphic disorder, gender dysphoria, and autism spectrum disorder, self and own body perception, as well as aspects of social communication are disturbed. Despite most of these conditions having skewed prevalence sex ratios, little is known about whether the neural basis of own body perception differs between the sexes. We addressed this question by investigating brain activation using functional magnetic resonance imaging during a Body Perception task in 15 male and 15 female healthy participants. Participants viewed their own body, bodies of same-sex, or opposite-sex other people, and rated the degree that they appeared like themselves. We found that men and women did not differ in the pattern of brain activation during own body perception compared to a scrambled control image. However, when viewing images of other bodies of same-sex or opposite-sex, men showed significantly stronger activations in attention-related and reward-related brain regions, whereas women engaged stronger activations in striatal, medial-prefrontal, and insular cortices, when viewing the own body compared to other images of the opposite sex. It is possible that other body images, particularly of the opposite sex, may be of greater salience for men, whereas images of own bodies may be more salient for women. These observations provide tentative neurobiological correlates to why women may be more vulnerable than men to conditions involving own body perception.
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| 14. |
- Burzynska, Agnieszka Z., et al.
(author)
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Cortical thickness is linked to executive functioning in adulthood and aging
- 2012
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 33:7, s. 1607-20
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Journal article (peer-reviewed)abstract
- Executive functions that are dependent upon the frontal-parietal network decline considerably during the course of normal aging. To delineate neuroanatomical correlates of age-related executive impairment, we investigated the relation between cortical thickness and executive functioning in 73 younger (20-32 years) and 56 older (60-71 years) healthy adults. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Cortical thickness was measured at each location of the cortical mantle using surface-based segmentation procedures on high-resolution T1-weighted magnetic resonance images. For regions involved in WCST performance, such as the lateral prefrontal and parietal cortices, we found that thicker cortex was related to higher accuracy. Follow-up ROI-based analyses revealed that these associations were stronger in older than in younger adults. Moreover, among older adults, high and low performers differed in cortical thickness within regions generally linked to WCST performance. Our results indicate that the structural cortical correlates of executive functioning largely overlap with previously identified functional patterns. We conclude that structural preservation of relevant brain regions is associated with higher levels of executive performance in old age, and underscore the need to consider the heterogeneity of brain aging in relation to cognitive functioning.
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| 15. |
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| 16. |
- Bussy, Aurélie, et al.
(author)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
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Journal article (peer-reviewed)abstract
- Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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| 17. |
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| 18. |
- Ching, C. R. K., et al.
(author)
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What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group
- 2022
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 56-82
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Journal article (peer-reviewed)abstract
- MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
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| 19. |
- Cocozza, Sirio, et al.
(author)
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Default mode network modifications in Fabry disease : A resting-state fMRI study with structural correlations
- 2018
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In: Human Brain Mapping. - : WILEY. - 1065-9471 .- 1097-0193. ; 39:4, s. 1755-1764
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Journal article (peer-reviewed)abstract
- Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty-two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 +/- 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 +/- 14.5). Resting-State fMRI data were analyzed using a seed-based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel-Based Morphometry (VBM) and Tract-Based Spatial Statistics analyses. Between-group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block-tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes.
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| 20. |
- Comasco, Erika, et al.
(author)
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Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder
- 2014
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 35:9, s. 4450-4458
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Journal article (peer-reviewed)abstract
- Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014.
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| 21. |
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| 22. |
- Dall'orso, Sofia, 1992, et al.
(author)
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Development of functional organization within the sensorimotor network across the perinatal period
- 2022
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In: Human Brain Mapping. - : Wiley. - 1097-0193 .- 1065-9471. ; 43:7, s. 2249-2261
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Journal article (peer-reviewed)abstract
- In the mature human brain, the neural processing related to different body parts is reflected in patterns of functional connectivity, which is strongest between functional homologs in opposite cortical hemispheres. To understand how this organization is first established, we investigated functional connectivity between limb regions in the sensorimotor cortex in 400 preterm and term infants aged across the equivalent period to the third trimester of gestation (32–45 weeks postmenstrual age). Masks were obtained from empirically derived functional responses in neonates from an independent data set. We demonstrate the early presence of a crude but spatially organized functional connectivity, that rapidly matures across the preterm period to achieve an adult-like configuration by the normal time of birth. Specifically, connectivity was strongest between homolog regions, followed by connectivity between adjacent regions (different limbs but same hemisphere) already in the preterm brain, and increased with age. These changes were specific to the sensorimotor network. Crucially, these trajectories were strongly dependent on age more than age of birth. This demonstrates that during the perinatal period the sensorimotor cortex undergoes preprogrammed changes determining the functional movement organization that are not altered by preterm birth in absence of brain injury.
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| 23. |
- de Almeida Martins, João P., et al.
(author)
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Computing and visualising intra-voxel orientation-specific relaxation–diffusion features in the human brain
- 2021
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 42:2, s. 310-328
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Journal article (peer-reviewed)abstract
- Diffusion MRI techniques are used widely to study the characteristics of the human brain connectome in vivo. However, to resolve and characterise white matter (WM) fibres in heterogeneous MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and constraints. We have recently introduced a 5D relaxation–diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo-times to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation–diffusion distributions where contributions from different sub-voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre-specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation-specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along with distinct fibre bundles. If combined with fibre-tracking algorithms, the methodology presented in this work has potential for increasing the depth of characterisation of microstructural properties along individual WM pathways.
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| 24. |
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| 25. |
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| 26. |
- de Pierrefeu, Amicie, et al.
(author)
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Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity
- 2018
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 39:4, s. 1777-1788
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Journal article (peer-reviewed)abstract
- Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty. Based on this approach, we obtained reliable classifying performances associated with interpretable predictive patterns, composed of two clearly identifiable clusters in speech-related brain regions. The variation in transition-to-hallucination functional patterns not only from one patient to another but also from one occurrence to the next (e.g., also depending on the sensory modalities involved) appeared to be the major difficulty when developing effective classifiers. Consequently, second, this article aimed to characterize the variability within the prehallucination patterns using an extension of principal component analysis with spatial constraints. The principal components (PCs) and the associated basis patterns shed light on the intrinsic structures of the variability present in the dataset. Such results are promising in the scope of innovative fMRI-guided therapy for drug-resistant hallucinations, such as fMRI-based neurofeedback.
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| 27. |
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| 28. |
- de Zwarte, Sonja M. C., et al.
(author)
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Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
- 2022
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 414-430
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Journal article (peer-reviewed)abstract
- First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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| 29. |
- Demnitz, Naiara, et al.
(author)
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Is it all in the baseline? Trajectories of chair stand performance over 4 years and their association with grey matter structure in older adults
- 2023
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 44:11, s. 4299-4309
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Journal article (peer-reviewed)abstract
- Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.
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| 30. |
- Dima, Danai, et al.
(author)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Journal article (peer-reviewed)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 31. |
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| 32. |
- Eklund, Anders, 1981-, et al.
(author)
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Cluster failure revisited: Impact of first level design and physiological noise on cluster false positive rates
- 2019
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:7, s. 2017-2032
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Journal article (peer-reviewed)abstract
- Methodological research rarely generates a broad interest, yet our work on the validity of cluster inference methods for functional magnetic resonance imaging (fMRI) created intense discussion on both the minutia of our approach and its implications for the discipline. In the present work, we take on various critiques of our work and further explore the limitations of our original work. We address issues about the particular event‐related designs we used, considering multiple event types and randomization of events between subjects. We consider the lack of validity found with one‐sample permutation (sign flipping) tests, investigating a number of approaches to improve the false positive control of this widely used procedure. We found that the combination of a two‐sided test and cleaning the data using ICA FIX resulted in nominal false positive rates for all data sets, meaning that data cleaning is not only important for resting state fMRI, but also for task fMRI. Finally, we discuss the implications of our work on the fMRI literature as a whole, estimating that at least 10% of the fMRI studies have used the most problematic cluster inference method (p = .01 cluster defining threshold), and how individual studies can be interpreted in light of our findings. These additional results underscore our original conclusions, on the importance of data sharing and thorough evaluation of statistical methods on realistic null data.
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| 33. |
- Eklund, Anders, 1981-, et al.
(author)
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Reply to Chen et al.: Parametric methods for cluster inference perform worse for two‐sided t‐tests
- 2019
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:5, s. 1689-1691
-
Journal article (pop. science, debate, etc.)abstract
- One‐sided t‐tests are commonly used in the neuroimaging field, but two‐sided tests should be the default unless a researcher has a strong reason for using a one‐sided test. Here we extend our previous work on cluster false positive rates, which used one‐sided tests, to two‐sided tests. Briefly, we found that parametric methods perform worse for two‐sided t‐tests, and that nonparametric methods perform equally well for one‐sided and two‐sided tests.
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| 34. |
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| 35. |
- Falgas, N., et al.
(author)
-
Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures
- 2020
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 41:8, s. 2004-2013
-
Journal article (peer-reviewed)abstract
- Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid‐long form of the amyloid‐beta protein [Aβ42], total‐tau protein [T‐tau], neurofilament light chain [NfL], neurogranin [Ng], and 14‐3‐3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the “AD signature” and “FTLD signature.” We tested multiple regression models to find which CSF‐biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14‐3‐3; whereas NfL and 14‐3‐3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.
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| 36. |
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| 37. |
- Finkel, Sebastian, et al.
(author)
-
Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch‐regulation in nonsingers
- 2019
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193.
-
Journal article (peer-reviewed)abstract
- While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch‐matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch‐matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx‐S1 iTBS enhanced pitch accuracy (50–250 ms after sound onset) and pitch stability (>250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx‐S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic‐proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx‐S1 in vocal pitch regulation during singing.
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| 38. |
- Frangou, Sophia, et al.
(author)
-
Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
-
In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
-
Journal article (peer-reviewed)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 39. |
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| 40. |
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| 41. |
- Fu, Jingru, et al.
(author)
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Fast three-dimensional image generation for healthy brain aging using diffeomorphic registration
- 2023
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:4, s. 1289-1308
-
Journal article (peer-reviewed)abstract
- Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2 ∈ [.924,.940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.
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| 42. |
- Gurholt, Tiril P., et al.
(author)
-
Intracranial and subcortical volumes in adolescents with early‐onset psychosis : A multisite mega‐analysis from the ENIGMA consortium
- 2020
-
In: Human Brain Mapping. - Stockholm : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 373-384
-
Journal article (peer-reviewed)abstract
- Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
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| 43. |
- Gutman, Boris A, et al.
(author)
-
A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium
- 2022
-
In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 352-372
-
Journal article (peer-reviewed)abstract
- Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
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| 44. |
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| 45. |
- Haugg, Amelie, et al.
(author)
-
Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity?
- 2020
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 41:14, s. 3839-3854
-
Journal article (peer-reviewed)abstract
- Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large inter-individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.
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| 46. |
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| 47. |
- Hedenius, Martina, et al.
(author)
-
Neural correlates of sequence learning in children with developmental dyslexia
- 2022
-
In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:11, s. 3559-3576
-
Journal article (peer-reviewed)abstract
- Developmental Dyslexia (DD) is a condition in which reading accuracy and/or fluency falls substantially below what is expected based on the individuals age, general level of cognitive ability, and educational opportunities. The procedural circuit deficit hypothesis (PDH) proposes that DD may be largely explained in terms of alterations of the cortico-basal ganglia procedural memory system (in particular of the striatum) whereas the (hippocampus-dependent) declarative memory system is intact, and may serve a compensatory role in the condition. The present study was designed to test this hypothesis. Using Magnetic Resonance Imaging, we examined the functional and structural brain correlates of sequence-specific procedural learning (SL) on the serial reaction time task, in 17 children with DD and 18 typically developing (TD) children. The study was performed over 2 days with a 24-h interval between sessions. In line with the PDH, the DD group showed less activation of the striatum during the processing of sequential statistical regularities. These alterations predicted the amount of SL at day 2, which in turn explained variance in children's reading fluency. Additionally, reduced hippocampal activation predicted larger SL gains between day 1 and day 2 in the TD group, but not in the DD group. At the structural level, caudate nucleus volume predicted the amount of acquired SL at day 2 in the TD group, but not in the DD group. The findings encourage further research into factors that promote learning in children with DD, including through compensatory mechanisms.
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| 48. |
- Jensen, Jimmy, et al.
(author)
-
Separate brain regions code for salience vs. valence during reward prediction in humans.
- 2007
-
In: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 28:4, s. 294-302
-
Journal article (peer-reviewed)abstract
- Predicting rewards and avoiding aversive conditions is essential for survival. Recent studies using computational models of reward prediction implicate the ventral striatum in appetitive rewards. Whether the same system mediates an organism's response to aversive conditions is unclear. We examined the question using fMRI blood oxygen level-dependent measurements while healthy volunteers were conditioned using appetitive and aversive stimuli. The temporal difference learning algorithm was used to estimate reward prediction error. Activations in the ventral striatum were robustly correlated with prediction error, regardless of the valence of the stimuli, suggesting that the ventral striatum processes salience prediction error. In contrast, the orbitofrontal cortex and anterior insula coded for the differential valence of appetitive/aversive stimuli. Given its location at the interface of limbic and motor regions, the ventral striatum may be critical in learning about motivationally salient stimuli, regardless of valence, and using that information to bias selection of actions.
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| 49. |
- Kaboodvand, Neda, et al.
(author)
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The retrosplenial cortex : a memory gateway between the cortical default mode network and the medial temporal lobe
- 2018
-
In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 39:5, s. 2020-2034
-
Journal article (peer-reviewed)abstract
- The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial-parietal subsystems, relates to episodic memory (EM) processes. However, past resting-state studies investigating the link between posterior DMN-MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64-68 years), who underwent comprehensive assessment of EM, along with resting-state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph-theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults.
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| 50. |
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