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Previous literature has focused on predicting a diagnostic label from structural brain imaging. Since subtle changes in the brain precede a cognitive decline in healthy and pathological aging, our study predicts future decline as a continuous trajectory instead. Here, we tested whether baseline multimodal neuroimaging data improve the prediction of future cognitive decline in healthy and pathological aging. Nonbrain data (demographics, clinical, and neuropsychological scores), structural MRI, and functional connectivity data from OASIS-3 (N = 662; age = 46-96 years) were entered into cross-validated multitarget random forest models to predict future cognitive decline (measured by CDR and MMSE), on average 5.8 years into the future. The analysis was preregistered, and all analysis code is publicly available. Combining non-brain with structural data improved the continuous prediction of future cognitive decline (best test-set performance: R2 = 0.42). Cognitive performance, daily functioning, and subcortical volume drove the performance of our model. Including functional connectivity did not improve predictive accuracy. In the future, the prognosis of age-related cognitive decline may enable earlier and more effective individualized cognitive, pharmacological, and behavioral interventions., Competing Interests: Disclosure statement The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

White matter hyperintensities (WMH) of presumed vascular origin are frequently found in MRIs of healthy older adults. WMH are also associated with aging and cognitive decline. Here, we compared and validated three algorithms for WMH extraction: FreeSurfer (T1w), UBO Detector (T1w + FLAIR), and FSL's Brain Intensity AbNormality Classification Algorithm (BIANCA; T1w + FLAIR) using a longitudinal dataset comprising MRI data of cognitively healthy older adults (baseline N = 231, age range 64-87 years). As reference we manually segmented WMH in T1w, three-dimensional (3D) FLAIR, and two-dimensional (2D) FLAIR images which were used to assess the segmentation accuracy of the different automated algorithms. Further, we assessed the relationships of WMH volumes provided by the algorithms with Fazekas scores and age. FreeSurfer underestimated the WMH volumes and scored worst in Dice Similarity Coefficient (DSC = 0.434) but its WMH volumes strongly correlated with the Fazekas scores (r s  = 0.73). BIANCA accomplished the highest DSC (0.602) in 3D FLAIR images. However, the relations with the Fazekas scores were only moderate, especially in the 2D FLAIR images (r s  = 0.41), and many outlier WMH volumes were detected when exploring within-person trajectories (2D FLAIR: ~30%). UBO Detector performed similarly to BIANCA in DSC with both modalities and reached the best DSC in 2D FLAIR (0.531) without requiring a tailored training dataset. In addition, it achieved very high associations with the Fazekas scores (2D FLAIR: r s  = 0.80). In summary, our results emphasize the importance of carefully contemplating the choice of the WMH segmentation algorithm and MR-modality., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Magnetic Resonance Imaging (MRI) studies have shown that cortical volume declines with age. Although volume is a multiplicative measure consisting of thickness and area, few studies have focused on both its components. Information on decline variability and associations between person-specific changes of different brain metrics, brain regions, and cognition is sparse. In addition, the estimates have often been biased by the measurement error, because three repeated measures are minimally required to separate the measurement error from person-specific changes. With a sample size of N = 231, five repeated measures, and an observational time span of seven years, this study explores the associations between changes of different brain metrics, brain regions, and cognitive abilities in aging. Person-specific changes were obtained by latent growth curve models using Bayesian estimation. Our data indicate that both thickness and area are important contributors to volumetric changes. In most brain regions, area clearly declined on average over the years, while thickness showed only little decline. However, there was also substantial variation around the average slope in thickness and area. The correlation pattern of changes in thickness between brain regions was strong and largely homogenous. The pattern for changes in area was similar but weaker, indicating that factors affecting area may be more region-specific. Changes in thickness and volume were substantially correlated with changes in cognition. In some brain regions, changes in area were also related to changes in cognition. Overall, studying the associations between the trajectories of brain regions in different brain metrics provides insights into the regional heterogeneity of structural changes. SIGNIFICANCE STATEMENT: Many studies have described volumetric brain changes in aging. Few studies have focused on both its individual components: area and thickness. Longitudinal studies with three or more time points are highly needed, because they provide more precise average change estimates and, more importantly, allow us to quantify the associations between changes in the different brain metrics, brain regions, and other variables (e.g. cognitive abilities). Studying these associations is important because they can provide information regarding possible underlying factors of these changes. Our study, with a large sample size, five repeated measures, and an observational time span of seven years, provides new insights about the associations between person-specific changes in thickness, area, volume, and cognitive abilities., (Copyright © 2021. Published by Elsevier Inc.)

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 ( n = 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jockwitz, Mérillat, Liem, Oschwald, Amunts, Jäncke and Caspers.)

Substantial evidence indicates that cognitive training can be efficacious for older adults, but findings regarding training-related brain plasticity have been mixed and vary depending on the imaging modality. Recent years have seen a growth in recognition of the importance of large-scale brain networks on cognition. In particular, task-induced deactivation within the default mode network (DMN) is thought to facilitate externally directed cognition, while aging-related decrements in this neural process are related to reduced cognitive performance. It is not yet clear whether task-induced deactivation within the DMN can be enhanced by cognitive training in the elderly. We previously reported durable cognitive improvements in a sample of healthy older adults (age range = 60-75) who completed 6 weeks of process-based object-location memory training ( N = 36) compared to an active control training group ( N = 31). The primary aim of the current study is to evaluate whether these cognitive gains are accompanied by training-related changes in task-related DMN deactivation. Given the evidence for heterogeneity of the DMN, we examine task-related activation/deactivation within two separate DMN branches, a ventral branch related to episodic memory and a dorsal branch more closely resembling the canonical DMN. Participants underwent functional magnetic resonance imaging (fMRI) while performing an untrained object-location memory task at four time points before, during, and after the training period. Task-induced (de)activation values were extracted for the ventral and dorsal DMN branches at each time point. Relative to visual fixation baseline: (i) the dorsal DMN was deactivated during the scanner task, while the ventral DMN was activated; (ii) the object-location memory training group exhibited an increase in dorsal DMN deactivation relative to the active control group over the course of training and follow-up; (iii) changes in dorsal DMN deactivation did not correlate with task improvement. These results indicate a training-related enhancement of task-induced deactivation of the dorsal DMN, although the specificity of this improvement to the cognitive task performed in the scanner is not clear., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mikos, Malagurski, Liem, Mérillat and Jäncke.)

This study used structural magnetic resonance imaging to examine whether specific anatomical features of Broca's and Wernicke's areas are related to language functions in typically developing older subjects with no specific language expertize. Data from 231 subjects from the Zurich LHAB-study are used for this study. For these subjects, we obtained several psychometric measures from which we calculated performance measures reflecting specific psychological functions (language comprehension, verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking). From the MRI measurements, we calculated the cortical thickness and cortical surface of Broca's and Wernicke's areas. Applying multiple regression analyses, we identified a moderately strong relationship between language comprehension and the brain metrics from Broca's and Wernicke's areas and showed that approximately 10% of the variance in language comprehension performance is explained by the linear combination of all perisylvian brain metrics. The other psychological functions (verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking) are not related to these brain metrics. Subsequent detailed analyses revealed that the cortical thickness of Wernicke's area, in particular, contributed most to this structure-function relationship. The better performance in the language comprehension tests was related to a thicker cortex in Wernicke's area. Thus, this study demonstrates a structure-function relationship between the anatomical features of the perisylvian language areas and language comprehension, suggesting that particular anatomical features are associated with better language performance., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Markers of cerebral small vessel disease (CSVD) have previously been associated with age-related cognitive decline. Using longitudinal data of cognitively healthy, older adults (N = 216, mean age at baseline = 70.9 years), we investigated baseline status and change in white matter hyperintensities (WMH) (total, periventricular, deep), normal appearing white matter (NAWM), brain parenchyma volume (BPV) and processing speed over seven years as well as the impact of different covariates by applying latent growth curve (LGC) models. Generally, we revealed a complex pattern of associations between the different CSVD markers. More specifically, we observed that changes of deep WMH (dWMH), as compared to periventricular WMH (pWMH), were more strongly related to the changes of other CSVD markers and also to baseline processing speed performance. Further, the number of lacunes rather than their volume reflected the severity of CSVD. With respect to the studied covariates, we revealed that higher education had a protective effect on subsequent total WMH, pWMH, lacunar number, NAWM volume, and processing speed performance. The indication of antihypertensive drugs was associated with lower lacunar number and volume at baseline and the indication of antihypercholesterolemic drugs came along with higher processing speed performance at baseline. In summary, our results confirm previous findings, and extend them by providing information on true within-person changes, relationships between the different CSVD markers and brain-behavior associations. The moderate to strong associations between changes of the different CSVD markers indicate a common pathological relationship and, thus, support multidimensional treatment strategies., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Healthy aging is associated with changes in cognitive performance and functional brain organization. In fact, cross-sectional studies imply lower modularity and significant heterogeneity in modular architecture across older subjects. Here, we used a longitudinal dataset consisting of four occasions of resting-state-fMRI and cognitive testing (spanning 4 years) in 150 healthy older adults. We applied a graph-theoretic analysis to investigate the time-evolving modular structure of the whole-brain network, by maximizing the multilayer modularity across four time points. Global flexibility, which reflects the tendency of brain nodes to switch between modules across time, was significantly higher in healthy elderly than in a temporal null model. Further, global flexibility, as well as network-specific flexibility of the default mode, frontoparietal control, and somatomotor networks, were significantly associated with age at baseline. These results indicate that older age is related to higher variability in modular organization. The temporal metrics were not associated with simultaneous changes in processing speed or learning performance in the context of memory encoding. Finally, this approach provides global indices for longitudinal change across a given time span and it may contribute to uncovering patterns of modular variability in healthy and clinical aging populations., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Describing the trajectories of age-related change for different brain structures has been of interest in many recent studies. However, our knowledge regarding these trajectories and their associations is still limited due to small sample sizes and low numbers of repeated measures. For the present study, we used a large longitudinal dataset (four measurements over 4 years) comprising anatomical data from a sample of healthy older adults ( N = 231 at baseline). This dataset enables us to gain new insights about volumetric cortical and subcortical changes and their associations in the context of healthy aging. Brain structure volumes were derived from T1-weighted MRI scans using FreeSurfer segmentation tools. Brain structure trajectories were fitted using mixed models and latent growth curve models to gain information about the mean extent and variability of decline trajectories for different brain structures as well as the associations between individual trajectories. On the group level, our analyses indicate similar linear changes for frontal and parietal brain regions, while medial temporal regions showed an accelerated decline with advancing age. Regarding subcortical regions, some structures showed strong declines (e.g., hippocampus), others showed little decline (e.g., pallidum). Our data provide little evidence for sex differences regarding the aforementioned trajectories. Between-person variability of the person-specific slopes (random slopes) was largest in subcortical and medial temporal brain structures. When looking at the associations between the random slopes from each brain structure, we found that the decline is largely homogenous across the majority of cortical brain structures. In subcortical and medial temporal brain structures, however, more heterogeneity of the decline was observed, meaning that the extent of the decline in one structure is less predictive of the decline in another structure. Taken together, our study contributes to enhancing our understanding of structural brain aging by demonstrating (1) that average volumetric change differs across the brain and (2) that there are regional differences with respect to between-person variability in the slopes. Moreover, our data suggest (3) that random slopes are highly correlated across large parts of the cerebral cortex but (4) that some brain regions (i.e., medial temporal regions) deviate from this homogeneity., (Copyright © 2020 Sele, Liem, Mérillat and Jäncke.)

Functional magnetic resonance imaging (fMRI) is a standard tool to investigate the neural correlates of cognition. fMRI noninvasively measures brain activity, allowing identification of patterns evoked by tasks performed during scanning. Despite the long history of this technique, the idiosyncrasies of each dataset have led to the use of ad-hoc preprocessing protocols customized for nearly every different study. This approach is time consuming, error prone and unsuitable for combining datasets from many sources. Here we showcase fMRIPrep (http://fmriprep.org), a robust tool to prepare human fMRI data for statistical analysis. This software instrument addresses the reproducibility concerns of the established protocols for fMRI preprocessing. By leveraging the Brain Imaging Data Structure to standardize both the input datasets (MRI data as stored by the scanner) and the outputs (data ready for modeling and analysis), fMRIPrep is capable of preprocessing a diversity of datasets without manual intervention. In support of the growing popularity of fMRIPrep, this protocol describes how to integrate the tool in a task-based fMRI investigation workflow.

Healthy aging is associated with weaker functional connectivity within resting state brain networks and stronger functional interaction between these networks. This phenomenon has been characterized as reduced functional segregation and has been investigated mainly in cross-sectional studies. Here, we used a longitudinal dataset which consisted of four occasions of resting state fMRI and psychometric cognitive ability data, collected from a sample of healthy older adults (baseline N = 232, age range: 64-87 y, age M = 70.8 y), to investigate the functional segregation of several well-defined resting state networks encompassing the whole brain. We characterized the ratio of within-network and between-network correlations via the well-established segregation index. Our findings showed a decrease over a 4-year interval in the functional segregation of the default mode, frontoparietal control and salience ventral attention networks. In contrast, we showed an increase in the segregation of the limbic network over the same interval. More importantly, the rate of change in functional segregation of the frontoparietal control network was associated with the rate of change in processing speed. These findings support the hypothesis of functional dedifferentiation in healthy aging as well as its role in cognitive function in elderly., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Electrophysiological methods, that is M/EEG, provide unique views into brain health. Yet, when building predictive models from brain data, it is often unclear how electrophysiology should be combined with other neuroimaging methods. Information can be redundant, useful common representations of multimodal data may not be obvious and multimodal data collection can be medically contraindicated, which reduces applicability. Here, we propose a multimodal model to robustly combine MEG, MRI and fMRI for prediction. We focus on age prediction as a surrogate biomarker in 674 subjects from the Cam-CAN dataset. Strikingly, MEG, fMRI and MRI showed additive effects supporting distinct brain-behavior associations. Moreover, the contribution of MEG was best explained by cortical power spectra between 8 and 30 Hz. Finally, we demonstrate that the model preserves benefits of stacking when some data is missing. The proposed framework, hence, enables multimodal learning for a wide range of biomarkers from diverse types of brain signals., Competing Interests: DE, OK, DS, GL, FL, AG No competing interests declared, GV Reviewing editor, eLife, (© 2020, Engemann et al.)

Much of our behaviour is driven by two motivational dimensions-approach and avoidance. These have been related to frontal hemispheric asymmetries in clinical and resting-state EEG studies: Approach was linked to higher activity of the left relative to the right hemisphere, while avoidance was related to the opposite pattern. Increased approach behaviour, specifically towards unhealthy foods, is also observed in obesity and has been linked to asymmetry in the framework of the right-brain hypothesis of obesity. Here, we aimed to replicate previous EEG findings of hemispheric asymmetries for self-reported approach/avoidance behaviour and to relate them to eating behaviour. Further, we assessed whether resting fMRI hemispheric asymmetries can be detected and whether they are related to approach/avoidance, eating behaviour and BMI. We analysed three samples: Sample 1 (n = 117) containing EEG and fMRI data from lean participants, and Samples 2 (n = 89) and 3 (n = 152) containing fMRI data from lean, overweight and obese participants. In Sample 1, approach behaviour in women was related to EEG, but not to fMRI hemispheric asymmetries. In Sample 2, approach/avoidance behaviours were related to fMRI hemispheric asymmetries. Finally, hemispheric asymmetries were not related to either BMI or eating behaviour in any of the samples. Our study partly replicates previous EEG findings regarding hemispheric asymmetries and indicates that this relationship could also be captured using fMRI. Our findings suggest that eating behaviour and obesity are likely to be mediated by mechanisms not directly relating to frontal asymmetries in neuronal activation quantified with EEG and fMRI., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Little is still known about the neuroanatomical substrates related to changes in specific cognitive abilities in the course of healthy aging, and the existing evidence is predominantly based on cross-sectional studies. However, to understand the intricate dynamics between developmental changes in brain structure and changes in cognitive ability, longitudinal studies are needed. In the present article, we review the current longitudinal evidence on correlated changes between magnetic resonance imaging-derived measures of brain structure (e.g. gray matter/white matter volume, cortical thickness), and laboratory-based measures of fluid cognitive ability (e.g. intelligence, memory, processing speed) in healthy older adults. To theoretically embed the discussion, we refer to the revised Scaffolding Theory of Aging and Cognition. We found 31 eligible articles, with sample sizes ranging from n = 25 to n = 731 (median n = 104), and participant age ranging from 19 to 103. Several of these studies report positive correlated changes for specific regions and specific cognitive abilities (e.g. between structures of the medial temporal lobe and episodic memory). However, the number of studies presenting converging evidence is small, and the large methodological variability between studies precludes general conclusions. Methodological and theoretical limitations are discussed. Clearly, more empirical evidence is needed to advance the field. Therefore, we provide guidance for future researchers by presenting ideas to stimulate theory and methods for development.

Aging is a known non-modifiable risk factor for stroke. Usually, this refers to chronological rather than biological age. Biological brain age can be estimated based on cortical and subcortical brain measures. For stroke patients, it could serve as a more sensitive marker of brain health than chronological age. In this study, we investigated whether there is a difference in brain age between stroke survivors and control participants matched on chronological age. We estimated brain age at 3 months after stroke, and then followed the longitudinal trajectory over three time-points: within 6 weeks (baseline), at 3 and at 12 months following their clinical event. We found that brain age in stroke participants was higher compared to controls, with the mean difference between the groups varying between 3.9 and 8.7 years depending on the brain measure used for prediction. This difference in brain age was observed at 6 weeks after stroke and maintained at 3 and 12 months after stroke. The presence of group differences already at baseline suggests that stroke might be an ultimate manifestation of gradual cerebrovascular burden accumulation and brain degeneration. Brain age prediction, therefore, has the potential to be a useful biomarker for quantifying stroke risk., (Copyright © 2019 Egorova, Liem, Hachinski and Brodtmann.)

Age-related differences in white matter (WM) microstructure have been linked to lower performance in tasks of processing speed in healthy older individuals. However, only few studies have examined this link in a longitudinal setting. These investigations have been limited to the correlation of simultaneous changes in WM microstructure and processing speed. Still little is known about the nature of age-related changes in WM microstructure, i.e., regionally distinct vs. global changes. In the present study, we addressed these open questions by exploring whether previous changes in WM microstructure were related to subsequent changes in processing speed: (a) 1 year later; or (b) 2 years later. Furthermore, we investigated whether age-related changes in WM microstructure were regionally specific or global. We used data from four occasions (covering 4 years) of the Longitudinal Healthy Aging Brain (LHAB) database project ( N = 232; age range at baseline = 64-86). As a measure of WM microstructure, we used mean fractional anisotropy (FA) in 10 major WM tracts averaged across hemispheres. Processing speed was measured with four cognitive tasks. Statistical analyses were conducted with bivariate latent change score (LCS) models. We found, for the first time, evidence for lagged couplings between preceding changes in FA and subsequent changes in processing speed 2 years, but not 1 year later in some of the WM tracts (anterior thalamic radiation, superior longitudinal fasciculus). Our results supported the notion that FA changes were different between regional WM tracts rather than globally shared, with some tracts showing mean declines in FA, and others remaining relatively stable across 4 years., (Copyright © 2019 Oschwald, Mérillat, Liem, Röcke, Martin and Jäncke.)

The question whether body height is related to different brain size measures has recently gained renewed interest as some studies have reported that body height correlates with intelligence and several brain size measures. In this study, we re-evaluated this question by examining the relationship between body height and different brain size measures including intracranial volume, total brain volume, total cortical surface area, total cortical volume, volume of normal-appearing white matter, white matter hyperintensity, cortical surface area, cortical thickness, subcortical grey matter volume, cerebellar cortex and cerebellar white matter in a relatively large sample (n = 216) of physically and cognitively healthy elderly subjects (mean age 71 years, age range 65-85 years). We identified small correlations (r = .11-.19) between body height and seven out of 10 brain metrics (total brain volume, cortical surface area, cortical volume, subcortical volume, normal-appearing white matter volume and cerebellar grey as well as white matter volumes) when controlling for sex and age. Based on these small relationships between body height and various brain size measures, we discuss the possible reasons and theoretical problems for these small relationships., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Normal aging is accompanied by an interindividually variable decline in cognitive abilities and brain structure. This variability, in combination with methodical differences and differences in sample characteristics across studies, pose a major challenge for generalizability of results from different studies. Therefore, the current study aimed at cross-validating age-related differences in cognitive abilities and brain structure (measured using cortical thickness [CT]) in two large independent samples, each consisting of 228 healthy older adults aged between 65 and 85 years: the Longitudinal Healthy Aging Brain (LHAB) database (University of Zurich, Switzerland) and the 1000BRAINS (Research Centre Jülich, Germany). Participants from LHAB showed significantly higher education, physical well-being, and cognitive abilities (processing speed, concept shifting, reasoning, semantic verbal fluency, and vocabulary). In contrast, CT values were larger for participants of 1000BRAINS. Though, both samples showed highly similar age-related differences in both, cognitive abilities and CT. These effects were in accordance with functional aging theories, for example, posterior to anterior shift in aging as was shown for the default mode network. Thus, the current two-study approach provides evidence that independently on heterogeneous metrics of brain structure or cognition across studies, age-related effects on cognitive ability and brain structure can be generalized over different samples, assuming the same methodology is used., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

In this study, we examine the relationship between total brain volume (BV) and the volumes of several main brain compartmental (BC) measures (cortical thickness, cortical surface area, corpus callosum, cortical gray matter, normal appearing cerebral white matter (NAWM), amygdala, accumbens, caudate, hippocampus, putamen, pallidum, thalamus, cerebellar gray matter, and cerebellar WM) of physically and cognitively healthy elderly individuals (mean age: 71 years, age range: 65-85 years). The statistical analysis uncovered extremely different relationships between total BV and the aforementioned BC metrics. These relationships ranged from extremely strong (BV explaining 85% of the variability of cerebral WM volume) to a very small relationship (for the caudate volume and the cortical thickness). In addition, cerebral WM and the accumbens volumes scaled out of proportion with BV, whereas most other BC measures scaled less than proportional to BV. Thus, larger brains exhibit relatively larger cerebral NAWM and accumbens volumes than do smaller brains. Cortical gray matter (and most other BC measures), on the other hand, relatively decreases as BV increases, resulting in relatively small cortical gray matter volumes (and relatively small BC measures) for large brains. These relationships are discussed within the context of general allometric scaling principles for the human brain. In addition, possible methodological consequences of analyzing anatomical data on the basis of MRI measurements are also discussed.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Broca's region can be subdivided into its constituent areas 44 and 45 based on established differences in connectivity to superior temporal and inferior parietal regions. The current study builds on our previous work manually parcellating Broca's area on the individual-level by applying these anatomical criteria to functional connectivity data. Here we present an automated observer-independent and anatomy-informed parcellation pipeline with comparable precision to the manual labels at the individual-level. The method first extracts individualized connectivity templates of areas 44 and 45 by assigning to each surface vertex within the ventrolateral frontal cortex the partial correlation value of its functional connectivity to group-level templates of areas 44 and 45, accounting for other template connectivity patterns. To account for cross-subject variability in connectivity, the partial correlation procedure is then repeated using individual-level network templates, including individual-level connectivity from areas 44 and 45. Each node is finally labeled as area 44, 45, or neither, using a winner-take-all approach. The method also incorporates prior knowledge of anatomical location by weighting the results using spatial probability maps. The resulting area labels show a high degree of spatial overlap with the gold-standard manual labels, and group-average area maps are consistent with cytoarchitectonic probability maps of areas 44 and 45. To facilitate reproducibility and to demonstrate that the method can be applied to resting-state fMRI datasets with varying acquisition and preprocessing parameters, the labeling procedure is applied to two open-source datasets from the Human Connectome Project and the Nathan Kline Institute Rockland Sample. While the current study focuses on Broca's region, the method is adaptable to parcellate other cortical regions with distinct connectivity profiles., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

We examined whether it is possible to identify individual subjects on the basis of brain anatomical features. For this, we analyzed a dataset comprising 191 subjects who were scanned three times over a period of two years. Based on FreeSurfer routines, we generated three datasets covering 148 anatomical regions (cortical thickness, area, volume). These three datasets were also combined to a dataset containing all of these three measures. In addition, we used a dataset comprising 11 composite anatomical measures for which we used larger brain regions (11LBR). These datasets were subjected to a linear discriminant analysis (LDA) and a weighted K-nearest neighbors approach (WKNN) to identify single subjects. For this, we randomly chose a data subset (training set) with which we calculated the individual identification. The obtained results were applied to the remaining sample (test data). In general, we obtained excellent identification results (reasonably good results were obtained for 11LBR using WKNN). Using different data manipulation techniques (adding white Gaussian noise to the test data and changing sample sizes) still revealed very good identification results, particularly for the LDA technique. Interestingly, using the small 11LBR dataset also revealed very good results indicating that the human brain is highly individual.

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Mind-wandering has a controversial relationship with cognitive control. Existing psychological evidence supports the hypothesis that episodes of mind-wandering reflect a failure to constrain thinking to task-relevant material, as well the apparently alternative view that control can facilitate the expression of self-generated mental content. We assessed whether this apparent contradiction arises because of a failure to consider differences in the types of thoughts that occur during mind-wandering, and in particular, the associated level of intentionality. Using multi-modal magnetic resonance imaging (MRI) analysis, we examined the cortical organisation that underlies inter-individual differences in descriptions of the spontaneous or deliberate nature of mind-wandering. Cortical thickness, as well as functional connectivity analyses, implicated regions relevant to cognitive control and regions of the default-mode network for individuals who reported high rates of deliberate mind-wandering. In contrast, higher reports of spontaneous mind-wandering were associated with cortical thinning in parietal and posterior temporal regions in the left hemisphere (which are important in the control of cognition and attention) as well as heightened connectivity between the intraparietal sulcus and a region that spanned limbic and default-mode regions in the ventral inferior frontal gyrus. Finally, we observed a dissociation in the thickness of the retrosplenial cortex/lingual gyrus, with higher reports of spontaneous mind-wandering being associated with thickening in the left hemisphere, and higher repots of deliberate mind-wandering with thinning in the right hemisphere. These results suggest that the intentionality of the mind-wandering state depends on integration between the control and default-mode networks, with more deliberation being associated with greater integration between these systems. We conclude that one reason why mind-wandering has a controversial relationship with control is because it depends on whether the thoughts emerge in a deliberate or spontaneous fashion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Impulsive behavior often occurs without forethought and can be driven by strong emotions or sudden impulses, leading to problems in cognition and behavior across a wide range of situations. Although neuroimaging studies have explored the neurocognitive indicators of impulsivity, the large-scale functional networks that contribute to different aspects of impulsive cognition remain unclear. In particular, we lack a coherent account of why impulsivity is associated with such a broad range of different psychological features. Here, we use resting state functional connectivity, acquired in two independent samples, to investigate the neural substrates underlying different aspects of self-reported impulsivity. Based on the involvement of the anterior cingulate cortex (ACC) in cognitive but also affective processes, five seed regions were placed along the caudal to rostral gradient of the ACC. We found that positive urgency was related to functional connectivity between subgenual ACC and bilateral parietal regions such as retrosplenial cortex potentially highlighting this connection as being important in the modulation of the non-prospective, hastiness - related aspects of impulsivity. Further, two impulsivity dimensions were associated with significant alterations in functional connectivity of the supragenual ACC: (i) lack of perseverance was positively correlated to connectivity with the bilateral dorsolateral prefrontal cortex and right inferior frontal gyrus and (ii) lack of premeditation was inversely associated with functional connectivity with clusters within bilateral occipital cortex. Further analysis revealed that these connectivity patterns overlapped with bilateral dorsolateral prefrontal and bilateral occipital regions of the multiple demand network, a large-scale neural system implicated in the general control of thought and action. Together these results demonstrate that different forms of impulsivity have different neural correlates, which are linked to the functional connectivity of a region of anterior cingulate cortex. This suggests that poor perseveration and premeditation might be linked to dysfunctions in how the rostral zone of the ACC interacts with the multiple demand network that allows cognition to proceed in a controlled way., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Structural neuroimaging techniques have been used to identify cortical and subcortical regions constituting the neuroarchitecture of tinnitus. One recent investigation used voxel-based morphometry (VBM) to analyze a sample of tinnitus patients (TI, n = 257) (Schecklmann et al., 2013). A negative relationship between individual distress and cortical volume (CV) in bilateral auditory regions was observed. However, CV has meanwhile been identified as a neuroanatomical measurement that confounds genetically distinct neuroanatomical traits, namely cortical thickness (CT) and cortical surface area (CSA). We performed a re-analysis of the identical sample using the automated FreeSurfer surface-based morphometry (SBM) approach (Fischl, 2012). First, we replicated the negative correlation between tinnitus distress and bilateral supratemporal gray matter volume. Second, we observed a negative correlation for CSA in the left periauditory cortex and anterior insula. Furthermore, we noted a positive correlation between tinnitus duration and CT in the left periauditory cortex as well as a negative correlation in the subcallosal anterior cingulate, a region collated to the serotonergic circuit and germane to inhibitory functions. In short, the results elucidate differential neuroanatomical alterations of CSA and CT for the two independent tinnitus-related psychological traits distress and duration. Beyond this, the study provides further evidence for the distinction and specific susceptibility of CSA and CT within the context of neuroplasticity of the human brain., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Age-related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulum's SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulum's SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well-educated sample of 165 older participants (aged 64-85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed-based resting-state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulum's SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulum's SC and FC for predicting cognitive/motor performance was apparent., (© 2015 Wiley Periodicals, Inc.)

Playing a musical instrument at a professional level is a complex multimodal task requiring information integration between different brain regions supporting auditory, somatosensory, motor, and cognitive functions. These kinds of task-specific activations are known to have a profound influence on both the functional and structural architecture of the human brain. However, until now, it is widely unknown whether this specific imprint of musical practice can still be detected during rest when no musical instrument is used. Therefore, we applied high-density electroencephalography and evaluated whole-brain functional connectivity as well as small-world topologies (i.e., node degree) during resting state in a sample of 15 professional musicians and 15 nonmusicians. As expected, musicians demonstrate increased intra- and interhemispheric functional connectivity between those brain regions that are typically involved in music perception and production, such as the auditory, the sensorimotor, and prefrontal cortex as well as Broca's area. In addition, mean connectivity within this specific network was positively related to musical skill and the total number of training hours. Thus, we conclude that musical training distinctively shapes intrinsic functional network characteristics in such a manner that its signature can still be detected during a task-free condition. Hum Brain Mapp 37:536-546, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only "male" or only "female" features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the "maleness-femaleness" continuum are rare. Rather, most brains are comprised of unique "mosaics" of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme processing., (Copyright © 2015 Elsevier Inc. All rights reserved.)