•LC-NE system is involved in motivation and cognition in humans.•This system participates in mechanisms of stress response.•LC-NE system may be connected to the cognitive and motivational deficits of ...SCZ.•A combination of methodological approaches is proposed to answer open questions.
Several lines of evidence have suggested for decades a role for norepinephrine (NE) in the pathophysiology and treatment of schizophrenia. Recent experimental findings reveal anatomical and physiological properties of the locus coeruleus-norepinephrine (LC-NE) system and its involvement in brain function and cognition. Here, we integrate these two lines of evidence. First, we review the functional and structural properties of the LC-NE system and its impact on functional brain networks, cognition, and stress, with special emphasis on recent experimental and theoretical advances. Subsequently, we present an update about the role of LC-associated functions for the pathophysiology of schizophrenia, focusing on the cognitive and motivational deficits. We propose that schizophrenia phenomenology, in particular cognitive symptoms, may be explained by an abnormal interaction between genetic susceptibility and stress-initiated LC-NE dysfunction. This in turn, leads to imbalance between LC activity modes, dysfunctional regulation of brain network integration and neural gain, and deficits in cognitive functions. Finally, we suggest how recent development of experimental approaches can be used to characterize LC function in schizophrenia.
Functional neuroimaging of small brainstem structures in humans is gaining interest due to their potential importance in aging and many clinical conditions. Researchers have used different methods to ...measure activity in the locus coeruleus (LC), the main noradrenergic nucleus in the brain. However, the extent to which these different LC localization methods yield similar results is unclear. In the present article, we compared four different approaches to estimate localization of the LC in a large sample (N = 98): 1) a probabilistic map from a previous study, 2) masks segmented from neuromelanin-sensitive scans, both manually and semi-automatically, 3) components from a masked-independent components analysis of the functional data, and 4) a mask from pupil regression of the functional data. The four methods have all been used previously in the imaging community to localize the LC in vivo in humans. We report several measures of similarity between the LC masks obtained from the different methods. In addition, we compare functional connectivity maps obtained from the different masks. We conclude that sample-specific masks appear more suitable than masks obtained from an independent sample, that masks based on structural versus functional methods may capture different portions of LC, and that, at the group level, the creation of a “consensus” mask using more than one approach may give a better estimate of LC localization.
Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We ...addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ(1-42) levels, and apolipoprotein ε4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.
Cognitive aging is accompanied by a range of structural and functional differences in the brain, even in the absence of neurodegenerative disease. Functional magnetic resonance imaging (fMRI) studies ...have reported increased bilateral activation during task performance in elderly participants compared to their younger counterparts, particularly in frontal regions. Alterations have also been observed in the functional architecture of the resting brain, suggesting that aging is associated with changes in the organization of the networks of the brain. However, previous studies have largely focused on the default mode network, and little is known about the effects of age on other resting state-networks (RSNs). The aim of the present study was to investigate age-differences in resting state functional connectivity (RSFC) using fMRI data obtained during rest from 238 healthy participants aged 21–80years. Using independent component analysis (ICA) and dual-regression, the results revealed age-related increases in RSFC across a range of RSNs, including task-positive networks in frontal and parietal regions. In contrast, age-related reductions in the default mode network and occipital visual networks were observed. Furthermore, whereas the effects of age on the various RSNs were found independent of age-related decreases in gray matter volume, sex and subject motion, we report strong positive and widespread effects of estimated subject motion on the RSFC across RSNs. The results provide support for the notion of network-specific effects in aging, manifested as increased tonic activation of task-positive networks, supporting higher-order cognitive functions and cognitive control, along with reduced task-negative default mode network and sensory visual networks during rest. The present results also corroborate recent evidence of strong influence of subject motion on estimated functional connectivity measures and strongly suggest that studies using RSFC measures as imaging phenotypes should adjust for individual differences in in-scanner subject motion.
► We delineated age-variance in resting functional connectivity in 238 adults. ► Increasing co-activation in frontal and parietal networks with increasing age ► Decreasing co-activation in the DMN and two posterior RSNs with increasing age ► Strong positive correlations between connectivity and motion in all tested RSNs ► Results support the notion of network-specific effects of aging.
To examine subjective and objective socioeconomic status (SSES and OSES, respectively) as predictors, cognitive abilities as confounders, and personal control perceptions as mediators of health ...behaviours.
A cross-sectional study including 197 participants aged 30-50 years, recruited from the crowd-working platform, Prolific.
The Good Health Practices Scale, a 16-item inventory of health behaviours.
SSES was the most important predictor of health behaviours (beta = 0.19,
< 0.01). Among the OSES indicators, education (beta = 0.16,
< 0.05), but not income, predicted health behaviours. Intelligence (
= -0.16,
< 0.05) and memory (
= -0.22,
< 0.01) were negatively correlated with health-promoting behaviours, and the effect of memory was upheld in the multivariate model (beta = -0.17,
< 0.05). Personal control perceptions (mastery and constraints) did not act as mediators.
SSES predicted health behaviours beyond OSES. The effect of socioeconomic indicators was not confounded by cognitive abilities. Surprisingly, cognitive abilities were negatively associated with health-promoting behaviours. Future research should emphasise SSES as a predictor of health behaviours. Delineating the psychological mechanisms linking SSES with health behaviours would be a valuable contribution toward improved understanding of socioeconomic disparities in health behaviours.
Abstract Magnetic resonance imaging (MRI) is the principal method for studying structural age-related brain changes in vivo . However, previous research has yielded inconsistent results, precluding ...understanding of structural changes of the aging brain. This inconsistency is due to methodological differences and/or different aging patterns across samples. To overcome these problems, we tested age effects on 17 different neuroanatomical structures and total brain volume across five samples, of which one was split to further investigate consistency (883 participants). Widespread age-related volume differences were seen consistently across samples. In four of the five samples, all structures, except the brainstem, showed age-related volume differences. The strongest and most consistent effects were found for cerebral cortex, pallidum, putamen and accumbens volume. Total brain volume, cerebral white matter, caudate, hippocampus and the ventricles consistently showed non-linear age functions. Healthy aging appears associated with more widespread and consistent age-related neuroanatomical volume differences than previously believed.
•Brain age CNNs achieve state-of-the-art performance in a large, multisite dataset.•A regression-based architecture outperform others in generalizing to new scanners.•Deviations in brain age ...associate with plausible biological and lifestyle variables.•Encoded representations are better predictors for disorder than the brain age delta.
The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data — the brain age delta — has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.
Over the past few years, several studies have explored the relationship between resting-state baseline pupil size and cognitive abilities, including fluid intelligence, working memory capacity, and ...attentional control. However, the results have been inconsistent. Here we present the findings from two experiments designed to replicate and expand previous research, with the aim of clarifying previous mixed findings. In both experiments, we measured baseline pupil size while participants were not engaged in any tasks, and assessed fluid intelligence using a matrix task. In one experiment we also measured working memory capacity (letter-number-sequencing task) and attentional control (attentional-capture task). We controlled for several personal and demographic variables known to influence pupil size, such as age and nicotine consumption. Our analyses revealed no relationship between resting-state pupil size (average or variability) and any of the measured constructs, neither before nor after controlling for confounding variables. Taken together, our results suggest that any relationship between resting-state pupil size and cognitive abilities is likely to be weak or non-existent.
Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school ...students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R
= 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country.
Human cognitive development is manifold, with different functions developing at different speeds at different ages. Attention is an important domain of this cognitive development, and involves ...distinct developmental trajectories for separate functions, including conflict processing, selection of sensory input and alertness. In children, several studies using the Attention Network Test (ANT) have investigated the development of three attentional networks that carry out the functions of executive control, orienting and alerting. There is, however, a lack of studies on the development of these attentional components across adolescence, limiting our understanding of their protracted development. To fill this knowledge gap, we performed a mixed cross-sectional and longitudinal study using mixed methods to examine the development of the attentional components and their intraindividual variability from late childhood to young adulthood (n = 287, n observations = 408, age range = 8.5–26.7 years, mean follow up interval = 4.4 years). The results indicated that executive control stabilized during late adolescence, while orienting and alerting continued to develop into young adulthood. In addition, a continuous development into young adulthood was observed for the intraindividual variability measures of orienting and alerting. In a subsample with available magnetic resonance imaging (MRI) data (n = 169, n observations = 281), higher alerting scores were associated with thicker cortices within a right prefrontal cortical region and greater age-related cortical thinning in left rolandic operculum, while higher orienting scores were associated with greater age-related cortical thinning in frontal and parietal regions. Finally, increased consistency of orienting performance was associated with thinner cortex in prefrontal regions and reduced age-related thinning in frontal regions.
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