Resting-state functional connectivity in an auditory network differs between aspiring professional and amateur musicians and correlates with performance.

Auditory experience-dependent plasticity is often studied in the domain of musical expertise. Available evidence suggests that years of musical practice are associated with structural and functional changes in auditory cortex and related brain regions. Resting-state functional magnetic resonance imaging (MRI) can be used to investigate neural correlates of musical training and expertise beyond specific task influences. Here, we compared two groups of musicians with varying expertise: 24 aspiring professional musicians preparing for their entrance exam at Universities of Arts versus 17 amateur musicians without any such aspirations but who also performed music on a regular basis. We used an interval recognition task to define task-relevant brain regions and computed functional connectivity and graph-theoretical measures in this network on separately acquired resting-state data. Aspiring professionals performed significantly better on all behavioral indicators including interval recognition and also showed significantly greater network strength and global efficiency than amateur musicians. Critically, both average network strength and global efficiency were correlated with interval recognition task performance assessed in the scanner, and with an additional measure of interval identification ability. These findings demonstrate that task-informed resting-state fMRI can capture connectivity differences that correspond to expertise-related differences in behavior.

Change in Latent Gray-Matter Structural Integrity Is Associated With Change in Cardiovascular Fitness in Older Adults Who Engage in At-Home Aerobic Exercise.

In aging humans, aerobic exercise interventions have been found to be associated with more positive or less negative changes in frontal and temporal brain areas, such as the anterior cingulate cortex (ACC) and hippocampus, relative to no-exercise control conditions. However, individual measures such as gray-matter (GM) probability may afford less reliable and valid conclusions about maintenance or losses in structural brain integrity than a latent construct based on multiple indicators. Here, we established a latent factor of GM structural integrity based on GM probability assessed by voxel-based morphometry, magnetization transfer saturation, and mean diffusivity. Based on this latent factor, we investigated changes in structural brain integrity during a six-month exercise intervention in brain regions previously reported in studies using volumetric approaches. Seventy-five healthy, previously sedentary older adults aged 63-76 years completed an at-home intervention study in either an exercise group (EG; n = 40) or in an active control group (ACG; n = 35). Measures of peak oxygen uptake (VO2peak) taken before and after the intervention revealed a time-by-group interaction, with positive average change in the EG and no reliable mean change in the ACG. Significant group differences in structural brain integrity changes were observed in the right and left ACC, right posterior cingulate cortex (PCC), and left juxtapositional lobule cortex (JLC). In all instances, average changes in the EG did not differ reliably from zero, whereas average changes in the ACG were negative, pointing to maintenance of structural brain integrity in the EG, and to losses in the ACG. Significant individual differences in change were observed for right ACC and left JLC. Following up on these differences, we found that exercising participants with greater fitness gains also showed more positive changes in structural integrity. We discuss the benefits and limitations of a latent-factor approach to changes in structural brain integrity, and conclude that aerobic fitness interventions are likely to contribute to brain maintenance in old age.

No Evidence for a Boost in Psychosocial Functioning in Older Age After a 6-Months Physical Exercise Intervention.

The beneficial effects of physical exercise on physical health and cognitive functioning have been repeatedly shown. However, evidence of its effect on psychosocial functioning in healthy adults is still scarce or inconclusive. One limitation of many studies examining this link is their reliance on correlational approaches or specific subpopulations, such as clinical populations. The present study investigated the effects of a physical exercise intervention on key factors of psychosocial functioning, specifically well-being, stress, loneliness, and future time perspective. We used data from healthy, previously sedentary older adults (N = 132) who participated in a 6-month at-home intervention, either engaging in aerobic exercise or as part of a control group who participated in foreign language-learning or reading of selected native-language literature. Before and after the intervention, comprehensive cardiovascular pulmonary testing and a psychosocial questionnaire were administered. The exercise group showed significantly increased fitness compared to the control group. Contrary to expectations, however, we did not find evidence for a beneficial effect of this fitness improvement on any of the four domains of psychosocial functioning we assessed. This may be due to pronounced stability of such psychological traits in older age, especially in older adults who show high levels of well-being initially. Alternatively, it may be that the well-documented beneficial effects of physical exercise on brain structure and function, as well as cognition differ markedly from beneficial effects on psychosocial functioning. While aerobic exercise may be the driving factor for the former, positive effects on the latter may only be invoked by other aspects of exercise, for example, experiences of mastery or a feeling of community.

Reliability of quantitative multiparameter maps is high for magnetization transfer and proton density but attenuated for R1 and R2 * in healthy young adults.

We investigate the reliability of individual differences of four quantities measured by magnetic resonance imaging-based multiparameter mapping (MPM): magnetization transfer saturation (MT), proton density (PD), longitudinal relaxation rate (R1 ), and effective transverse relaxation rate (R2 *). Four MPM datasets, two on each of two consecutive days, were acquired in healthy young adults. On Day 1, no repositioning occurred and on Day 2, participants were repositioned between MPM datasets. Using intraclass correlation effect decomposition (ICED), we assessed the contributions of session-specific, day-specific, and residual sources of measurement error. For whole-brain gray and white matter, all four MPM parameters showed high reproducibility and high reliability, as indexed by the coefficient of variation (CoV) and the intraclass correlation (ICC). However, MT, PD, R1 , and R2 * differed markedly in the extent to which reliability varied across brain regions. MT and PD showed high reliability in almost all regions. In contrast, R1 and R2 * showed low reliability in some regions outside the basal ganglia, such that the sum of the measurement error estimates in our structural equation model was higher than estimates of between-person differences. In addition, in this sample of healthy young adults, the four MPM parameters showed very little variability over four measurements but differed in how well they could assess between-person differences. We conclude that R1 and R2 * might carry only limited person-specific information in some regions of the brain in healthy young adults, and, by implication, might be of restricted utility for studying associations to between-person differences in behavior in those regions.

Spend time outdoors for your brain - an in-depth longitudinal MRI study.

OBJECTIVES: The effects of nature on physical and mental health are an emerging topic in empirical research with increasing influence on practical health recommendations. Here we set out to investigate the association between spending time outdoors and brain structural plasticity in conjunctions with self-reported affect. METHODS: We established the Day2day study, which includes an unprecedented in-depth assessment of variability of brain structure in a serial sequence of 40-50 structural magnetic resonance imaging (MRI) acquisitions of each of six young healthy participants for 6-8 months (n = 281 MRI scans in total). RESULTS: A whole-brain analysis revealed that time spent outdoors was positively associated with grey matter volume in the right dorsolateral prefrontal cortex and positive affect, also after controlling for physical activity, fluid intake, free time, and hours of sunshine. CONCLUSIONS: Results indicate remarkable and potentially behaviorally relevant plasticity of cerebral structure within a short time frame driven by the daily time spent outdoors. This is compatible with anecdotal evidence of the health and mood-promoting effects of going for a walk. The study may provide the first evidence for underlying cerebral mechanisms of so-called green prescriptions with possible consequences for future interventions in mental disorders.

Observing Plasticity of the Auditory System: Volumetric Decreases Along with Increased Functional Connectivity in Aspiring Professional Musicians.

Playing music relies on several sensory systems and the motor system, and poses strong demands on control processes, hence, offering an excellent model to study how experience can mold brain structure and function. Although most studies on neural correlates of music expertise rely on cross-sectional comparisons, here we compared within-person changes over time in aspiring professionals intensely preparing for an entrance exam at a University of the Arts to skilled amateur musicians not preparing for a music exam. In the group of aspiring professionals, we observed gray-matter volume decrements in left planum polare, posterior insula, and left inferior frontal orbital gyrus over a period of about 6 months that were absent among the amateur musicians. At the same time, the left planum polare, the largest cluster of structural change, showed increasing functional connectivity with left and right auditory cortex, left precentral gyrus, left supplementary motor cortex, left and right postcentral gyrus, and left cingulate cortex, all regions previously identified to relate to music expertise. In line with the expansion-renormalization pattern of brain plasticity (Wenger et al., 2017a. Expansion and renormalization of human brain structure during skill acquisition. Trends Cogn Sci. 21:930-939.), the aspiring professionals might have been in the selection and refinement period of plastic change.

Identifying predictors of within-person variance in MRI-based brain volume estimates.

Adequate reliability of measurement is a precondition for investigating individual differences and age-related changes in brain structure. One approach to improve reliability is to identify and control for variables that are predictive of within-person variance. To this end, we applied both classical statistical methods and machine-learning-inspired approaches to structural magnetic resonance imaging (sMRI) data of six participants aged 24-31 years gathered at 40-50 occasions distributed over 6-8 months from the Day2day study. We explored the within-person associations between 21 variables covering physiological, affective, social, and environmental factors and global measures of brain volume estimated by VBM8 and FreeSurfer. Time since the first scan was reliably associated with Freesurfer estimates of grey matter volume and total cortex volume, in line with a rate of annual brain volume shrinkage of about 1 percent. For the same two structural measures, time of day also emerged as a reliable predictor with an estimated diurnal volume decrease of, again, about 1 percent. Furthermore, we found weak predictive evidence for the number of steps taken on the previous day and testosterone levels. The results suggest a need to control for time-of-day effects in sMRI research. In particular, we recommend that researchers interested in assessing longitudinal change in the context of intervention studies or longitudinal panels make sure that, at each measurement occasion, (a) a given participant is measured at the same time of day; (b) all participants are measured at about the same time of day. Furthermore, the potential effects of physical activity, including moderate amounts of aerobic exercise, and testosterone levels on MRI-based measures of brain structure deserve further investigation.

Assessing reliability in neuroimaging research through intra-class effect decomposition (ICED).

Magnetic resonance imaging has become an indispensable tool for studying associations of structural and functional properties of the brain with behavior in humans. However, generally recognized standards for assessing and reporting the reliability of these techniques are still lacking. Here, we introduce a new approach for assessing and reporting reliability, termed intra-class effect decomposition (ICED). ICED uses structural equation modeling of data from a repeated-measures design to decompose reliability into orthogonal sources of measurement error that are associated with different characteristics of the measurements, for example, session, day, or scanning site. This allows researchers to describe the magnitude of different error components, make inferences about error sources, and inform them in planning future studies. We apply ICED to published measurements of myelin content and resting state functional connectivity. These examples illustrate how longitudinal data can be leveraged separately or conjointly with cross-sectional data to obtain more precise estimates of reliability.

Expansion and Renormalization of Human Brain Structure During Skill Acquisition.

Research on human brain changes during skill acquisition has revealed brain volume expansion in task-relevant areas. However, the large number of skills that humans acquire during ontogeny militates against plasticity as a perpetual process of volume growth. Building on animal models and available theories, we promote the expansion-renormalization model for plastic changes in humans. The model predicts an initial increase of gray matter structure, potentially reflecting growth of neural resources like neurons, synapses, and glial cells, which is followed by a selection process operating on this new tissue leading to a complete or partial return to baseline of the overall volume after selection has ended. The model sheds new light on available evidence and current debates and fosters the search for mechanistic explanations.

Day2day: investigating daily variability of magnetic resonance imaging measures over half a year.

BACKGROUND: Most studies of brain structure and function, and their relationships to cognitive ability, have relied on inter-individual variability in magnetic resonance (MR) images. Intra-individual variability is often ignored or implicitly assumed to be equivalent to the former. Testing this assumption empirically by collecting enough data on single individuals is cumbersome and costly. We collected a dataset of multiple MR sequences and behavioural covariates to quantify and characterize intra-individual variability in MR images for multiple individuals. METHODS AND DESIGN: Eight participants volunteered to undergo brain scanning 40-50 times over the course of 6 months. Six participants completed the full set of sessions. T1-weighted, T2*-weighted during rest, T2-weighted high-resolution hippocampus, diffusion-tensor imaging (DTI), and proton magnetic resonance spectroscopy sequences were collected, along with a rich set of stable and time-varying physical, behavioural and physiological variables. Participants did not change their lifestyle or participated in any training programs during the period of data collection. CONCLUSION: This imaging dataset provides a large number of MRI scans in different modalities for six participants. It enables the analysis of the time course and correlates of intra-individual variability in structural, chemical, and functional aspects of the human brain.

Resting-state fMRI correlations: From link-wise unreliability to whole brain stability.

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze within- and between-subject variability and test-retest reliability of resting-state functional connectivity (FC) in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. We adopt a statistical framework that enables us to identify different sources of variability in FC. We show that the low reliability of single links can be significantly improved by using multiple scans per subject. Moreover, in contrast to earlier studies, we show that spatial heterogeneity in FC reliability is not significant. Finally, we demonstrate that despite the low reliability of individual links, the information carried by the whole-brain FC matrix is robust and can be used as a functional fingerprint to identify individual subjects from the population.

Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions.

It is widely accepted that the brain and the immune system continuously interact during normal as well as pathological functioning. Human aging is commonly accompanied by low-grade inflammation in both the immune and central nervous systems, thought to contribute to many age-related diseases. This review of the current literature focuses first on the normal neuroimmune interactions occurring in the brain, which promote learning, memory and neuroplasticity. Further, we discuss the protective and dynamic role of barriers to neuroimmune interactions, which have become clearer with the recent discovery of the meningeal lymphatic system. Next, we consider age-related changes of the immune system and possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. We survey the major immunomodulators and neuroregulators in the aging brain and their highly tuned dynamic and reciprocal interactions. Finally, we consider our current understanding of how physical activity, as well as a combination of physical and cognitive interventions, may mediate anti-inflammatory effects and thus positively impact brain aging.

Repeated Structural Imaging Reveals Nonlinear Progression of Experience-Dependent Volume Changes in Human Motor Cortex.

Evidence for experience-dependent structural brain change in adult humans is accumulating. However, its time course is not well understood, as intervention studies typically consist of only 2 imaging sessions (before vs. after training). We acquired up to 18 structural magnetic resonance images over a 7-week period while 15 right-handed participants practiced left-hand writing and drawing. After 4 weeks, we observed increases in gray matter of both left and right primary motor cortices relative to a control group; 3 weeks later, these differences were no longer reliable. Time-series analyses revealed that gray matter in the primary motor cortices expanded during the first 4 weeks and then partially renormalized, in particular in the right hemisphere, despite continued practice and increasing task proficiency. Similar patterns of expansion followed by partial renormalization are also found in synaptogenesis, cortical map plasticity, and maturation, and may qualify as a general principle of structural plasticity. Research on human brain plasticity needs to encompass more than 2 measurement occasions to capture expansion and potential renormalization processes over time.

Neurotransmitter changes during interference task in anterior cingulate cortex: evidence from fMRI-guided functional MRS at 3 T.

Neural activity as indirectly observed in blood oxygenation level-dependent (BOLD) response is thought to reflect changes in neurotransmitter flux. In this study, we used fMRI-guided functional magnetic resonance spectroscopy (MRS) to measure metabolite/BOLD associations during a cognitive task at 3 T. GABA and glutamate concentration in anterior cingulate cortex (ACC) were determined by means of MRS using the SPECIAL pulse sequence before, during and after the performance of a manual Stroop task. MRS voxel positions were centred around individuals' BOLD activity during Stroop performance. Levels of GABA and glutamate showed inverted U-shape patterns across measurement time points (before, during, and after task), glutamine increased linearly and total creatine did not change. The GABA increase during task performance was associated with ACC BOLD signal changes in both congruent and incongruent Stroop conditions. Using an fMRI-guided MRS approach, an association between induced inhibitory neurotransmitter increase and BOLD changes was observed. The proposed procedure might allow the in vivo investigation of normal and dysfunctional associations between neurotransmitters and BOLD signal crucial for cerebral functioning.

Behavioral correlates of changes in hippocampal gray matter structure during acquisition of foreign vocabulary.

Experience can affect human gray matter volume. The behavioral correlates of individual differences in such brain changes are not well understood. In a group of Swedish individuals studying Italian as a foreign language, we investigated associations among time spent studying, acquired vocabulary, baseline performance on memory tasks, and gray matter changes. As a way of studying episodic memory training, the language learning focused on acquiring foreign vocabulary and lasted for 10weeks. T1-weighted structural magnetic resonance imaging and cognitive testing were performed before and after the studies. Learning behavior was monitored via participants' use of a smartphone application dedicated to the study of vocabulary. A whole-brain analysis showed larger changes in gray matter structure of the right hippocampus in the experimental group (N=33) compared to an active control group (N=23). A first path analyses revealed that time spent studying rather than acquired knowledge significantly predicted change in gray matter structure. However, this association was not significant when adding performance on baseline memory measures into the model, instead only the participants' performance on a short-term memory task with highly similar distractors predicted the change. This measure may tap similar individual difference factors as those involved in gray matter plasticity of the hippocampus.

Plasticity of brain and cognition in older adults.

Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.

Comparing manual and automatic segmentation of hippocampal volumes: reliability and validity issues in younger and older brains.

We compared hippocampal volume measures obtained by manual tracing to automatic segmentation with FreeSurfer in 44 younger (20-30 years) and 47 older (60-70 years) adults, each measured with magnetic resonance imaging (MRI) over three successive time points, separated by four months. Retest correlations over time were very high for both manual and FreeSurfer segmentations. With FreeSurfer, correlations over time were significantly lower in the older than in the younger age group, which was not the case with manual segmentation. Pearson correlations between manual and FreeSurfer estimates were sufficiently high, numerically even higher in the younger group, whereas intra-class correlation coefficient (ICC) estimates were lower in the younger than in the older group. FreeSurfer yielded higher volume estimates than manual segmentation, particularly in the younger age group. Importantly, FreeSurfer consistently overestimated hippocampal volumes independently of manually assessed volume in the younger age group, but overestimated larger volumes in the older age group to a less extent, introducing a systematic age bias in the data. Age differences in hippocampal volumes were significant with FreeSurfer, but not with manual tracing. Manual tracing resulted in a significant difference between left and right hippocampus (right > left), whereas this asymmetry effect was considerably smaller with FreeSurfer estimates. We conclude that FreeSurfer constitutes a feasible method to assess differences in hippocampal volume in young adults. FreeSurfer estimates in older age groups should, however, be interpreted with care until the automatic segmentation pipeline has been further optimized to increase validity and reliability in this age group.

Structural brain plasticity in adult learning and development.

Recent research using magnetic resonance imaging has documented changes in the adult human brain's grey matter structure induced by alterations in experiential demands. We review this research and relate it to models of brain plasticity from related strands of research, such as work on animal models. This allows us to generate recommendations and predictions for future research that may advance the understanding of the function, sequential progression, and microstructural nature of experience-dependent changes in regional brain volumes. Informed by recent evidence on adult age differences in structural brain plasticity, we show how understanding learning-related changes in human brain structure can expand our knowledge about adult development and aging. We hope that this review will promote research on the mechanisms regulating experience-dependent structural plasticity of the adult human brain.

The dynamics of change in striatal activity following updating training.

Increases in striatal activity have been suggested to mediate training-related improvements in working-memory ability. We investigated the temporal dynamics of changes in task-related brain activity following training of working memory. Participants in an experimental group and an active control group, trained on easier tasks of a constant difficulty in shorter sessions than the experimental group, were measured before, after about 1 week, and after more than 50 days of training. In the experimental group an initial increase of working-memory related activity in the functionally defined right striatum and anatomically defined right and left putamen was followed by decreases, resulting in an inverted u-shape function that relates activity to training over time. Activity increases in the striatum developed slower in the active control group, observed at the second posttest after more than 50 days of training. In the functionally defined left striatum, initial activity increases were maintained after more extensive training and the pattern was similar for the two groups. These results shed new light on the relation between activity in the striatum (especially the putamen) and the effects of working memory training, and illustrate the importance of multiple measurements for interpreting effects of training on regional brain activity.