The combination of transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) can provide original data to investigate age‐related brain changes. We examined ...neural activity modulations induced by two multifocal tDCS procedures based on two distinct montages fitting two N‐back task‐based fMRI patterns (“compensatory” and “maintenance”) related to high working memory (WM) in a previous publication (Fernández‐Cabello et al. Neurobiol Aging (2016);48:23–33). We included 24 participants classified as stable or decliners according to their 4‐year WM trajectories following a retrospective longitudinal approach. Then, we studied longitudinal fMRI differences between groups (stable and decliners) and across multifocal tDCS montages (“compensatory” and “maintenance”) applied using a single‐blind sham‐controlled cross‐over design. Decliners evidenced over‐activation of non‐related WM areas after 4 years of follow‐up. Focusing on tDCS effects, among the decliner group, the “compensatory”‐tDCS montage reduced the activity over the posterior regions where these subjects showed longitudinal hyperactivation. These results reinforce the notion that tDCS effects are characterized by an activity reduction and might be more noticeable in compromised systems. Importantly, the data provide novel evidence that cognitive trajectories predict tDCS effects in older adults.
Twenty‐four participants were classified as stable or decliners according to their 4‐year working memory (WM) trajectories following a retrospective longitudinal approach. Then, we studied longitudinal functional magnetic resonance imaging (fMRI) differences between groups (stable and decliners) and across two multifocal transcranial direct current stimulation (tDCS) montages (fitting “compensatory” and “maintenance” fMRI patterns related to high WM performance) applied inside the scan using a single‐blind sham‐controlled cross‐over design. Among the decliner group, the “compensatory”‐tDCS montage reduced the activity over the posterior regions where these subjects showed longitudinal hyperactivation.
Abstract Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The ‘passive model’ considers head or brain measures as anatomical substrates ...of CR, whereas the ‘active model’ emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the ‘passive’ and ‘active’ models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), ‘education–occupation’, a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables.
Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in ...patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Stakeholder engagement remains scarce in basic brain research. However, it can greatly improve the relevance of investigations and accelerate the translation of study findings to policy. ...The Lifebrain consortium investigated risk and protective factors influencing brain health using cognition, lifestyle and imaging data from European cohorts. Stakeholder activities of Lifebrain—organized in a separate work package—included organizing stakeholder events, investigating public perceptions of brain health and dissemination. Here, we describe the experiences of researchers and stakeholders regarding stakeholder engagement in the Lifebrain project.
Methods
Stakeholder engagement in Lifebrain was evaluated through surveys among researchers and stakeholders and stakeholders' feedback at stakeholder events through evaluation forms. Survey data were analysed using a simple content analysis approach, and results from evaluation forms were summarized after reviewing the frequency of responses.
Results
Consortium researchers and stakeholders experienced the engagement activities as meaningful and relevant. Researchers highlighted that it made the research and research processes more visible and contributed to new networks, optimized data collection on brain health perceptions and the production of papers and provided insights into stakeholder views. Stakeholders found research activities conducted in the stakeholder engagement work package to be within their field of interest and research results relevant to their work. Researchers identified barriers to stakeholder engagement, including lack of time, difficulties in identifying relevant stakeholders, and challenges in communicating complex scientific issues in lay language and maintaining relationships with stakeholders over time. Stakeholders identified barriers such as lack of budget, limited resources in their organization, time constraints and insufficient communication between researchers and stakeholders.
Conclusion
Stakeholder engagement in basic brain research can greatly benefit researchers and stakeholders alike. Its success is conditional on dedicated human and financial resources, clear communication, transparent mutual expectations and clear roles and responsibilities.
Public Contribution
Patient organizations, research networks, policymakers and members of the general public were involved in engagement and research activities throughout the project duration.
Abstract
Background and Objectives
A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in ...brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain.
Design and Methods
We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis.
Results
Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries.
Discussion and Implications
Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.
Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that ...genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow ...fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume–volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.
Cortical surface area and thickness abnormalities have been observed in patients with schizophrenia and bipolar disorders; however, no study thus far has examined cortical morphologic measurements in ...children and adolescents at genetic risk for the disorders comparatively.
One hundred thirty-seven participants, including 36 offspring of patients with schizophrenia (SzO), 54 offspring of patients with bipolar disorder (BpO), and 47 offspring of community controls (CcO), 6 to 17 years old, were assessed with clinical and neuroimaging methods. Sixty-nine percent of the sample was reassessed at a 27.6-month (mean) follow-up. Cortical surface reconstruction was applied to measure cortical area and thickness using FreeSurfer; mixed-effects models were used to investigate cross-sectional and longitudinal differences in global and lobar morphologic measurements.
The SzO group exhibited a cross-sectional decrease in global, parietal, and occipital lobe surface area compared with the CcO group, and in the occipital lobe compared with the BpO group. In the SzO group, global and parietal surface area values were inversely associated with attenuated positive and negative prodromal symptom scores. No cross-sectional differences in cortical thickness were observed. Division of the sample by pubertal status showed group-by-time interactions in the pubertal and postpubertal SzO subgroup, with less longitudinal decrease in cortical surface area and thickness than in the CcO and BpO subgroups, respectively.
The SzO, but not the BpO, group was characterized by cross-sectional decreases in surface area, and this was associated with prodromal symptoms. Longitudinal changes in cortical morphology associated with risk for schizophrenia may be expressed differently according to developmental stage.
Repetitive Negative Thinking (RNT) includes negative thoughts about the future and past, and is a risk factor for depression and anxiety. Prefrontal and anterior cingulate cortices have been linked ...to RNT but several regions within large-scale networks are also involved, the efficiency of which depends on their ability to remain segregated.
Associations between RNT and system segregation (SyS) of the Anterior Salience Network (ASN), Default Mode Network (DMN) and Executive Control Network (ECN) were explored in healthy middle-aged adults (
= 341), after undergoing resting-state functional magnetic resonance imaging. Regression analyses were conducted with RNT as outcome variable. Explanatory variables were: SyS, depression, emotional stability, cognitive complaints, age and sex.
Analyses indicated that RNT was associated with depression, emotional stability, cognitive complaints, age and segregation of the left ECN (LECN) and ASN. Further, the ventral DMN (vDMN) presented higher connectivity with the ASN and decreased connectivity with the LECN, as a function of RNT.
Higher levels of perseverative thinking were related to increased segregation of the LECN and decreased segregation of the ASN. The dissociative connectivity of these networks with the vDMN may partially account for poorer cognitive control and increased self-referential processes characteristic of RNT.
Combining non-invasive brain stimulation (NIBS) with resting-state functional magnetic resonance imaging (rs-fMRI) is a promising approach to characterize and potentially optimize the brain networks ...subtending cognition that changes as a function of age. However, whether multifocal NIBS approaches are able to modulate rs-fMRI brain dynamics in aged populations, and if these NIBS-induced changes are consistent with the simulated electric current distribution on the brain remains largely unknown. In the present investigation, thirty-one cognitively healthy older adults underwent two different multifocal real transcranial direct current stimulation (tDCS) conditions (C1 and C2) and a sham condition in a crossover design during a rs-fMRI acquisition. The real tDCS conditions were designed to electrically induce two distinct complex neural patterns, either targeting generalized frontoparietal cortical overactivity (C1) or a detachment between the frontal areas and the posteromedial cortex (C2). Data revealed that the two tDCS conditions modulated rs-fMRI differently. C1 increased the coactivation of multiple functional couplings as compared to sham, while a smaller number of connections increased in C1 as compared to C2. At the group level, C1-induced changes were topographically consistent with the calculated electric current density distribution. At the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was related with the magnitude of the simulated electric current density estimates. These results highlight that multifocal tDCS procedures can effectively change rs-fMRI neural functioning in advancing age, being the induced modulation consistent with the spatial distribution of the simulated electric current on the brain. Moreover, our data supports that individually tailoring NIBS-based interventions grounded on subject-specific structural data might be crucial to increase tDCS potential in future studies amongst older adults.
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