Longitudinal functional connectivity patterns of the default mode network in healthy older adults.

Cross-sectional studies have consistently identified age-associated alterations in default mode network (DMN) functional connectivity (FC). Yet, research on longitudinal trajectories of FC changes of the DMN in healthy aging is less conclusive. For the present study, we used a resting state functional MRI dataset drawn from the Longitudinal Healthy Aging Brain Database Project (LHAB) collected in 5 occasions over a course of 7 years (baseline N = 232, age range: 64-87 y, mean age = 70.85 y). FC strength changes within the DMN and its regions were investigated using a network-based statistical method suitable for the analysis of longitudinal data. The average DMN FC strength remained stable, however, various DMN components showed differential age- and time-related effects. Our results revealed a complex pattern of longitudinal change seen as decreases and increases of FC strength encompassing the majority of DMN regions, while age-related effects were negative and present in select brain areas. These findings testify to the growing importance of longitudinal studies using more sophisticated fine-grained tools needed to highlight the complexity of the functional reorganization of DMN with healthy aging.

Performance of three freely available methods for extracting white matter hyperintensities: FreeSurfer, UBO Detector, and BIANCA.

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 (rs  = 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 (rs  = 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: rs  = 0.80). In summary, our results emphasize the importance of carefully contemplating the choice of the WMH segmentation algorithm and MR-modality.

Functional dedifferentiation of associative resting state networks in older adults - A longitudinal study.

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.

Longitudinal functional brain network reconfiguration in healthy aging.

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.

Topological disintegration of resting state functional connectomes in coma.

Graph theory has been playing an increasingly important role in understanding the organizational properties of brain networks, subsequently providing new tools for the search of neural correlates of consciousness, particularly in the context of patients recovering from severe brain injury. However, this approach is not without challenges, as it usually relies on arbitrarily fixing a threshold in order to retain the strongest connections proportionally equal across subjects. This method increases the comparability between individuals or groups but it risks the inclusion of false positive and therefore spurious connections, especially in the context of brain disorders. Resting state data acquired in 25 coma patients and 22 healthy subjects was compared. We obtained a representative fixed density of significant connections by first applying a p-value-based threshold on healthy subjects' networks and then choosing a threshold at which all individuals exhibited meaningful connections. The obtained threshold (i.e. 10%) was used to construct graphs in the patient group. The findings showed that coma patients have lower number of significant connections with approximately 50% of them not fulfilling the criteria of the fixed density threshold. The remaining patients with relatively preserved global functional connectivity had sufficient significant connections between regions, but showed signs of major whole-brain network reorganization. These results warrant careful consideration in the construction of functional connectomes in patients with disorders of consciousness and set the scene for future studies investigating potential clinical implications of such an approach.

A longitudinal resting-state functional connectivity analysis on trauma exposure and post-traumatic stress symptoms in older individuals.

BACKGROUND: Given the present demographic shift towards an aging society, there is an increased need to investigate the brain's functional connectivity in the context of aging. Trauma exposure and post-traumatic stress disorder (PTSD) symptoms are factors known to impact healthy aging and have been reported to be associated with functional connectivity differences. In the present study, we examined and compared differences in within-default mode network (DMN), within-salience network (SN) and between-DMN-SN functional connectivity, between trauma-exposed individuals with and without PTSD symptoms as well as non-traumatized individuals in a non-clininical older adult sample. METHODS: Resting state functional MRI and behavioral data is taken from the Longitudinal Healthy Aging Brain Database Project (LHAB). For the present analysis, participants who completed the questionnaires on trauma exposure and PTSD symptoms (N = 110 individuals of which n = 50 individuals reported previous trauma exposure and n = 25 individuals reported PTSD symptoms; mean age = 70.55 years, SD = 4.82) were included. RESULTS: The reporting of PTSD symptoms relative to no symptoms was associated with lower within-DMN connectivity, while on a trend level trauma-exposed individuals showed higher within-SN connectivity compared to non-trauma exposed individuals. Consistent with existing models of healthy aging, between-DMN-SN functional connectivity showed an increase across time in older age. CONCLUSION: Present results suggest that alterations in within-DMN and within-SN functional connectivity also occur in non-treatment seeking older adult populations with trauma exposure and in association with PTSD symptoms. These changes manifest, alongside altered between-DMN-SN functional connectivity, in older age supposedly independent of aging-related functional desegregation.

Object-Location Memory Training in Older Adults Leads to Greater Deactivation of the Dorsal Default Mode Network.

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.

Neurocognitive profile of HIV-positive adults on combined antiretroviral therapy: A single-centre study in Serbia.

The advent of combined antiretroviral therapy (cART) has prolonged the life expectancy of HIV + individuals and decreased the incidence of HIV-associated dementia. However, milder forms of neurocognitive impairment remain common and are often associated with poor daily functioning and lower medication adherence. This paper presents a research aimed at exploring the cognitive status differences between HIV + subjects (N = 39) on cART therapy and a group of demographically comparable healthy subjects (N = 39) in Serbia. The significance of differences between the HIV + group and the healthy control group in performance in six cognitive domains was tested using the multivariate analysis of variance. Results showed a lower performance of the HIV + group in the domains of attention/working memory, and learning. HIV-related clinical variables were not significantly associated with cognitive performance. An older age in HIV + patients was significantly related to a lower performance in all six cognitive domains, as opposed to healthy subjects, implying a synergistic interaction between HIV and aging, resulting in accentuated cognitive difficulties. Our findings suggest that even with the absence of a subjective experience of cognitive deficits and with a good basic control of the illness, a certain degree of cognitive deficit can be observed in the tested group.