Resting-state functional dynamic connectivity and healthy aging: A sliding-window network analysis.

Dynamic functional connectivity underlying temporal summation of pain in fibromyalgia

This study examines the relationship of engagement in different lifestyle activities to connectivity in large-scale functional brain networks, and whether network connectivity modifies cognitive decline, independent of brain amyloid levels. Participants (N = 153, mean age = 69years, including N = 126 with amyloid imaging) were cognitively normal when they completed resting-state functional magnetic resonance imaging, a lifestyle activity questionnaire, and cognitive testing. They were followed with annual cognitive tests up to 5years (mean = 3.3years). Linear regressions showed positive relationships between cognitive activity engagement and connectivity within the dorsal attention network, and between physical activity levels and connectivity within the default-mode, limbic, and frontoparietal control networks, and global within-network connectivity. Additionally, higher cognitive and physical activity levels were independently associated with higher network modularity, a measure of functional network specialization. These associations were largely independent of APOE4 genotype, amyloid burden, global brain atrophy, vascular risk, and level of cognitive reserve. Moreover, higher connectivity in the dorsal attention, default-mode, and limbic networks, and greater global connectivity and modularity were associated with reduced cognitive decline, independent of APOE4 genotype and amyloid burden. These findings suggest that changes in functional brain connectivity may be one mechanism by which lifestyle activity engagement reduces cognitive decline.

Multiple sclerosis impairs regional functional connectivity in the cerebellum☆

Changes in resting-state brain connectivity following computerized cognitive behavioral therapy for insomnia in dialysis patients: A pilot study

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and SC or instead is mapped by distinct sets of distributed connectivity patterns. To this end, we used a longitudinal, within-subject, multimodal approach aiming to combine brain data from diffusion-weighted MRI (DW-MRI), and functional MRI (fMRI) with behavioral evaluation, to better understand how changes in FC and SC correlate with changes in cognition in a sample of older adults. FC and SC measures were derived from the multimodal scans acquired at two time points. Change in FC and SC was correlated with 13 behavioral measures of cognitive function using Partial Least Squares Correlation (PLSC). Two of the measures indicate an age-related change in cognition and the rest indicate baseline cognitive performance. FC and SC—cognition correlations were expressed across several cognitive measures, and numerous structural and functional cortical connections, mainly cingulo-opercular, dorsolateral prefrontal, somatosensory and motor, and temporo-parieto-occipital, contributed both positively and negatively to the brain-behavior relationship. Whole-brain FC and SC captured distinct and independent connections related to the cognitive measures. Overall, we examined age-related function-structure associations of the brain in a comprehensive and integrated manner, using a multimodal approach. We pointed out the behavioral relevance of age-related changes in FC and SC. Taken together, our results highlight that the heterogeneity in distributed FC and SC connectivity patterns provide unique information about the variable nature of healthy cognitive aging.

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis

Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72h and 7days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition.

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been proven effective in post-stroke motor function enhancement, yet whether the combination of MI-BCI and tDCS may further benefit the rehabilitation of motor functions remains unknown. This study investigated brain functional activity and connectivity changes after a 2 week MI-BCI and tDCS combined intervention in 19 chronic subcortical stroke patients. Patients were randomized into MI-BCI with tDCS group and MI-BCI only group who underwent 10 sessions of 20 min real or sham tDCS followed by 1 h MI-BCI training with robotic feedback. We derived amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) from resting-state functional magnetic resonance imaging (fMRI) data pre- and post-intervention. At baseline, stroke patients had lower ALFF in the ipsilesional somatomotor network (SMN), lower ReHo in the contralesional insula, and higher ALFF/Reho in the bilateral posterior default mode network (DMN) compared to age-matched healthy controls. After the intervention, the MI-BCI only group showed increased ALFF in contralesional SMN and decreased ALFF/Reho in the posterior DMN. In contrast, no post-intervention changes were detected in the MI-BCI + tDCS group. Furthermore, higher increases in ALFF/ReHo/FC measures were related to better motor function recovery (measured by the Fugl-Meyer Assessment scores) in the MI-BCI group while the opposite association was detected in the MI-BCI + tDCS group. Taken together, our findings suggest that brain functional re-normalization and network-specific compensation were found in the MI-BCI only group but not in the MI-BCI + tDCS group although both groups gained significant motor function improvement post-intervention with no group difference. MI-BCI and tDCS may exert differential or even opposing impact on brain functional reorganization during post-stroke motor rehabilitation; therefore, the integration of the two strategies requires further refinement to improve efficacy and effectiveness.

Motor-cognitive interactive interventions, such as action observation training (AOT), have shown great potential in restoring cognitive function and motor behaviors. It is expected that an advanced AOT incorporating specific Tai Chi movements with continuous and spiral characteristics can facilitate the shift from automatic to intentional actions and thus enhance motor control ability for early-stage PD. Nonetheless, the underlying neural mechanisms remain unclear. The study aimed to investigate changes in brain functional connectivity (FC) and clinical improvement after 12 weeks of Tai Chi-based action observation training (TC-AOT) compared to traditional physical therapy (TPT). Thirty early-stage PD patients were recruited and randomly assigned to the TC-AOT group (N = 15) or TPT group (N = 15). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after 12 weeks of training and clinical assessments. The FCs were evaluated by seed-based correlation analysis based on the default mode network (DMN). The rehabilitation effects of the two training methods were compared while the correlations between significant FC changes and clinical improvement were investigated. The results showed that the TC-AOT group exhibited significantly increased FCs between the dorsal medial prefrontal cortex and cerebellum crus I, between the posterior inferior parietal lobe and supramarginal gyrus, and between the temporal parietal junction and clusters of middle occipital gyrus and superior temporal. Moreover, these FC changes had a positive relationship with patients' improved motor and cognitive performance. The finding supported that the TC-AOT promotes early-stage PD rehabilitation outcomes by promoting brain neuroplasticity where the FCs involved in the integration of sensorimotor processing and motor learning were strengthened.

Changes in regional brain activity and functional connectivity (FC) in patients with neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI) remain unclear. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate regional brain activity and FC in NDO patients after SCI. Resting-state fMRI scans were obtained from 20 NDO patients after SCI and 20 healthy controls (HCs). Regional brain activity was measured using regional homogeneity (ReHo). Subsequently, a seed-based whole-brain FC analysis was performed using the regions with significantly different ReHo as seeds. Partial correlation analysis was conducted to examine the relationship between FC values and clinical scores in the NDO patients with SCI. Compared to HC, patients with NDO exhibited significantly decreased ReHo in the right medial frontal gyrus (MFG). Furthermore, compared to HC, NDO patients demonstrated stronger FC between the seed (right MFG) and voxels in the left pyramis, right cerebellum posterior lobe, and left middle temporal gyrus. Weaker FC was observed between the seed (right MFG) and voxels in the right paracentral lobule. Correlation analyses revealed that the Overactive Bladder Symptom Score and urgency urinary incontinence scores were positively correlated with FC values between the right MFG and the left pyramis. SCI-related NDO patients exhibit abnormalities in both regional brain activity and FC, with supraspinal connectivity deviation extent associated with the severity of lower urinary tract symptom. This study contributes to a better understanding of the potential supraspinal neural mechanisms underlying SCI-related NDO.

BackgroundChanges in brain functional connectivity obtained from resting state MRI (rs‐fMRI) have been found to be associated with cognitive decline and neurodegeneration in clinical trial participants with Alzheimer’s disease (AD). This study investigates whether and how this technique can be used in AD clinical trials to monitor treatment effects. Specifically, we analyzed changes in brain functional connectivity over a period of 116 weeks in participants with AD treated with gantenerumab, an investigational anti‐amyloid beta monoclonal antibody. Although this drug did not meet the primary clinical endpoints, some significant associations were found with exploratory biomarkers.MethodWe analyzed rs‐fMRI of participants with MCI due to AD and mild AD at screening and week 116 collected in a subgroup of the randomized, double‐blind, pivotal, Phase III trials GRADUATE I (273 patients, 52% female, 50% placebo) and GRADUATE II (335 patients, 59% female, 57% placebo) (NCT03444870, NCT04374253). Using group Independent Components Analysis (GIFT, Calhoun et al., 2001), we extracted 25 resting states components in each clinical trial and grouped them into 7 networks (Sensory Motor, Cerebellar, Visual, SubCortical, Auditory, Default Mode and Cognitive Control). Using a linear model, we investigated changes in between‐ and within‐networks brain connectivity at screening and week 116 in gantenerumab and placebo participants. The components‐wise Pearson’s correlation (Z‐Fisher score) was used as the dependent variable, group (gantenerumab vs placebo), visit (screening vs week 116) and the interaction term group‐by‐visit as covariates of interest, while controlling for sex, age and scanner magnetic field strength (1.5T vs 3T). This analysis was exploratory in nature and no adjustment for multiple components‐wise comparisons was applied.ResultIn both GRADUATE I and II, we found a significant group‐by‐visit effect (p < 0.05). Specifically, we found decreasing within‐ and between‐networks functional connectivity in the placebo group at week 116 compared to screening. Conversely, the gantenerumab group reported stable or higher connectivity at week 116 compared to screening (Fig. 1‐2).ConclusionThese results suggest a potential relationship between amyloid removal and changes in brain functional connectivity. Due to the exploratory nature of this study further investigation is needed to confirm these findings.

Decision letter for "Functional brain connectivity changes across the human life span: From fetal development to old age"

Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms. We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings. The right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment. The pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression.

Review for "Functional brain connectivity changes across the human life span: From fetal development to old age"

A novel edge rewiring strategy for tuning structural properties in networks