Functional Connectivity In Default Network Research Articles

Interaction effect of sex and diagnosis on functional connectivity within the default network in healthy controls, mild cognitive impairment and Alzheimer Disease

AbstractBackgroundAge and sex are major risk factors for late onset Alzheimer’s disease (AD). Almost 70% of AD patients are women, but reasons for sex disparities are not well understood. One potential avenue of inquiry is investigation of default network (DN) functional connectivity (FC) differences between men and women.MethodWe studied amyloid positive individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), clinically diagnosed as healthy elderly controls (HCs), Mild Cognitive Impairment (MCI) and AD, with resting‐state functional Magnetic Resonance Imaging available at the diagnostic and cognitive testing visit (Table 1). We selected seven regions of interest (ROIs) in the DN (Figure 1), including bilateral angular gyrus (ANG), calcarine (CAL), precuneus (PCUN), medial orbital frontal gyrus (ORBmed) and bilateral middle occipital gyrus (MOG). Pearson’s correlation characterized FC between ROIs. Linear mixed effect models adjusted for covariates (education, handedness, presence of apolipoprotein [APOE] ε4 and intra‐subject effect), and analysis of variance (ANOVA) evaluated the effects of diagnosis, sex and their interaction, using Bonferroni correction.ResultsANOVA showed significant differences between diagnostic groups in FC of left ANG – PCUN/CAL and bilateral MOG – CAL. Significant diagnosis by interaction effects were observed in FC especially at the level of posterior‐ventral DN. Specifically, between ANG‐CAL, and PCUN‐MOG (Table 2). Post‐hoc analysis demonstrated distinct effect sizes and/or opposite direction effects in women compared to men (Figure 2). Left ANG – CAL and left ANG – PCUN connectivity had medium effect (|d| >0.5) for men in the MCI versus HC comparison, although small effect (|d| <0.2) across sexes. The discrepancies between women and men were observed in the AD versus MCI comparison, such as the left ANG – left MOG and right ANG – CAL, where they show an opposite direction of FC.ConclusionsOur study found that the sex differences in DN FC did not remain consistent across the clinical AD spectrum. Instead, significant sex by diagnosis interaction effects suggest that treating sex as a covariate overlooks sex‐specific pathological changes in brain FC.

Altered Static and Dynamic Spontaneous Neural Activity in Drug-Naïve and Drug-Receiving Benign Childhood Epilepsy With Centrotemporal Spikes.

The present study aims to investigate intrinsic abnormalities of brain and the effect of antiepileptic treatment on brain activity in Benign childhood epilepsy with centrotemporal spikes (BECTS). Twenty-six drug-naïve patients (DNP) and 22 drug-receiving patients (DRP) with BECTS were collected in this study. Static amplitude of low frequency fluctuation (sALFF) and dynamic ALFF (dALFF) were applied to resting-state fMRI data. Functional connectivity (FC) analysis was further performed for affected regions identified by static and dynamic analysis. One-way analysis of variance and post hoc statistical analyses were performed for between-group differences. Abnormal sALFF and dALFF values were correlated with clinical features of patients. Compared with healthy controls (HC), DNP group demonstrated alterations of sALFF and/or dALFF in medial prefrontal cortex (MPFC), supplementary motor areas (SMA), cerebellum, hippocampus, pallidum and cingulate cortex, in which the values were close to normal in DRP. Notably, sALFF and dALFF showed specific sensitivity in detecting abnormalities in basal ganglia and cerebellum. Additionally, DRP showed additional changes in precuneus, inferior temporal gyrus, superior frontal gyrus and occipital visual cortex. Compared with HC, the DNP showed increased FC in default network and motion-related networks, and the DRP showed decreased FC in default network. The MPFC, hippocampus, SMA, basal ganglia and cerebellum are indicated to be intrinsically affected regions and effective therapeutic targets. And the FC profiles of default and motion-related networks might be potential core indicators for clinical treatment. This study revealed potential neuromodulatory targets and helped understand pathomechanism of BECTS. Static and dynamic analyses should be combined to investigate neuropsychiatric disorders.

Decreased regional homogeneity and increased functional connectivity of default network correlated with neurocognitive deficits in subjects with genetic high-risk for schizophrenia: A resting-state fMRI study

The complex symptoms of schizophrenia (SCZ) have been associated with dysfunction of the default mode network (DMN). Subjects at genetic high risk (GHR) for SCZ exhibit similar but milder brain abnormalities. This study aimed to investigate functional alterations of DMN from the local to the whole and their relationships with cognitive deficits in GHR subjects. 42 GHR subjects and 38 matched healthy controls (HC) were studied by resting-state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) analysis was performed to measure the local brain function of the DMN, derived by the group independent component analysis, and areas with aberrant ReHo were used as seeds in functional connectivity (FC). Compared with the HC group, the GHR group exhibited significantly decreased ReHo and increased FC in the fronto-limbic-striatal system within the DMN. Furthermore, a significant negative correlation was found between decreased ReHo in the right superior frontal gyrus and the delayed recall in GHR subjects. Our findings revealed decreased local function and hyper-connectivity in the fronto-limbic-striatal system of the DMN in GHR subjects, which is associated with cognitive deficits. This may improve our understanding of the neurophysiological endophenotypes of SCZ and the neural substrate underlying the cognitive deficits of the disease.

Hard to wake up? The cerebral correlates of sleep inertia assessed using combined behavioral, EEG and fMRI measures

The first minutes following awakening from sleep are typically marked by reduced vigilance, increased sleepiness and impaired performance, a state referred to as sleep inertia. Although the behavioral aspects of sleep inertia are well documented, its cerebral correlates remain poorly understood. The present study aimed at filling this gap by measuring in 34 participants the changes in behavioral performance (descending subtraction task, DST), EEG spectral power, and resting-state fMRI functional connectivity across three time points: before an early-afternoon 45-min nap, 5 min after awakening from the nap and 25 min after awakening. Our results showed impaired performance at the DST at awakening and an intrusion of sleep-specific features (spectral power and functional connectivity) into wakefulness brain activity, the intensity of which was dependent on the prior sleep duration and depth for the functional connectivity (14 participants awakened from N2 sleep, 20 from N3 sleep). Awakening in N3 (deep) sleep induced the most robust changes and was characterized by a global loss of brain functional segregation between task-positive (dorsal attention, salience, sensorimotor) and task-negative (default mode) networks. Significant correlations were observed notably between the EEG delta power and the functional connectivity between the default and dorsal attention networks, as well as between the percentage of mistake at the DST and the default network functional connectivity. These results highlight (1) significant correlations between EEG and fMRI functional connectivity measures, (2) significant correlations between the behavioral aspect of sleep inertia and measures of the cerebral functioning at awakening (both EEG and fMRI), and (3) the important difference in the cerebral underpinnings of sleep inertia at awakening from N2 and N3 sleep.

Directed connectivity of brain default networks in resting state using GCA and motif.

Nowadays, there is a lot of interest in assessing functional interactions between key brain regions. In this paper, Granger causality analysis (GCA) and motif structure are adopted to study directed connectivity of brain default mode networks (DMNs) in resting state. Firstly, the time series of functional magnetic resonance imaging (fMRI) data in resting state were extracted, and the causal relationship values of the nodes representing related brain regions are analyzed in time domain to construct a default network. Then, the network structures were searched from the default networks of controls and patients to determine the fixed connection mode in the networks. The important degree of motif structures in directed connectivity of default networks was judged according to p-value and Z-score. Both node degree and average distance were used to analyze the effect degree an information transfer rate of brain regions in motifs and default networks, and efficiency of the network. Finally, activity and functional connectivity strength of the default brain regions are researched according to the change of energy distributions between the normals and the patients' brain regions. Experimental results demonstrate that, both normal subjects and stroke patients have some corresponding fixed connection mode of three nodes, and the efficiency and power spectrum of the patient's default network is somewhat lower than that of the normal person. In particular, the Right Posterior Cingulate Gyrus (PCG.R) has a larger change in functional connectivity and its activity. The research results verify the feasibility of the application of GCA and motif structure to study the functional connectivity of default networks in resting state.

Reduced executive and default network functional connectivity in cigarette smokers.

Altered functional connectivity has been associated with acute and chronic nicotine use. Connectivity alterations, specifically in the right and left executive control networks (RECN/LECN) and the default mode network (DMN), may contribute to the addiction cycle. The objective of this study was to determine if executive control network (ECN) and DMN connectivity is different between non-smokers and smokers and whether reductions in connectivity are related to chronic cigarette use. The RECN, LECN, and DMN were identified in resting state functional magnetic resonance imaging data in 650 subjects. Analyses tested for group differences in network connectivity strength, controlling for age and alcohol use. There was a significant group effect on LECN and DMN connectivity strength with smokers (n = 452) having lower network strengths than non-smokers (n = 198). Smokers had lower connectivity than non-smokers associated with key network hubs: the dorsolateral prefrontal cortex, and parietal nodes within ECNs. Further, ECN connectivity strength was negatively associated with pack years of cigarette use. Our data suggest that chronic nicotine use negatively impacts functional connectivity within control networks that may contribute to the difficulty smokers have in quitting.

Default network connectivity is linked to memory status in multiple sclerosis.

Memory impairment affects 50% of multiple sclerosis (MS) patients. Altered resting-state functional connectivity (FC) has been observed in the default network (DN) of MS patients. No study to date has examined the association of DN FC to its behavioral concomitant, memory. The approach of the present study represents a methodological shift allowing straightforward interpretation of FC alterations in MS, as it presupposes specificity of a network to its paired cognitive function. We examined FC from fMRI collected during rest in the DN of 43 MS patients with and without memory-impairment. Memory-intact patients showed increased DN FC relative to memory-impaired patients. There were no regions of higher FC in memory-impaired patients. DN FC was positively correlated with memory function, such that higher FC was associated with better memory performance. Results were unchanged after controlling for cognitive efficiency, supporting specificity of the DN to memory and not cognitive status more generally. These findings support DN FC as a marker of memory function in MS patients that can be targeted by future treatment interventions. Pairing a functional network with its behavioral concomitant represents a straightforward method for interpreting FC alterations in patients with MS.

Age differences in the default network at rest and the relation to self-referential processing

Older adults show a 'positivity bias' in tasks involving emotion and self-referential processing. A critical network that is involved in self-referencing and shows age-related decline is the default network (DN). The purpose of the current study was to investigate age differences in pre- and post-task DN functional connectivity (FC) and signal variability, and to examine whether they are predictive of the positivity bias in self-referencing. We measured FC and within-subject variability of the DN in resting-state scans preceding and following tasks involving personality judgements on the self and a close other. Older adults endorsed more positive traits than younger adults on both tasks. FC was weaker post-task in older vs younger adults, and younger adults had greater variability than older adults in DN nodes. Younger adults with higher post-task DN variability had more negative self-ratings. For both age groups, greater FC in the DN was associated with more negative self-ratings. Neither FC nor variability was related to other ratings, despite the potential for self-processing when making other judgements. Our findings suggest that ageing leads to reduced FC and variability in the DN, which is most apparent after task, and may be one mechanism underlying the positive bias with age.

A potential ethnic difference in the association between 5-HTTLPR polymorphisms and the brain default mode network

The serotonin-transporter-linked polymorphic region (5-HTTLPR) is associated with mood disorders. This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced frontal cortical control. In Caucasians, the short form is associated with this effect, but in Han Chinese we recently found that the long form is involved. Serotonin receptors have rich expression in default mode network (DMN) regions and the recent studies have found an association between the short form of the 5-HTTLPR and DMN functional connectivity (FC) in Caucasians. The present study has investigated whether there may also be an ethnic difference in this influence of 5-HTTLPR on the DMN. We recruited 233 young Han Chinese subjects and calculated the resting-state default-network FC. Our study found that the L carriers had decreased FC in the bilateral medial prefrontal cortex, right parahippocampal gyrus, left middle temporal gyrus, and increased FC in left precuneus (Pcu) compared to SS. The PCC-Pcu FC in L carriers was significantly negatively correlated with the depression scores. Our findings, therefore, suggest that there is also a difference between Caucasian and Han Chinese subjects in the association between the different forms of the 5-HTTLPR and DMN functional connectivity.