Abnormal salience network in normal aging and in amnestic mild cognitive impairment and Alzheimer's disease.
ABSTRACT: The salience network (SN) serves to identify salient stimuli and to switch between the central executive network (CEN) and the default-mode network (DMN), both of which are impaired in Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI). We hypothesized that both the structural and functional organization of the SN and functional interactions between the SN and CEN/DMN are altered in normal aging and in AD/aMCI. Gray matter volume (GMV) and resting-state functional connectivity (FC) were analyzed from healthy younger (HYC) to older controls (HOC) and from HOC to aMCI and AD patients. All the SN components showed significant differences in the GMV, intranetwork FC, and internetwork FC between the HYC and HOC. Most of the SN components showed differences in the GMV between the HOC and AD and between the aMCI and AD. Compared with the HOC, AD patients exhibited significant differences in intra- and internetwork FCs of the SN, whereas aMCI patients demonstrated differences in internetwork FC of the SN. Most of the GMVs and internetwork FCs of the SN and part of the intranetwork FC of the SN were correlated with cognitive differences in older subjects. Our findings suggested that structural and functional impairments of the SN may occur as early as in normal aging and that functional disconnection between the SN and CEN/ DMN may also be associated with both normal aging and disease progression.
Project description:We examined whether interindividual differences in habitual sleep patterns, quantified as the cumulative habitual total sleep time (cTST) over a 2-w period, were reflected in waking measurements of intranetwork and internetwork functional connectivity (FC) between major nodes of three intrinsically connected networks (ICNs): default mode network (DMN), salience network (SN), and central executive network (CEN).Resting state functional magnetic resonance imaging (fMRI) study using seed-based FC analysis combined with 14-d wrist actigraphy, sleep diaries, and subjective questionnaires (N = 33 healthy adults, mean age 34.3, standard deviation ± 11.6 y). Data were statistically analyzed using multiple linear regression. Fourteen consecutive days of wrist actigraphy in participant's home environment and fMRI scanning on day 14 at the Birmingham University Imaging Centre. Seed-based FC analysis on ICNs from resting-state fMRI data and multiple linear regression analysis performed for each ICN seed and target. cTST was used to predict FC (controlling for age).cTST was specific predictor of intranetwork FC when the mesial prefrontal cortex (MPFC) region of the DMN was used as a seed for FC, with a positive correlation between FC and cTST observed. No significant relationship between FC and cTST was seen for any pair of nodes not including the MPFC. Internetwork FC between the DMN (MPFC) and SN (right anterior insula) was also predicted by cTST, with a negative correlation observed between FC and cTST.This study improves understanding of the relationship between intranetwork and internetwork functional connectivity of intrinsically connected networks (ICNs) in relation to habitual sleep quality and duration. The cumulative amount of sleep that participants achieved over a 14-d period was significantly predictive of intranetwork and inter-network functional connectivity of ICNs, an observation that may underlie the link between sleep status and cognitive performance.
Project description:OBJECTIVE:Increasingly, studies have identified abnormalities in the functional connectivity (FC) of large-scale neural networks in early psychosis, but the findings thus far have been inconclusive. Therefore, the aim of this study was to identify robust alterations in FC of the default mode (DMN), salience (SN), and central executive networks (CEN), in patients with first-episode psychosis (FEP) using a meta-analytic approach. METHODS:Included studies were required to be resting-state, seed-to-whole brain, FC neuroimaging studies, comparing FEP patients to healthy controls (HC), with seeds within the boundaries of the region-of-interest networks. Peak effect coordinates and peak t, z, or p values were meta-analyzed using Seed-based d Mapping software. RESULTS:The DMN seeds primarily displayed within-network hypoconnectivity (largest clusters including the middle orbital gyrus; and ventral anterior cingulate gyrus). The SN seeds displayed hypoconnectivity with regions in the DMN and CEN (largest clusters located in the bilateral middle temporal gyri). Review of the limited CEN data revealed hypo- and hyperconnectivity across the networks. Negative symptoms were positively correlated with all DMN FC abnormalities in the FEP group. Antipsychotic-treated patients displayed greater hypoconnectivity than antipsychotic-naïve patients between both the DMN/SN seeds and prefrontal regions. CONCLUSIONS:These findings provide substantial evidence of widespread resting-state FC abnormalities of the DMN, SN, and CEN in early psychosis; particularly implicating DMN and SN dysconnectivity as a core deficit underlying the psychopathology of psychosis. Additionally, we highlight the importance of disentangling connectivity abnormalities resulting from disease processes, from those that result from antipsychotic treatment.
Project description:Background: The early progression continuum of Alzheimer's disease (AD) has been considered to advance through subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI). Altered functional connectivity (FC) in the default mode network (DMN) is regarded as a hallmark of AD. Furthermore, the DMN can be divided into two subnetworks, the anterior and posterior subnetworks. However, little is known about distinct disruptive patterns in the subsystems of the DMN across the preclinical AD spectrum. This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in the DMN subnetworks in 20 healthy controls (HC), eight SCD, 11 naMCI, and 28 aMCI patients. Moreover, a correlation analysis was used to examine associations between the altered connectivity of the DMN subnetworks and the neurocognitive performance. Results: Compared to the HC, SCD patients showed increased FC in the bilateral superior frontal gyrus (SFG), naMCI patients showed increased FC in the left inferior parietal lobule (IPL), and aMCI patients showed increased FC in the bilateral IPL in the aDMN; while SCD patients showed decreased FC in the precuneus, naMCI patients showed increased FC in the left middle temporal gyrus (MTG), and aMCI patients also showed increased FC in the right middle frontal gyrus (MFG) in the pDMN. Notably, the FC between the ventromedial prefrontal cortex (vmPFC) and the left MFG and the IPL in the aDMN was associated with episodic memory in the SCD and aMCI groups. Interestingly, the FC between the posterior cingulated cortex (PCC) and several regions in the pDMN was associated with other cognitive functions in the SCD and naMCI groups. Conclusions: This study demonstrates that the three preclinical stages of AD exhibit distinct FC alternations in the DMN subnetworks. Furthermore, the patient group data showed that the altered FC involves cognitive function. These findings can provide novel insights for tailored clinical intervention across the preclinical AD spectrum.
Project description:Optimal levels of intrinsic Blood-Oxygenation-Level-Dependent (BOLD) signal variability (variability hereafter) are important for normative brain functioning. However, it remains largely unknown how network-specific and frequency-specific variability changes along the Alzheimer's disease (AD) spectrum and relates to cognitive decline. We hypothesized that cognitive impairment was related to distinct BOLD variability alterations in two brain networks with reciprocal relationship, i.e., the AD-specific default mode network (DMN) and the salience network (SN). We examined variability of resting-state fMRI data at two characteristic slow frequency-bands of slow4 (0.027-0.073?Hz) and slow5 (0.01-0.027?Hz) in 96 AD, 98 amnestic mild cognitive impairment (aMCI), and 48 age-matched healthy controls (HC) using two commonly used pre-processing pipelines. Cognition was measured with a neuropsychological assessment battery. Using both global signal regression (GSR) and independent component analysis (ICA), results generally showed a reciprocal DMN-SN variability balance in aMCI (vs. AD and/or HC), although there were distinct frequency-specific variability patterns in association with different pre-processing approaches. Importantly, lower slow4 posterior-DMN variability correlated with poorer baseline cognition/smaller hippocampus and predicted faster cognitive decline in all patients using both GSR and ICA. Altogether, our findings suggest that reciprocal DMN-SN variability balance in aMCI might represent an early signature in neurodegeneration and cognitive decline along the AD spectrum.
Project description:In schizophrenia, consistent structural and functional changes have been demonstrated for the insula including aberrant salience processing, which is critical for psychosis. Interactions within and across default mode and central executive network (DMN, CEN) are impaired in schizophrenia. The question arises whether these 2 types of changes are related. Recently, the anterior insula has been demonstrated to control DMN/CEN interactions. We hypothesized that aberrant insula and DMN/CEN activity in schizophrenia is associated with an impaired dependence of DMN/CEN interactions on anterior insular salience network (SN) activity. Eighteen patients with schizophrenia during psychosis and 20 healthy controls were studied by resting-state-fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed spatiotemporal patterns of synchronized ongoing blood-oxygenation-level-dependent (BOLD) activity including SN, DMN, and CEN. Scores of functional and time-lagged connectivity across networks' time courses were calculated. Connectivity scores and spatial network maps were compared between groups and related with patients' hallucination and delusion severity. Spatial BOLD-synchronicity was altered in patients' SN, DMN, and CEN, including decreased activity in the right anterior insula (rAI). Patients' functional connectivity between DMN and CEN was increased and related with hallucinations severity. Importantly, patients' time-lagged connectivity between SN and DMN/CEN was reduced, and decreased rAI activity of the SN was associated with both hallucinations and increased functional connectivity between DMN and CEN. Data provide evidence for an aberrant dependence of DMN/CEN interactions on anterior insular SN activity, linking impaired insula, DMN, CEN activity, and psychosis in schizophrenia.
Project description:The brain continuously receives input from the internal and external environment. Using this information, the brain exerts its influence on both itself and the body to facilitate an appropriate response. The dynamic interplay between the brain and the heart and how external conditions modulate this relationship deserves attention. In high-stress situations, synchrony between various brain regions such as the prefrontal cortex and the heart may alter. This flexibility is believed to facilitate transitions between functional states related to cognitive, emotional, and especially autonomic activity. This study examined the dynamic temporal functional association of heart rate variability (HRV) with the interaction between three main canonical brain networks in 38 healthy male subjects at rest and directly after a psychosocial stress task. A sliding window approach was used to estimate the functional connectivity (FC) among the salience network (SN), central executive network (CEN), and default mode network (DMN) in 60-s windows on time series of blood-oxygen-level dependent (BOLD) signal. FC between brain networks was calculated by Pearson correlation. A multilevel linear mixed model was conducted to examine the window-by-window association between the root mean square of successive differences between normal heartbeats (RMSSD) and FC of network-pairs across sessions. Our findings showed that the minute-by-minute correlation between the FC and RMSSD was significantly stronger between DMN and CEN than for SN and CEN in the baseline session [b = 4.36, t(5025) = 3.20, p = 0.006]. Additionally, this differential relationship between network pairs and RMSSD disappeared after the stress task; FC between DMN and CEN showed a weaker correlation with RMSSD in comparison to baseline [b = -3.35, t(5025) = -3.47, p = 0.006]. These results suggest a dynamic functional interplay between HRV and the functional association between brain networks that varies depending on the needs created by changing conditions.
Project description:This study aimed to investigate the changes in functional connectivity (FC) within each resting-state network (RSN) and between RSNs in subcortical stroke patients who were well recovered in global motor function. Eleven meaningful RSNs were identified via functional magnetic resonance imaging data from 25 subcortical stroke patients and 22 normal controls using independent component analysis. Compared with normal controls, stroke patients exhibited increased intranetwork FC in the sensorimotor (SMN), visual (VN), auditory (AN), dorsal attention (DAN), and default mode (DMN) networks; they also exhibited decreased intranetwork FC in the frontoparietal network (FPN) and anterior DMN. Stroke patients displayed a shift from no FC in controls to negative internetwork FC between the VN and AN as well as between the VN and SMN. Stroke patients also exhibited weakened positive (anterior and posterior DMN; posterior DMN and right FPN) or negative (AN and right FPN; posterior DMN and dorsal SMN) internetwork FC when compared with normal controls. We suggest that subcortical stroke may induce connectivity changes in multiple functional networks, affecting not only the intranetwork FC within RSNs but also the internetwork FC between these RSNs.
Project description:Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN's hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders.
Project description:Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.
Project description:BACKGROUND AND PURPOSE:The interrelation of cognitive performance, cerebrovascular damage and brain functional connectivity (FC) in advanced arteriosclerosis remains unclear. Our aim was to investigate the associations between FC, white matter damage and cognitive impairment in carotid artery disease. METHODS:Seventy-one participants with a recent cerebrovascular event and with written informed consent underwent resting-state functional magnetic resonance imaging and the Addenbrooke's Cognitive Examination - Revised (ACE-R). Network and inter-hemispheric FC metrics were compared between cognitively normal and impaired subjects, and interrelated with cognition. In order to explore the nature of FC changes, their associations with microstructural damage of related white matter tracts and cognitive performance were investigated, followed by mediation analysis. RESULTS:Participants with global cognitive impairment showed reduced FC compared to the cognitively intact subjects within the central executive network (CEN), and between hemispheres. Patients with executive dysfunction had decreased CEN FC whilst patients with memory loss demonstrated low FC in both the CEN and the default mode network (DMN). Global performance correlated with connectivity metrics of the CEN hub with DMN nodes, and between hemispheres. Cingulum mean diffusivity (MD) was negatively correlated with ACE-R and CEN-DMN FC. The cingulum MD-cognition association was partially mediated by CEN-DMN FC. CONCLUSIONS:Long-range functional disconnection of the CEN with DMN nodes is the main feature of cognitive impairment in elderly subjects with symptomatic carotid artery disease. Our findings provide further support for the connectional diaschisis concept of vascular cognitive disorder, and highlight a mediation role of functional disconnection to explain associations between microstructural white matter tract damage and cognitive impairment.