PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (921515)

Clipboard (0)
None

Related Articles

1.  Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment 
NeuroImage : Clinical  2014;4:473-480.
Amnestic mild cognitive impairment (aMCI) is believed to represent a transitional stage between normal healthy ageing and the development of dementia. In particular, aMCI patients have been shown to have higher annual transition rates to Alzheimer's Disease (AD) than individuals without cognitive impairment. Despite intensifying interest investigating the neuroanatomical basis of this transition, there remain a number of questions regarding the pathophysiological process underlying aMCI itself. A number of recent studies in aMCI have shown specific impairments in connectivity within the default mode network (DMN), which is a group of regions strongly related to episodic memory capacities. However to date, no study has investigated the integrity of the DMN between patients with aMCI and those with a non-amnestic pattern of MCI (naMCI), who have cognitive impairment, but intact memory storage systems. In this study, we contrasted the DMN connectivity in 24 aMCI and 33 naMCI patients using seed-based resting state fMRI. The two groups showed no statistical difference in their DMN intra-connectivity. However when connectivity was analysed according to performance on measures of episodic memory retrieval, the two groups were separable, with aMCI patients demonstrating impaired functional connectivity between the hippocampal formation and the posterior cingulate cortex. We provide evidence that this lack of connectivity is driven by impaired communication from the posterior cingulate hub and does not simply represent hippocampal atrophy, suggesting that posterior cingulate degeneration is the driving force behind impaired DMN connectivity in aMCI.
Highlights
•First trial to explore Default Mode Network (DMN) connectivity between MCI and naMCI•Amnestic and nonamnestic MCI groups show similar overall DMN intra-connectivity.•aMCI patients have connectivity deficits related to impaired memory retention.•Impaired DMN connectivity is driven by deficits in posterior cingulate cortex.•Alzheimer’s disease pathology likely evolves from PCC to hippocampus
doi:10.1016/j.nicl.2014.02.010
PMCID: PMC3952352  PMID: 24634833
Functional magnetic resonance imaging; Resting state functional connectivity; Mild cognitive impairment; Memory; Amnestic; Default mode network
2.  Default mode network connectivity in stable vs progressive mild cognitive impairment 
Neurology  2011;76(6):511-517.
Objective:
Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline.
Methods:
fMRI scans during a face–name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline.
Results:
GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p < 0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating–sum of boxes) (r = −0.40, p < 0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models.
Conclusions:
fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for “early” vs “late” MCI, which are associated with different baseline memory scores and different rates of progression and conversion.
doi:10.1212/WNL.0b013e31820af94e
PMCID: PMC3053179  PMID: 21228297
3.  Patterns of altered functional connectivity in mesial temporal lobe epilepsy 
Epilepsia  2012;53(6):1013-1023.
Summary
Purpose
In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction.
Methods
We selected electroencephalography–functional magnetic resonance imaging (EEG-fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG-fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated.
Key Findings
In patients with right MTLE, group difference functional connectivity maps (RMTLE – controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE – controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus.
Significance
In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.
doi:10.1111/j.1528-1167.2012.03464.x
PMCID: PMC3767602  PMID: 22578020 CAMSID: cams3332
EEG-fMRI; Resting state functional connectivity; Mesial temporal lobe epilepsy; Default mode network
4.  The Influence of Rest Period Instructions on the Default Mode Network 
The default mode network (DMN) refers to regional brain activity that is greater during rest periods than during attention-demanding tasks; many studies have reported DMN alterations in patient populations. It has also been shown that the DMN is suppressed by scanner background noise (SBN), which is the noise produced by functional magnetic resonance imaging (fMRI). However, it is unclear whether different approaches to “rest” in the noisy MR environment can alter the DMN and constitute a confound in studies investigating the DMN in particular patient populations (e.g., individuals with schizophrenia, Alzheimer's disease). We examined 27 healthy adult volunteers who completed an fMRI experiment with three different instructions for rest: (1) relax and be still, (2) attend to SBN, or (3) ignore SBN. Region of interest analyses were performed to determine the influence of rest period instructions on core regions of the DMN and DMN regions previously reported to be altered in patients with or at risk for Alzheimer's disease or schizophrenia. The dorsal medial prefrontal cortex (dmPFC) exhibited greater activity when specific resting instructions were given (i.e., attend to or ignore SBN) compared to when non-specific resting instructions were given. Condition-related differences in connectivity were also observed between regions of the dmPFC and inferior parietal/posterior superior temporal cortex. We conclude that rest period instructions and SBN levels should be carefully considered for fMRI studies on the DMN, especially studies on clinical populations and groups that may have different approaches to rest, such as first-time research participants and children.
doi:10.3389/fnhum.2010.00218
PMCID: PMC2999982  PMID: 21151779
default mode; fMRI; resting state; scanner background noise
5.  Resting-State Brain Organization Revealed by Functional Covariance Networks 
PLoS ONE  2011;6(12):e28817.
Background
Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN) and structural covariance network (SCN) have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization.
Methodology and Principal Findings
We proposed a functional covariance network (FCN) method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF) in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network.
Conclusion
The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.
doi:10.1371/journal.pone.0028817
PMCID: PMC3236756  PMID: 22174905
6.  Functional Brain Imaging 
Executive Summary
Objective
The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD).
Clinical Need: Target Population and Condition
Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006.
In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging.
Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci.
Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people.
Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy.
The Technology Being Reviewed
Functional Brain Imaging
Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex.
In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application.
Review Strategy
The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers.
General inclusion criteria were applied to all conditions. Those criteria included the following:
Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies.
Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).
English-language studies.
Human studies.
Any age.
Studying at least one of the following: fMRI, PET, MRS, or MEG.
Functional brain imaging modality must be compared with a clearly defined reference standard.
Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost.
Summary of Findings
There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients.
The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results.
The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another.
There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research.
Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG.
The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG.
There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy.
Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients.
There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS.
PMCID: PMC3379170  PMID: 23074493
7.  Episodic memory retrieval, parietal cortex, and the Default Mode Network: functional and topographic analyses 
The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g. episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative “default” processes such as episodic memory retrieval. Using fMRI, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal parietal regions that were anatomically separate from the DMN. The two sets of parietal regions showed different resting-state functional connectivity and response profiles. During memory retrieval, responses in DMN regions peaked sooner than non-DMN regions, which in turn showed responses that were sustained until a final memory judgment was reached. Moreover, a parahippocampal region that showed strong resting-state connectivity with parietal DMN regions also exhibited a pattern of task-evoked activity similar to that exhibited by DMN regions. These results suggest that DMN parietal regions directly supported memory retrieval, whereas non-DMN parietal regions were more involved in post-retrieval processes such as memory-based decision making. Finally, a robust functional dissociation within the DMN was observed. While angular gyrus and posterior cingulate/precuneus were significantly activated during memory retrieval, an anterior DMN node in medial prefrontal cortex was strongly deactivated. This latter finding demonstrates functional heterogeneity rather than homogeneity within the DMN during episodic memory retrieval.
doi:10.1523/JNEUROSCI.3335-10.2011
PMCID: PMC3098040  PMID: 21430142
fMRI; default mode network; episodic memory; medial prefrontal; parietal; functional connectivity
8.  Epileptic Discharges Affect the Default Mode Network – fMRI and Intracerebral EEG Evidence 
PLoS ONE  2013;8(6):e68038.
Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50–150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve.
doi:10.1371/journal.pone.0068038
PMCID: PMC3695970  PMID: 23840805
9.  Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load 
PLoS ONE  2009;4(5):e5743.
Background
Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed.
Methodology/Principal Findings
Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2–4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2–4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity.
Conclusions/Significance
Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design.
doi:10.1371/journal.pone.0005743
PMCID: PMC2683943  PMID: 19492040
10.  Investigation of long-term reproducibility of intrinsic connectivity network mapping: A resting-state fMRI study 
BACKGROUND AND PURPOSE
Connectivity mapping based on resting-state fMRI is rapidly developing and this methodology has great potential for clinical applications. However, before resting-state fMRI can be applied for diagnosis, prognosis, and monitoring treatment for an individual patient with neurologic or psychiatric diseases, it is essential to assess its long-term reproducibility and between-subject variations among healthy individuals. The purpose of the study is to (1) quantify the long-term test-retest reproducibility of intrinsic connectivity network (ICN) measures derived from resting-state fMRI, and (2) assess the between-subject variation of ICN measures across the whole brain.
MATERIALS AND METHODS
Longitudinal resting-state fMRI data of six healthy volunteers were acquired from nine scan sessions over a period of more than one year. The within-subject reproducibility and between-subject variation of ICN measures, across 1) the whole brain and 2) major nodes of the default mode network, were quantified with intraclass correlation coefficient (ICC) and coefficient of variance (COV).
RESULTS
Our data show that the long-term test-retest reproducibility of ICN measures is outstanding, with over 70% of the connectivity networks showing an ICC greater than 0.60. COV across six healthy volunteers in this sample was greater than 0.2, suggesting significant between-subject variation.
CONCLUSION
Our data indicate that resting-state ICN measures (e.g., the correlation coefficients between fMRI signal profiles from two different brain regions) are potentially suitable as biomarkers for monitoring disease progression and treatment effects in clinical trials and individual patients. Because between-subject variation is significant, it may be difficult to use quantitative ICN measures, in their current state, as a diagnostic tool.
doi:10.3174/ajnr.A2894
PMCID: PMC3584561  PMID: 22268094
11.  Treatment with Olanzapine is Associated with Modulation of the Default Mode Network in Patients with Schizophrenia 
Neuropsychopharmacology  2009;35(4):904-912.
Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.
doi:10.1038/npp.2009.192
PMCID: PMC3055362  PMID: 19956088
default mode network; schizophrenia; antipsychotics; working memory; ventromedial prefrontal cortex; fMRI; Biological Psychiatry; Imaging; Clinical or Preclinical; Schizophrenia/Antipsychotics; Cognition; default mode network; ventromedial prefrontal cortex; fMRI; olanzapine
12.  Fast transient networks in spontaneous human brain activity 
eLife  2014;3:e01867.
To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states.
DOI: http://dx.doi.org/10.7554/eLife.01867.001
eLife digest
When subjects lie motionless inside scanners without any particular task to perform, their brains show stereotyped patterns of activity across regions known as resting state networks. Each network consists of areas with a common function, such as the ‘motor’ network or the ‘visual’ network. The role of resting state networks is unclear, but these spontaneous activity patterns are altered in disorders including autism, schizophrenia, and Alzheimer’s disease.
One puzzling feature of resting state networks is that they seem to last for relatively long times. However, the majority of studies into resting state networks have used fMRI brain scans, in which changes in the level of oxygen in the blood are used as a proxy for the activity of a given brain region. Since changes in blood oxygen occur relatively slowly, the ability of fMRI to detect rapid changes in activity is limited: it is thus possible that the long-lived nature of resting state networks is an artefact of the use of fMRI.
Now, Baker et al. have used a different type of brain scan known as an MEG scan to show that the activity of resting state networks is shorter lived than previously thought. MEG scanners measure changes in the magnetic fields generated by electrical currents in the brain, which means that they can detect alterations in brain activity much more rapidly than fMRI.
MEG recordings from the brains of nine healthy subjects revealed that individual resting state networks were typically stable for only 100 ms to 200 ms. Moreover, transitions between different networks did not occur randomly; instead, certain networks were much more likely to become active after others. The work of Baker et al. suggests that the resting brain is constantly changing between different patterns of activity, which enables it to respond quickly to any given situation.
DOI: http://dx.doi.org/10.7554/eLife.01867.002
doi:10.7554/eLife.01867
PMCID: PMC3965210  PMID: 24668169
magnetoencephalography; resting state; connectivity; non-stationary; hidden Markov model; microstates; human
13.  Functional Brain Network Modularity Captures Inter- and Intra-Individual Variation in Working Memory Capacity 
PLoS ONE  2012;7(1):e30468.
Background
Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity.
Methodology/Principal Findings
Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability.
Conclusions/Significance
The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise.
doi:10.1371/journal.pone.0030468
PMCID: PMC3262818  PMID: 22276205
14.  Antidepressants Normalize the Default Mode Network in Patients With Dysthymia 
JAMA psychiatry  2013;70(4):373-382.
Importance
The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain’s DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown.
Objective
To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity.
Design
After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011.
Setting
University research institute.
Participants
Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex.
Main Outcome Measures
We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain’s DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity.
Results
Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain’s DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity.
Conclusions and Relevance
The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.
doi:10.1001/jamapsychiatry.2013.455
PMCID: PMC3935731  PMID: 23389382
15.  Insular dysfunction within the salience network is associated with severity of symptoms and aberrant inter-network connectivity in major depressive disorder 
Major depressive disorder (MDD) is characterized by altered intrinsic functional connectivity within (intra-iFC) intrinsic connectivity networks (ICNs), such as the Default Mode- (DMN), Salience- (SN) and Central Executive Network (CEN). It has been proposed that aberrant switching between DMN-mediated self-referential and CEN-mediated goal-directed cognitive processes might contribute to MDD, possibly explaining patients' difficulties to disengage the processing of self-focused, often negatively biased thoughts. Recently, it has been shown that the right anterior insula (rAI) within the SN is modulating DMN/CEN interactions. Since structural and functional alterations within the AI have been frequently reported in MDD, we hypothesized that aberrant intra-iFC in the SN's rAI is associated with both aberrant iFC between DMN and CEN (inter-iFC) and severity of symptoms in MDD. Twenty-five patients with MDD and 25 healthy controls were assessed using resting-state fMRI (rs-fMRI) and psychometric examination. High-model-order independent component analysis (ICA) of rs-fMRI data was performed to identify ICNs including DMN, SN, and CEN. Intra-iFC within and inter-iFC between distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Patients with MDD showed (1) decreased intra-iFC within the SN's rAI, (2) decreased inter-iFC between the DMN and CEN, and (3) increased inter-iFC between the SN and DMN. Moreover, decreased intra-iFC in the SN's rAI was associated with severity of symptoms and aberrant DMN/CEN interactions, with the latter losing significance after correction for multiple comparisons. Our results provide evidence for a relationship between aberrant intra-iFC in the salience network's rAI, aberrant DMN/CEN interactions and severity of symptoms, suggesting a link between aberrant salience mapping, abnormal coordination of DMN/CEN based cognitive processes and psychopathology in MDD.
doi:10.3389/fnhum.2013.00930
PMCID: PMC3896989  PMID: 24478665
intrinsic functional connectivity; intrinsic networks; central executive network; default mode network; salience network; triple network hypothesis; anterior insula; major depressive disorder
16.  Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI 
Magnetic resonance imaging  2011;30(1):48-61.
Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging, and frequently represents the prodromal phase of Alzheimer’s disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed increased DMN activity in middle cingulate cortex, medial prefrontal cortex, and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus, and right angular gyrus. Although MTL volume difference between the two groups was not statistical significant, decreased activity in left MTL was observed for the aMCI group. Positive correlations between DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus, and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture, that correlate with memory function, even before significant medial temporal lobe atrophy is detectable by structural MRI.
doi:10.1016/j.mri.2011.07.007
PMCID: PMC3232317  PMID: 21982164
default mode network (DMN); amnestic mild cognitive impairment (aMCI); resting-state fMRI; medial temporal lobe (MTL)
17.  Study on the Relationships between Intrinsic Functional Connectivity of the Default Mode Network and Transient Epileptic Activity 
Rationale: Simultaneous recording of electroencephalogram and functional MRI (EEG–fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness.
Method: We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period.
Results: No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus).
Conclusion: Results suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort.
doi:10.3389/fneur.2014.00201
PMCID: PMC4193009  PMID: 25346721
default mode network; functional connectivity; dynamic; epileptic interictal event; temporal lobe epilepsy; idiopathic generalized epilepsy; posterior cingulate gyrus; precuneus
18.  Altered Functional and Anatomical Connectivity in Schizophrenia 
Schizophrenia Bulletin  2009;37(3):640-650.
Background: Schizophrenia is characterized by a lack of integration between thought, emotion, and behavior. A disruption in the connectivity between brain processes may underlie this schism. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were used to evaluate functional and anatomical brain connectivity in schizophrenia. Methods: In all, 29 chronic schizophrenia patients (11 females, age: mean = 41.3, SD = 9.28) and 29 controls (11 females, age: mean = 41.1, SD = 10.6) were recruited. Schizophrenia patients were assessed for severity of negative and positive symptoms and general cognitive abilities of attention/concentration and memory. Participants underwent a resting-fMRI scan and a DTI scan. For fMRI data, a hybrid independent components analysis was used to extract the group default mode network (DMN) and accompanying time-courses. Voxel-wise whole-brain multiple regressions with corresponding DMN time-courses was conducted for each subject. A t-test was conducted on resulting DMN correlation maps to look between-group differences. For DTI data, voxel-wise statistical analysis of the fractional anisotropy data was carried out to look for between-group differences. Voxel-wise correlations were conducted to investigate the relationship between brain connectivity and behavioral measures. Results: Results revealed altered functional and anatomical connectivity in medial frontal and anterior cingulate gyri of schizophrenia patients. In addition, frontal connectivity in schizophrenia patients was positively associated with symptoms as well as with general cognitive ability measures. Discussion: The present study shows convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior.
doi:10.1093/schbul/sbp131
PMCID: PMC3080691  PMID: 19920062
fMRI; DTI; default mode network; medial frontal; behavioral correlates
19.  Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease 
PLoS Computational Biology  2008;4(6):e1000100.
Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging.
Author Summary
Alzheimer's disease (AD) is a brain disorder characterized by progressive impairment of episodic memory and other cognitive domains resulting in dementia and, ultimately, death. Functional neuroimaging studies have identified brain regions that show abnormal brain function in AD. Although there is converging evidence about the identity of these regions, it is not clear how this abnormality affects the functional organization of the whole brain. In order to characterize the functional organization of the brain, our approach uses small-world measures, which have also been used to study systems such as social networks and the internet. We use graph analytical methods to compute these measures of functional connectivity brain networks, which are derived from fMRI data obtained from healthy elderly controls and AD patients. The AD patients had significantly lower regional connectivity, and showed disrupted global functional organization, when compared to healthy controls. Moreover, our results indicate that cognitive decline in Alzheimer's disease patients is associated with disrupted functional connectivity in the entire brain. Our findings further suggest that small-world measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging.
doi:10.1371/journal.pcbi.1000100
PMCID: PMC2435273  PMID: 18584043
20.  Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits 
Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). Understanding the neural mechanisms of this deficit is crucial for the development of efficient methods for treatment monitoring and augmentation of cognitive functions in PD patients. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson's Progression Marker Initiative (PPMI) database. Eighteen patients from this sample were also scanned with 123I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs) defined from the AAL brain atlas. The Brain Connectivity Toolbox (BCT) was used to extract nodal strength from all ROIs, and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable (LV) scores were matched with the performances in the three cognitive domains (memory, visuospatial, and executive) and striatal dopamine transporter binding ratios (SBR) using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on the modularity of the “cognitive network” was analyzed. For the range of deficits studied, better executive performance was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This profile was also characterized by a relative preservation of nigrostriatal dopaminergic function. The profile associated with better memory performance correlated with increased prefronto-limbic processing, and was not associated with presynaptic striatal dopamine uptake. SBR ratios were negatively correlated with modularity of the “cognitive network,” suggesting integrative effects of the preserved nigrostriatal dopamine system on this circuitry.
doi:10.3389/fnsys.2014.00045
PMCID: PMC3982053  PMID: 24765065
parkinson's disease; cognition; dopamine; resting state fMRI; SPECT; graph theory; nodal strength; modularity
21.  Insights into the Mechanisms of Absence Seizure Generation Provided by EEG with Functional MRI 
Absence seizures (AS) are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning, and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation, which relies heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI) is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time-course analysis, and functional connectivity (FC) have identified a common network of structures involved in AS. This network comprises the thalamus, midline, and lateral parietal cortex [the default mode network (DMN)], caudate nuclei, and the reticular structures of the pons. The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time-course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered FC in patients with AS. Hence, it appears that engagement of this network is central to AS. In this review, we will explore the insights of EEG-fMRI studies into the mechanisms of AS and consider how the DMN is likely to be the major large-scale brain network central to both seizure generation and seizure manifestations.
doi:10.3389/fneur.2014.00162
PMCID: PMC4150362  PMID: 25225491
epilepsy; absence seizures; functional MRI; default mode network; functional connectivity
22.  Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly 
Biological psychiatry  2009;67(6):584-587.
Background
Important functional connections within the “default mode network” (DMN) are disrupted in Alzheimer’s disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here we sought to determine if pathological effects of Aβ amyloid plaques could be seen even in the absence of a task by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition.
Methods
Participants with Alzheimer’s disease (AD) (n= 35) were compared with 68 cognitively normal participants who were further subdivided by PET PIB imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition.
Results
Resting state fMRI demonstrated that, compared with the PIB− group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus and visual cortex. These differences were in the same regions, and in the same direction, as differences found in the AD group.
Conclusions
Thus, prior to any manifestations of cognitive or behavioral changes there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI.
doi:10.1016/j.biopsych.2009.08.024
PMCID: PMC2829379  PMID: 19833321
PIB; fMRI; amyloid; Alzheimers Disease; resting state; precuneus; hippocampus
23.  Development of functional and structural connectivity within the default mode network in young children 
NeuroImage  2010;52(1):290-301.
Functional and structural maturation of networks comprised of discrete regions is an important aspect of brain development. The default-mode network (DMN) is a prominent network which includes the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), medial temporal lobes (MTL), and angular gyrus (AG). Despite increasing interest in DMN function, little is known about its maturation from childhood to adulthood. Here we examine developmental changes in DMN connectivity using a multimodal imaging approach by combining resting-state fMRI, voxel-based morphometry and diffusion tensor imaging-based tractography. We found that the DMN undergoes significant developmental changes in functional and structural connectivity, but these changes are not uniform across all DMN nodes. Convergent structural and functional connectivity analyses suggest that PCC-mPFC connectivity along the cingulum bundle is the most immature link in the DMN of children. Both PCC and mPFC also showed gray matter volume differences, as well as prominent macrostructural and microstructural differences in the dorsal cingulum bundle linking these regions. Notably, structural connectivity between PCC and left MTL was either weak or non-existent in children, even though functional connectivity did not differ from that of adults. These results imply that functional connectivity in children can reach adult-like levels despite weak structural connectivity. We propose that maturation of PCC-mPFC structural connectivity plays an important role in the development of self-related and social-cognitive functions that emerge during adolescence. More generally, our study demonstrates how quantitative multimodal analysis of anatomy and connectivity allows us to better characterize the heterogeneous development and maturation of brain networks.
doi:10.1016/j.neuroimage.2010.04.009
PMCID: PMC2976600  PMID: 20385244
brain development; default mode network; DTI; functional brain connectivity; structural brain connectivity
24.  Characterization of resting state activity in MCI individuals 
PeerJ  2013;1:e135.
Objectives. Aging is the major risk factor for Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). The aim of this study was to identify novel modifications of brain functional connectivity in MCI patients. MCI individuals were compared to healthy elderly subjects.
Methods. We enrolled 37 subjects (age range 60–80 y.o.). Of these, 13 subjects were affected by MCI and 24 were age-matched healthy elderly control (HC). Subjects were evaluated with Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and prose memory (Babcock story) tests. In addition, with functional Magnetic Resonance Imaging (fMRI), we investigated resting state network (RSN) activities. Resting state (Rs) fMRI data were analyzed by means of Independent Component Analysis (ICA). Subjects were followed-up with neuropsychological evaluations for three years.
Results. Rs-fMRI of MCI subjects showed increased intrinsic connectivity in the Default Mode Network (DMN) and in the Somatomotor Network (SMN). Analysis of the DMN showed statistically significant increased activation in the posterior cingulate cortex (PCC) and left inferior parietal lobule (lIPL). During the three years follow-up, 4 MCI subjects converted to AD. The subset of MCI AD-converted patients showed increased connectivity in the right Inferior Parietal Lobule (rIPL). As for SMN activity, MCI and MCI-AD converted groups showed increased level of connectivity in correspondence of the right Supramarginal Gyrus (rSG).
Conclusions. Our findings indicate alterations of DMN and SMN activity in MCI subjects, thereby providing potential imaging-based markers that can be helpful for the early diagnosis and monitoring of these patients.
doi:10.7717/peerj.135
PMCID: PMC3757508  PMID: 24010015
rs-fMRI; MCI; Aging; AD; Alzheimer
25.  Bayesian Network Analysis Reveals Alterations to Default Mode Network Connectivity in Individuals at Risk for Alzheimer's Disease 
PLoS ONE  2013;8(12):e82104.
Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.
doi:10.1371/journal.pone.0082104
PMCID: PMC3855765  PMID: 24324753

Results 1-25 (921515)