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Connectivity of Default-Mode Network Is Associated with Cerebral Edema in Hepatic Encephalopathy  [PDF]
Wei-Che Lin, Tun-Wei Hsu, Chao-Long Chen, Changwei W. Wu, Cheng-Hsien Lu, Hsiu-Ling Chen, Shau-Hsuan Li, Pin-Yang Yeh, Yu-Fan Cheng, Ching-Po Lin
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036986
Abstract: Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.
Default Mode Network Connectivity in Stroke Patients  [PDF]
Anil Man Tuladhar, Liselore Snaphaan, Elena Shumskaya, Mark Rijpkema, Guillén Fernandez, David G. Norris, Frank-Erik de Leeuw
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066556
Abstract: The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 ‘first-ever’ stroke patients. Patients were scanned 9–12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in ‘first-ever’ stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.
Decreased Default Mode Network connectivity correlates with age-associated structural and cognitive changes  [PDF]
Didac Vidal-Pi?eiro,Eider M. Arenaza-Urquijo,Roser Sala-Llonch,Nuria Bargallo,Carme Junque,David Bartrés-Faz
Frontiers in Aging Neuroscience , 2014, DOI: 10.3389/fnagi.2014.00256
Abstract: Ageing entails cognitive and motor decline as well as brain changes such as loss of grey and white matter integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of white matter integrity, grey matter integrity and cerebral blood flow, assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of white matter and grey matter integrity but not to cerebral blood flow. Grey and white matter correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing.
Altered Cerebellar-Cerebral Functional Connectivity in Geriatric Depression  [PDF]
Emmanuel Alalade, Kevin Denny, Guy Potter, David Steffens, Lihong Wang
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020035
Abstract: Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II–vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis–posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum–vmPFC coupling may be related to cognitive function whereas cerebellum–PCC coupling may be related to emotion processing in geriatric depression.
Abnormal Brain Default-Mode Network Functional Connectivity in Drug Addicts  [PDF]
Ning Ma,Ying Liu,Xian-Ming Fu,Nan Li,Chang-Xin Wang,Hao Zhang,Ruo-Bing Qian,Hu-Sheng Xu,Xiaoping Hu,Da-Ren Zhang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016560
Abstract: The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN.
Age differences in the intrinsic functional connectivity of default network subsystems  [PDF]
Karen L. Campbell,Cheryl L. Grady
Frontiers in Aging Neuroscience , 2013, DOI: 10.3389/fnagi.2013.00073
Abstract: Recent work suggests that the default mode network (DMN) includes two core regions, the ventromedial prefrontal cortex and posterior cingulate cortex (PCC), and several unique subsystems that are functionally distinct. These include a medial temporal lobe (MTL) subsystem, active during remembering and future projection, and a dorsomedial prefrontal cortex (dmPFC) subsystem, active during self-reference. The PCC has been further subdivided into ventral (vPCC) and dorsal (dPCC) regions that are more strongly connected with the DMN and cognitive control networks, respectively. The goal of this study was to examine age differences in resting state functional connectivity within these subsystems. After applying a rigorous procedure to reduce the effects of head motion, we used a multivariate technique to identify both common and unique patterns of functional connectivity in the MTL vs. the dmPFC, and in vPCC vs. dPCC. All four areas had robust functional connectivity with other DMN regions, and each also showed distinct connectivity patterns in both age groups. Young and older adults had equivalent functional connectivity in the MTL subsystem. Older adults showed weaker connectivity in the vPCC and dmPFC subsystems, particularly with other DMN areas, but stronger connectivity than younger adults in the dPCC subsystem, which included areas involved in cognitive control. Our data provide evidence for distinct subsystems involving DMN nodes, which are maintained with age. Nevertheless, there are age differences in the strength of functional connectivity within these subsystems, supporting prior evidence that DMN connectivity is particularly vulnerable to age, whereas connectivity involving cognitive control regions is relatively maintained. These results suggest an age difference in the integrated activity among brain networks that can have implications for cognition in older adults.
Aberrant Default Mode Functional Connectivity in Early Onset Schizophrenia  [PDF]
Jinsong Tang, Yanhui Liao, Ming Song, Jia-Hong Gao, Bing Zhou, Changlian Tan, Tieqiao Liu, Yanqing Tang, Jindong Chen, Xiaogang Chen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071061
Abstract: Background The default mode network (DMN) has been linked to a number of mental disorders including schizophrenia. However, the abnormal connectivity of DMN in early onset schizophrenia (EOS) has been rarely reported. Methods Independent component analysis (ICA) was used to investigate functional connectivity (FC) of the DMN in 32 first-episode adolescents with EOS and 32 age and gender-matched healthy controls. Results Compared to healthy controls, patients with EOS showed increased FC between the medial frontal gyrus and other areas of the DMN. Partial correlation analyses showed that the FC of medial frontal gyrus significantly correlated with PANSS-positive symptoms (partial correlation coefficient = 0.538, Bonferoni corrected P = 0.018). Limitations Although the sample size of participants was comparable with most fMRI studies to date, it was still relatively small. Pediatric brains were registered to the MNI adult brain template. However, possible age-specific differences in spatial normalization that arise from registering pediatric brains to the MNI adult brain template may have little effect on fMRI results. Conclusion This study provides evidence for functional abnormalities of DMN in first-episode EOS. These abnormalities could be a source of abnormal introspectively-oriented mental actives.
Default Mode, Dorsal Attention and Auditory Resting State Networks Exhibit Differential Functional Connectivity in Tinnitus and Hearing Loss  [PDF]
Sara A. Schmidt, Kwaku Akrofi, Jake R. Carpenter-Thompson, Fatima T. Husain
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076488
Abstract: We investigated auditory, dorsal attention, and default mode networks in adults with tinnitus and hearing loss in a resting state functional connectivity study. Data were obtained using continuous functional magnetic resonance imaging (fMRI) while the participants were at “rest” and were not performing any task. Participants belonged to one of three groups: middle-aged adults with tinnitus and mild-to-moderate high frequency hearing loss (TIN), age-matched controls with normal hearing and no tinnitus (NH), and a second control group with mild-to-moderate high frequency hearing loss without tinnitus (HL). After standard preprocessing, (a) a group independent component analysis (ICA) using 30 components and (b) a seeding-based connectivity analysis were conducted. In the group ICA, the default mode network was the only network to display visual differences between subject groups. In the seeding analysis, we found increased connectivity between the left parahippocampus and the auditory resting state network in the TIN group when compared to NH controls. Similarly, there was also an increased correlation between the right parahippocampus and the dorsal attention network when compared to HL controls. Other group differences in this attention network included decreased correlations between the seed regions and the right supramarginal gyrus in TIN patients when compared to HL controls. In the default mode network, there was a strong decrease in correlation between the seed regions and the precuneus when compared to both control groups. The findings of this study identify specific alterations in the connectivity of the default mode, dorsal attention, and auditory resting state networks due to tinnitus. The results suggest that therapies for tinnitus that mitigate the increased connectivity of limbic regions with auditory and attention resting state networks and the decreased coherence of the default mode network could be effective at reducing tinnitus-related distress.
Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network  [PDF]
Vincent van de Ven, Marleen Wingen, Kim P. C. Kuypers, Johannes G. Ramaekers, Elia Formisano
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068355
Abstract: The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain’s intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.
Differential Deactivation during Mentalizing and Classification of Autism Based on Default Mode Network Connectivity  [PDF]
Donna L. Murdaugh, Svetlana V. Shinkareva, Hrishikesh R. Deshpande, Jing Wang, Mark R. Pennick, Rajesh K. Kana
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050064
Abstract: The default mode network (DMN) is a collection of brain areas found to be consistently deactivated during task performance. Previous neuroimaging studies of resting state have revealed reduced task-related deactivation of this network in autism. We investigated the DMN in 13 high-functioning adults with autism spectrum disorders (ASD) and 14 typically developing control participants during three fMRI studies (two language tasks and a Theory-of-Mind (ToM) task). Each study had separate blocks of fixation/resting baseline. The data from the task blocks and fixation blocks were collated to examine deactivation and functional connectivity. Deficits in the deactivation of the DMN in individuals with ASD were specific only to the ToM task, with no group differences in deactivation during the language tasks or a combined language and self-other discrimination task. During rest blocks following the ToM task, the ASD group showed less deactivation than the control group in a number of DMN regions, including medial prefrontal cortex (MPFC), anterior cingulate cortex, and posterior cingulate gyrus/precuneus. In addition, we found weaker functional connectivity of the MPFC in individuals with ASD compared to controls. Furthermore, we were able to reliably classify participants into ASD or typically developing control groups based on both the whole-brain and seed-based connectivity patterns with accuracy up to 96.3%. These findings indicate that deactivation and connectivity of the DMN were altered in individuals with ASD. In addition, these findings suggest that the deficits in DMN connectivity could be a neural signature that can be used for classifying an individual as belonging to the ASD group.
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