Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

2008 ◽  
Vol 38 (8) ◽  
pp. 1185-1193 ◽  
Author(s):  
E. Pomarol-Clotet ◽  
R. Salvador ◽  
S. Sarró ◽  
J. Gomar ◽  
F. Vila ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Default Mode Network ◽  
Sense Of Self ◽  
Memory Task ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Default Mode ◽  
Schizophrenic Patients ◽  
Back Task

BackgroundFunctional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation.MethodThirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups.ResultsThe controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent.ConclusionsPatients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the ‘default mode network’ implicated in functions related to maintaining one's sense of self.

scholarly journals Aberrant Dynamic Functional Connectivity of Default Mode Network in Schizophrenia and Links to Symptom Severity

2021 ◽  
Vol 15 ◽  
Author(s):  
Mohammad S. E. Sendi ◽  
Elaheh Zendehrouh ◽  
Charles A. Ellis ◽  
Zhijia Liang ◽  
Zening Fu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Default Mode Network ◽  
Resting State ◽  
Symptom Severity ◽  
Transition Probability ◽  
Feature Selection Method ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Dynamic Functional Connectivity ◽  
Default Mode

Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized.Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects.Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity.Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics.

Cortical and subcortical changes in resting-state functional connectivity before and during an episode of postoperative delirium

2019 ◽  
Vol 53 (8) ◽  
pp. 794-806 ◽  
Author(s):  
Jooyoung Oh ◽  
Jung Eun Shin ◽  
Kyu Hyun Yang ◽  
Sunghyon Kyeong ◽  
Woo Suk Lee ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Default Mode Network ◽  
Resting State ◽  
Postoperative Delirium ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Default Mode ◽  
Posterior Cingulate ◽  
Subcortical Regions

Objective: Delirium is an acute brain failure related to uncertain problems in neural connectivity, including aberrant functional interactions between remote cortical regions. This study aimed to elucidate the underlying neural mechanisms of delirium by clarifying the changes in resting-state functional connectivity induced by postoperative delirium using imaging data scanned before and after surgery. Method: Fifty-eight patients with a femoral neck fracture were preoperatively scanned using resting-state functional magnetic resonance imaging. Twenty-five patients developed postoperative delirium, and 14 of those had follow-up scans during delirium. Eighteen patients without delirium completed follow-up scans 5 or 6 days after surgery. We assessed group differences in voxel-based connectivity, in which the seeds were the posterior cingulate cortex, medial prefrontal cortex and 11 subcortical regions. Connections between the subcortical regions were also examined. Results: The results showed four major findings during delirium. Both the posterior cingulate cortex and medial prefrontal cortex were strongly connected to the dorsolateral prefrontal cortex. The posterior cingulate cortex had hyperconnectivity with the inferior parietal lobule, whereas the medial prefrontal cortex had hyperconnectivity with the frontopolar cortex and hypoconnectivity with the superior frontal gyrus. Connectivity of the striatum with the anterior cingulate cortex and insula was increased. Disconnections were found between the lower subcortical regions including the neurotransmitter origins and the striatum/thalamus in the upper level. Conclusions: Our findings suggest that cortical dysfunction during delirium is characterized by a diminution of the anticorrelation between the default mode network and task-positive regions, excessive internal connections in the posterior default mode network and a complex imbalance of internal connectivity in the anterior default mode network. These dysfunctions can be attributed to the loss of reciprocity between the default mode network and central executive network associated with defective function in the salience network, which might be closely linked to aberrant subcortical neurotransmission-related connectivity and striato-cortical connectivity.

Failure of deactivation in the default mode network: a trait marker for schizophrenia?

2014 ◽  
Vol 45 (6) ◽  
pp. 1315-1325 ◽  
Author(s):  
R. Landin-Romero ◽  
P. J. McKenna ◽  
P. Salgado-Pineda ◽  
S. Sarró ◽  
C. Aguirre ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Default Mode Network ◽  
Memory Task ◽  
Medial Frontal Cortex ◽  
Matched Pair ◽  
Healthy Controls ◽  
Default Mode ◽  
Trait Marker ◽  
Significant Difference ◽  
Schizophrenic Patients

Background.Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen.Method.A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups.Results.In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives.Conclusions.Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.

scholarly journals Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

2015 ◽  
Vol 35 (33) ◽  
pp. 11595-11605 ◽  
Author(s):  
Marta Čeko ◽  
John L. Gracely ◽  
Mary-Ann Fitzcharles ◽  
David A. Seminowicz ◽  
Petra Schweinhardt ◽  
...  
Keyword(s):  
Working Memory ◽  
Task Performance ◽  
Default Mode Network ◽  
Memory Task ◽  
Default Mode

scholarly journals Biophysical mechanism of the interaction between default mode network and working memory network

2021 ◽  
Author(s):  
Yue Yuan ◽  
Xiaochuan Pan ◽  
Rubin Wang
Keyword(s):  
Working Memory ◽  
Neural Activity ◽  
Default Mode Network ◽  
Phase Synchronization ◽  
Memory Task ◽  
Inhibitory Neurons ◽  
Default Mode ◽  
Functional Connections ◽  
Functional Brain Network ◽  
Memory Network

AbstractDefault mode network (DMN) is a functional brain network with a unique neural activity pattern that shows high activity in resting states but low activity in task states. This unique pattern has been proved to relate with higher cognitions such as learning, memory and decision-making. But neural mechanisms of interactions between the default network and the task-related network are still poorly understood. In this paper, a theoretical model of coupling the DMN and working memory network (WMN) is proposed. The WMN and DMN both consist of excitatory and inhibitory neurons connected by AMPA, NMDA, GABA synapses, and are coupled with each other only by excitatory synapses. This model is implemented to demonstrate dynamical processes in a working memory task containing encoding, maintenance and retrieval phases. Simulated results have shown that: (1) AMPA channels could produce significant synchronous oscillations in population neurons, which is beneficial to change oscillation patterns in the WMN and DMN. (2) Different NMDA conductance between the networks could generate multiple neural activity modes in the whole network, which may be an important mechanism to switch states of the networks between three different phases of working memory. (3) The number of sequentially memorized stimuli was related to the energy consumption determined by the network's internal parameters, and the DMN contributed to a more stable working memory process. (4) Finally, this model demonstrated that, in three phases of working memory, different memory phases corresponded to different functional connections between the DMN and WMN. Coupling strengths that measured these functional connections differed in terms of phase synchronization. Phase synchronization characteristics of the contained energy were consistent with the observations of negative and positive correlations between the WMN and DMN reported in referenced fMRI experiments. The results suggested that the coupled interaction between the WMN and DMN played important roles in working memory.

Multimorbidity and Regional Volumes of the Default Mode Network in Brain Aging

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Jen-Hung Wang ◽  
Joshua Oon Soo Goh ◽  
Yu-Ling Chang ◽  
Shu-Cin Chen ◽  
Yu-Ying Li ◽  
...  
Keyword(s):  
Default Mode Network ◽  
Structural Integrity ◽  
Rating Scale ◽  
Brain Aging ◽  
Fasting Blood Glucose ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Cross Sectional ◽  
Default Mode ◽  
Posterior Cingulate

<b><i>Introduction:</i></b> The default mode network (DMN) is selectively vulnerable in brain aging. Little is known about the effect of multimorbidity as a whole onto the brain structural integrity. <b><i>Objective:</i></b> We aimed to investigate the association between multimorbidity and the structural integrity of DMN. <b><i>Methods:</i></b> We enrolled senior volunteers aged between 60 and 80 years in Hualien County during 2014–2018 and conducted in-person interview to collect information on chronic diseases. Fasting blood glucose and glycated hemoglobin (HbA1c) were tested. We assessed multimorbidity burden by the cumulative illness rating scale-geriatric (CIRS-G). MRI brain scans were standardized to measure the regional volume within the DMN. In a cross-sectional design, we employed stepwise regression models to evaluate the effects of age, sex, hyperglycemia, and multimorbidity on the DMN. <b><i>Results:</i></b> A total of 170 volunteers were enrolled with a mean age of 66.9 years, female preponderance (71%), an average mini-mental state examination score of 27.6, a mean HbA1c of 6.0, and a mean CIRS-G total score (TS) of 7.2. We found that older age was associated with reduced volumes in the hippocampus, left rostral anterior cingulate cortex, right posterior cingulate, right isthmus, precuneus, and right supramarginal. Higher levels of HbA1c and fasting glucose were associated with a reduced volume in the hippocampus only. A higher CIRS-G-TS was associated with reduced volumes in the left posterior cingulate cortex and right supramarginal gyrus; while a higher CIRS-G severity index was associated with a smaller right precuneus and right supramarginal. <b><i>Conclusions:</i></b> In the DMN, hippocampal volume shows vulnerability to aging and hyperglycemia, whereas the posterior cingulate, supramarginal, and precuneus cortices may be the key sites to reflect the total effects of multimorbidity.

scholarly journals Dynamic connectivity modulates local activity in the core regions of the default-mode network

2017 ◽  
Vol 114 (36) ◽  
pp. 9713-9718 ◽  
Author(s):  
Wei Tang ◽  
Hesheng Liu ◽  
Linda Douw ◽  
Mark A. Kramer ◽  
Uri T. Eden ◽  
...  
Keyword(s):  
Default Mode Network ◽  
Resting State ◽  
Large Scale ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Anterior Cingulate ◽  
Default Mode ◽  
Local Activity ◽  
The Core ◽  
Dynamic Connectivity

Segregation and integration are distinctive features of large-scale brain activity. Although neuroimaging studies have been unraveling their neural correlates, how integration takes place over segregated modules remains elusive. Central to this problem is the mechanism by which a brain region adjusts its activity according to the influence it receives from other regions. In this study, we explore how dynamic connectivity between two regions affects the neural activity within a participating region. Combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same group of subjects, we analyzed resting-state data from the core of the default-mode network. We observed directed influence from the posterior cingulate cortex (PCC) to the anterior cingulate cortex (ACC) in the 10-Hz range. This time-varying influence was associated with the power alteration in the ACC: strong influence corresponded with a decrease of power around 13–16 Hz and an increase of power in the lower (1–7 Hz) and higher (30–55 Hz) ends of the spectrum. We also found that the amplitude of the 30- to 55-Hz activity was coupled to the phase of the 3- to 4-Hz activity in the ACC. These results characterized the local spectral changes associated with network interactions. The specific spectral information both highlights the functional roles of PCC–ACC connectivity in the resting state and provides insights into the dynamic relationship between local activity and coupling dynamics of a network.

scholarly journals Modafinil modulates anterior cingulate function in chronic schizophrenia

2005 ◽  
Vol 187 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Sean A. Spence ◽  
Russell D. Green ◽  
Iain D. Wilkinson ◽  
Mike D. Hunter
Keyword(s):  
Working Memory ◽  
Anterior Cingulate Cortex ◽  
Cognitive Performance ◽  
Cognitive Deficits ◽  
Brain Activity ◽  
Memory Task ◽  
Cingulate Cortex ◽  
Chronic Schizophrenia ◽  
Anterior Cingulate ◽  
Double Blind

BackgroundSchizophrenia is associated with widespread cognitive deficits that have an impact on social function. Modafinil promotes wakefulness and is reported to enhance cognition.AimsTo study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia.MethodIn a randomised double-blind placebo-controlled crossover design, 19 patients received either modafinil (100 mg) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging.ResultsSeventeen patients completed the study and another underwent acute relapse 4 days post-drug. Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task. The anterior cingulate cortex signal correlated with cognitive performance, although only a subset of patients exhibited ‘enhancement’.ConclusionsModafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.

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