Default Mode Network Dysfunction Research Articles

Shared and distinct patterns of default mode network dysfunction in major depressive disorder and bipolar disorder: A comparative meta-analysis

BackgroundWhile patients with major depressive disorder (MDD) and bipolar disorder (BD) exhibited default mode network (DMN) dysfunction revealed by aberrant resting-state functional connectivity (rsFC) patterns, previous findings have been inconsistent. Little is known about the similarities and differences in DMN rsFC between MDD and BD. MethodsA voxel-wise meta-analysis of seed-based DMN rsFC studies on MDD or BD was performed using the Seed-based d Mapping software with permutation of subject images (SDM-PSI). Aberrant DMN rsFC in both disorders was investigated separately, followed by conjunction and between-disorder comparison analyses. Functional decoding was performed to implicate the psychophysiological underpinnings of derived brain abnormalities. ResultsThirty-four studies comparing 1316 MDD patients with 1327 HC, and 22 studies comparing 1059 BD patients with 1396 HC were included. Compared to HC, MDD patients exhibited DMN hyperconnectivity with frontolimbic systems, and hypoconnectivity with temporal lobe and posterior cingulate cortex. BD patients displayed increased DMN connectivity with bilateral precuneus, and reduced connectivity with prefrontal cortex and middle temporal gyrus. No common patterns of DMN rsFC abnormalities were observed between MDD and BD. Compared to BD, MDD patients showed DMN hyperconnectivity with triangular part of the left inferior frontal gyrus and left fusiform gyrus. Functional decoding found that patterns of DMN rsFC alteration between MDD and BD were primarily related to action and perception domains. ConclusionDistinct DMN dysfunction patterns in MDD and BD enhance current understanding of the neural substrates of mood disorders and may provide a potential biomarker for differentiation.

Active suicidal ideation associated with dysfunction in default mode network using resting-state EEG and functional MRI - Findings from the T-RAD Study

Suicide in youth and young adults is a serious public health problem. However, the biological mechanisms of suicidal ideation (SI) remain poorly understood. The primary goal of these analyses was to identify the connectome profile of suicidal ideation using resting state electroencephalography (EEG). We evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10–26 years, n = 111) with current or past diagnoses of either a depressive disorder or bipolar disorder who were enrolled in the Texas Resilience Against Depression Study (T-RAD). Neurocircuitry was analyzed using orthogonalized power envelope connectivity computed from resting state EEG. Suicidal ideation was assessed with the 3-item Suicidal Thoughts factor of the Concise Health Risk Tracking self-report scale. The statistical pipeline involved dimension reduction using principal component analysis, and the association of neuroimaging data with SI using regularized canonical correlation analysis. From the original 111 participants and the correlation matrix of 4950 EEG connectivity pairs in each band (alpha, beta, theta), dimension reduction generated 1305 EEG connectivity pairs in the theta band, 2337 EEG pairs in the alpha band, and 914 EEG connectivity pairs in the beta band. Overall, SI was consistently involved with dysfunction of the default mode network (DMN). This report provides preliminary evidence of DMN dysfunction associated with active suicidal ideation in adolescents. Using EEG using power envelopes to compute connectivity moves us closer to using neurocircuit dysfunction in the clinical setting to identify suicidal ideation.

Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Regional cerebral metabolism alterations and functional connectivity in individuals with opioid use disorder: An integrated resting-state PET/fMRI study

Individuals with opioid use disorder (OUD) have been reported to show abnormal brain metabolism and impaired coupling among brain networks such as the default mode network (DMN), salience network (SN), and executive control network (ECN). However, the characteristics of brain glucose metabolism and its related functions in the brain networks in individuals with OUD remain unknown. Thirty-six individuals with OUD and thirty matched healthy controls (HCs) were recruited in this integrated positron emission tomography/magnetic resonance imaging (PET/MRI) study. Differences in glucose metabolism were analyzed by using 18F-fluorodeoxyglucose (18F-FDG), and the corresponding coupling characteristics of the individuals with OUD were also analyzed. The individuals with OUD showed widespread bilateral hypometabolism in the middle temporal gyrus (MTG), superior temporal gyrus, angular gyrus, supramarginal gyrus, inferior parietal lobe, Rolandic operculum, and left insula, but obvious hypermetabolism in the brainstem and left cerebellum. Meanwhile, in individuals with OUD, the hypometabolism of right MTG which is included in the DMN was accompanied by decreased coupling with the left superior frontal gyrus and right superior parietal gyrus which are included in the ECN. Furthermore, individuals with OUD showed a positive correlation between the duration of heroin use and glucose metabolism of the left MTG. The individuals with OUD were characterized by widespread bilateral hypometabolism in the temporal and parietal regions but obvious hypermetabolism in the brainstem and left cerebellum. The results suggest that the hypometabolism in the temporal and parietal regions might be related to DMN dysfunction and the hypermetabolism in the brainstem and left cerebellum may be compensate for other brain regions showing hypometabolism. In particular, hypometabolism in the self-referential-related DMN regions in OUD might attenuate their relationships with the inhibitory-control-related ECN regions. These findings highlight the importance of evaluating the metabolic and functional profiles of the right MTG in future studies on the treatment of OUD.

Replicable Patterns of Memory Impairments in Children With Autism and Their Links to Hyperconnected Brain Circuits

BackgroundMemory impairments have profound implications for social communication and educational outcomes in children with autism spectrum disorder (ASD). However, the precise nature of memory dysfunction in children with ASD and the underlying neural circuit mechanisms remain poorly understood. The default mode network (DMN) is a brain network that is associated with memory and cognitive function, and DMN dysfunction is among the most replicable and robust brain signatures of ASD. MethodsWe used a comprehensive battery of standardized episodic memory assessments and functional circuit analyses in 25 8- to 12-year-old children with ASD and 29 matched typically developing control children. ResultsMemory performance was reduced in children with ASD compared with control children. General and face memory emerged as distinct dimensions of memory difficulties in ASD. Importantly, findings of diminished episodic memory in children with ASD were replicated in 2 independent data sets. Analysis of intrinsic functional circuits associated with the DMN revealed that general and face memory deficits were associated with distinct, hyperconnected circuits: Aberrant hippocampal connectivity predicted diminished general memory while aberrant posterior cingulate cortex connectivity predicted diminished face memory. Notably, aberrant hippocampal-posterior cingulate cortex circuitry was a common feature of diminished general and face memory in ASD. ConclusionsOur results represent a comprehensive appraisal of episodic memory function in children with ASD and identify extensive and replicable patterns of memory reductions in children with ASD that are linked to dysfunction of distinct DMN-related circuits. These findings highlight a role for DMN dysfunction in ASD that extends beyond face memory to general memory function.

Dysfunction of default mode network characterizes generalized anxiety disorder relative to social anxiety disorder and post-traumatic stress disorder

BackgroundThe perseverative cognition of generalized anxiety disorder (GAD) is distinctive compared to other anxiety disorders. However, the disease-specific and shared neuropathophysiological mechanisms of GAD remain unclear. MethodsWe recruited medication-free patients of GAD (N = 33), social anxiety disorder (SAD; N = 36), post-traumatic stress disorder (PTSD; N = 59), and healthy controls (HC; N = 50). All subjects underwent clinical assessments and resting-state functional magnetic resonance imaging. We compared both the amplitude low-frequency fluctuation (ALFF) and seed-based functional connectivity across the whole brain, using the significantly different regions from the ALFF analyses as seed regions, followed by post-hoc tests. ResultsWe found that ALFF of the left angular gyrus (AG), left inferior parietal lobule (IPL), left precentral gyrus, left middle temporal gyrus, and left cerebellum were higher in GAD compared with SAD, PTSD and HC. This trend was further corroborated by the higher functional connectivity between left AG and bilateral IPL, left inferior temporal gyrus, and left medial prefrontal cortex (mPFC) in GAD. In addition, GAD and SAD both showed abnormally higher left AG-right insula connectivity. Significant correlations were found between anxiety symptom severity and the left AG regional activity and left AG-left mPFC connectivity. LimitationsWe did not compare the differences in neuroimaging between GAD and other anxiety disorders, such as panic disorder. ConclusionsThe default mode network dysfunction may underlie the distinctive perseverative thoughts of GAD relative to other anxiety disorders, and left AG-right insula connectivity may reflect somatic anxiety of anxiety disorder spectrum.

Brain functional abnormality in drug treated and drug naïve adolescents with borderline personality disorder: Evidence for default mode network dysfunction

BackgroundPatients with borderline personality disorder (BPD) have been found to show functional brain abnormality, including in the medial frontal cortex and other areas of the default mode network (DMN). The current study aimed to examine activations and de-activations in drug treated and medication-free female adolescents with the disorder. Methods39 DSM-5 adolescent female patients with BPD without psychiatric comorbidity and 31 matched healthy female adolescents underwent fMRI during the performance of 1-back and 2-back versions of the n-back working memory task. Linear models were used to obtain maps of within-group activations and de-activations and areas of differences between the groups. ResultsOn corrected whole-brain analysis, the BPD patients showed failure to de-activate a region of the medial frontal cortex in the 2-back > 1-back comparison. The 30 never-medicated patients additionally showed a failure to de-activate the right hippocampus in the 2-back versus baseline contrast. ConclusionsEvidence of DMN dysfunction was observed in adolescent patients with BPD. Because the relevant medial frontal and hippocampal changes were seen in unmedicated young patients without comorbidity, they might be considered intrinsic to the disorder.

Default mode network failure and neurodegeneration across aging and amnestic and dysexecutive Alzheimer's disease.

From a complex systems perspective, clinical syndromes emerging from neurodegenerative diseases are thought to result from multiscale interactions between aggregates of misfolded proteins and the disequilibrium of large-scale networks coordinating functional operations underpinning cognitive phenomena. Across all syndromic presentations of Alzheimer's disease, age-related disruption of the default mode network is accelerated by amyloid deposition. Conversely, syndromic variability may reflect selective neurodegeneration of modular networks supporting specific cognitive abilities. In this study, we leveraged the breadth of the Human Connectome Project-Aging cohort of non-demented individuals (N = 724) as a normative cohort to assess the robustness of a biomarker of default mode network dysfunction in Alzheimer's disease, the network failure quotient, across the aging spectrum. We then examined the capacity of the network failure quotient and focal markers of neurodegeneration to discriminate patients with amnestic (N = 8) or dysexecutive (N = 10) Alzheimer's disease from the normative cohort at the patient level, as well as between Alzheimer's disease phenotypes. Importantly, all participants and patients were scanned using the Human Connectome Project-Aging protocol, allowing for the acquisition of high-resolution structural imaging and longer resting-state connectivity acquisition time. Using a regression framework, we found that the network failure quotient related to age, global and focal cortical thickness, hippocampal volume, and cognition in the normative Human Connectome Project-Aging cohort, replicating previous results from the Mayo Clinic Study of Aging that used a different scanning protocol. Then, we used quantile curves and group-wise comparisons to show that the network failure quotient commonly distinguished both dysexecutive and amnestic Alzheimer's disease patients from the normative cohort. In contrast, focal neurodegeneration markers were more phenotype-specific, where the neurodegeneration of parieto-frontal areas associated with dysexecutive Alzheimer's disease, while the neurodegeneration of hippocampal and temporal areas associated with amnestic Alzheimer's disease. Capitalizing on a large normative cohort and optimized imaging acquisition protocols, we highlight a biomarker of default mode network failure reflecting shared system-level pathophysiological mechanisms across aging and dysexecutive and amnestic Alzheimer's disease and biomarkers of focal neurodegeneration reflecting distinct pathognomonic processes across the amnestic and dysexecutive Alzheimer's disease phenotypes. These findings provide evidence that variability in inter-individual cognitive impairment in Alzheimer's disease may relate to both modular network degeneration and default mode network disruption. These results provide important information to advance complex systems approaches to cognitive aging and degeneration, expand the armamentarium of biomarkers available to aid diagnosis, monitor progression and inform clinical trials.

Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task

IntroductionFew studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. MethodsTwenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. ResultsBoth the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. ConclusionsThe failure to find activation differences between BD patients and controls suggests that the ‘regulative’ component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Altered default mode network causal connectivity patterns in autism spectrum disorder revealed by Liang information flow analysis.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with severe cognitive impairment in social communication and interaction. Previous studies have reported that abnormal functional connectivity patterns within the default mode network (DMN) were associated with social dysfunction in ASD. However, how the altered causal connectivity pattern within the DMN affects the social functioning in ASD remains largely unclear. Here, we introduced the Liang information flow method, widely applied to climate science and quantum mechanics, to uncover the brain causal network patterns in ASD. Compared with the healthy controls (HC), we observed that the interactions among the dorsal medial prefrontal cortex (dMPFC), ventral medial prefrontal cortex (vMPFC), hippocampal formation, and temporo-parietal junction showed more inter-regional causal connectivity differences in ASD. For the topological property analysis, we also found the clustering coefficient of DMN and the In-Out degree of anterior medial prefrontal cortex were significantly decreased in ASD. Furthermore, we found that the causal connectivity from dMPFC to vMPFC was correlated with the clinical symptoms of ASD. These altered causal connectivity patterns indicated that the DMN inter-regions information processing was perturbed in ASD. In particular, we found that the dMPFC acts as a causal source in the DMN in HC, whereas it plays a causal target in ASD. Overall, our findings indicated that the Liang information flow method could serve as an important way to explore the DMN causal connectivity patterns, and it also can provide novel insights into the nueromechanisms underlying DMN dysfunction in ASD.

A global functional network biomarker across aging and dysexecutive Alzheimer’s disease

AbstractBackgroundDisruption of the default mode network (DMN) is thought to be a common feature of aging and across Alzheimer’s disease (AD) clinical phenotypes, while syndromic variability could be reflected in selective degeneration of macro‐scale networks optimally supporting specific mental abilities (Fig 1). As part of a collaborative effort between Mayo Clinic and the Human Connectome Project‐Aging (HCP‐A), we aimed to delineate a biomarker of global network failure across aging and the dysexecutive (dAD) and amnestic phenotypes of AD, and biomarkers of focal degeneration specific to each AD phenotype.MethodWe used a regression framework to assess the relationships between a marker of DMN dysfunction, the network failure quotient (NFQ), and factors relevant to AD such as age, cortical thickness (global cortical thickness, inferior parietal lobe), hippocampal volume, and cognition (episodic memory, cognitive flexibility) in the HCP‐A cohort, which consists of 725 non‐demented older adults. We then fit centile curves to the HCP‐A cohort to assess whether the NFQ and focal degeneration markers could distinguish dAD (n=10) and amnestic AD (n=8) patients from the HCP‐A cohort at the group‐ and individual‐level. Participants were scanned using the HCP‐A protocol, allowing for the acquisition of high‐resolution multi‐echo structural images and longer resting‐state connectivity acquisition time compared to traditional protocols.ResultThe NFQ related to age, cortical thickness, hippocampal volume, and cognition in the HCP‐A cohort. It also strongly discriminated dAD and amnestic AD from the HCP‐A cohort but did not discriminate between AD phenotypes. In contrast, markers of focal degeneration were phenotype‐specific; parieto‐frontal areas yielded largest effect sizes for dAD patients, and hippocampal and temporal areas best discriminated patients with amnestic AD (Fig 2).ConclusionThe NFQ may reflect shared system‐level pathophysiological mechanisms across aging and the dysexecutive and amnestic phenotypes of AD whereas focal degeneration markers highlight distinct pathognomonic processes across AD phenotypes. These findings suggest that inter‐individual variability in cognitive impairment in AD would be closely tied to modular, phenotype‐specific network degeneration combined with a common global functional disruption of the DMN. Such information has crucial implications for clinical biomarkers and to provide a deeper understanding of heterogeneity in AD.

Mindfulness-induced endogenous theta stimulation occasions self-transcendence and inhibits addictive behavior.

Self-regulation is instantiated by theta oscillations (4 to 8 Hz) in neurons of frontal midline brain regions. Frontal midline theta (FMΘ) is inversely associated with default mode network (DMN) activation, which subserves self-referential processing. Addiction involves impaired self-regulation and DMN dysfunction. Mindfulness is an efficacious self-regulatory practice for treating addiction, but little is known about the mechanisms by which mindfulness reduces addictive behavior. In this mechanistic study of long-term opioid users (N = 165), we assessed meditation-induced FMΘ as a mediator of changes in opioid misuse. Relative to a supportive psychotherapy control, participants treated with Mindfulness-Oriented Recovery Enhancement (MORE) exhibited increased FMΘ during a laboratory-based meditation session. FMΘ during meditation was associated with self-transcendent experiences characterized by ego dissolution, nondual awareness, and bliss. MORE’s effects on decreasing opioid misuse were mediated by increased FMΘ. Given the role of aberrant self-referential processing in addiction, mindfulness-induced endogenous theta stimulation might “reset” DMN dysfunction to inhibit addictive behavior.

Charting the dorsal-medial functional gradient of the default mode network in major depressive disorder

Major depressive disorder (MDD) is a common and disabling psychiatric condition associated with aberrant functional activity of the default mode network (DMN). However, it is unclear how the DMN dysfunction in MDD patients is characterized by functional connectivity diversity or gradient and whether antidepressant therapy causes the abnormal functional gradient of the DMN to change toward normalization. In current work, we estimated the functional gradient of the DMN derived from resting state functional magnetic resonance imaging in MDD patients (n = 70) and matching healthy controls (n = 43) and identified MDD-related functional connectivity diversity of the DMN. The longitudinal changes of the DMN functional gradient in 36 MDD patients were assessed before and after 12-week antidepressant treatment. Compared to the healthy controls, the functional gradient of the DMN exhibited relatively relative compression along the dorsal-medial axis in MDD patients at baseline and antidepressant treatment could normalize these DMN gradient abnormalities. A regularized least-squares regression model based on DMN gradient features at baseline significantly predicted the change of Hamilton Depression Rating (HAMD) Scale scores after antidepressant treatment. The medial prefrontal cortex gradient had a more contribution to prediction of antidepressant efficacy. Our findings provided a novel insight into the neurobiological mechanism underlying MDD from the perspective of the DMN functional gradient.

Treatment Effect of Long-Term Antipsychotics on Default-Mode Network Dysfunction in Drug-Naïve Patients With First-Episode Schizophrenia: A Longitudinal Study.

Background: The maintenance of antipsychotic treatment is an efficient way to prevent the relapse of schizophrenia (SCZ). Previous studies have identified beneficial effects of antipsychotics on brain structural and functional abnormalities during mostly the acute phase in SCZ, but seldom is known about the effects of long-term antipsychotics on the brain. The present study focused on the long-term antipsychotic effect on the default mode network (DMN) dysfunction in SCZ. Methods: A longitudinal study of the functional connectivity (FC) of 11 DMN subdivisions was conducted in 86 drug-naive first-episode patients with SCZ at the baseline and after a long-term atypical antipsychotic treatment (more than 6 months) based on the resting-state functional magnetic resonance image. In total, 52 patients completed the follow-up of clinical and neuroimaging investigations. Results: At the baseline, relative to healthy controls, altered connectivities within the DMN and between the DMN and the external attention system (EAS) were observed in patients. After treatment, along with significant relief of symptoms, most FC alterations between the DMN and the EAS at the baseline were improved after treatment, although the rehabilitation of FC within the DMN was only observed at the link between the posterior cingulate cortex and precuneus. Greater reductions in negative and positive symptoms were both related to the changes of DMN-EAS FC in patients. Conclusion: Our findings provide evidence that maintenance antipsychotics on SCZ is beneficial for the improvement of DMN-EAS competitive imbalance, which may partly contribute to the efficient relapse prevention of this severe mental disorder.

Functional Connectome Analysis in Mild Cognitive Impairment: Comparing Alzheimer's Disease Continuum and Suspected Non-Alzheimer Pathology.

Introduction: Research in brain resting-state functional connectivity (FC) analysis in mild cognitive impairment (MCI) has conflicting results. This work intends to find differences in resting-state FC of 2 groups of MCI subjects due to Alzheimer's disease (MCI-AD) continuum or to suspected non-Alzheimer pathology (MCI-SNAP). Materials and Methods: Ninety-two subjects older than 55 years were enrolled. MCI and controls were grouped using clinical dementia rating and neuropsychological data. Cerebrospinal fluid biomarkers were collected from MCI subjects, resulting in 32 MCI-AD, 25 MCI-SNAP, and 35 controls. A region of interest (ROI)-to-ROI analysis was carried out looking at inter- and intranetwork interactions selecting the following networks: default mode network (DMN), salience network (SN), visuospatial network (VN), and executive network. Pearson correlation coefficients, converted to Z-scores, were compared by T-tests with alpha set to 0.05, and false discovery rate corrected. Results: Groups were similar in age, education, and demographic measures, there were no differences in neuropsychological data between the MCI groups. The ROI-to-ROI analysis of MCI-AD versus MCI-SNAP showed no differences. MCI-AD versus controls showed decreased FC between ROIs of the SN and between ROIs from SN and VN. MCI-SNAP versus controls showed increased FC between an ROI of DMN and VN. Discussion: SN, DMN, and VN are multimodal networks with high value/high cost and may be more vulnerable to AD pathogenic processes. SN and VN were affected in the MCI-AD group, with maintained anticorrelation between DMN and VN. This may indicate subthreshold DMN dysfunction. The result in MCI-SNAP, although discrete, reflects a rearrangement of brain FC, as DMN and VN are expected to be anticorrelated. More research is necessary to confirm these findings.

Altered Functional Connectivity in a Triple-Network Model in Autism With Co-occurring Attention Deficit Hyperactivity Disorder.

Purpose: This study aimed to explore alterations in functional connectivity (FC) within and between default mode network (DMN), central executive network, and salience network in autism spectrum disorder (ASD) with co-occurring attention deficit hyperactivity disorder (ADHD).Method: A total of 135 individuals' date of the Autism Brain Imaging Data Exchange II was used to compare the ASD+ADHD group with the ASD group in relation to the abnormal within-network and between-network connectivity of the ASD group relative to the TD group; consequently, the correlation analysis between abnormal FC and behavior was performed.Results: The ASD+ADHD group exhibited decreased within-network connectivity in the precuneus of the ventral DMN compared with the ASD group. Among the three groups, the ASD+ADHD group showed lower connectivity, whereas the ASD group had higher connectivity than the TD group, although the effect of the separate post hoc test was not significant. Meanwhile, the ASD+ADHD group showed increased between-network connectivity between the ventral DMN and dorsal DMN and between the ventral DMN and left executive control network, compared with the ASD and TD groups.Conclusion: Dysfunction of DMN in the “triple-network model” is the core evidence for ASD with co-occurring ADHD.

Distinct Functional and Metabolic Alterations of DMN Subsystems in Alzheimer's Disease: A Simultaneous FDG-PET/fMRI Study.

The default mode network (DMN) dysfunction has been widely identified in Alzheimer's disease (AD). Increasing evidence has shown that the functional heterogeneity of DMN has been associated with distinct cognitive functions. The pathophysiological changes of these two DMN subsystems, i.e., anterior DMN (aDMN) and posterior DMN (pDMN), also showed different patterns in the AD patients. Yet the underlying metabolic mechanism remains not clear. In this work, we performed a simultaneous FDG-PET/fMRI study, to investigate the distinct functional and metabolic alterations of DMN subsystems in AD. Significantly decreased functional connectivity strength (FCS) in pDMN but not aDMN was found in AD patients. The retaining connectivity in aDMN might represent a compensatory strategy. Concurrently, significant glucose hypometabolism was shown in pDMN and aDMN of AD patients, respectively. Moreover, the reduction of FCS in pDMN was positively correlated with MMSE score of patients. Our study suggests that resting state functional connectivity and glucose metabolism changed differently in the aDMN and pDMN of AD. Our findings brought new insights in understanding the underlying metabolism changes along with functional alterations in AD.

Targeting Default Mode Network Dysfunction in Persons at Risk of Alzheimer's Disease with Transcranial Magnetic Stimulation (NEST4AD): Rationale and Study Design.

Default mode network (DMN) dysfunction is well established in Alzheimer's disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

Activation and deactivation patterns in schizophrenia during performance of an fMRI adapted version of the stroop task

The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.

Dysfunction of default mode network is associated with active suicidal ideation in youths and young adults with depression: Findings from the T-RAD study

Deaths due to suicide are one of the leading causes of mortality among youths and young adults. Active suicidal ideation (SI) is considered one of the strongest risk factors for suicide. Here, we evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10–26 years) with current or past diagnosis of either major depression or bipolar disorder who were enrolled in Texas Resilience Against Depression Study (T-RAD), and had neuroimaging and SI (assessed with the 3-item Suicidal Thoughts factor of Concise Health Risk Tracking self-report scale) data available (n = 72, 53 females). Resting-state functional connectivity (FC) was computed amongst 121 cortical and subcortical regions of interest resulting in 7260 FC pairs. Mean (SD) age and SI levels of participants were 19.6 years (4.01) and 1.48 (2.36) respectively. In univariate analyses, 34 out of the 7260 FC pairs were correlated with SI (p < .005). Stronger connectivity of default mode network (DMN) with striatum was associated with higher SI. Conversely, higher SI was associated with weaker connectivity of limbic network with hippocampus, DMN, dorsal attention network, and executive control network. In multivariate analyses, these 34 FC pairs together had an average correlation of 0.54 after five-fold cross-validation. In conclusion, SI was associated with distinct patterns of resting-state functional connectivity among youths and young adults with regions in DMN and the ventral striatum as key nodes.