Suppression Of Default Mode Network Research Articles

Cholinergic modulation supports dynamic switching of resting state networks through selective DMN suppression.

Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that change in excitability and recurrent connections, due to cholinergic modulation, impacts resting-state activity. The results of such modulation in the model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We further extended our study to the human connectome derived from diffusion-weighted MRI. In human resting-state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Furthermore, selective cholinergic modulation of DMN closely captured experimentally observed transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for the effects of cholinergic neuromodulation on resting-state activity and its dynamics.

Modeling the neurocognitive dynamics of language across the lifespan.

Healthy aging is associated with a heterogeneous decline across cognitive functions, typically observed between language comprehension and language production (LP). Examining resting-state fMRI and neuropsychological data from 628 healthy adults (age 18-88) from the CamCAN cohort, we performed state-of-the-art graph theoretical analysis to uncover the neural mechanisms underlying this variability. At the cognitive level, our findings suggest that LP is not an isolated function but is modulated throughout the lifespan by the extent of inter-cognitive synergy between semantic and domain-general processes. At the cerebral level, we show that default mode network (DMN) suppression coupled with fronto-parietal network (FPN) integration is the way for the brain to compensate for the effects of dedifferentiation at a minimal cost, efficiently mitigating the age-related decline in LP. Relatedly, reduced DMN suppression in midlife could compromise the ability to manage the cost of FPN integration. This may prompt older adults to adopt a more cost-efficient compensatory strategy that maintains global homeostasis at the expense of LP performances. Taken together, we propose that midlife represents a critical neurocognitive juncture that signifies the onset of LP decline, as older adults gradually lose control over semantic representations. We summarize our findings in a novel synergistic, economical, nonlinear, emergent, cognitive aging model, integrating connectomic and cognitive dimensions within a complex system perspective.

Abnormal functional activation during response inhibition in mild cognitive impairment: an fMRI study

AbstractBackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Method31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha <.05 was defined to correct for errors of multiple comparisons.ResultBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p<.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p<0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p<0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p<0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

Abnormal functional activation during response inhibition in mild cognitive impairment: an fMRI study

AbstractBackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Methods31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha <.05 was defined to correct for errors of multiple comparisons.ResultsBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p<.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p<0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p<0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p<0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

Altered coordination between frontal delta and parietal alpha networks underlies anhedonia and depressive rumination in major depressive disorder.

A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear. We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals. We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination. The sample size was small. Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future.

A distinct intra-individual suppression subnetwork in the brain's default mode network across cognitive tasks.

Suppression of the brain's default mode network (DMN) during external goal-directed cognitive tasks has been consistently observed in neuroimaging studies. However, emerging insights suggest the DMN is not a monolithic "task-negative" network but is comprised of subsystems that show functional heterogeneity. Despite considerable research interest, no study has investigated the consistency of DMN activity suppression across multiple cognitive tasks within the same individuals. In this study, 85 healthy 15- to 25-year-olds completed three functional magnetic resonance imaging tasks that were designed to reliably map DMN suppression from a resting baseline. Our findings revealed a distinct suppression subnetwork across the three tasks that comprised traditional DMN and adjacent regions. Specifically, common suppression was observed in the medial prefrontal cortex, the dorsal-to-mid posterior cingulate cortex extending to the precuneus, and the posterior insular cortex and parietal operculum. Further, we found the magnitude of suppression of these regions were significantly correlated within participants across tasks. Overall, our findings indicate that externally oriented cognitive tasks elicit common suppression of a distinct subnetwork of the broader DMN. The consistency to which the DMN is suppressed within individuals suggests a domain-general mechanism that may reflect a stable feature of cognitive function that optimizes external goal-directed behavior.

An evolutionary gap in primate default mode network organization

SUMMARYThe human default mode network (DMN) is engaged at rest and in cognitive states such as self-directed thoughts. Interconnected homologous cortical areas in primates constitute a network considered as the equivalent. Here, based on a cross-species comparison of the DMN between humans and non-hominoid primates (macaques, marmosets, and mouse lemurs), we report major dissimilarities in connectivity profiles. Most importantly, the medial prefrontal cortex (mPFC) of non-hominoid primates is poorly engaged with the posterior cingulate cortex (PCC), though strong correlated activity between the human PCC and the mPFC is a key feature of the human DMN. Instead, a fronto-temporal resting-state network involving the mPFC was detected consistently across non-hominoid primate species. These common functional features shared between non-hominoid primates but not with humans suggest a substantial gap in the organization of the primate’s DMN and its associated cognitive functions.

HIV infection is linked with reduced error-related default mode network suppression and poorer medication management abilities

ObjectiveBrain activity linked with error processing has rarely been examined among persons living with HIV (PLWH) despite importance for monitoring and modifying behaviors that could lead to adverse health outcomes (e.g., medication non-adherence, drug use, risky sexual practices). Given that cannabis (CB) use is prevalent among PLWH and impacts error processing, we assessed the influence of HIV serostatus and chronic CB use on error-related brain activity while also considering associated implications for everyday functioning and clinically-relevant disease management behaviors. MethodsA sample of 109 participants, stratified into four groups by HIV and CB (HIV+/CB+, n = 32; HIV+/CB−, n = 27; HIV−/CB+, n = 28; HIV−/CB−, n = 22), underwent fMRI scanning while completing a modified Go/NoGo paradigm called the Error Awareness Task (EAT). Participants also completed a battery of well-validated instruments including a subjective report of everyday cognitive failures and an objective measure of medication management abilities. ResultsAcross all participants, we observed expected error-related anterior insula (aI) activation which correlated with better task performance (i.e., less errors) and, among HIV− participants, fewer self-reported cognitive failures. Regarding awareness, greater insula activation as well as greater posterior cingulate cortex (PCC) deactivation were notably linked with aware (vs. unaware) errors. Regarding group effects, unlike HIV− participants, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) regions (i.e., PCC, medial prefrontal cortex [mPFC]). No CB main or interaction effects were detected. Across all participants, reduced error-related PCC deactivation correlated with reduced medication management abilities and PCC deactivation mediated the effect of HIV on such abilities. More lifetime CB use was linked with reduced error-related mPFC deactivation among HIV− participants and poorer medication management across CB users. ConclusionsThese results demonstrate that insufficient error-related DMN suppression linked with HIV infection, as well as chronic CB use among HIV− participants, has real-world consequences for medication management behaviors. We speculate that insufficient DMN suppression may reflect an inability to disengage task irrelevant mental operations, ultimately hindering error monitoring and behavior modification.

Multimodal investigation of dopamine D2/D3 receptors, default mode network suppression, and cognitive control in cocaine-use disorder.

Stimulant-use disorders have been associated with lower availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R). Links between D2R levels, cognitive performance, and suppression of the default mode network (DMN) during executive functioning have been observed in healthy and addicted populations; however, there is limited evidence regarding a potential role of elevated D3R in influencing cognitive control processes in groups with and without addictions. Sixteen individuals with cocaine-use disorder (CUD) and 16 healthy comparison (HC) participants completed [11C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task of cognitive control. Independent component analysis was performed on fMRI data to assess DMN suppression during Stroop performance. In HC individuals, lower D2R-related binding in the dorsal putamen was associated with improved task performance and greater DMN suppression. By comparison, in individuals with CUD, greater D3R-related binding in the substantia nigra was associated with improved performance and greater DMN suppression. Exploratory moderated-mediation analyses indicated that DMN suppression was associated with Stroop performance indirectly through D2R in HC and D3R in CUD participants, and these indirect effects were different between groups. To our knowledge, this is the first evidence of a dissociative and potentially beneficial role of elevated D3R availability in executive functioning in cocaine-use disorder.

Synchronous brain networks for passive auditory perception in depressive states: A pilot study

Recent studies have revealed a strong relationship between the default mode network (DMN) and major depression disorder (MDD). The DMN consists of several areas in the brain where activity simultaneously increases during the resting state and is suppressed during cognitive tasks (i.e., DMN suppression). Although the DMN has been evaluated in patients with MDD, it has not been studied in people with self-measured depressive symptoms without medication. Although most studies have used high-demand cognitive tasks, the relationships between MDD and passive sensory tasks remain unclear. Here, we recorded electroencephalograph (EEG) data under two sessions: a resting session and an auditory session. Moreover, we assessed depressive states with a Self-Rating Depression Scale (SDS) score. To reveal the DMN suppression mechanism in the depressive states, we used EEG time-frequency analysis. As a result, the alpha-band phase synchronization in the DMN increased during the resting session and decreased during the auditory session. The results suggest that participants in a depressive state have both an abnormal DMN connectivity and a suppressed DMN connectivity via a passive stimulus. Moreover, we were able to estimate the DMN suppression mechanism during the depressive states: (1) the beta-band phase resetting was found in the auditory and parietal areas via the auditory stimulus; (2) the beta-band transfer entropy from the auditory area to the parietal area was high as information flow among these area; and (3) the beta-band systems (information flow) were synchronized with the alpha-band DMN systems. Although the sample size was small, these results suggest that the DMN systems may already be altered during self-measured depressive symptoms like the early stages of the depressive states.

Deficits in executive function and suppression of default mode network in obesity.

Although nutritional and metabolic factors are well established in obesity, neurocognitive determinants are less understood. Using data from the Human Connectome Project, this study concurrently investigated neurocognitive performance, neural activation during a working memory task, and cortical brain morphometry in relation to obesity in a group of young adults, 22-35 years old. Using a case-control design, obese individuals (n = 243, body mass index [BMI] ≥ 30 kg/m2) were compared to a control group of lean BMI individuals (n = 469, BMI = 18-24.9 kg/m2). Performance tests comprised a battery of behavioral neurocognitive assessments. Neural activity was measured as blood-oxygenation-level-dependent (BOLD) activity during an N-Back task using functional magnetic resonance imaging (fMRI). Cortical morphometry included indices of volume, thickness, and surface area. Relative to the control group, the obese group exhibited significantly worse performance in terms of the National Institutes of Health Toolkit (NIH) 9-Hole Peg Board, Penn Working Memory Test, Delay Discounting, Penn Progressive Matrices, NIH Picture Vocabulary Test, Dimensional Change Card Sort Test and the in-scanner N-Back working memory test (FDR-corrected ps<0.05;ds = 0.231-0.405). The obese group also exhibited significantly greater BOLD activation in N-Back task-negative regions, including the ventromedial prefrontal cortex, posterior cingulate, and right precentral gyrus (FDR-corrected ps<0.05). Supplemental functional connectivity analyses provided evidence that the implicated regions were part of the default mode network. Significant differences in morphometry were present in the medial orbitofrontal cortex, rostral anterior cingulate cortex, inferior and superior parietal gyri, and temporal pole (FDR-corrected p<0.001). A data-driven integrative model classified 73.8% of participants correctly. This multimodal investigation suggests diverse aspects of neurocognition are associated with obesity, particularly implicating deficits in executive function and ineffective suppression of the default mode network.

Contributions of default mode network stability and deactivation to adolescent task engagement

Out of the several intrinsic brain networks discovered through resting-state functional analyses in the past decade, the default mode network (DMN) has been the subject of intense interest and study. In particular, the DMN shows marked suppression during task engagement, and has led to hypothesized roles in internally-directed cognition that need to be down-regulated in order to perform goal-directed behaviors. Previous work has largely focused on univariate deactivation as the mechanism of DMN suppression. However, given the transient nature of DMN down-regulation during task, an important question arises: Does the DMN need to be strongly, or more stably suppressed to promote successful task learning? In order to explore this question, 65 adolescents (Mage = 13.32; 21 females) completed a risky decision-making task during an fMRI scan. We tested our primary question by examining individual differences in absolute level of deactivation against the stability of activation across time in predicting levels of feedback learning on the task. To measure stability, we utilized a model-based functional connectivity approach that estimates the stability of activation across time within a region. In line with our hypothesis, the stability of activation in default mode regions predicted task engagement over and above the absolute level of DMN deactivation, revealing a new mechanism by which the brain can suppress the influence of brain networks on behavior. These results also highlight the importance of adopting model-based network approaches to understand the functional dynamics of the brain.

MAOA genotype modulates default mode network deactivation during inhibitory control

It has been demonstrated, in a long line of research, that the low-activity genotype of the monoamine oxidase A (MAOA) gene is associated with aggression. Previous work has linked impaired response inhibition to aggression, but little is known about how this relates to the purported MAOA-aggression relationship in adolescents. Here, we examined how MAOA genotype influences neural correlates of inhibitory control in 74 healthy male adolescents using a GoStop and a Go/Nogo task while differentiating between action cancelation and action restraint. Carriers of the low-expressing MAOA alleles (MAOA-L) did not show altered brain activation in the prefrontal-subcortical inhibition network relative to carriers of the high-expressing alleles across inhibition conditions. However, they exhibited a more pronounced deactivation during response inhibition in the posterior cingulate cortex (PCC) and precuneus, areas belonging to the default mode network (DMN). Larger DMN suppression in MAOA-L carriers might represent a compensation mechanism for impaired cognitive control.

Default mode network deactivation during emotion processing predicts early antidepressant response

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6–8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.

Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD.

Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance.

Brain Function Is Linked to LDL Cholesterol in Older Adults with Cardiovascular Risk.

To determine how cardiovascular risk is associated with working memory task performance and task-related suppression of default-mode network (DMN) activity in cognitively intact older adults. A cross-sectional functional magnetic resonance imaging study of older adults with cardiovascular risk factors. Rotman Research Institute, Baycrest Health Sciences. Thirty older adults with cardiovascular risk factors. Participants provided health information and a blood sample, and underwent functional magnetic resonance imaging during a working memory task and during a breath-hold task to assess cerebrovascular reactivity. Higher plasma low-density lipoprotein cholesterol (LDL-C) was associated with poorer working memory task performance (P = 0.008) and reduced task-related DMN suppression (P = 0.005). A composite index of cardiovascular risk, the Framingham General Cardiovascular Risk Profile, showed no associations with task performance or task-related DMN suppression. These findings were independent of white matter burden and cerebrovascular reactivity and thus cannot be accounted for by individual differences in neurovascular health. These findings suggest a deleterious effect of elevated LDL-C on working memory task performance and task-related DMN suppression in older adults with cardiovascular risk. The relations between the Framingham General Cardiovascular Risk Profile, cognitive task performance, and DMN function require further study.

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function.

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

Failed cooperative, but not competitive, interaction between large-scale brain networks impairs working memory in schizophrenia.

A large-scale network named the default mode network (DMN) dynamically cooperates and competes with an external attention system (EAS) to facilitate various cognitive functioning that is prominently impaired in schizophrenia. However, it is unclear whether the cognitive deficit in schizophrenia is related to the disrupted competition and/or cooperation between these two networks. A total of 35 schizophrenia patients and 30 healthy controls were scanned using gradient-echo echo-planar imaging during n-back working memory (WM) processing. Brain activities of the DMN and EAS were measured using general linear modelling of the functional magnetic resonance imaging data. Dynamic interaction between the DMN and EAS was decomposed into two directions using Granger causality analysis. We observed a significant failure of DMN suppression in patients with schizophrenia, which was significantly related to WM/attentional deficit. Granger causality modelling showed that in healthy controls, while the EAS inhibitorily influenced the DMN, the DMN exerted an 'excitatory' or cooperative influence back on the EAS, especially in those with lower WM accuracy. In schizophrenia, this 'excitatory' DMN→EAS influence within the reciprocal EAS-DMN loop was significantly reduced, especially in patients with WM/attentional deficit. The dynamic interaction between the DMN and EAS is likely to be comprised of both competitive and cooperative influences. In healthy controls, both the 'inhibitory' EAS→DMN interaction and 'excitatory' DMN→EAS interaction are correlated with WM performance. In schizophrenia, reduced 'cooperative' influence from the DMN to dorsal nodes of the EAS occurs in the context of non-suppression of the DMN and may form a possible pathophysiological substrate of WM deficit and attention disorder.

Reduced default mode network suppression during a working memory task in remitted major depression

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.

Dysfunctional modulation of default mode network activity in attention-deficit/hyperactivity disorder.

The state regulation deficit model posits that individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulty applying mental effort effectively under suboptimal conditions such as very fast and very slow event rates (ERs). ADHD is also associated with diminished suppression of default mode network (DMN) activity and related performance deficits on tasks requiring effortful engagement. The current study builds on these 2 literatures to test the hypothesis that failure to modulate DMN activity in ADHD might be especially pronounced at ER extremes. Nineteen adults with ADHD and 20 individuals without any neuropsychiatric condition successfully completed a simple target detection task under 3 ER conditions (2-, 4-, and 8-s interstimulus intervals) inside the scanner. Task-related DMN deactivations were compared between 2 groups. There was a differential effect of ER on DMN activity for individuals with ADHD compared to controls. Individuals with ADHD displayed excessive DMN activity at the fast and slow, but not at the moderate ER. The results indicate that DMN attenuation in ADHD is disrupted in suboptimal energetic states where additional effort is required to optimize task engagement. DMN dysregulation may be an important element of the neurobiological underpinnings of state regulation deficits in ADHD.