Angular default mode network connectivity across working memory load

Initially identified during no‐task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large‐scale brain networks. Nevertheless, its contribution to whole‐brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI‐based n‐back paradigm with parametric increases in difficulty. Using a voxel‐wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n‐back task load. Subsequent seed‐based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large‐scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n‐back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41–52, 2017. © 2016 Wiley Periodicals, Inc.     

Similarities and differences in the default mode network across rest,retrieval, and future imagining

The default mode network (DMN) has been identified reliably during rest, as well as during the performance of tasks such as episodic retrieval and future imagining. It remains unclear why this network is engaged across these seemingly distinct conditions, though many hypotheses have been proposed to account for these effects. Prior to generating hypotheses explaining common DMN involvement, the degree of commonality in the DMN across these conditions, within individuals, must be statistically determined to test whether or not the DMN is truly a unitary network, equally engaged across rest, retrieval and future imagining. To provide such a test, we used comparable paradigms (self‐directed, uninterrupted thought of equal duration) across the three conditions (rest, retrieval, and future imagining) in a within‐participant design. We found lower than expected pattern similarity in DMN functional connectivity across the three conditions. Similarity in connectivity accounted for only 40–50% of the total variance. Partial Least Squares (PLS) analyses revealed the medial temporal regions of the DMN were preferentially coupled with one another during episodic retrieval and future imagining, whereas the non‐medial temporal regions of the DMN (e.g., medial prefrontal cortex, lateral temporal cortex, and temporal pole) were preferentially coupled during rest. These results suggest that DMN connectivity may be more flexible than previously considered. Our findings are in line with emerging evidence that the DMN is not a static network engaged commonly across distinct cognitive processes, but is instead a dynamic system, topographically changing in relation to ongoing cognitive demands. Hum Brain Mapp 38:1155–1171, 2017. © 2016 Wiley Periodicals, Inc.     

Altered functional connectivity in default mode network in absence epilepsy: a resting-state fMRI study

Dysfunctional default mode network (DMN) has been observed in various mental disorders, including epilepsy (see review Broyd et al. [2009]: Neurosci Biobehav Rev 33:279–296). Because interictal epileptic discharges may affect DMN, resting-state fMRI was used in this study to determine DMN functional connectivity in 14 healthy controls and 12 absence epilepsy patients. To avoid interictal epileptic discharge effects, testing was performed within interictal durations when there were no interictal epileptic discharges. Cross-correlation functional connectivity analysis with seed at posterior cingulate cortex, as well as region-wise calculation in DMN, revealed decreased integration within DMN in the absence epilepsy patients. Region-wise functional connectivity among the frontal, parietal, and temporal lobe was significantly decreased in the patient group. Moreover, functional connectivity between the frontal and parietal lobe revealed a significant negative correlation with epilepsy duration. These findings indicated DMN abnormalities in patients with absence epilepsy, even during resting interictal durations without interictal epileptic discharges. Abnormal functional connectivity in absence epilepsy may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure.     

Dysmaturation of the default mode network in autism

Two hypotheses of autism spectrum disorder (ASD) propose that this condition is characterized by deficits in Theory of Mind and by hypoconnectivity between remote cortical regions with hyperconnectivity locally. The default mode network (DMN) is a set of remote, functionally connected cortical nodes less active during executive tasks than at rest and is implicated in Theory of Mind, episodic memory, and other self‐reflective processes. We show that children with ASD have reduced connectivity between DMN nodes and increased local connectivity within DMN nodes and the visual and motor resting‐state networks. We show that, like the trajectory of synaptogenesis, internodal DMN functional connectivity increased as a quadratic function of age in typically developing children, peaking between, 11 and 13 years. In children with ASD, these long‐distance connections fail to develop during adolescence. These findings support the “developmental disconnection model” of ASD, provide a possible mechanistic explanation for the Theory‐of‐Mind hypothesis of ASD, and show that the window for effectively treating ASD could be wider than previously thought. Hum Brain Mapp 35:1284–1296, 2014. © 2013 Wiley Periodicals, Inc.     

Modulation of steady state functional connectivity in the default mode and working memory networks by cognitive load

Interregional correlations between blood oxygen level dependent (BOLD) magnetic resonance imaging (fMRI) signals in the resting state have been interpreted as measures of connectivity across the brain. Here we investigate whether such connectivity in the working memory and default mode networks is modulated by changes in cognitive load. Functional connectivity was measured in a steady-state verbal identity N-back task for three different conditions (N = 1, 2, and 3) as well as in the resting state. We found that as cognitive load increases, the functional connectivity within both the working memory the default mode network increases. To test whether functional connectivity between the working memory and the default mode networks changed, we constructed maps of functional connectivity to the working memory network as a whole and found that increasingly negative correlations emerged in a dorsal region of the posterior cingulate cortex. These results provide further evidence that low frequency fluctuations in BOLD signals reflect variations in neural activity and suggests interaction between the default mode network and other cognitive networks.     

Temporal stability of network centrality in control and default mode networks: Specific associations with externalizing psychopathology in children and adolescents

Abnormal connectivity patterns have frequently been reported as involved in pathological mental states. However, most studies focus on “static,” stationary patterns of connectivity, which may miss crucial biological information. Recent methodological advances have allowed the investigation of dynamic functional connectivity patterns that describe non‐stationary properties of brain networks. Here, we introduce a novel graphical measure of dynamic connectivity, called time‐varying eigenvector centrality (tv‐EVC). In a sample 655 children and adolescents (7–15 years old) from the Brazilian “High Risk Cohort Study for Psychiatric Disorders” who were imaged using resting‐state fMRI, we used this measure to investigate age effects in the temporal in control and default‐mode networks (CN/DMN). Using support vector regression, we propose a network maturation index based on the temporal stability of tv‐EVC. Moreover, we investigated whether the network maturation is associated with the overall presence of behavioral and emotional problems with the Child Behavior Checklist. As hypothesized, we found that the tv‐EVC at each node of CN/DMN become more stable with increasing age (P < 0.001 for all nodes). In addition, the maturity index for this particular network is indeed associated with general psychopathology in children assessed by the total score of Child Behavior Checklist (P = 0.027). Moreover, immaturity of the network was mainly correlated with externalizing behavior dimensions. Taken together, these results suggest that changes in functional network dynamics during neurodevelopment may provide unique insights regarding pathophysiology. Hum Brain Mapp 36:4926–4937, 2015. © 2015 Wiley Periodicals, Inc.     

Frequency‐specific changes in the default mode network in patients with cingulate gyrus epilepsy

To identify abnormal functional connectivity of the default mode network in cingulate gyrus epilepsy, which may yield new information about the default mode network and suggest a new cingulate gyrus epilepsy biomarker. Fifteen patients with cingulate gyrus epilepsy (mean age = 21 years) and 15 healthy controls (mean age = 24 years) were studied in the resting state using magnetoencephalography. Twelve brain areas of interest in the default mode network were extracted and investigated with multifrequency signals that included alpha (α, 8–13 Hz), beta (β, 14–30 Hz), and gamma (γ, 31–80 Hz) band oscillations. Patients with cingulate gyrus epilepsy had significantly greater connectivity in all three frequency bands (α, β, γ). A frequency‐specific elevation of functional connectivity was found in patients compared to controls. The greater functional connectivity in the γ band was significantly more prominent than that of the α and β bands. Patients with cingulate gyrus epilepsy and controls differed significantly in functional connectivity between the left angular gyrus and left posterior cingulate cortex in the α, β, and γ bands. The results of the node degree analysis were similar to those of the functional connectivity analysis. Our findings reveal for the first time that brain activity in the γ band may play a key role in the default mode network in cingulate gyrus epilepsy. Altered functional connectivity of the left angular gyrus and left posterior cingulate cortex may be a new biomarker for cingulate gyrus epilepsy.     

Studying the default mode and its mindfulness-induced changes using EEG functional connectivity

The default mode network (DMN) has been largely studied by imaging, but not yet by neurodynamics, using electroencephalography (EEG) functional connectivity (FC). mindfulness meditation (MM), a receptive, non-elaborative training is theorized to lower DMN activity. We explored: (i) the usefulness of EEG-FC for investigating the DMN and (ii) the MM-induced EEG-FC effects. To this end, three MM groups were compared with controls, employing EEG-FC (–MPC, mean phase coherence). Our results show that: (i) DMN activity was identified as reduced overall inter-hemispheric gamma MPC during the transition from resting state to a time production task and (ii) MM-induced a state increase in alpha MPC as well as a trait decrease in EEG-FC. The MM-induced EEG-FC decrease was irrespective of expertise or band. Specifically, there was a relative reduction in right theta MPC, and left alpha and gamma MPC. The left gamma MPC was negatively correlated with MM expertise, possibly related to lower internal verbalization. The trait lower gamma MPC supports the notion of MM-induced reduction in DMN activity, related with self-reference and mind-wandering. This report emphasizes the possibility of studying the DMN using EEG-FC as well as the importance of studying meditation in relation to it.     

Increased resting state functional connectivity in the default mode network in recovered anorexia nervosa

Functional brain imaging studies have shown abnormal neural activity in individuals recovered from anorexia nervosa (AN) during both cognitive and emotional task paradigms. It has been suggested that this abnormal activity which persists into recovery might underpin the neurobiology of the disorder and constitute a neural biomarker for AN. However, no study to date has assessed functional changes in neural networks in the absence of task‐induced activity in those recovered from AN. Therefore, the aim of this study was to investigate whole brain resting state functional connectivity in nonmedicated women recovered from anorexia nervosa. Functional magnetic resonance imaging scans were obtained from 16 nonmedicated participants recovered from anorexia nervosa and 15 healthy control participants. Independent component analysis revealed functionally relevant resting state networks. Dual regression analysis revealed increased temporal correlation (coherence) in the default mode network (DMN) which is thought to be involved in self‐referential processing. Specifically, compared to healthy control participants the recovered anorexia nervosa participants showed increased temporal coherence between the DMN and the precuneus and the dorsolateral prefrontal cortex/inferior frontal gyrus. The findings support the view that dysfunction in resting state functional connectivity in regions involved in self‐referential processing and cognitive control might be a vulnerability marker for the development of anorexia nervosa. Hum Brain Mapp 35:483–491, 2014. © 2012 Wiley Periodicals, Inc.     

Impact of meditation training on the default mode network during a restful state

Mindfulness meditation has been shown to promote emotional stability. Moreover, during the processing of aversive and self-referential stimuli, mindful awareness is associated with reduced medial prefrontal cortex (MPFC) activity, a central default mode network (DMN) component. However, it remains unclear whether mindfulness practice influences functional connectivity between DMN regions and, if so, whether such impact persists beyond a state of meditation. Consequently, this study examined the effect of extensive mindfulness training on functional connectivity within the DMN during a restful state. Resting-state data were collected from 13 experienced meditators (with over 1000 h of training) and 11 beginner meditators (with no prior experience, trained for 1 week before the study) using functional magnetic resonance imaging (fMRI). Pairwise correlations and partial correlations were computed between DMN seed regions’ time courses and were compared between groups utilizing a Bayesian sampling scheme. Relative to beginners, experienced meditators had weaker functional connectivity between DMN regions involved in self-referential processing and emotional appraisal. In addition, experienced meditators had increased connectivity between certain DMN regions (e.g. dorso-medial PFC and right inferior parietal lobule), compared to beginner meditators. These findings suggest that meditation training leads to functional connectivity changes between core DMN regions possibly reflecting strengthened present-moment awareness.     

Intrinsic functional connectivity in the default mode network predicts mnemonic discrimination: A connectome-based modeling approach

The ability to distinguish existing memories from similar perceptual experiences is a core feature of episodic memory. This ability is often examined using the mnemonic similarity task in which people discriminate memories of studied objects from perceptually similar lures. Studies of the neural basis of such mnemonic discrimination have mostly focused on hippocampal function and connectivity. However, default mode network (DMN) connectivity may also support such discrimination, given that the DMN includes the hippocampus, and its connectivity supports many aspects of episodic memory. Here, we used connectome-based predictive modeling to identify associations between intrinsic DMN connectivity and mnemonic discrimination. We leveraged a wide range of abilities across healthy younger and older adults to facilitate this predictive approach. Resting-state functional connectivity in the DMN predicted mnemonic discrimination outside the MRI scanner, especially among prefrontal and temporal regions and including several hippocampal regions. This predictive relationship was stronger for younger than older adults, primarily for temporal–prefrontal connectivity. The novel associations established here are consistent with mounting evidence that broader cortical networks including the hippocampus support mnemonic discrimination. They also suggest that age-related network disruptions undermine the extent that the DMN supports this ability. This study provides the first indication of how intrinsic functional properties of the DMN support mnemonic discrimination.     

Default mode network abnormalities in mesial temporal lobe epilepsy: A study combining fMRI and DTI

Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender‐ and age‐matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between‐group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Partially impaired functional connectivity states between right anterior insula and default mode network in autism spectrum disorder

Time‐invariant resting‐state functional connectivity studies have illuminated the crucial role of the right anterior insula (rAI) in prominent social impairments of autism spectrum disorder (ASD). However, a recent dynamic connectivity study demonstrated that rather than being stationary, functional connectivity patterns of the rAI vary significantly across time. The present study aimed to explore the differences in functional connectivity in dynamic states of the rAI between individuals with ASD and typically developing controls (TD). Resting‐state functional magnetic resonance imaging data obtained from a publicly available database were analyzed in 209 individuals with ASD and 298 demographically matched controls. A k‐means clustering algorithm was utilized to obtain five dynamic states of functional connectivity of the rAI. The temporal properties, frequency properties, and meta‐analytic decoding were first identified in TD group to obtain the characteristics of each rAI dynamic state. Multivariate analysis of variance was then performed to compare the functional connectivity patterns of the rAI between ASD and TD groups in obtained states. Significantly impaired connectivity was observed in ASD in the ventral medial prefrontal cortex and posterior cingulate cortex, which are two critical hubs of the default mode network (DMN). States in which ASD showed decreased connectivity between the rAI and these regions were those more relevant to socio‐cognitive processing. From a dynamic perspective, these findings demonstrate partially impaired resting‐state functional connectivity patterns between the rAI and DMN across states in ASD, and provide novel insights into the neural mechanisms underlying social impairments in individuals with ASD.     

The developmental trajectory of fronto‐temporoparietal connectivity as a proxy of the default mode network: a longitudinal fNIRS investigation

The default mode network (DMN) is a network of brain regions that is activated while we are not engaged in any particular task. While there is a large volume of research documenting functional connectivity within the DMN in adults, knowledge of the development of this network is still limited. There is some evidence for a gradual increase in the functional connections within the DMN during the first 2 years of life, in contrast to other functional resting‐state networks that support primary sensorimotor functions, which are online from very early in life. Previous studies that investigated the development of the DMN acquired data from sleeping infants using fMRI. However, sleep stages are known to affect functional connectivity. In the current longitudinal study, fNIRS was used to measure spontaneous fluctuations in connectivity within fronto‐temporoparietal areas—as a proxy for the DMN—in awake participants every 6 months from 11 months till 36 months. This study validates a method for recording resting‐state data from awake infants, and presents a data analysis pipeline for the investigation of functional connections with infant fNIRS data, which will be beneficial for researchers in this field. A gradual development of fronto‐temporoparietal connectivity was found, supporting the idea that the DMN develops over the first years of life. Functional connectivity reached its maximum peak at about 24 months, which is consistent with previous findings showing that, by 2 years of age, DMN connectivity is similar to that observed in adults.     

Maladaptive self-focused attention and default mode network connectivity: a transdiagnostic investigation across social anxiety and body dysmorphic disorders

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention.     

Altered resting state connectivity of the default mode network in alexithymia

Alexithymia is a trait characterized by a diminished capacity to describe and distinguish emotions and to fantasize; it is associated with reduced introspection and problems in emotion processing. The default mode network (DMN) is a network of brain areas that is normally active during rest and involved in emotion processing and self-referential mental activity, including introspection. We hypothesized that connectivity of the DMN might be altered in alexithymia. Twenty alexithymic and 18 non-alexithymic healthy volunteers underwent a resting state fMRI scan. Independent component analysis was used to identify the DMN. Differences in connectivity strength were compared between groups. Within the DMN, alexithymic participants showed lower connectivity within areas of the DMN (medial frontal and temporal areas) as compared to non-alexithymic participants. In contrast, connectivity in the high-alexithymic participants was higher for the sensorimotor cortex, occipital areas and right lateral frontal cortex than in the low-alexithymic participants. These results suggest a diminished connectivity within the DMN of alexithymic participants, in brain areas that may also be involved in emotional awareness and self-referential processing. On the other hand, alexithymia was associated with stronger functional connections of the DMN with brain areas involved in sensory input and control of emotion.     

An examination of the default mode network in individuals with autonomous sensory meridian response (ASMR)

Autonomous Sensory Meridian Response (ASMR) is a perceptual condition in which specific visual and auditory stimuli consistently trigger tingling sensations on the scalp and neck, sometimes spreading to the back and limbs. These triggering stimuli are often social, almost intimate, in nature (e.g., hearing whispering, or watching someone brush her hair), and often elicit a calm and positive emotional state. Surprisingly, despite its prevalence in the general population, no published study has examined the neural underpinnings of ASMR. In the current study, the default mode network (DMN) of 11 individuals with ASMR was contrasted to that of 11 matched controls. The results indicated that the DMN of individuals with ASMR showed significantly less functional connectivity than that of controls. The DMN of individuals with ASMR also demonstrated increased connectivity between regions in the occipital, frontal, and temporal cortices, suggesting that ASMR was associated with a blending of multiple resting-state networks. This atypical functional connectivity likely influences the unique sensory-emotional experiences associated with ASMR.