Posterior Default Mode Network Research Articles

The characteristics of glucose metabolism and functional connectivity in posterior default network during nondemented aging: relationship with executive function performance.

Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults. This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults. We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance. The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits. Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.

Effects of Acupuncture at Neiguan in Neural Activity of Related Brain Regions: A Resting-State fMRI Study in Anxiety.

BackgroundAcupuncture of PC6 points has the effects of calming, tranquilizing, regulating qi, and relieving pain and has been clinically found to alleviate anxiety disorders. To explore the mechanism of improvement at the Neiguan point acupuncture in anxiety patients, we used fMRI to observe the changes in brain function in patients with immediate anxiety before and after acupuncture at the Neiguan point.Subjects and MethodsThe experiment followed the principle of randomized, single-blind design. Twenty-four anxiety volunteers (14 males and 10 females, 20–35 years old) were divided randomly into two groups: a group of acupuncture at Neiguan and a group of acupuncture at non-acupoint. Functional magnetic resonance imaging (fMRI) was applied to measure brain activity pre- and post-acupuncture. The amplitude of low-frequency fluctuations (ALFF) and seed-based functional connectivity (FC) was used to analyze the activity and network of brain regions. Statistical analysis was done using SPSS 21.0 and REST 1.8 software.ResultsALFF results revealed that post-acupuncture at Neiguan increased the activity of the left parahippocampal gyrus, fusiform gyrus, and right superior temporal gyrus and decreased the activity of the right middle frontal gyrus, right precuneus, and cuneus. Post-acupuncture at non-acupoint led to a significant ALFF increase in the thalamus and middle frontal gyrus. The ALFF in the left middle frontal gyrus was decreased. Functional connectivity in several anterior default mode network (DMN) regions and vermis cerebelli at left parahippocampal/fusiform gyri was increased, and connectivity in bilateral superior temporal gyri was decreased. FC with posterior DMN regions decreased at the right middle frontal gyrus, right precuneus, and cuneus.ConclusionOur study elucidates that acupuncture at Neiguan modulates anxiety by activating or deactivating these brain anxiety-related regions and provides potential explanations for the application of PC6 acupuncture in mental diseases.

Neural distinctiveness of fatigue and low sleep quality in multiple sclerosis.

Fatigue and low sleep quality in multiple sclerosis (MS) are closely related symptoms. Here, the associations between the brain's functional connectivity (FC) and fatigue and low sleep quality were investigated to determine the degree of neural distinctiveness of these symptoms. A hundred and four patients with relapsing-remitting MS (age 38.9 ± 10.2 years, 66 females) completed the Modified Fatigue Impact Scale and the Pittsburgh Sleep Quality Index and underwent resting-state functional magnetic resonance imaging. FC was analyzed using independent-component analysis in sensorimotor, default-mode, fronto-parietal and basal-ganglia networks. Multiple linear regression models allowed us to test the association between FC and fatigue and sleep quality whilst controlling for one another as well as for demographic, disease-related and imaging variables. Higher fatigue correlated with lower sleep quality (r=0.54, p < 0.0001). Higher fatigue was associated with lower FC of the precentral gyrus in the sensorimotor network, the precuneus in the posterior default-mode network and the superior frontal gyrus in the left fronto-parietal network, independently of sleep quality. Lower sleep quality was associated with lower FC of the left intraparietal sulcus in the left fronto-parietal network, independently of fatigue. Specific associations were found between fatigue and the sensorimotor network's global FC and between low sleep quality and the left fronto-parietal network's global FC. Despite the high correlation between fatigue and low sleep quality in the clinical picture, our findings clearly indicate that, on the neural level, fatigue and low sleep quality in MS are associated with decreased FC in distinct functional brain networks.

Effects of Methylphenidate on Somatic Symptoms and Brain Functional Connectivity in Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study.

ObjectiveThis study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment.MethodsFifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul’s ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting-state functional magnetic resonance imaging scan was conducted.ResultsMethylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms.ConclusionMethylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

Fitness and arterial stiffness in healthy aging: Modifiable cardiovascular risk factors contribute to altered default mode network patterns during executive function

Increases in cardiovascular risks such as high blood pressure and low physical fitness have been independently associated with altered default mode network (DMN) activation patterns in healthy aging. However, cardiovascular risk is a multidimensional health problem. Therefore, we need to investigate multiple cardiovascular risk factors and their contributions to cognition and DMN activations in older adults, which has not yet been done. The current fMRI study examined contributions of two common modifiable cardiovascular risk factors (arterial stiffness and physical fitness) on DMN activations involved during random n-back, a task of executive functioning and working memory, in older adults. The results show that high cardiovascular risk of either increased arterial stiffness or decreased fitness independently contributed to worse task performance and reduced deactivations in two DMN regions: the anterior and posterior cingulate cortices. We then examined not only the potential interaction between the two risk factors, but also their additive (i.e., combined) effect on performance and DMN deactivations. A significant interaction between the two cardiovascular risk factors was observed on performance, with arterial stiffness moderating the relationship between physical fitness and random n-back accuracy. The additive effect of the two factors on task performance was driven by arterial stiffness. Arterial stiffness was also found to be the driving factor when the additive effect of the two risk factors was examined on DMN deactivations. However, in posterior cingulate cortex, a hub region of the DMN, the additive effect on its deactivation was significantly higher than the effect of each risk factor alone. These results suggest that the effects of cardiovascular risks on the aging brain are complicated and multi-dimensional, with arterial stiffness moderating or driving the combined effects on performance and anterior DMN deactivations, but physical fitness contributing additional effect to posterior DMN deactivation during executive functioning.

Cognitive outcome is related to functional thalamo-cortical connectivity after paediatric stroke

The thalamus has complex connections with the cortex and is involved in various cognitive processes. Despite increasing interest in the thalamus and the underlying thalamo-cortical interaction, little is known about thalamo-cortical connections after paediatric arterial ischaemic stroke. Therefore, the aim of this study was to investigate thalamo-cortical connections and their association with cognitive performance after arterial ischaemic stroke. Twenty patients in the chronic phase after paediatric arterial ischaemic stroke (≥2 years after diagnosis, diagnosed <16 years; aged 5–23 years, mean: 15.1 years) and 20 healthy controls matched for age and sex were examined in a cross-sectional study design. Cognitive performance (selective attention, inhibition, working memory, and cognitive flexibility) was evaluated using standardized neuropsychological tests. Resting-state functional magnetic resonance imaging was used to examine functional thalamo-cortical connectivity. Lesion masks were integrated in the preprocessing pipeline to ensure that structurally damaged voxels did not influence functional connectivity analyses. Cognitive performance (selective attention, inhibition, and working memory) was significantly reduced in patients compared to controls. Network analyses revealed significantly lower thalamo-cortical connectivity for the motor, auditory, visual, default mode network, salience, left/right executive, and dorsal attention network in patients compared with controls. Interestingly, analyses additionally revealed higher thalamo-cortical connectivity in some subdivisions of the thalamus for the default mode network (medial nuclei), motor (lateral nuclei), dorsal attention (anterior nuclei), and the left executive network (posterior nuclei) in patients compared with controls. Increased and decreased thalamo-cortical connectivity strength within the same networks was, however, found in different thalamic subdivisions. Thus, alterations in thalamo-cortical connectivity strength after paediatric stroke seem to point in both directions, with stronger as well as weaker thalamo-cortical connectivity in patients compared with controls. Multivariate linear regression, with lesion size and age as covariates, revealed significant correlations between cognitive performance (selective attention, inhibition, and working memory) and the strength of thalamo-cortical connectivity in the motor, auditory, visual, default mode network, posterior default mode network, salience, left/right executive, and dorsal attention network after childhood stroke. Our data suggest that the interaction between different sub-nuclei of the thalamus and several cortical networks relates to post-stroke cognition. The variability in cognitive outcomes after paediatric stroke might partly be explained by functional thalamo-cortical connectivity strength.

Brain network hierarchy reorganization in Alzheimer's disease: A resting-state functional magnetic resonance imaging study.

Hierarchy is a fundamental organizational principle of the human brain network. Whether and how the network hierarchy changes in Alzheimer's disease (AD) remains unclear. To explore brain network hierarchy alterations in AD and their clinical relevance. Forty‐nine healthy controls (HCs), 49 patients with mild cognitive impairment (MCI), and 49 patients with AD were included. The brain network hierarchy of each group was depicted by connectome gradient analyses. We assessed the network hierarchy changes by comparing the gradient values in each network across the AD, MCI, and HC groups. Whole‐brain voxel‐level gradient values were compared across the AD, MCI, and HC groups to identify abnormal brain regions. Finally, we examined the relationships between altered gradient values and clinical features. In the secondary gradient, the posterior default mode network (DMN) gradient values decreased significantly in patients with AD compared with HCs. Regionally, compared with HCs, both MCI and AD groups showed that most of the brain regions with increased gradient values were located in anterior DMN, while most of the brain regions with decreased gradient values were located in posterior DMN. The decrease of gradients in the left middle occipital gyrus was associated with better logical memory performance. The increase of gradients in the right middle frontal gyrus was associated with lower rates of dementia. The network hierarchy changed characteristically in patients with AD and was closely related to memory function and disease severity. These results provide a novel view for further understanding the underlying neuro‐mechanisms of AD.

Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia

To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

Amyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease

The human brain is composed of functional networks that have a modular topology, where brain regions are organized into communities that form internally dense (segregated) and externally sparse (integrated) subnetworks that underlie higher-order cognitive functioning. It is hypothesized that amyloid-β and tau pathology in preclinical Alzheimer’s disease (AD) spread through functional networks, disrupting neural communication that results in cognitive dysfunction. We used high-resolution (voxel-level) graph-based network analyses to test whether in vivo amyloid-β and tau burden was associated with the segregation and integration of brain functional connections, and episodic memory, in cognitively unimpaired Presenilin-1 E280A carriers who are expected to develop early-onset AD dementia in ∼13 y on average. Compared to noncarriers, mutation carriers exhibited less functional segregation and integration in posterior default-mode network (DMN) regions, particularly the precuneus, and in the retrospenial cortex, which has been shown to link medial temporal regions and cortical regions of the DMN. Mutation carriers also showed greater functional segregation and integration in regions connected to the salience network, including the striatum and thalamus. Greater tau burden was associated with lower segregated and integrated functional connectivity of DMN regions, particularly the precuneus and medial prefrontal cortex. In turn, greater tau pathology was related to higher segregated and integrated functional connectivity in the retrospenial cortex and the anterior cingulate cortex, a hub of the salience network. These findings enlighten our understanding of how AD-related pathology distinctly alters the brain’s functional architecture in the preclinical stage, possibly contributing to pathology propagation and ultimately resulting in dementia.

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.

Internetwork Connectivity Predicts Cognitive Decline in Parkinson's and Is Altered by Genetic Variants.

In Parkinson’s disease (PD) functional changes in the brain occur years before significant cognitive symptoms manifest yet core large-scale networks that maintain cognition and predict future cognitive decline are poorly understood. The present study investigated internetwork functional connectivity of visual (VN), anterior and posterior default mode (aDMN, pDMN), left/right frontoparietal (LFPN, RFPN), and salience (SN) networks in 63 cognitively normal PD (PDCN) and 43 healthy controls who underwent resting-state functional MRI. The functional relevance of internetwork coupling topologies was tested by their correlations with baseline cognitive performance in each group and with 2-year cognitive changes in a PDCN subsample. To disentangle heterogeneity in neurocognitive functioning, we also studied whether α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) variants alter internetwork connectivity and/or accelerate cognitive decline. We found that internetwork connectivity was largely preserved in PDCN, except for reduced pDMN-RFPN/LFPN couplings, which correlated with poorer baseline global cognition. Preserved internetwork couplings also correlated with domain-specific cognition but differently for the two groups. In PDCN, stronger positive internetwork coupling topologies correlated with better cognition at baseline, suggesting a compensatory mechanism arising from less effective deployment of networks that supported cognition in healthy controls. However, stronger positive internetwork coupling topologies typically predicted greater longitudinal decline in most cognitive domains, suggesting that they were surrogate markers of neuronal vulnerability. In this regard, stronger aDMN-SN, LFPN-SN, and/or LFPN-VN connectivity predicted longitudinal decline in attention, working memory, executive functioning, and visual cognition, which is a risk factor for dementia. Coupling strengths of some internetwork topologies were altered by genetic variants. PDCN carriers of the SNCA risk allele showed amplified anticorrelations between the SN and the VN/pDMN, which supported cognition in healthy controls, but strengthened pDMN-RFPN connectivity, which maintained visual memory longitudinally. PDCN carriers of the MAPT risk allele showed greater longitudinal decline in working memory and increased VN-LFPN connectivity, which in turn predicted greater decline in visuospatial processing. Collectively, the results suggest that cognition is maintained by functional reconfiguration of large-scale internetwork communications, which are partly altered by genetic risk factors and predict future domain-specific cognitive progression.

Social mentalizing in male perpetrators of intimate partner violence against women is associated with resting-state functional connectivity of the Crus II

Social mentalizing refers to the ability to understand the intentions, causes, emotions and beliefs of another person or the self and is crucial for interpersonal understanding. Disturbances in this process may lead to aggressive and violent behaviors. Literature has shown that male perpetrators convicted for intimate partner crime (IPVAW) present alterations in different measures related to social mentalizing, in particular, they present more irrational thoughts toward women and difficulties in emotional recognition and empathy processes. However, the brain mechanisms underlying this process are still unknown. The aim of this study is to examine the resting-state functional connectivity of the cerebellar Crus II area, as a core component of social mentalizing in male perpetrators, and to explore if this connectivity is associated with social mentalizing processes. To achieve these objectives, we compared the resting-state connectivity of 25 men convicted for an IPVAW crime (male perpetrators) with 29 men convicted for other crimes (other offenders) and 28 men with no criminal records (non-offenders) using a seed-based whole brain analysis. Subsequently, correlations were performed to explore the association between the significant connectivity networks and social mentalizing measures only in male perpetrators of IPVAW. Analyses showed that male perpetrators of IPVAW exhibit hyperconnectivity between Crus II and posterior areas of the default mode network, frontoparietal and limbic areas compared to other offenders and non-offenders. In addition, the greater connectivity found between the Crus II and the posterior default mode network was related to a greater number of distorted thoughts about women and less affective empathy in male perpetrators of IPVAW. These results show that connectivity between the cerebellum and the default mode network may underlie the social processes that are at the basis of intimate partner violence perpetration.

Alteration in Functional Magnetic Resonance Imaging Signal Complexity Across Multiple Time Scales in Patients With Migraine Without Aura.

BackgroundMigraine is a primary neurological disorder associated with complex brain activity. Recently, mounting evidence has suggested that migraine is underpinned by aberrant dynamic brain activity characterized by linear and non-linear changes across a variety of time scales. However, the abnormal dynamic brain activity at different time scales is still unknown in patients with migraine without aura (MWoA). This study aimed to assess the altered patterns of brain activity dynamics over different time scales and the potential pathophysiological mechanisms of alterations in patients with MWoA.MethodsMultiscale entropy in 50 patients and 20 healthy controls (HCs) was calculated to investigate the patterns and altered brain complexity (BC) across five different time scales. Spearman rank correlation analysis between BC in regions showing significant intergroup differences and clinical scores (i.e., frequency of migraine attacks, duration, headache impact test) was conducted in patients with MWoA.ResultsThe spatial distribution of BC varied across different time scales. At time scale1, BC was higher in the posterior default mode network (DMN) across participants. Compared with HCs, patients with MWoA had higher BC in the DMN and sensorimotor network. At time scale2, BC was mainly higher in the anterior DMN across participants. Patients with MWoA had higher BC in the sensorimotor network. At time scale3, BC was mainly higher in the frontoparietal network across participants. Patients with MWoA had increased BC in the parietal gyrus. At time scale4, BC is mainly higher in the sensorimotor network. Patients with MWoA had higher BC in the postcentral gyrus. At time scale5, BC was mainly higher in the DMN. Patients with MWoA had lower BC in the posterior DMN. In particular, BC values in the precuneus and paracentral lobule significantly correlated with clinical symptoms.ConclusionMigraine is associated with alterations in dynamic brain activity in the sensorimotor network and DMN over multiple time scales. Time-varying BC within these regions could be linked to instability in pain transmission and modulation. Our findings provide new evidence for the hypothesis of abnormal dynamic brain activity in migraine.

Converging evidence of impaired brain function in systemic lupus erythematosus: changes in perfusion dynamics and intrinsic functional connectivity.

Τhe study examined changes in hemodynamics and functional connectivity in patients with systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations. Participants were 44 patients with neuropsychiatric SLE (NPSLE), 20 SLE patients without such manifestations (non-NPSLE), and 35 healthy controls. Resting-state functional MRI (rs-fMRI) was used to obtain whole-brain maps of (a) perfusion dynamics derived through time shift analysis (TSA), (b) regional functional connectivity (intrinsic connectivity contrast (ICC) coefficients), and (c) hemodynamic-connectivity coupling. Group differences were assessed through independent samples t-tests, and correlations of rs-fMRI indices with clinical variables and neuropsychological test scores were, also, computed. Compared to HC, NPSLE patients demonstrated intrinsic hypoconnectivity of anterior Default Mode Network (DMN) and hyperconnectivity of posterior DMN components. These changes were paralleled by elevated hemodynamic lag. In NPSLE, cognitive performance was positively related to higher intrinsic connectivity in these regions, and to higher connectivity-hemodynamic coupling in posterior DMN components. Uncoupling between hemodynamics and connectivity in the posterior DMN was associated with worse task performance. Non-NPSLE patients displayed hyperconnectivity in posterior DMN and sensorimotor regions paralleled by relatively increased hemodynamic lag. Adaptation of regional brain function to hemodynamic changes in NPSLE may involve locally decreased or locally increased intrinsic connectivity (which can be beneficial for cognitive function). This process may also involve elevated coupling of hemodynamics with functional connectivity (beneficial for cognitive performance) or uncoupling, which may be detrimental for the cognitive skills of NPSLE patients.

Disrupted Cerebellar-Default Mode Network Functional Connectivity in Major Depressive Disorder With Gastrointestinal Symptoms.

Gastrointestinal (GI) symptoms are one of the common somatic symptoms presented in patients with major depressive disorder (MDD). Higher frequency of GI symptoms and higher GI symptom burden were linked to greater depression severity and increased risk of suicide ideation. However, few studies have explored the underlying mechanisms of GI symptoms in MDD. Based on previous studies, the cerebellar-DMN circuits may play a potentially critical role in GI symptoms comorbid with depression. Fifty-two first-episode drug-naive patients with MDD (35 with GI symptoms and 17 without GI symptoms) and 28 matched healthy controls were recruited in the current study and underwent resting-state functional magnetic resonance imaging scan. Cerebellar seed-based functional connectivity maps were established. Relative to depressed patients without GI symptoms, significantly increased cerebellar-anterior default mode network (DMN) connectivities were found in those with GI symptoms. Both increased and decreased functional connectivities were found between cerebellum and posterior DMN in patients with GI symptoms compared with those without GI symptoms and healthy controls. Moreover, the right Crus I - right superior temporal gyrus connectivity value was related to severity of GI symptoms and depression in all patients with MDD. The support vector machine analysis demonstrated a satisfactory classification accuracy (89%) of the disrupted cerebellar-DMN connectivities for correctly identifying MDD patients with GI symptoms. These results revealed the possible neural mechanisms for the involvement of cerebellar-DMN circuits in GI symptoms co-occurred with MDD.

Tau and the fractionated default mode network in atypical Alzheimer's disease.

Alzheimer’s disease-related atrophy in the posterior cingulate cortex, a key node of the default mode network, is present in the early stages of disease progression across clinical phenotypic variants of the disease. In the typical amnestic variant, posterior cingulate cortex neuropathology has been linked with disrupted connectivity of the posterior default mode network, but it remains unclear if this relationship is observed across atypical variants of Alzheimer’s disease. In the present study, we first sought to determine if tau pathology is consistently present in the posterior cingulate cortex and other posterior nodes of the default mode network across the atypical Alzheimer’s disease syndromic spectrum. Second, we examined functional connectivity disruptions within the default mode network and sought to determine if tau pathology is related to functional disconnection within this network. We studied a sample of 25 amyloid-positive atypical Alzheimer’s disease participants examined with high-resolution MRI, tau (18F-AV-1451) PET, and resting-state functional MRI. In these patients, high levels of tau pathology in the posteromedial cortex and hypoconnectivity between temporal and parietal nodes of the default mode network were observed relative to healthy older controls. Furthermore, higher tau signal and reduced grey matter density in the posterior cingulate cortex and angular gyrus were associated with reduced parietal functional connectivity across individual patients, related to poorer cognitive scores. Our findings converge with what has been reported in amnestic Alzheimer’s disease, and together these observations offer a unifying mechanistic feature that relates posterior cingulate cortex tau deposition to aberrant default mode network connectivity across heterogeneous clinical phenotypes of Alzheimer’s disease.

The "two-brain" approach reveals the active role of task-deactivated default mode network in speech comprehension.

Exhibiting deactivation and anticorrelation with task-positive networks, the default mode network (DMN) has been traditionally thought to be suppressed to support externally oriented cognitive processes during spoken language comprehension. In contrast, recent studies examining listener-listener intersubject correlation (ISC) have proposed an active role of DMN in language comprehension. How can we reconcile those seemingly conflicting results? This study adopted a "two-brain" paradigm and combined "within-brain" and "across-brain" analyses to address this issue. We found, despite being deactivated and anticorrelated with the language network (LN) and executive control network (ECN), both the anterior and posterior DMN in the listeners' brains were temporally coupled with the homologous networks in the speaker's brain. Interestingly, the listener-speaker neural couplings persisted even after controlling for listener-listener ISC. Moreover, the coupling strength of posterior DMN positively correlated with the listeners' speech comprehension. Further dynamic causal modeling showed that the LN and ECN, the anterior DMN, and the posterior DMN occupied the bottom, intermediate, and top layers of a hierarchical system, respectively. We suggest the DMN may primarily serve as an internal module that cooperates with the externally oriented modules, potentially supporting the transformation of external acoustic signals into internal mental representations during successful language comprehension.

Intrinsic Structural Connectivity of the Default Mode Network and Behavioral Correlates of Executive Function and Social Skills in Youth with Autism Spectrum Disorders.

Brain connectivity of individuals with autism spectrum disorders (ASD) is heterogenous, as are the behavioral manifestations. The current study investigated brain-behavior relationships in the context of social skills and executive function profiles with data from the Autism Brain Imaging Database Exchange II. We calculated connectivity measures from diffusion tensor imaging using Bayesian estimation and probabilistic tractography. Subsequently, we performed structural equation modeling by regressing three latent factors, yielded from an exploratory factor analysis, onto total default mode network (DMN) connectivity. Both social regulation processing and self-directed cognitive processing factors moderately, negatively correlated with total DMN connectivity. Our findings indicate social regulation processing difficulties in youth with ASD may be attributable to impaired connectivity between the anterior and posterior DMN.

Interplay Between the Salience and the Default Mode Network in a Social-Cognitive Task Toward a Close Other.

Social cognition relies on two main subsystems to construct the understanding of others, which are sustained by different social brain networks. One of these social networks is the default mode network (DMN) associated with the socio-cognitive subsystem (i.e., mentalizing), and the other is the salience network (SN) associated with the socio-affective route (i.e., empathy). The DMN and the SN are well-known resting state networks that seem to constitute a baseline for the performance of social tasks. We aimed to investigate both networks' functional connectivity (FC) pattern in the transition from resting state to social task performance. A sample of 38 participants involved in a monogamous romantic relationship completed a questionnaire of dyadic empathy and underwent an fMRI protocol that included a resting state acquisition followed by a task in which subjects watched emotional videos of their romantic partner and elaborated on their partner's (Other condition) or on their own experience (Self condition). Independent component and ROI-to-ROI correlation analysis were used to assess alterations in task-independent (Rest condition) and task-dependent (Self and Other conditions) FC. We found that the spatial FC maps of the DMN and SN evidenced the traditional regions associated with these networks in the three conditions. Anterior and posterior DMN regions exhibited increased FC during the social task performance compared to resting state. The Other condition revealed a more limited SN's connectivity in comparison to the Self and Rest conditions. The results revealed an interplay between the main nodes of the DMN and the core regions of the SN, particularly evident in the Self and Other conditions.

Modulation of the brain's core-self network by self-appraisal processes

The ‘core’ regions of the default mode network (DMN) – the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) – show consistent engagement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswered question. In the current functional magnetic resonance imaging (fMRI) study, we examined dynamic interactions of the ‘core-self’ DMN regions during two forms of self-referential cognition: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about oneself from a third-person perspective). One-hundred and eleven participants completed our dual self-appraisal task during fMRI, and general linear models were used to characterize common and distinct neural responses to these conditions. Informed by these results, we then applied dynamic causal modelling to examine causal interactions among the ‘core-self’ regions, and how they were specifically modulated under the influence of direct and reflected self-appraisal. As a primary observation, this network modelling revealed a distinct inhibitory influence of the left IPL on the PCC during reflected compared to direct self-appraisal, which was accompanied by evidence of greater activation in both regions during the reflected self-appraisal condition. We suggest that the greater engagement of posterior DMN regions during reflected self-appraisal is a function of the higher-order processing needed for this form of self-appraisal, with the left IPL supporting abstract self-related processes including episodic memory retrieval and shifts of perspective. Overall, we show that core DMN regions interact in functionally unique ways in support of self-referential processes, even when these processes are inter-related. Further characterization of DMN functional interactions across self-related mental states is likely to inform a deeper understanding of how this brain network orchestrates the self.