Resting-state Default Mode Network Research Articles

Impact of sex and reproductive status on the default mode network in early midlife: implications for aging of memory circuitry and function.

Alterations to the resting-state default mode network (rsDMN) are early indicators of memory decline and Alzheimer's disease (AD). Brain regions shared by the rsDMN and memory circuitry are highly sexually dimorphic. However, data are limited regarding the impact of sex and reproductive status on rsDMN connectivity and memory circuitry and function. In the current investigation, rsDMN connectivity was assessed in 180 early midlife adults aged 45 to 55 by sex and reproductive status (87 women; 93 men). Associations between left and right hippocampal connectivity of rsDMN and verbal memory encoding circuitry were examined using linear mixed models, controlled for age and parental socioeconomic status, testing interactions by sex and reproductive status. Relative to men, women exhibited greater rsDMN connectivity between the left and right hippocampus. In relation to rsDMN-memory encoding connectivity, sex differences were revealed across the menopausal transition, such that only postmenopausal women exhibited loss of the ability to decrease rsDMN left-right hippocampal connectivity during memory encoding associated with poorer memory performance. Results demonstrate that sex and reproductive status play an important role in aging of the rsDMN and interactions with memory circuitry/function. This suggests the critical importance of sex and reproductive status when studying early midlife indicators of memory decline and AD risk.

24 Functional Distinctions in Metabolic Network Patterns in Parkinson's Disease

Objective:Cognitive decline is a common non-motor feature of Parkinson's disease (PD). However, the underlying mechanisms of cognitive impairment in PD require further elucidation. FDG PET imaging data analyses have revealed distinct brain metabolic patterns associated with the cognitive features of PD. The PD cognition-related pattern (PDCP) and default mode network (DMN) are two overlapping, but topographically distinct, networks that may serve as biomarkers of cognitive decline in PD. Decreased activity of the resting-state DMN and increased expression of the PDCP are associated with cognitive impairment in PD. Studies have consistently demonstrated the association between neuropsychological memory test performance and PDCP expression. Thus, we examined whether memory performance could offer additional value in predicting PDCP expression in PD patients. We hypothesized that DMN and memory performance would predict greater variance in PDCP expression than the DMN alone.Participants and Methods:Participants included 48 PD patients ages 46-80 (mean (SD) Age: 61.9 (8.1), Education: 15.0 (2.8), IQ: 112.5 (14.9), DRS total: 136.7 (5.8)). All participants completed the FDG PET and neuropsychological evaluation 8-12 hours after their last dose of Levodopa. Neuropsychological memory testing included the California Verbal Learning Test (CVLT) z score of sum of learning trials. PDCP and DMN values were z scores generated from normal controls in previous studies. Data were analyzed using linear regression analyses.Results:A hierarchical regression was performed to predict PDCP as a function of DMN and CVLT learning performance. Variables were entered in two separate blocks. The first block included DMN as a predictor, and the overall regression was significant (R2 = 0.55, F(1, 39)= 47.0, p < 0.001). As hypothesized, DMN significantly predicted PCDP expression (β= -0.74, p < 0.001). The second block of the regression included CVLT learning memory performance. Both DMN and CVLT performance explained a significant amount of variance in PDCP (R2 change = 0.05, F(2, 39)= 27.6, p < 0.001). CVLT performance significantly predicted PDCP (β= -0.22, p =0.048). The final model accounted for 60.0% of the variance in PDCP.Conclusions:Disruptions in functional connectivity within brain networks have become increasingly recognized as mechanisms responsible for cognitive impairment in patients. As demonstrated in previous studies, our results indicated that DMN loss is a strong predictor of PDCP expression, likely due to the networks' overlapping spatial regions. However, we found that the addition of memory performance to the model could explain a small amount of variance (5%) over and above DMN expression. Overall, the current findings demonstrate a functional (i.e., learning) distinction between population-specific (PDCP) and more general brain networks (DMN).

Resting state default mode network is associated with wise advising

Default mode network (DMN) may be associated with wisdom (i.e., mature understanding of life featured by perspectival metacognition) when advising from a self-referential perspective due to the involvement of the DMN in reflecting on personal life experiences. After a resting-state functional MRI scan, 52 adults advised some youths going through life dilemmas, half from a second-person perspective and half from a third. After advising each youth, participants indicated the psychological distance they felt between themselves and the youth. The amplitude of low-frequency fluctuation (ALFF) was measured in the DMN during resting states. Moreover, trained raters rated the participants' advice on wisdom criteria (i.e., metacognitive humility (MH), meta-level flexibility, and perspective-taking). The results showed that participants felt a significantly smaller psychological distance from the youth when advising from the second- than the third-person perspective. Moreover, only when advising from the second-person perspective was MH associated with ALFF in regions within the DMN (i.e., right rostral anterior cingulate cortex (ACC) and left dorsomedial prefrontal cortex). The right rostral ACC showed a significantly greater association with MH from the second- than the third-person perspective. Therefore, resting-state DMN activities may be important for self-involved wisdom performance (e.g., giving advice directly to others).

Depression Is Associated with the Aberration of Resting State Default Mode Network Functional Connectivity in Patients with Amyloid-Positive Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia, and a significant number of individuals with MCI progress to develop dementia. Depression is prevalent in MCI patients and has been found to influence the disease progression of MCI. The default mode network (DMN), a brain network associated with Alzheimer's disease (AD), and its functional connectivity might be a neurological mechanism linking depression and AD. However, the relationship between depression, DMN functional connectivity, and cerebral beta-amyloid (Aβ) pathology remains unclear. This study aimed to investigate DMN functional connectivity differences in Aβ-positive MCI patients with depression compared to those without depression. A total of 126 Aβ-positive MCI patients were included, with 66 having depression and 60 without depression. The results revealed increased functional connectivity in the anterior DMN in the depression group compared to the non-depression group. The functional connectivity of the anterior DMN positively correlated with depression severity but not with Aβ deposition. Our findings suggest that depression influences DMN functional connectivity in Aβ-positive MCI patients, and the depression-associated DMN functional connectivity aberrance might be an important neural mechanism linking depression, Aβ pathology, and disease progression in the trajectory of AD.

Sleep mediates the effect of stressful environments on youth development of impulsivity: The moderating role of within default mode network resting-state functional connectivity

ObjectivesYouth raised in stressful environments are at increased risk for developing impulsive traits, which are a robust precursor of problem behaviors. Sleep may mediate the link between stress and problem behaviors as it is both sensitive to stress and essential for neurocognitive development underlying behavioral control during adolescence. The default mode network (DMN) is a brain network implicated in stress regulation and sleep. Yet, it is poorly understood how individual differences in resting-state DMN moderate the effect of stressful environments on impulsivity via sleep problems. MethodsThree waves of data spanning 2 years were obtained from the Adolescent Brain and Cognitive Development Study, a national longitudinal sample of 11,878 children (Mage at baseline = 10.1; 47.8% female). Structural equation modeling was used to test (a) the mediating role of sleep at T3 in the link between stressful environments at baseline and impulsivity at T5 and (b) the moderation of this indirect association by baseline levels of within-DMN resting-state functional connectivity. ResultsSleep problems, shorter sleep duration, and longer sleep latency significantly mediated the link between stressful environments and youth impulsivity. Youth with elevated within-DMN resting-state functional connectivity showed intensified associations between stressful environments and impulsivity via shorter sleep duration. ConclusionOur findings suggest that sleep health can be a target for preventive intervention and thereby mitigate the link between stressful environments and increased levels of youth impulsivity.

The Importance of Low-frequency Alpha (8-10 Hz) Waves and Default Mode Network in Behavioral Inhibition.

: Alpha wave of electroencephalography (EEG) is known to be related to behavioral inhibition. Both the alpha wave and default mode network (DMN) are predominantly activated during resting-state. To study the mechanisms of the trait inhibition, this research investigating the relations among alpha wave, DMN and behavioral inhibition in resting-state. : We explored the relationship among behavioral inhibition, resting-state alpha power, and DMN. Resting-state EEG, behavioral inhibition/behavioral activation scale (BIS/BAS), Barratt impulsivity scale, and no-go accuracy were assessed in 104 healthy individuals. Three groups (i.e., participants with low/middle/high band power) were formed based on the relative power of each total-alpha, low-alpha (LA), and high-alpha band. Source-reconstructed EEG and functional network measures of 25 DMN regions were calculated. : Significant differences and correlations were found based on LA band power alone. The high LA group had significantly greater BIS, clustering coefficient, efficiency, and strength, and significantly lower path length than low/middle LA group. BIS score showed a significant correlation with functional network measures of DMN. : Our study revealed that LA power is related to behavioral inhibition and functional network measures of DMN of LA band appear to represent significant inhibitory function.

The relationship between resting-state amplitude fluctuations and memory-related deactivations of the default mode network in young and older adults.

The default mode network (DMN) typically exhibits deactivations during demanding tasks compared to periods of relative rest. In functional magnetic resonance imaging (fMRI) studies of episodic memory encoding, increased activity in DMN regions even predicts later forgetting in young healthy adults. This association is attenuated in older adults and, in some instances, increased DMN activity even predicts remembering rather than forgetting. It is yet unclear whether this phenomenon is due to a compensatory mechanism, such as self-referential or schema-dependent encoding, or whether it reflects overall reduced DMN activity modulation in older age. We approached this question by systematically comparing DMN activity during successful encoding and tonic, task-independent, DMN activity at rest in a sample of 106 young (18-35 years) and 111 older (60-80 years) healthy participants. Using voxel-wise multimodal analyses, we assessed the age-dependent relationship between DMN resting-state amplitude (mean percent amplitude of fluctuation, mPerAF) and DMN fMRI signals related to successful memory encoding, as well as their modulation by age-related hippocampal volume loss, while controlling for regional grey matter volume. Older adults showed lower resting-state DMN amplitudes and lower task-related deactivations. However, a negative relationship between resting-state mPerAF and subsequent memory effect within the precuneus was observed only in young, but not older adults. Hippocampal volumes showed no relationship with the DMN subsequent memory effect or mPerAF. Lastly, older adults with higher mPerAF in the DMN at rest tend to show higher memory performance, pointing towards the importance of a maintained ability to modulate DMN activity in old age.

Reduced coupling between offline neural replay events and default mode network activation in schizophrenia.

Schizophrenia is characterized by an abnormal resting state and default mode network brain activity. However, despite intense study, the mechanisms linking default mode network dynamics to neural computation remain elusive. During rest, sequential hippocampal reactivations, known as 'replay', are played out within default mode network activation windows, highlighting a potential role of replay-default mode network coupling in memory consolidation and model-based mental simulation. Here, we test a hypothesis of reduced replay-default mode network coupling in schizophrenia, using magnetoencephalography and a non-spatial sequence learning task designed to elicit off-task (i.e. resting state) neural replay. Participants with a diagnosis of schizophrenia (n = 28, mean age 28.2 years, range 20-40, 6 females, 13 not taking antipsychotic medication) and non-clinical control participants (n = 29, mean age 28.1 years, range 18-45, 6 females, matched at group level for age, intelligence quotient, gender, years in education and working memory) underwent a magnetoencephalography scan both during task completion and during a post-task resting state session. We used neural decoding to infer the time course of default mode network activation (time-delay embedding hidden Markov model) and spontaneous neural replay (temporally delayed linear modelling) in resting state magnetoencephalography data. Using multiple regression, we then quantified the extent to which default mode network activation was uniquely predicted by replay events that recapitulated the learned task sequences (i.e. 'task-relevant' replay-default mode network coupling). In control participants, replay-default mode network coupling was augmented following sequence learning, an augmentation that was specific for replay of task-relevant (i.e. learned) state transitions. This task-relevant replay-default mode network coupling effect was significantly reduced in schizophrenia (t(52) = 3.93, P = 0.018). Task-relevant replay-default mode network coupling predicted memory maintenance of learned sequences (ρ(52) = 0.31, P = 0.02). Importantly, reduced task-relevant replay-default mode network coupling in schizophrenia was not explained by differential replay or altered default mode network dynamics between groups nor by reference to antipsychotic exposure. Finally, task-relevant replay-default mode network coupling during rest correlated with stimulus-evoked default mode network modulation as measured in a separate task session. In the context of a proposed functional role of replay-default mode network coupling, our findings shed light on the functional significance of default mode network abnormalities in schizophrenia and provide for a consilience between task-based and resting state default mode network findings in this disorder.

Neural Networks Implicated in Autobiographical Memory Training.

Training of autobiographical memory has been proposed as an intervention to improve cognitive function. The neural substrates for such improvements are poorly understood. Several brain areas have been previously linked to autobiographical recollection, including structures in the default mode network (DMN) and the sensorimotor network. Here, we tested the hypothesis that changes in connectivity within different neural networks support distinct aspects of memory improvement in response to training on a group of 59 human subjects. We found that memory training using olfactory cues increases resting-state intranetwork DMN connectivity, and this associates with improved recollection of cue-specific memories. On the contrary, training decreased resting-state connectivity within the sensorimotor network, a decrease that correlated with improved ability for voluntary recall. Moreover, preliminary data indicate that only the decrease in sensorimotor connectivity associated with the training-induced decrease in the tumor necrosis factor α (TNFα) factor, an immune modulation previously linked to improved cognitive performance. We identified functional and biochemical factors that associate with distinct memory processes improved by autobiographical training. Pathways which connect autobiographical memory with both high-level cognition and somatic physiology are discussed.

Is Mindfulness Associated With Lower Pain Reactivity and Connectivity of the Default Mode Network? A Replication and Extension Study in Healthy and Episodic Migraine Participants

Formal training in mindfulness-based practices promotes reduced experimental and clinical pain, which may be driven by reduced emotional pain reactivity and undergirded by alterations in the default mode network, implicated in mind-wandering and self-referential processing. Recent results published in this journal suggest that mindfulness, defined here as the day-to-day tendency to maintain a non-reactive mental state in the absence of training, associates with lower pain reactivity, greater heat-pain thresholds, and resting-state default mode network functional connectivity in healthy adults in a similar manner to trained mindfulness. The extent to which these findings extend to chronic pain samples and replicate in healthy samples is unknown. Using data from healthy adults (n = 36) and episodic migraine patients (n = 98) and replicating previously published methods, we observed no significant association between mindfulness and heat-pain threshold, pain intensity or unpleasantness, or pain catastrophizing in healthy controls, or between mindfulness and headache frequency, severity, impactor pain catastrophizing in patients. There was no association between default mode network connectivity and mindfulness in either sample when probed via seed-based functional connectivity analyses. In post-hoc whole brain exploratory analyses, a meta-analytically derived default mode network node (ie, posterior cingulate cortex) showed connectivity with regions unassociated with pain processing as a function of mindfulness, such that healthy adults higher in mindfulness showed greater functional connectivity between the posterior cingulate cortex-and cerebellum. Collectively, these findings suggest that the relationship between mindfulness and default mode network functional connectivity may be nuanced or non-robust, and encourage further investigation of how mindfulness relates to pain. PerspectiveThis study found few significant associations between dispositional mindfulness and pain, pain reactivity and default mode connectivity in healthy adults and migraine patients. The relationship between mindfulness and default mode network connectivity may be nuanced or non-robust.

Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0.0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = 0.162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

Resting-State Brain Variability in Youth With Attention-Deficit/Hyperactivity Disorder.

In this study, we sought to determine the nature of the abnormality in resting-state default mode network (DMN) activation and explore its correlation with functional connectivity in attention-deficit/hyperactivity disorder (ADHD). We obtained resting-state functional magnetic resonance images of youth with ADHD and typically developing counterparts from the publicly available ADHD-200 database. We used data from Peking University (232 scans) and New York University (172 scans); the scan repetition time was 2 s for both data collection sites. We applied generalized estimating equations to estimate the variability of the averaged blood-oxygen-level-dependent (BOLD) time series extracted from the DMN at rest. We performed network-based statistics to determine the association between the observed differences in BOLD signal variability and altered functional connectivity. We analyzed data from 105 youth with ADHD (age: mean 12.17, standard deviation 2.31, median 12.25; 15.2% female, 84.8% male) and 140 typically developing youth (age: mean 11.99, standard deviation 2.28, median 11.85; 47.1% female, 52.9% male), who aged 7–17 years. The imaging data were cross-sectionally collected for each participant at one time point. We observed a greater number of significant BOLD signal changes and higher-order polynomial significant associations in youth with ADHD. Moreover, there were significant between-group differences in BOLD signal change after the first 140 s, which coincided with decreased resting-state functional connectivity within the DMN in youth with ADHD. Increased variability of neural signaling was intermittently observed in the brains of youth with ADHD at rest, thereby indicating their default mode state was more unstable than that of typically developing youth.

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Tasks activating the default mode network map multiple functional systems

Recent developments in network neuroscience suggest reconsidering what we thought we knew about the default mode network (DMN). Although this network has always been seen as unitary and associated with the resting state, a new deconstructive line of research is pointing out that the DMN could be divided into multiple subsystems supporting different functions. By now, it is well known that the DMN is not only deactivated by tasks, but also involved in affective, mnestic, and social paradigms, among others. Nonetheless, it is starting to become clear that the array of activities in which it is involved, might also be extended to more extrinsic functions. The present meta-analytic study is meant to push this boundary a bit further. The BrainMap database was searched for all experimental paradigms activating the DMN, and their activation likelihood estimation maps were then computed. An additional map of task-induced deactivations was also created. A multidimensional scaling indicated that such maps could be arranged along an anatomo-psychological gradient, which goes from midline core activations, associated with the most internal functions, to that of lateral cortices, involved in more external tasks. Further multivariate investigations suggested that such extrinsic mode is especially related to reward, semantic, and emotional functions. However, an important finding was that the various activation maps were often different from the canonical representation of the resting-state DMN, sometimes overlapping with it only in some peripheral nodes, and including external regions such as the insula. Altogether, our findings suggest that the intrinsic–extrinsic opposition may be better understood in the form of a continuous scale, rather than a dichotomy.

Cross-lagged Relationships Between Depressive Symptoms and Altered Default Mode Network Connectivity Over the Course of Adolescence

BackgroundAlthough the peak onset of depressive symptoms occurs during adolescence, very few studies have directly examined depression-related changes in resting-state (RS) default mode network activity during adolescence, controlling for potential neural markers of risk. MethodsThis study used data from a longitudinal adolescent cohort to investigate age-specific, persistent (i.e., lagged), and dynamic associations between RS functional connectivity within the default mode network and depressive symptoms during adolescence using a random intercept cross-lagged panel framework. The Neuroventure sample consisted of 151 adolescents ages 12–14 at study entry without any neurological illness who were assessed three times during a 5-year follow-up with 97% follow-up across the three assessments. Depressive symptoms were measured using the depression subscale of the Brief Symptoms Inventory. RS functional magnetic resonance imaging data were collected using a 3T Siemens Magnetom Trio scanner in a single 6-minute sequence. ResultsAfter controlling for relationships between random intercepts, future depression risk was predicted by RS couplings in the perigenual anterior cingulate cortex and anterior dorsomedial prefrontal cortex (β = −0.69, p = .014) and in the left inferior parietal lobule and anterior superior frontal gyrus (β = −0.43, p = .035). Increases in depressive symptoms at previous time points significantly predicted changes in functional connectivity between the posterior cingulate cortex and the precuneus and posterior middle temporal gyrus (β = 0.37, p = .039) and between the dorsal precuneus and posterior middle temporal gyrus (β = 0.47, p = .036). ConclusionsThis study was able to disassociate the RS brain markers of depression from those that appear to follow early-onset depression.

Effective connectivity in the default mode network after paediatric traumatic brain injury.

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7weeks after injury; post-concussion and anxiety symptoms were assessed 7months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting-state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post-concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal-parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post-concussion symptoms and anxiety.

Characterization of Resting State Default Mode Network in Individuals with HbSS and HbSC, and Healthy Controls Using 7-Tesla Human MRI

Sickle cell disease (SCD) is complicated by accelerated brain aging and cerebrovascular complications leading to structural brain damage and altered resting state functional connectivity (RS-FC). Investigation of the Default Mode Network (DMN), the most studied of the RS-FC networks, by functional MRI may provide insight into the neurological and neuropsychiatric complications of SCD. Prior studies have largely focused on the HbSS genotype of SCD as opposed to the HbSC genotype, which accounts for 30% of the total SCD cases in the US. Both genotypes are expected to impact brain disease, but in different manner.The aim of this study was to characterize the DMN in patients with HbSC, HbSS and healthy race and age-matched controls using state of the art 7-Tesla (7T) magnetic resonance imaging (MRI) with high contrast- and signal- to-noise ratios. On the day of the MRI scanning, participants were administered the brief pain inventory questionnaire (BPI), the digit symbol substitution test of cognitive function, and underwent basic blood work. Controls (n= 43, 53% female, mean age = 36+/-12 years), patients with HbSS (n=19, 63% female, mean age= 36+/-12) and HbSC (n=16 (50% female, mean age=36+/-13) were scanned using a 7T Siemens Magnetom scanner with the Tic Tac Toe radiofrequency coil system (Ibrahim et al., 2013). We obtained whole brain structural T1-weighted images and blood oxygenations level dependent resting state functional MRI (RS-fMRI). During the RS-fMRI, participants were instructed to keep their eyes open, look at a fixation cross, and lie without motion in the scanner. To identify significant differences in RS-FC between the groups, we conducted voxel-wise nonparametric analysis of variance. In the cortical areas with significant clusters, we ran ad-hoc t-tests (controls vs. HbSS, HbSC vs. HbSS, 1000 permutations, uncorrected cluster forming threshold = p < 0.001, family-wise error (FWE) rate=0.05) and we added age and sex as confounders. Then, we correlated RS-FC and the following variables: age, hemoglobin, BPI total, and DSST score.We found a significant difference between the three groups in the DMN (Fig 1) (p=0.0002). The ad-hoc t-tests showed that in the DMN, the RS-FC for the medial prefrontal cortex (mPFC) was significantly higher for the controls when compared to patients with HbSS (p=0.002). RS-FC for the mPFC was also significantly higher in patients with HbSC as compared to HbSS (p=0.001). There was a non-significant trend towards lower RS-FC in patients with HbSC as compared to controls. We also found weak non-significant negative correlation, (r= -0.24, p=0.1315), a strong significant negative correlation (r=-0.5, p=0.04) and very strong significant negative correlation (r=-0.8, p=0.001) between age and RS-FC in the mPFC for controls, HbSC, and HbSS patients, respectively. (Fig 2). We did not find any significant correlation between the RS-FC in the three groups and Hb levels, BPI total, and DSST score.In this work and for the first time, using 7T human MRI we identified altered RS-FC between SCD genotypes and between controls and patients with HbSS. It is notable that the RS-FC for HbSC patients was intermediate between that of the other two groups. Our results imply the RS-FC levels might be susceptible to disease genotype and not necessarily Hb levels, cognition and pain. The finding of a stronger correlation between age and FC in patients with SCD as compared to controls corroborates the notion that accelerated brain aging is operant in SCD. [Display omitted] DisclosuresNovelli: Novartis Pharmaceuticals: Consultancy.

Alterations in the Magnetoencephalography Default Mode Effective Connectivity following Concussion

Magnetoencephalography is sensitive to functional connectivity changes associated with concussion. However, the directional influences between functionally related regions remain unexplored. In this study, we therefore evaluated concussion-related magnetoencephalography-based effective connectivity changes within resting-state default mode network regions. Resting-state magnetoencephalography was acquired for 8 high school football players with concussion at 3 time points (preseason, postconcussion, postseason), as well as 8 high school football players without concussion and 8 age-matched controls at 2 time points (preseason, postseason). Time-series from the default mode network regions were extracted, and effective connectivity between them was computed for 5 different frequency bands. The default mode network regions were grouped into anterior and posterior default mode networks. The combined posterior-to-anterior and anterior-to-posterior effective connectivity values were averaged to generate 2 sets of values for each subject. The effective connectivity values were compared using a repeated measures ANOVA across time points for the concussed, nonconcussed, and control groups, separately. A significant increase in posterior-to-anterior effective connectivity from preseason to postconcussion (corrected P value = .013) and a significant decrease in posterior-to-anterior effective connectivity from postconcussion to postseason (corrected P value = .028) were observed in the concussed group. Changes in effective connectivity were only significant within the delta band. Anterior-to-posterior connectivity demonstrated no significant change. Effective connectivity in the nonconcussed group and controls did not show significant differences. The unidirectional increase in effective connectivity postconcussion may elucidate compensatory processes, invoking use of posterior regions to aid the function of susceptible anterior regions following brain injury. These findings support the potential value of magnetoencephalography in exploring directional changes of the brain network following concussion.

Metabolic syndrome components moderate the association between executive function and functional connectivity in the default mode network.

Middle aged individuals with Metabolic Syndrome are at high risk for cognitive decline. Dyssynchrony in the resting state Default Mode Network is one early indicator of brain vulnerability. We set out to explore the relationship between default mode resting state functional connectivity and cognitive performance in both memory and executive domains at midlife in the presence of Metabolic Syndrome components. Seed-based Correlation Analyses were performed between the seed voxel in the posterior cingulate cortex and the medial prefrontal cortex on 200 participants (ages 40-61). Executive domain scores were significantly predicted by the interaction between number of Metabolic Syndrome components and resting state connectivity in the Default Mode Network (p = .004) such that connectivity was negatively related to executive function at higher numbers of Metabolic Syndrome components. Results were not significant for memory. Our findings indicate that clusters of cardiovascular disease risk factors alter functional relationships in the brain and highlights the need to continue exploring how compensatory techniques might operate to support cognitive performance at midlife.

Abnormal functional connectivity and effective connectivity between the default mode network and attention networks in patients with alcohol-use disorder.

Patients with alcohol-use disorder (AUD) demonstrate dysfunctional cerebral network connectivity. However, limited studies have investigated attention systems in AUD. To assess functional (FC) and effective connectivity (EC) in the dorsal (DAN) and ventral attention networks (VAN) and default mode network (DMN) in patients with AUD using resting-state functional magnetic resonance imaging (rs-fMRI). MRI and rs-fMRI data were obtained from 28 men with AUD and 30 age-matched healthy controls. Independent component analysis was used to identify and extract network data, for comparison between the two groups. Effective connectivity was evaluated using Granger causality analysis (GCA) by selecting significantly different brain areas as regions of interest (ROI). Signed-path coefficients between ROIs were computed in bivariate mode. In patients with AUD, FC decreased in the left superior parietal gurus (SPG) and left interparietal sulcus (IPS, in DAN); FC decreased in the right superior frontal gyrus (SPG) and right middle frontal gyrus (MFG, in DMN). GCA values indicated that the DMN exerts a positive causal effect on the DAN (P = 0.007/0.027), which consequently exerts a negative causal effect on the DMN (P = 0.032). Signed-path coefficients from the right MFG to the left IPS correlated negatively with MAST scores (P = 0.015). We found novel inter-network connectivity dysfunction in patients with AUD, which indicates abnormal causal relations between resting-state DAN and DMN. Thus, patients with AUD may have abnormal top-down attention modulation and cognition.