Default Mode Network Functional Connectivity Research Articles

Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Plasma NfL and neuroimaging data from patients with bvFTD (n = 16) and AD or mild cognitive impairment (n = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD.

Default mode network perturbations in Alzheimer's disease: an fMRI study in Klang Valley, Malaysia

The default mode network (DMN) is a large neural network that has a significant correlation with Alzheimer's disease (AD). Grey matter volume (GMV) and functional connectivity (FC) involving the regions of the DMN have been noted to differ significantly between AD and healthy older adults. Nevertheless, there is a paucity of data on the structural and functional changes in the DMN of AD patients in Malaysia. We conducted a cross-sectional study in Klang Valley, Malaysia, to evaluate AD subjects compared to healthy controls (HC) using a resting-state functional MRI (rs-fMRI) experiment. We recruited 22 subjects (AD=11, HC=11) and conducted neuropsychological tests such as the Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). The subjects then underwent rs-fMRI scans, and subsequently, we quantitatively analysed the GMV by Voxel based Morphometry (VBM) using the structural data. We also utilised the CONN toolbox on Statistical Parametric Mapping (SPM) software to evaluate the FC and activation of the nodes of the DMN. In comparison with the HC group, the AD group demonstrated a reduction in GMV in the right and left inferior temporal gyrus, left superior frontal gyrus, right superior frontal gyrus medial segment, right gyrus rectus, right temporal lobe, left putamen, and right precuneus. Moreover, there was a significant decrease in the FC of the nodes of the DMN noted on rs-fMRI (cluster-size corrected p<0.05). In particular, the precuneus and anterior cingulate cortex had decreased FC in AD compared to HC. Hence, structural and resting-state fMRI can detect distinct imaging biomarkers of AD based on GMV and DMN functional connectivity profiles. This tool can be used as a non-invasive tool for improving the feature detection and diagnosis of AD in the Malaysian population.

Affective dysfunction mediates the link between neuroimmune markers and the default mode network functional connectivity, and the somatic symptoms in somatic symptom disorder

ObjectiveSomatic symptom disorder (SSD) is characterized by physical symptoms and associated functional impairments that are often comorbid with depression and anxiety disorders. In this study, we explored relationships between affective symptoms and the functional connectivity of the default mode network (DMN) in SSD patients, as well as the impact of peripheral inflammation. We employed mediation analyses to investigate the potential pathways between these factors. MethodsWe recruited a total of 119 individuals (74 unmedicated SSD patients and 45 healthy controls), who were subjected to comprehensive psychiatric and clinical evaluations, blood tests, and resting-state functional magnetic resonance imaging scanning. We assessed neuroimmune markers (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), tryptophan, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA)), clinical indicators of somatic symptoms, depression, anxiety, anger, alexithymia, and functional connectivity (FC) within the DMN regions. Data were analyzed using correlation and mediation analysis, with a focus on exploring potential relations between clinical symptoms, blood indices, and DMN FCs. ResultsPatients with SSD had higher clinical scores as well as IL-6 and TNF-α levels compared with those in the control group (P < 0.05). The SSD group exhibited lower FC strength between the left inferior parietal lobule and left prefrontal cortex (Pfalse discovery rate (FDR) < 0.05). Exploratory correlation analysis revealed that somatic symptom scores were positively correlated with affective symptom scores, negatively correlated with the FC strength between the intra prefrontal cortex regions, and correlated with levels of IL-6, TNF- α, and tryptophan (uncorrected P < 0.01). Mediation analysis showed that levels of anxiety and trait anger significantly mediated the relations between DMN FC strength and somatic symptoms. In addition, the DMN FC mediated the level of trait anger with respect to somatic symptoms (all PFDR < 0.05). The levels of depression and trait anger exhibited significant mediating effects as suppressors of the relations between the level of 5-HIAA and somatic symptom score (all PFDR < 0.05). Further, the level of 5-HIAA had a mediating effect as a suppressor on the relation between DMN FC and state anger. Meanwhile, the levels of hs-CRP and IL-6 had full mediating effects as suppressors when explaining the relations of DMN FC strengths with the level of depression (all PFDR < 0.05). The patterns of valid mediation pathways were different in the control group. ConclusionsAffective symptoms may indirectly mediate the associations between DMN connectivity, somatic symptoms, and neuroimmune markers. Inflammatory markers may also mediate the impact of DMN connectivity on affective symptoms. These results emphasize the importance of affective dysregulation in understanding the mechanisms of SSD and have potential implications for the development of tailored therapeutic approaches for SSD patients with affective symptoms. Furthermore, in SSD research using DMN FC or neuroimmune markers, considering and incorporating such mediating effects of affective symptoms suggests the possibility of more accurate prediction and explanation.

Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep in Individuals With Insomnia Symptoms: Protocol for a Double-Blind Randomized Controlled Trial.

Cortical hyperarousal and ruminative thinking are common aspects of insomnia that have been linked with greater connectivity in the default mode network (DMN). Therefore, disrupting network activity within the DMN may reduce cortical and cognitive hyperarousal and facilitate better sleep. This trial aims to establish a novel, noninvasive method for treating insomnia through disruption of the DMN with repetitive transcranial magnetic stimulation, specifically with continuous theta burst stimulation (cTBS). This double-blind, pilot randomized controlled trial will assess the efficacy of repetitive transcranial magnetic stimulation as a novel, nonpharmacological approach to improve sleep through disruption of the DMN prior to sleep onset for individuals with insomnia. Primary outcome measures will include assessing changes in DMN functional connectivity before and after stimulation. A total of 20 participants between the ages of 18 to 50 years with reported sleep disturbances will be recruited as a part of the study. Participants will then conduct an in-person screening and follow-on enrollment visit. Eligible participants then conduct at-home actigraphic collection until their first in-residence overnight study visit. In a double-blind, counterbalanced, crossover study design, participants will receive a 40-second stimulation to the left inferior parietal lobule of the DMN during 2 separate overnight in-residence visits. Participants are randomized to the order in which they receive the active stimulation and sham stimulation. Study participants will undergo a prestimulation functional magnetic resonance imaging scan and a poststimulation functional magnetic resonance imaging scan prior to sleep for each overnight study visit. Sleep outcomes will be measured using clinical polysomnography. After their first in-residence study visit, participants conduct another at-home actigraphic collection before returning for their second in-residence overnight study visit. Our study was funded in September 2020 by the Department of Defense (W81XWH2010173). We completed the enrollment of our target study population in the October 2022 and are currently working on neuroimaging processing and analysis. We aim to publish the results of our study by 2024. Primary neuroimaging outcome measures will be tested using independent components analysis, seed-to-voxel analyses, and region of interest to region of interest analyses. A repeated measures analysis of covariance (ANCOVA) will be used to assess the effects of active and sham stimulation on sleep variables. Additionally, we will correlate changes in functional connectivity to polysomnography-graded sleep. The presently proposed cTBS protocol is aimed at establishing the initial research outcomes of the effects of a single burst of cTBS on disrupting the network connectivity of the DMN to improve sleep. If effective, future work could determine the most effective stimulation sites and administration schedules to optimize this potential intervention for sleep problems. ClinicalTrials.gov NCT04953559; https://clinicaltrials.gov/ct2/show/NCT04953559. DERR1-10.2196/51212.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. NCT05516680, ClinicalTrials.gov (registered in August 2022).

Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral Aβ Deposition.

Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer's disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.

9 Connecting memory and functional brain networks in older adults: a resting state fMRI study

Objective:Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.

44 Functional Connectivity In The Default Mode Network Of ASD and ADHD

Objective:Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are neurodevelopmental disorders with overlapping symptomatology and shared genetic makeup. Numerous previous studies have investigated ASD and ADHD using resting state functional networks. One functional network of particular interest is the Default Mode Network (DMN), as it has been shown to be abnormal in several mental disorders. Previous studies have investigated the DMN in ASD and ADHD separately but reported mixed trends of increased and decreased functional connectivity (FC) in the DMN in ASD and increased FC in ADHD. Additionally, little studies have investigated executive and attentional network dysfunction in the DMN for ASD and ADHD populations. To better understand the shared characteristics between ASD and ADHD, this study analyzed the DMN FC in children with ASD and ADHD.Participants and Methods:Archival datasets from Autism Brain Imaging Data Exchange (ABIDE)-I and ADHD-200 datasets were used, with 33 ADHD, 35 ASD, and 32 typically developing (TD) males (ages = 7-17 years). After applying a standard pre-processing pipeline, 11 regions of interest (ROIs) from the Dosenbach-160 atlas were examined with 55 ROI pairs generated for the 100 subjects.Results:Significant differences were noted between ASD-ADHD groups in attentional networks and executive functioning networks. Specifically, significant Group x VIQ interactions were noted for FC between the following pairs of regions: medial prefrontal cortex - ventromedial prefrontal cortex, anterior cingulate cortex -ventromedial prefrontal cortex, inferior temporal lobe - ventromedial prefrontal cortex, angular -ventromedial prefrontal cortex, angular -anterior cingulate cortex, inferior temporal lobe -ventrolateral prefrontal cortex, angular -superior frontal lobe, and intraparietal sulcus -superior frontal lobe. In the above FC pairs, FC in ADHD was negatively correlated with VIQ, with no correlation for ASD and positive correlation for TD. Previous literature has indicated that ADHD individuals demonstrate increased executive functioning deficits compared to ASD individuals. This study provides evidence at a neural level for these findings by demonstrating decreased FC trends in ADHD in attentional and executive functioning networks compared to ASD individuals. Group and VIQ main effects demonstrated mixed patterns across the three groups, as well as shared decreased FC in attention/executive networks for both ASD and ADHD groups.Conclusions:In summary, this study found similar findings from previous studies regarding mixed connectivity patterns, as well as shared dysfunction between ASD and ADHD groups. These results help in solidifying the theory that ASD and ADHD share clinical and neural patterns which need to be examined further. Future directions include utilizing more ASD+ADHD comorbid individuals in studies comparing ASD and ADHD FC trends as well as seeking to further understand the neuropsychological and neuroimaging profiles in ASD and ADHD.

The Association between Default-mode Network Functional Connectivity and Childhood Trauma on the Symptom Load in Male Adults with Methamphetamine Use Disorder.

: The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse. We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. : Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. : There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences. Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. : Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.

Effects of family income on brain functional connectivity in US children: associations with cognition.

Higher family income (FI) is associated with larger cortical gray matter volume and improved cognitive performance in children. However, little is known about the effects of FI on brain functional and structural connectivity. This cross-sectional study investigates the effects of FI on brain connectivity and cognitive performance in 9- to 11-years old children (n = 8739) from the Adolescent Brain Cognitive Development (ABCD) study. Lower FI was associated with decreased global functional connectivity density (gFCD) in the default-mode network (DMN), inferior and superior parietal cortices and in posterior cerebellum, and increased gFCD in motor, auditory, and extrastriate visual areas, and in subcortical regions both for girls and boys. Findings demonstrated high reproducibility in Discovery and Reproducibility samples. Cognitive performance partially mediated the association between FI and DMN connectivity, whereas DMN connectivity did not mediate the association between FI and cognitive performance. In contrast, there was no significant association between FI and structural connectivity. Findings suggest that poor cognitive performance, which likely reflects multiplefactors (genetic, nutritional, the level and quality of parental interactions, and educational exposure [1]), contributes to reduced DMN functional connectivity in children from low-income families. Follow-up studies are needed to help clarify if this leads to reductions in structural connectivity as these children age.

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.

The mediating role of default mode network during meaning-making aroused by mental simulation between stressful events and stress-related growth: a task fMRI study

BackgroundStressful events and meaning-making toward them play an important role in adolescents’ life and growth. However, ignoring positive stressful events leads to negativity bias; further, the neural mechanisms of meaning-making are unclear. We aimed to verify the mediating role of meaning-making in stressful events and stress-related growth and the function of the default mode network (DMN) during meaning-making in this functional magnetic resonance imaging (fMRI) study.MethodsParticipants comprised 59 university students. Stressful life events, meaning-making, and stress-related growth were assessed at baseline, followed by fMRI scanning during a meaning-making task aroused by mental simulation. General linear modeling and psychophysiological interaction (PPI) analyses were used to explore the activation and functional connectivity of DMN during meaning-making.ResultsMental simulation triggered meaning-making, and DMN activity decreased during meaning-making. Activation of the DMN was negatively correlated with coping flexibility, an indicator of stress-related growth. PPI analysis showed that meaning-making was accompanied by diminished connectivity in the DMN. DMN activation during meaning-making can mediate the relationship between positive stressful events and coping flexibility.ConclusionsDecreased DMN activity and diminished functional connectivity in the DMN occurred during meaning-making. Activation of the DMN during meaning-making could mediate the relationship between positive stressful events and stress-related growth, which provides a cognitive neural basis for the mediating role of meaning-making in the relationship between stressful events and indicators of stress-related growth.ImplicationsThis study supports the idea that prosperity makes heroes, expands the meaning-making model, and suggests the inclusion of enhancing personal resources and meaning-making in education. This study was the first to validate the activation pattern and functional connectivity of the DMN during meaning-making aroused by mental simulation using an fMRI task-state examination, which can enhance our sense of meaning and provide knowledge that can be used in clinical psychology interventions.Trial RegistrationThe study protocol was pre-registered in Open Science Framework (see osf.io/ahm6e for details).

Psychological resilience mediates the protective role of default-mode network functional connectivity against COVID-19 vicarious traumatization

Vicarious traumatization (VT), a negative reaction to witnessing others’ trauma, has been experienced by some people during the COVID-19 pandemic, and can lead to mental health problems. This study aimed to identify functional brain markers of COVID-specific VT and explore the psychological mechanism underlying the brain-VT link. One hundred healthy participants underwent resting-state functional magnetic resonance imaging before the pandemic (October 2019–January 2020) and completed VT measurement during the pandemic (February–April 2020). Whole-brain correlation analysis based on global functional connectivity density (FCD) mapping revealed that VT was negatively correlated with FCD in the right inferior temporal gyrus (ITG) (i.e., the lower FCD in ITG, the worse the VT), identified by mapping onto known large-scale networks as part of the default-mode network (DMN). Resting-state functional connectivity (RSFC) analysis using ITG as seed found that VT was predicted by lower functional connectivity between ITG and other DMN regions including left medial prefrontal cortex, left orbitofrontal cortex, right superior frontal gyrus, right inferior parietal lobule and bilateral precuneus (i.e., the lower the ITG-DMN connectivity, the worse the VT). Mediation analyses suggested that psychological resilience served as a mediator in these associations of ITG FCD and ITG-DMN RSFC with VT. Our results provide novel evidence on the brain basis of VT and emphasize psychological resilience as an important link from DMN functional connectivity to COVID-specific-VT. This may facilitate public health interventions by helping identify individuals at risk of stress- and trauma-related psychopathologies.

Effects of spaceflight on the EEG alpha power and functional connectivity

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN’s alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.

Differential associations between plasma neurofilament light and brain functional connectivity in patients with Alzheimer’s disease and fronto‐temporal dementia

AbstractBackgroundNeurofilament light chain (NfL), a marker of axonal loss, is elevated in both Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD)[1‐6]. AD and bvFTD have been shown to spread along specific networks reflective of their symptom profiles[7,8], with AD associated with declines in default mode network (DMN) functional connectivity (FC), and bvFTD linked to disruptions in salience network (SN) FC[9]. However, the association between plasma NfL and FC in these two groups remains unknown. Given evidence linking plasma NfL to hypometabolism in circumscribed regions within the DMN in mild cognitive impairment (MCI) patients[10], we hypothesize that NfL would similarly be associated with FC in a network‐specific manner in AD and bvFTD.MethodPlasma NfL and neuroimaging data from young‐onset patients with bvFTD (n = 16) and AD (n = 38; including AD and MCI of AD type (AD+MCI)) were analyzed. Plasma NfL was measured by single molecule array (SIMOA). Seed‐based FC maps using regions‐of‐interest from DMN (left posterior cingulate cortex) and SN (right anterior insula) were derived for each patient. Voxelwise analyses examining associations between plasma NfL and seed‐based FC were first performed in each group separately. Clusters showing significant FC‐NfL associations were then examined for group differences between AD+MCI and bvFTD, and correlated with neuropsychological performance. All analyses accounted for age, sex, education, handedness and total intracranial volumes.ResultsWe demonstrated differential associations between plasma NfL and FC in AD+MCI and bvFTD patients: AD+MCI patients showed significantly lower DMN FC with higher plasma NfL compared to bvFTD patients (Figure 1A), while bvFTD patients showed lower SN FC (Figure 1B) with higher plasma NfL relative to AD+MCI patients. Further, lower NfL‐related DMN FC in AD+MCI patients was significantly associated with lower MoCA scores (Figure 2).ConclusionPlasma NfL is associated with FC changes in a network‐specific manner in bvFTD and AD+MCI patients, which may be in turn be predictive of cognitive decline. Our study suggest that axonal protein loss has differential effects on functional brain networks in different dementia subtypes. Future studies are warranted to confirm these findings in a larger cohort.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.

Alternation in functional connectivity within default mode network after psychodynamic psychotherapy in borderline personality disorder

BackgroundBorderline personality disorder (BPD) is characterized by impairments in emotion regulation, impulse control, and interpersonal and social functioning along with a deficit in emotional awareness and empathy. In this study, we investigated whether functional connectivity (FC) within the default mode network (DMN) is affected by 1-year psychodynamic psychotherapy in patients with BPD.MethodsNine BPD patients filled out the demography, Interpersonal Reactive Index (IRI), Toronto Alexithymia Scale 20 (TAS 20), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the Borderline Evaluation Severity over Time (BEST) questionnaire. The BPD group (9F) and the control group (9F) had a mean ± SD age of 28.2 ± 5.3 years and 30.4 ± 6.1 years, respectively. BPD subjects underwent longitudinal resting-state fMRI before psychodynamic psychotherapy and then every 4 months for a year after initiating psychotherapy. FC in DMN was characterized by calculating the nodal degree, a measure of centrality in the graph theory.ResultsThe results indicated that patients with BPD present with aberrant DMN connectivity compared to healthy controls. Over a year of psychotherapy, the patients with BPD showed both FC changes (decreasing nodal degree in the dorsal anterior cingulate cortex and increasing in other cingulate cortex regions) and behavioral improvement in their symptoms and substance use. There was also a significant positive association between the decreased nodal degree in regions of the dorsal cingulate cortex and a decrease in the score of the TAS-20 indicating difficulty in identifying feelings after psychotherapy.ConclusionIn BPD, there is altered FC within the DMN and disruption in self-processing and emotion regulation. Psychotherapy may modify the DMN connectivity and that modification is associated with positive changes in BPD emotional symptoms.

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, &amp; Neuroimaging Advancing the Field of Neurology

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, &amp; Neuroimaging Advancing the Field of Neurology

Altered longitudinal trajectory of default mode network connectivity in healthy youth with subclinical depressive and posttraumatic stress symptoms

The default mode network (DMN) plays a crucial role in internal self-processing, rumination, and social functions. Disruptions to DMN connectivity have been linked with early adversity and the emergence of psychopathology in adolescence and early adulthood. Herein, we investigate how subclinical psychiatric symptoms can impact DMN functional connectivity during the pubertal transition. Resting-state fMRI data were collected annually from 190 typically-developing youth (9–15 years-old) at three timepoints and within-network DMN connectivity was computed. We used latent growth curve modeling to determine how self-reported depressive and posttraumatic stress symptoms predicted rates of change in DMN connectivity over the three-year period. In the baseline model without predictors, we found no systematic changes in DMN connectivity over time. However, significant modulation emerged after adding psychopathology predictors; greater depressive symptomatology was associated with significant decreases in connectivity over time, whereas posttraumatic stress symptoms were associated with significant increases in connectivity over time. Follow-up analyses revealed that these effects were driven by connectivity changes involving the dorsal medial prefrontal cortex subnetwork. In conclusion, these data suggest that subclinical depressive and posttraumatic symptoms alter the trajectory of DMN connectivity, which may indicate that this network is a nexus of clinical significance in mental health disorders.