Altered Default Mode Network Research Articles

Factors associated with cancer-related cognitive impairment in patients with lung cancer: A systematic review

PurposeCognitive impairment is common in lung cancer patients and impacts their quality of life. Little is known about the etiology of cognitive impairment in lung cancer patients. However, the associated factors of cognitive impairment among lung cancer patients have not been systematically reviewed. This review aimed to summarize the factors related to cognitive impairment among lung cancer patients. MethodsPubMed, EMBASE, PsycINFO, CINAHL Plus, and Web of Science were searched to retrieve articles published from data inception until January 21, 2024, focusing on factors associated with cognitive impairment among lung cancer patients. Critical appraisal was undertaken by two reviewers independently using the Newcastle–Ottawa Scale. ResultsA total of 17 observational studies were included. The results showed that 20 factors are associated with cognitive impairment, including psychological factors (loneliness, fatigue, anxiety, depression, high symptom burden, and baseline cognitive impairment), lifestyle and functional factors (daily step counts, smoking, and activities of daily living or instrumental activities of daily living impairments), medical treatment factors (cranial irradiation, chemotherapy, lobar resection, postoperative delirium, and on medication), and neuroimmunological factors (have neuronal autoantibodies, altered Default Mode Network connectivity, dysregulation in glutamate and glutamate metabolism, mitochondrial dysfunction, blood-brain barrier leakage, and reduced T-lymphocytes). ConclusionThis is the first study to systematically review 20 factors associated with cognitive impairment among lung cancer patients, encompassing psychology, lifestyle and functional, medical treatment, and neuroimmunological factors. These findings can help clinicians identify at-risk patients and develop evidence-based interventions to prevent cognitive impairment among lung cancer patients.

P346 Assessing Brain Morphology in Functional Gastrointestinal and Inflammatory Bowel Disorders Using Functional Magnetic Resonance Imaging (fMRI)

Abstract Background Functional gastrointestinal disorders (FGIDs) and non-specific inflammatory bowel diseases (IBD) are increasingly common in young adults. Studies have shown abnormal interhemispheric interactions in FGIDs and altered Default Mode Network (DMN) connectivity in brain regions linked to gastric sensations and emotional regulation. This study explores these neural mechanisms in FGIDs and IBDs, focusing on chronic visceral pain and its association with DMN reorganization. Methods The study included patients with functional dyspepsia (FD), N=18; irritable bowel syndrome (IBS), N=20 and IBD, N=18 alongside a control group of 18 healthy volunteers. Selection criteria included the Rome III Criteria for FGIDs and various diagnostic tests for IBDs. MRI scans were conducted using a 3T Achieva TX Scanner, applying standard T1 and T2 sequences without contrast agents. Functional imaging utilized T2 Gradient Echo-Planar Imaging. Results DMN analysis showed no anterior-posterior split. Significant differences were observed in the IBD group compared to controls, particularly in the left superior frontal gyrus. When comparing all patient groups with controls, increased DMN connectivity was noted in the left cingulum and supplementary motor area. These areas were also significant when comparing only FGIDs patients with controls, indicating altered DMN connectivity in these disorders. Please see: Figure 1 and Table 1. Conclusion The study highlights differences in DMNs between patient and control groups, especially in the left superior frontal gyrus, left cingulum, and left supplementary motor area. All disease groups showed variations from controls in the DMN pattern within the left cingulum. Significant differences in the DMN of the supplementary motor area were observed in functional gastric disease groups compared to controls. These findings suggest a link between brain areas involved in sensorimotor processes and symptoms of FD and IBS, providing insights into the neural basis of these conditions. Despite varied changes, common features differentiating the entire study group from healthy controls were identified. This condensed version focuses on the key aspects of your original text, ensuring that the main findings and methodology are clearly presented within the character limit.

State rumination predicts inhibitory control failures and dysregulation of default, salience, and cognitive control networks in youth at risk of depressive relapse: Findings from the RuMeChange trial

BackgroundTrait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. MethodsFifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. ResultsGreater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsal-medial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. LimitationsThe correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. ConclusionsState rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder

ObjectiveAttention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. MethodsResting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. ResultsSocial dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. ConclusionPreliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology.

The default mode of chronic pain: What does it mean and how should we frame it to our patients?

The brain can be organised into defined networks based on the coherent activity fluctuations between certain regions at rest when no external task or stimuli are applied. In patients with chronic pain, alterations in the way these networks act and interact become apparent, especially within the default mode network (DMN) and in the way it functionally interacts with the salience network (SN). However, the implications of these cortical alterations remain speculative, and a clear framework for how we might explain the meaning of them to the patient with chronic pain is lacking. Therefore, here we provide an up-to-date theoretical model for the implications of the DMN alterations observed in the state of chronic pain, and to integrate the key points of this model into an explanatory framework to use in the clinical meeting with chronic pain patients (e.g., during pain neuroscience education).

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Neural reactivity to neutral and aversive stimuli: Evidence for altered precuneus function in internalizing psychopathologies

Individuals with internalizing psychopathologies (IPs) demonstrate a negativity bias in emotion and self-related processing that contributes to negative interpretation of neutral information. However, most neuroimaging studies of emotional experience in IPs do not specifically investigate reactivity to neutral stimuli. Thus, little is known about the neural processes underlying emotional experience for neutral stimuli and how those processes may differ between groups and during neutral versus negative stimuli. To address this gap, we asked: (1) does neural reactivity to neutral and negative stimuli differ between IPs and control groups in brain regions associated with emotional and self-referential processing, and (2) does neural activity during neutral condition relate to clinical symptoms? Adults with IPs (n = 103) and healthy volunteers (HVs; n = 40) completed a well-validated fMRI task probing neural responses to neutral and negative images. A flexible factorial model revealed a significant group-by-condition interaction, such that individuals with IPs had less precuneus activation during the neutral condition relative to HVs. In IPs, precuneus activation during the neutral condition was negatively correlated with depression symptom severity. Individuals with IPs demonstrate abnormal precuneus reactivity to neutral stimuli that is associated with depression symptoms. This may reflect altered default mode network activity and/or self-referential processing in IPs.

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.

Neuroimaging of mild behavioral impairment: A systematic review.

There are many neuroimaging studies of mild behavioral impairment (MBI), but the results have been somewhat inconsistent. Moreover, it remains unclear whether MBI is a risk factor or prodromal symptom of dementia. Therefore, a systematic review was conducted to summarize the results of neuroimaging studies of MBI and consider whether MBI is a prodromal symptom of dementia in terms of its neural correlates. A systematic review supported by a JSPS Grant-in-Aid for Scientific Research (C) was conducted using MBI neuroimaging studies identified using PubMed, PsycINFO, CINAHL, and Google Scholar on November 1, 2022. The inclusion criteria were (i) neuroimaging study; (ii) research on human subjects; (iii) papers written in English; and (iv) not a case study, review, book, comments, or abstract only. Joanna Briggs Institute critical appraisal checklists were used to assess the quality of selected studies, and 23 structural and functional imaging studies were ultimately included in the systematic review. The structural studies suggested an association of MBI with atrophy in the hippocampus, parahippocampal gyrus, entorhinal cortex, and temporal lobe, whereas the functional studies indicated involvement of an altered default mode network, frontoparietal control network, and salience network in MBI. A limitation in many studies was the use of region-of-interest analysis. The brain areas detected as neural correlates of MBI are considered to be alterations in the early stage of each dementia. Therefore, MBI may emerge against a background of pathological changes in dementia.

Altered default mode network causal connectivity patterns in autism spectrum disorder revealed by Liang information flow analysis.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with severe cognitive impairment in social communication and interaction. Previous studies have reported that abnormal functional connectivity patterns within the default mode network (DMN) were associated with social dysfunction in ASD. However, how the altered causal connectivity pattern within the DMN affects the social functioning in ASD remains largely unclear. Here, we introduced the Liang information flow method, widely applied to climate science and quantum mechanics, to uncover the brain causal network patterns in ASD. Compared with the healthy controls (HC), we observed that the interactions among the dorsal medial prefrontal cortex (dMPFC), ventral medial prefrontal cortex (vMPFC), hippocampal formation, and temporo-parietal junction showed more inter-regional causal connectivity differences in ASD. For the topological property analysis, we also found the clustering coefficient of DMN and the In-Out degree of anterior medial prefrontal cortex were significantly decreased in ASD. Furthermore, we found that the causal connectivity from dMPFC to vMPFC was correlated with the clinical symptoms of ASD. These altered causal connectivity patterns indicated that the DMN inter-regions information processing was perturbed in ASD. In particular, we found that the dMPFC acts as a causal source in the DMN in HC, whereas it plays a causal target in ASD. Overall, our findings indicated that the Liang information flow method could serve as an important way to explore the DMN causal connectivity patterns, and it also can provide novel insights into the nueromechanisms underlying DMN dysfunction in ASD.

Plasma NfL predicts default mode network functional connectivity in older adults at higher risk for Alzheimer’s disease

AbstractBackgroundNeurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer’s disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship.MethodResting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants’ APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates.ResultPlasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871).ConclusionOur results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia.

Plasma NfL predicts default mode network functional connectivity in older adults at higher risk for Alzheimer’s disease

AbstractBackgroundNeurofilament light (NfL) is a measure of neuronal damage and has the potential as a monitoring and prognostic biomarker of Alzheimer’s disease (AD) (Mattsson et al., 2019). Likewise, alterations in default mode network (DMN) functional connectivity (FC) may predict AD progression (Jones et al., 2016). Here, we investigated the relationship between plasma NfL levels and DMN FC along the continuum of AD, and explored whether APOE ε4 status influenced this relationship.MethodResting‐state functional MRI data and blood samples were available for 103 older adults (17 with AD dementia, age: 69.2±6.9; m/f: 8/9; CDR: 0.7±0.3; and 86 without dementia (includes amnestic MCI and control), age: 71.7±7.4; m/f: 21/65; CDR: 0.3±0.2). Plasma NfL was measured using a single‐molecule array (Simoa) assay. We calculated DMN FC using 32 high consensus DMN ROIs from Dworetsky et al. (2021). DMN FC was defined as the average correlation between the mean time‐series of three ROIs labeled as posterior cingulate cortex and those of all the other ROIs. Participants’ APOE status was defined as APOE ε4 carriers (ε3/ε4 or ε4/ε4) and noncarriers (ε3/ε3). Multiple regression was run with DMN FC as the outcome variable, plasma NfL as the predictor, and age and sex as covariates.ResultPlasma NfL levels were higher in those with dementia compared to those without dementia (t = 4.4608, p = 0.0002) but did not differ between amnestic MCI and control (t = 1.6116, p = 0.1130). Across all participants, plasma NfL did not predict DMN FC (Β = 0.0045, p = 0.4830). However, higher plasma NfL was marginally associated with higher DMN FC in those with dementia (Β = 0.0045, p = 0.0657) but not in those without dementia (Β = 0.0021, p = 0.3160). Moreover, in those without dementia, higher plasma NfL predicted higher DMN FC in APOE ε4 carriers (Β = 0.0079, p = 0.0312) but not in APOE ε4 noncarriers (Β = 0.0023, p = 0.4871).ConclusionOur results indicate that the increase of DMN FC, seen at early stages of AD (Damoiseaux et al., 2012), is significantly associated with more neuronal damage in APOE ε4 carriers without dementia.

Alteration of default mode network: association with executive dysfunction in frontal glioma patients.

Patients with frontal gliomas often experience executive dysfunction (EF-D) before surgery, and the changes in brain plasticity underlying this effect remain obscure. In this study, the authors aimed to assess whole-brain structural and functional alterations by using structural MRI and resting-state functional MRI (rs-fMRI) in frontal glioma patients with or without EF-D. Fifty-seven patients with frontal gliomas were admitted prospectively to the authors' institution and assigned to one of two groups: 1) the normal executive function (EF-N) group and 2) the EF-D group, based on patient results for the Trail Making Test, Part B and Stroop Color-Word Test, Part C. Twenty-nine baseline-matched healthy controls were also recruited. All participants underwent multimodal MRI examination. Cortical surface thickness, surface-based resting-state activity (fractional amplitude of low-frequency fluctuation [fALFF] and regional homogeneity [ReHo]), and edge-based network functional connectivity (FC) were measured with FreeSurfer and fMRIPrep. The correlation between altered MRI parameters and executive function (EF) was assessed using Pearson correlation and receiver operating characteristic (ROC) analysis. Demographic characteristics (sex, age, and education level) and clinical characteristics (location, volume, grade of tumor, and preoperative epilepsy) were not significantly different between the groups, but the Karnofsky Performance Scale score was worse in the EF-D group. There was no significant difference in cortical surface thickness between the EF-D and EF-N groups. In both low-grade and high-grade glioma patients the fALFF value (permutation test + threshold-free cluster enhancement, p value after family-wise error correction < 0.05) and ReHo value (t-test, p < 0.001) of the left precuneus cortex in the EF-D group were greater than those in the EF-N group, which were negatively correlated with EF (p < 0.05) and enabled prediction of EF (area under the ROC curve 0.826 for fALFF and 0.855 for ReHo, p < 0.001). Compared with the EF-N group, the FCs between the default mode network (DMN) from DMN node to DMN node (DMN-DMN) and from the DMN to the central executive network (DMN-CEN) in the EF-D group were increased significantly (network-based statistics corrected p < 0.05) and negatively correlated with EF (Pearson correlation, p < 0.05). Apart from local disruption, the abnormally activated DMN in the resting state is related to EF-D in frontal glioma patients. DMN activity should be considered during preoperative planning and postoperative neurorehabilitation for frontal glioma patients to preserve EF. Clinical trial registration no.: NCT03087838 (ClinicalTrials.gov).

Analysis of effective connectivity in default mode network in male long-term smokers based on dynamic causal modeling

Objective: To investigate the alterations in effective connection of default mode network (DMN) in long-term male smokers and its correlation with clinical characteristics of smoking. Methods: A total of 131 subjects through WeChat platform and underwent resting-state functional magnetic resonance (rs-fMRI) examinations were recruited, including 76 long-term smokers [long-term smoking group, male, aged 20 to 55 (32.1±6.3) years] and 55 non-smokers [healthy controls, male, aged 20 to 55(32.3±7.4) years] from January 2014 to December 2018. Long-term smokers were defined as those who smoked at least 10 cigarettes per day for more than 2 years, and met the Diagnostic and Statistical Manual of Mental Disorders-Four Edition (DSM-Ⅳ) criteria for substance dependence. Four major nodes of DMN, including left inferior parietal lobule (LIPL), right inferior parietal lobule (RIPL), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) were chosen as for the region of interest. The effective connectivity (EC) alterations of DMN between smoking group and healthy controls were compared using dynamic causal modeling (DCM). The correlation between EC with significant difference among the two groups and Nicotine Dependence Scale (FTND) score, pack-year score and smoking duration were evaluated. Results: Compared to the healthy controls, the EC of LIPL to PCC and PCC to mPFC were decreased in the smoking group (EC = -0.091, -0.174, respectively, Bayesian-PP>0.95), and the EC of RIPL to PCC was increased (EC = 0.136, Bayesian-PP>0.95). Besides, EC of LIPL to PCC showed negative correlation with pack-year scores(r=-0.282,P=0.017). No significant linear correlations were observed between EC with significant group difference and FTND score or smoking duration (r=-0.103、-0.089,all P>0.05). Conclusion: Long-term smokers showed multiple abnormalities in IPL-PCC-mPFC circuits, and associated with the pack-year scores.

Neural signatures of default mode network in major depression disorder after electroconvulsive therapy.

Functional abnormalities of default mode network (DMN) have been well documented in major depressive disorder (MDD). However, the association of DMN functional reorganization with antidepressant treatment and gene expression is unclear. Moreover, whether the functional interactions of DMN could predict treatment efficacy is also unknown. Here, we investigated the link of treatment response with functional alterations of DMN and gene expression with a comparably large sample including 46 individuals with MDD before and after electroconvulsive therapy (ECT) and 46 age- and sex-matched healthy controls. Static and dynamic functional connectivity (dFC) analyses showed increased intrinsic/static but decreased dynamic functional couplings of inter- and intra-subsystems and between nodes of DMN. The changes of static functional connections of DMN were spatially correlated with brain gene expression profiles. Moreover, static and dFC of the DMN before treatment as features could predict depressive symptom improvement following ECT. Taken together, these results shed light on the underlying neural and genetic basis of antidepressant effect of ECT and the intrinsic functional connectivity of DMN have the potential to serve as prognostic biomarkers to guide accurate personalized treatment.

Default mode network alterations underlie auditory verbal hallucinations in schizophrenia

Although alterations of the default mode network (DMN) in schizophrenia (SZ) have been largely investigated, less research has been carried out on DMN alterations in different sub-phenotypes of this disorder. The aim of this pilot study was to compare DMN features among SZ patients with and without auditory verbal hallucinations (AVH). Three groups of 17 participants each were considered: patients with hallucinations (AVH-SZ), patients without hallucinations (nAVH-SZ) and age-matched healthy controls (HC). The DMN spatial pattern was similar between the nAVH-SZ and HC, but the comparison between these two groups and the AVH-SZ group revealed alterations in the left Angular Gyrus (lAG) node of the DMN. Using a novel approach based on normalized fractional Amplitude of Low-Frequency Fluctuations (fALFF), the AVH-SZ subgroup showed altered spectral activity in the DMN compared with the other two groups, especially in the lower-frequency bands (0.017–0.04 Hz). Significant positive correlations were found for both SZ groups collapsed, and for the nAVH-SZ group alone between delusional scores (PANSS-P1) and slow fALFF bands of the DMN. Narrowing the analysis to the ROI centered on the lAG, significant correlations were found in the AVH-SZ group for hallucination scores (PANSS-P3) and Slow-5 and Slow-4 (both positive), and Slow-3 (negative) fALFF bands. Our results reveal the central role of the lAG in relation to hallucinations, an important cortical area connecting auditory cortex with several hubs (including frontal linguistic centers) and involved in auditory process monitoring.

Longitudinal functional connectivity patterns of the default mode network in healthy older adults

Cross-sectional studies have consistently identified age-associated alterations in default mode network (DMN) functional connectivity (FC). Yet, research on longitudinal trajectories of FC changes of the DMN in healthy aging is less conclusive.For the present study, we used a resting state functional MRI dataset drawn from the Longitudinal Healthy Aging Brain Database Project (LHAB) collected in 5 occasions over a course of 7 years (baseline N = 232, age range: 64–87 y, mean age = 70.85 y). FC strength changes within the DMN and its regions were investigated using a network-based statistical method suitable for the analysis of longitudinal data. The average DMN FC strength remained stable, however, various DMN components showed differential age- and time-related effects. Our results revealed a complex pattern of longitudinal change seen as decreases and increases of FC strength encompassing the majority of DMN regions, while age-related effects were negative and present in select brain areas. These findings testify to the growing importance of longitudinal studies using more sophisticated fine-grained tools needed to highlight the complexity of the functional reorganization of DMN with healthy aging.

Altered Default Mode Network Functional Connectivity in Parkinson's Disease: A Resting-State Functional Magnetic Resonance Imaging Study.

PurposeWhether the intrinsic functional connectivity pattern of the default mode network (DMN) is involved in the progression of cognitive decline in Parkinson’s disease (PD) remains unclear. This study aimed to investigate the intrinsic functional connectivity (FC) pattern of the DMN anchored on the posterior cingulate cortex (PCC) in patients with PD by resting-state functional magnetic resonance imaging (fMRI).MethodsFifty patients with PD and 50 healthy controls (HCs) were included for resting-state fMRI scanning. A seed-based FC method was used to reveal FC patterns in the DMN with region of interest (ROI) in the PCC. Relationships between FC patterns and disease severity (UPDRS-III) were detected.ResultsCompared with the HCs, the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus. In the PD group, the increased FC values in the right precuneus were significantly and positively correlated with motor severity as assessed with UPDRS-III scores (rho = 0.337, p = 0.02).ConclusionOur result highlights that the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus in the DMN. The altered connectivity pattern in the DMN may play a crucial role in the neurophysiological mechanism of cognitive decline in patients with PD. These findings might provide new insights into neural mechanisms of cognitive decline in PD.

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.

Altered default mode network associated with pesticide exposure in Latinx children from rural farmworker families

Pesticide exposure has been associated with adverse cognitive and neurological effects. However, neuroimaging studies aimed at examining the impacts of pesticide exposure on brain networks underlying abnormal neurodevelopment in children remain limited. It has been demonstrated that pesticide exposure in children is associated with disrupted brain anatomy in regions that make up the default mode network (DMN), a subnetwork engaged across a diverse set of cognitive processes, particularly higher-order cognitive tasks. This study tested the hypothesis that functional brain network connectivity/topology in Latinx children from rural farmworker families (FW children) would differ from urban Latinx children from non-farmworker families (NFW children). We also tested the hypothesis that probable historic childhood exposure to pesticides among FW children would be associated with network connectivity/topology in a manner that parallels differences between FW and NFW children. We used brain networks from functional magnetic resonance imaging (fMRI) data from 78 children and a mixed-effects regression framework to test our hypotheses. We found that network topology was differently associated with the connection probability between FW and NFW children in the DMN. Our results also indicated that, among 48 FW children, historic reports of exposure to pesticides from prenatal to 96 months old were significantly associated with DMN topology, as hypothesized. Although the cause of the differences in brain networks between FW and NFW children cannot be determined using a cross-sectional study design, the observed associations between network connectivity/topology and historic exposure reports in FW children provide compelling evidence for a contribution of pesticide exposure on altering the DMN network organization in this vulnerable population. Although longitudinal follow-up of the children is necessary to further elucidate the cause and reveal the ultimate neurological implications, these findings raise serious concerns about the potential adverse health consequences from developmental neurotoxicity associated with pesticide exposure in this vulnerable population.