Default Mode Network Functional Connectivity Research Articles

Unresponsiveness induced by sevoflurane and propofol is associated with reduced basal forebrain cholinergic nuclei functional connectivity in humans, a pilot exploratory study

Studies suggest the cholinergic system is involved in anesthesia-induced unconsciousness, hence unresponsiveness. A significant source of cholinergic innervation comes from basal forebrain cholinergic nuclei (BFCN), with bi-directional connections between anterior BFCN and the default mode network (DMN). Since DMN functional connectivity (FC) is consistently reduced during anesthesia-induced unresponsiveness in humans, we hypothesized that BFCN-FC during anesthesia-induced unresponsiveness is reduced and particularly, anterior BFCN-FC reductions might be related to DMN-FC reductions. Resting-state fMRI (rs-fMRI) signal correlations (i.e., a proxy for FC) were calculated. FC seeds were anterior and posterior BFCN and the DMN. Rs-fMRI data come from healthy male controls during wakefulness and anesthesia with sevoflurane (n = 15) (at fixed concentrations: 2 and 3 vol%) and propofol titrated to the endpoint of clinical unresponsiveness (n = 12), respectively. FC state differences were tested via paired t-tests; FC changes for anterior BFCN and DMN were associated via correlation analysis. We found reduced anterior and posterior BFCN-FC with sevoflurane and propofol compared to wakefulness. The correlation between reduced DMN-FC-and anterior BFCN-FC reductions was r = 0.57 (p = 0.01) for sevoflurane 3 vol%, r = 0.34 (p = 0.11) for sevoflurane 2 vol% and r = 0.47 (p = 0.06) for propofol. In summary, in this exploratory pilot study, we demonstrated reduced BFCN-FC and a potential correlation between reduced anterior BFCN-FC and DMN-FC during sevoflurane and propofol anesthesia. This suggests DMN changes as a potential factor of anterior BFCN-FC reductions during anesthesia-induced unresponsiveness and BFCN-FC reduction as a potential sign of such state.

Specific Associations in the Alpha Frequency Between the Subcomponents of Rumination and the Subsystems of the Default Mode Network Among Bipolar I Disorder Patients.

Introduction: Rumination in bipolar disorder (BD) is well documented. Recent neuroimaging studies highlight the role of the default mode network (DMN) in rumination, while few studies have evaluated the DMN activity in BD rumination, particularly the underlying neuroelectrophysiology. Methods: A total of 44 patients with depressed bipolar I disorder (BD-I) and 46 healthy controls underwent resting-state magnetoencephalography. Two core hubs of the DMN, the posterior cingulate cortex (PCC), and anterior medial prefrontal cortex, together with the dorsal medial prefrontal cortex (dmPFC) and the medial temporal lobe (MTL) subsystems, were identified as the regions of interest. The power envelope method was used to determine the alpha band's cross-subsystem functional connectivity (FC). After comparing the rumination and DMN FC between the groups, Spearman partial correlation analysis was performed to evaluate the relationship between aberrant FC and rumination in BD-I patients. Results: BD-I patients demonstrated more global rumination, including higher subcomponent scores of brooding and reflection. In addition, the alpha frequency FC of the PCC-dmPFC and dmPFC-MTL subsystems within the DMN was dramatically increased in the BD-I group. The former was strongly associated with reflection, whereas the latter was related to brooding. Conclusion: The findings suggest that the reflection and brooding components of rumination are selectively related to the alpha frequency FC of the PCC-dmPFC and dmPFC-MTL subsystems, respectively. These associations highlight the significance of DMN activities in rumination among BD-I patients and have implications for future rumination interventions.

Integration patterns of functional brain networks can predict the response to abdominal acupuncture in patients with major depressive disorder

Abdominal acupuncture has definite efficacy for major depressive disorder (MDD). Our study examined how abdominal acupuncture regulates the integration within and between brain networks of MDD patients by neuroimaging and whether this functional integration can predict the efficacy. Forty-six female MDD patients were randomly divided into a fluoxetine + real acupuncture group (n = 22) and a fluoxetine + sham acupuncture group (n = 24). The differences in functional magnetic resonance imaging data in the intra- and inter-network functional connectivity (FC) of the default mode network (DMN), affective network (AN), salience network (SN), and cognitive control network (CCN) between the two groups were analyzed. The FCs in brain regions with the inter-group differences and support vector regression were used to predict the efficacy of abdominal acupuncture. Our results showed: that the intra- and inter-network FCs of DMN, AN, SN, and CCN could be changed by abdominal acupuncture. Using the baseline FCs within AN and DMN or AN–DMN as characteristics, combined with support vector regression, could better predict the efficacy of acupuncture. Our study suggests that abdominal acupuncture could treat MDD by regulating the integration of the functional networks DMN, AN, SN, and CCN. The baseline FCs within the DMN and AN or between them could be used as neural markers for predicting the efficacy of abdominal acupuncture.

Metabolic syndrome is associated with reduced default mode network functional connectivity in young post-9/11 Veterans.

Metabolic syndrome is a collection of health factors that increases risk for cardiovascular disease. A condition of aging, metabolic syndrome is associated with reduced brain network integrity, including functional connectivity alterations among the default mode, regions vulnerable to neurodegeneration. Prevalence of metabolic syndrome is elevated in younger populations including post-9/11 Veterans and individuals with posttraumatic stress disorder, but it is unclear whether metabolic syndrome affects brain function in earlier adulthood. Identifying early effects of metabolic syndrome on brain network integrity is critical, as these impacts could contribute to increased risk for cognitive disorders later in life for Veterans. The current study examined whether metabolic syndrome and its individual components were associated with default mode functional connectivity. We also explored the contribution of posttraumatic stress disorder and traumatic brain injury on these metabolic syndrome-brain relationships. Post-9/11 Veterans with combat deployment history (95 with and 325 without metabolic syndrome) underwent functional magnetic resonance imaging to capture seed-based resting-state functional connectivity within the default mode. The metabolic syndrome group demonstrated reduced positive functional connectivity between the posterior cingulate cortex seed and the bilateral superior frontal gyrus. Data-driven analyses demonstrated that metabolic syndrome components, particularly cholesterol and central adiposity, were associated with widespread reductions in default mode network connectivity. Functional connectivity was also reduced in participants with metabolic syndrome but without current posttraumatic stress disorder diagnosis and with traumatic brain injury history. These results suggest that metabolic syndrome disrupts resting-state functional connectivity decades earlier than prior work has shown.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40-60%) and higher functional connectivity within the salience network (R2 = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

Altered Development of the Hurst Exponent in the Medial Prefrontal Cortex in Preschoolers With Autism

BackgroundAtypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent (H). A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism. MethodsThe current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5–5 years, underwent natural sleep fMRI as part of a longitudinal study. ResultsIn a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC H was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically). ConclusionsThese results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study)

BackgroundMindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients.MethodsThe present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes.Results177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02).ConclusionsIncreased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients.Trial RegistrationName of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018

Disrupted default mode network connectivity in bipolar disorder: a resting-state fMRI study

BackgroundTheoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD.MethodsA total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis.ResultsCompared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies.ConclusionsOur findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.

Resting-state networks and anosognosia in Alzheimer's disease.

Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer's Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN). Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient's and carer's judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity. We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age. Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.

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 network reorganization after endovascular thrombectomy in patients with anterior circulation stroke

BackgroundEndovascular thrombectomy has been confirmed to be an effective therapy for acute ischemic stroke (AIS). However, how functional brain networks reorganize after restoration of blood supply in AIS patients, and whether the degree of reperfusion associates with functional network changes remains unclear. MethodsResting-state fMRI data were collected from 43 AIS patients with anterior circulation occlusion after thrombectomy and 37 healthy controls (HCs). Both static and dynamic functional connectivity (FC) within four advanced functional networks including dorsal attention network (DAN), ventral attention network (VAN), executive control network (ECN) and default mode network (DMN), were calculated and compared between post-thrombectomy patients and HCs, and between two subgroups of post-thrombectomy patients with different reperfusion conditions. ResultsAs compared to HCs, patients showed significant differences in static FC of four functional networks, and in dynamic FC of DAN, ECN and DMN. Furthermore, patients with better reperfusion conditions exhibited increased static FC with precuneus, and altered dynamic FC within precuneus. Moreover, these alterations were associated with clinical assessments of stroke severity and functional recovery in post-thrombectomy patients. ConclusionsCollectively, these findings may provide the potential imaging markers for assessment of thrombectomy efficacy and help establish the specific rehabilitation treatments for post-thrombectomy patients.

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.