Default Mode Network Connectivity In Patients Research Articles

Default mode network changes in fibromyalgia patients are largely dependent on current clinical pain

Differences in fMRI resting-state connectivity of the default mode network (DMN) seen in chronic pain patients are often interpreted as brain reorganization due to the chronic pain condition. Nevertheless, patients’ pain at the time of fMRI might influence the DMN because pain, like cognitive stimuli, engages attentional mechanisms and cognitive engagement is known to alter DMN activity. Here, we aimed to dissociate the influence of chronic pain condition (trait) from the influence of current pain experience (state) on DMN connectivity in patients with fibromyalgia (FM). We performed resting-state fMRI scans to test DMN connectivity in FM patients and matched healthy controls in two separate cohorts: (1) in a cohort not experiencing pain during scanning (27 FM patients and 27 controls), (2) in a cohort with current clinical pain during scanning (16 FM patients and 16 controls). In FM patients without pain during scanning, the connectivity of the DMN did not differ significantly from controls. By contrast, FM patients with current clinical pain during the scan had significantly increased DMN connectivity to bilateral anterior insula (INS) similar to previous studies. Regression analysis showed a positive relationship between DMN-midINS connectivity and current pain. We therefore suggest that transient DMN disruptions due to current clinical pain during scanning (current pain state) may be a substantial contributor to DMN connectivity disruptions observed in chronic pain patients.

Divergent default mode network connectivity during social perception in 22q11.2 deletion syndrome

AimThe 22q11.2 deletion (22q11DS) syndrome is a neurogenetic condition marked by social dysfunction. A major network involved in social cognition is the default mode network (DMN). To date, no study has investigated DMN functional connectivity during socio-cognitive paradigms in 22q11DS. MethodWe used the psychophysiological analysis (PPI) to investigate functional connectivity of the DMN during social perception in 22 participants with 22q11DS and 22 healthy controls. Association between DMN connectivity and prodromal symptoms was also examined. Results22q11DS patients exhibited stronger connectivity between the inferior parietal lobule (IPL) and the posterior cingulate cortex (PCC)/precuneus as well as lower connectivity between the precuneus and middle/superior frontal regions compared to controls. Association between IPL-PCC/precuneus connectivity and negative symptoms was also found in individuals with 22q11DS. ConclusionOur results point to (1) divergent DMN connectivity in patients with 22q11DS compared to controls; (2) association between DMN connectivity and negative symptom severity in patients. Results support the role of the DMN in social deficits of the 22q11DS population.

Symptoms of fatigue and depression is reflected in altered default mode network connectivity in multiple sclerosis.

BackgroundFatigue and depression are frequent and often co-occurring symptoms in multiple sclerosis (MS). Resting-state functional magnetic resonance imaging (rs-fMRI) represents a promising tool for disentangling differential associations between depression and fatigue and brain network function and connectivity. In this study we tested for associations between symptoms of fatigue and depression and DMN connectivity in patients with MS.Materials and methodsSeventy-four MS patients were included on average 14 months after diagnosis. They underwent MRI scanning of the brain including rs-fMRI, and symptoms of fatigue and depression were assessed with Fatigue Severity Scale (FSS) and Beck Depression Inventory II (BDI). A principal component analysis (PCA) on FSS and BDI scores was performed, and the component scores were analysed using linear regression models to test for associations with default mode network (DMN) connectivity.ResultsWe observed higher DMN connectivity with higher scores on the primary principal component reflecting common symptom burden for fatigue and depression (Cohen’s f2 = 0.075, t = 2.17, p = 0.03). The secondary principal component reflecting a pattern of low fatigue scores with high scores of depression was associated with lower DMN connectivity (Cohen’s f2 = 0.067, t = -2.1, p = 0.04). Using continuous mean scores of FSS we also observed higher DMN connectivity with higher symptom burden (t = 3.1, p = 0.003), but no significant associations between continuous sum scores of BDI and DMN connectivity (t = 0.8, p = 0.4).ConclusionMultivariate decomposition of FSS and BDI data supported both overlapping and unique manifestation of fatigue and depression in MS patients. Rs-fMRI analyses showed that symptoms of fatigue and depression were reflected in altered DMN connectivity, and that higher DMN activity was seen in MS patients with fatigue even with low depression scores.

Mindfulness-based therapy modulates default-mode network connectivity in patients with opioid dependence

Recently, mindfulness-based programs have shown promising clinical effects in the treatment of substance-use disorders (SUD). While several studies linked mindfulness to decreased default mode network (DMN) connectivity in meditators, only a few studies investigated its effects in patients with SUD. This study aimed to detect changes in DMN connectivity in opiate dependent patients receiving mindfulness based therapy (MBT) during their first month of treatment. Data from 32 patients that were assigned to MBT or treatment as usual (TAU) groups was investigated using resting-state functional MRI at 1.5 T before and after four weeks of treatment. Independent Component Analysis was used to investigate distinct (anterior vs. posterior) DMN subsystems. Connectivity changes after treatment were related to measures of impulsivity, distress tolerance and mindfulness. Increased mindfulness scores after treatment were found in patients receiving MBT compared to TAU. Within the anterior DMN, decreased right inferior frontal cortical connectivity was detected in patients who received MBT compared to TAU. In addition, within the MBT-group decreased right superior frontal cortex connectivity was detected after treatment. Inferior frontal cortex function was significantly associated with mindfulness measures. The data suggest that MBT can be useful during abstinence from opiates. In opiate-dependent patients distinct functional connectivity changes within the DMN are associated with MBT.

The effects of medication on default mode network (DMN) connectivity in attention deficit/hyperactivity disorder (ADHD): Bibliographic review

IntroductionADHD is a neurodevelopmental disorder comprising brain structural and functional alterations, especially in default mode network (DMN), as MRI studies have recently shown. However, it is not clear in which extent medication for ADHD may influence the activity of these networks.ObjectivesThe main purpose is to look up published evidence about the effects of ADHD medication on the connectivity of DMN in patients as measured with functional-MRI.MethodsA review was conducted with Pubmed, using search terms ‘default mode network’+ ‘ADHD’ + ‘medication’/‘methylphenidate’/‘atomoxetine’/‘stimulant’/‘lisdexanfetamine’. Original research studies in English using f-MRI to assess DMN connectivity in ADHD patients were included in a more comprehensive review.ResultsThe searches found 124 articles, 8 meeting the review criteria. A total size of 146 ADHD patients was comprised (mean size: 18.25 patients). Three studies used specific resting-state f-MRI. Seven were drug trials, 3 of them short-term, randomized and controlled ones. Six included methylphenidate, 2 atomoxetine, 1 lisdexanfetamine and 3 amphetamines. Two also assessed drugs clinical effects. Evidence seems heterogeneous, but mostly consistent with normalizing drug effects on DMN in patients (in some studies also compared with healthy controls), associated with a measured clinical improvement in one study with amphetamines and one with atomoxetine. One trial found little differences on DMN activity.ConclusionsPsychostimulant drugs and atomoxetine are clinically effective medications; DMN connectivity may partially explain their action mechanisms and constitute a potential response predictor. Further f-MRI studies might more deeply assess the imaging-clinical relationships for each drug.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clinical significance of increased cerebellar default-mode network connectivity in resting-state patients with drug-naive somatization disorder.

The cerebellum has been proven to be connected to the brain network, as in the default-mode network (DMN), among healthy subjects and patients with psychiatric disorders. However, whether or not abnormal cerebellar DMN connectivity exists and what its clinical significance is among drug-naive patients with somatization disorder (SD) at rest remain unclear.A total of 25 drug-naive patients with SD and 28 healthy controls were enrolled for a resting-state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method.Compared with the controls, patients with SD showed increased left/right Crus I-left/right angular gyrus (AG) connectivity and Lobule IX-left superior medial prefrontal cortex (MPFC) connectivity. The FC values of the left/right Crus I-right AG connectivity of the patients were positively correlated with their scores in the somatization subscale of the symptom checklist-90 (Scl-90). A trend level of correlations was observed between the FC values of the left Crus I-left AG connectivity of the patients and their scores for the somatization subscale of Scl-90, as well as between the FC values of their Lobule IX-left superior MPFC connectivity and their scores for the Eysenck personality questionnaire (EPQ) extraversion.Our findings show the increased cerebellar DMN connectivity in patients with SD and therefore highlight the importance of the DMN in the neurobiology of SD. Increased cerebellar DMN connectivities are also correlated with their somatization severity and personality, both of which bear clinical significance.

Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient's clinical symptoms. Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients' clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)-based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis. Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus. This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.

Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. University research institute. Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

Reduced default mode network connectivity in treatment‐resistant idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Therefore, the aim of this study was to examine resting-state default mode network (DMN) functional connectivity in patients with treatment-resistant IGE. Treatment resistance was defined as continuing seizures despite an adequate dose of valproic acid (valproate, VPA). Data from 60 epilepsy patients and 38 healthy controls who underwent simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) were included (EEG/fMRI). Independent component analysis (ICA) and dual regression were used to quantify DMN connectivity. Confirmatory analysis using seed-based voxel correlation was performed. There was a significant reduction of DMN connectivity in patients with treatment-resistant epilepsy when compared to patients who were treatment responsive and healthy controls. Connectivity was negatively correlated with duration of epilepsy. Our findings in this large sample of patients with IGE indicate the presence of reduced DMN connectivity in IGE and show that connectivity is further reduced in treatment-resistant epilepsy. DMN connectivity may be useful as a biomarker for treatment resistance.

Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia

Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia. Method First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms. Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention. These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

Modifications of Default-Mode Network Connectivity in Patients with Cerebral Glioma

PurposeThe aim of the study was to evaluate connectivity modifications in the Default Mode Network (DMN) in patients with cerebral glioma, and to correlate these modifications to tumor characteristics.MethodsTwenty-four patients with a left-hemisphere cerebral tumor (14 grade II and 10 grade IV gliomas) and 14 healthy age-matched right-hand volunteers were enrolled in the study. Subjects underwent fMRI while performing language tasks for presurgical mapping. Data was analyzed with independent component analysis in order to identify the DMN. DMN group maps were produced by random-effect analysis (p<0.001, FDR-corrected). An analysis of variance across the three groups (p<0.05) and post-hoc t-test contrasts between pairs of groups were calculated (p<0.05, FDR-corrected).ResultsAll three groups showed typical DMN areas. However, reduced DMN connectivity was detected in tumor patients with respect to controls. A significantly increased and reduced integration of DMN areas was observed in the hippocampal and prefrontal regions, respectively. Modifications were closely related to tumor grading. Moreover, the DMN lateralized to the hemisphere contralateral to tumor in the low-grade, but not in the high-grade tumor patients.ConclusionModifications of DMN connectivity were induced by gliomas and differed for high and low grade tumors.

SU-E-I-137: Incorporation of Regional Homogeneity in Seed-Based Resting-State Functional MRI Analysis Improves Default-Mode Network Detection in Patients with ICA Stenosis

Purpose: Functional connectivity (FC) within the default mode network (DMN) as detected by resting‐state (RS) functional MRI (fMRI) has generated significant interests in neuroscience and clinical studies. We proposed a method for improving the sensitivity of the conventional seed‐ based correlation analysis (SCAC) by incorporating the regional homogeneity information (SCAReHo). The study aimed to analyze DMN connectivity in patients with stenosis of the internal carotid artery (ICA), before and after stenting, and compare the results of SCAC and SCAReHo. Materials and Methods: Nine patients with unilateral ICA stenosis (1 Female; age: 66±7.84y) were scanned twice (before and six months after stenting) at a 3T MRI scanner. A T2*‐weighted single‐shot gradient‐echo EPI sequence was applied for the RS‐fMRI with TR/TE/FA=2000ms/50ms/90° and 150 phases. For SCAC analysis, the correlation coefficients between the reference time course (obtained from the posterior cingulate cortex (PCC) seed region at (0,−51,30) and radius=4mm) and the time course of each voxel were computed across the whole‐brain. For SCAReHo analysis, first Kendall coefficient of concordance (KCC) maps were computed for each subject and then the reference time curve were obtained from the common voxels of a PCC mask and the KCC mask (KCC>0.5). Results: With the SCAC analysis, only few or no voxels in the seed and the DMN regions were detected in most patients. The SCAReHo method significantly improved the detection in all patients. Heterogeneous and bipolar distributions of correlation coefficients were found in the conventional PCC region, which may explain the failure of the SCAC analysis in this patient group. Improvement of FC was found after the treatment with the SCAReHo analysis. Conclusion: The SCAReHo analysis improved the detection of FC in DMN using the RS‐ fMRI. This method may be particular helpful for subject groups with functional anatomy that likely differs from the normal population.