Default Mode Network Functional Connectivity Research Articles

Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression

BackgroundFunctional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD. MethodsWe collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13–17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level–dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset. ResultsRelative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC–subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset. ConclusionsAdolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.

Resting state brain default network in patients with motor aphasia resulting from cerebral infarction

To explore the brain default mode network (DMN) in patients with motor aphasia resulting from cerebral infarction, we used resting state functional magnetic resonance imaging (fMRI) to investigate the possible neural mechanism. Thirteen patients with motor aphasia resulting from cerebral infarction and ten matched controls were selected in this study. All subjects were examined using resting state fMRI. We chose the posterior cingulate cortex as the region of interest and then used functional connectivity analysis to calculate the DMN functional connectivity and analyze differences in the functional connectivity between the two groups. Compared with normal controls, aphasia patient group showed a significantly decreased functional connectivity in bilateral medial frontal gyrus, superior frontal gyrus, middle frontal gyrus, middle temporal gyrus, precuneus and cuneus. The aphasia patient group showed increased functional connectivity mainly in bilateral medial frontal gyrus, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula. The DMN in cerebral infarction motor aphasia patients showed significantly decreased functional connectivity in the resting state. The DMN most likely plays an important role in motor aphasia resulting from cerebral infarction. Furthermore, functional connectivity in the brain regions surrounding the left and right Broca’s areas was significantly enhanced due to compensatory mechanisms. This may be helpful for the recovery of language function in cerebral infarction patients with motor aphasia.

Recognition memory is associated with altered resting‐state functional connectivity in people at genetic risk for Alzheimer's disease

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80 years old), of which 20 carried the ε4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing.

Abnormal Functional Brain Connectivity and Personality Traits in Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Biological vulnerability to depression: linked structural and functional brain network findings

Patients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD. To test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities. A multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy controls. The MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus). This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.

Longitudinal assessment of default-mode brain function in aging

Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49–79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.

A potential ethnic difference in the association between 5-HTTLPR polymorphisms and the brain default mode network

The serotonin-transporter-linked polymorphic region (5-HTTLPR) is associated with mood disorders. This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced frontal cortical control. In Caucasians, the short form is associated with this effect, but in Han Chinese we recently found that the long form is involved. Serotonin receptors have rich expression in default mode network (DMN) regions and the recent studies have found an association between the short form of the 5-HTTLPR and DMN functional connectivity (FC) in Caucasians. The present study has investigated whether there may also be an ethnic difference in this influence of 5-HTTLPR on the DMN. We recruited 233 young Han Chinese subjects and calculated the resting-state default-network FC. Our study found that the L carriers had decreased FC in the bilateral medial prefrontal cortex, right parahippocampal gyrus, left middle temporal gyrus, and increased FC in left precuneus (Pcu) compared to SS. The PCC-Pcu FC in L carriers was significantly negatively correlated with the depression scores. Our findings, therefore, suggest that there is also a difference between Caucasian and Han Chinese subjects in the association between the different forms of the 5-HTTLPR and DMN functional connectivity.

Aberrant Default-Mode Functional Connectivity in Patients with End-Stage Renal Disease: A Resting-State Functional MR Imaging Study

To investigate the functional connectivity of the default-mode network (DMN) in patients with end-stage renal disease (ESRD) by using independent component analysis of resting-state functional magnetic resonance (MR) imaging and to correlate these DMN connectivity changes with neuropsychological test results and clinical biomarkers. Medical research ethics committee approval and written informed consent were obtained. Forty-six patients with ESRD, including 22 with minimal nephrotic encephalopathy (MNE) and 24 without nephrotic encephalopathy, and 23 healthy control subjects underwent resting-state functional MR imaging. All patients were asymptomatic and without history of neurologic or psychiatric disease. Independent component analysis was used to isolate the DMN. To display the voxels that contributed most strongly to an independent component, the intensity values in each spatial map were converted to z scores, which indirectly provided a measurement of functional connectivity in the DMN. Maps of the DMN were compared among the groups. Pearson correlation analysis was performed to correlate abnormal DMN functional connectivity with serum urea, creatinine, duration of dialysis, duration of disease, and neuropsychological test scores. Patients with ESRD showed significantly less functional connectivity in the posterior cingulate cortex, precuneus, and medial prefrontal cortex (MPFC) (P < .01) than did control subjects. Comparison of the two patient groups showed significantly reduced functional connectivity in the superior and MPFC in the MNE group (P < .01). The functional connectivity of the MPFC was positively correlated with digital symbol test score (R = 0.293, P = .048). Serum creatinine level was negatively correlated with functional connectivity of the posterior cingulate cortex and precuneus in patients with ESRD (R = -0.51, P = .002). Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.

Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders.

Cerebral White Matter Integrity and Resting-State Functional Connectivity in Middle-aged Patients With Type 2 Diabetes

Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We examined whether middle-aged type 2 diabetic patients show reduced white matter integrity in fiber tracts important for cognition and whether this abnormality is related to preestablished altered resting-state functional connectivity in the default mode network (DMN). Diabetic and nondiabetic participants underwent diffusion tensor imaging, functional magnetic resonance imaging, and cognitive assessment. Multiple diffusion measures were calculated using streamline tractography, and correlations with DMN functional connectivity were determined. Diabetic patients showed lower fractional anisotropy (FA) (a measure of white matter integrity) in the cingulum bundle and uncinate fasciculus. Control subjects showed stronger functional connectivity than patients between the posterior cingulate and both left fusiform and medial frontal gyri. FA of the cingulum bundle was correlated with functional connectivity between the posterior cingulate and medial frontal gyrus for combined groups. Thus, middle-aged patients with type 2 diabetes show white matter abnormalities that correlate with disrupted functional connectivity in the DMN, suggesting that common mechanisms may underlie structural and functional connectivity. Detecting brain abnormalities in middle age enables implementation of therapies to slow progression of neuropathology.

Linking DMN connectivity to episodic memory capacity: what can we learn from patients with medial temporal lobe damage?

Computational models predict that focal damage to the Default Mode Network (DMN) causes widespread decreases and increases of functional DMN connectivity. How such alterations impact functioning in a specific cognitive domain such as episodic memory remains relatively unexplored. Here, we show in patients with unilateral medial temporal lobe epilepsy (mTLE) that focal structural damage leads indeed to specific patterns of DMN functional connectivity alterations, specifically decreased connectivity between both medial temporal lobes (MTLs) and the posterior part of the DMN and increased intrahemispheric anterior–posterior connectivity. Importantly, these patterns were associated with better and worse episodic memory capacity, respectively. These distinct patterns, shown here for the first time, suggest that a close dialogue between both MTLs and the posterior components of the DMN is required to fully express the extensive repertoire of episodic memory abilities.

White matter lesion load is associated with resting state functional MRI activity and amyloid PET but not FDG in mild cognitive impairment and early Alzheimer's disease patients.

To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [(18)F]-Florbetapir tracer and metabolism of glucose by means of [(18)F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). Whole-brain WMLL and amyloid deposition were significantly higher (P < 0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P < 0.05) DMN connectivity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P < 0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. Our quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Significant correlations between MRI metrics, including WMLL/functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD.

Plastic modulation of PTSD resting‐state networks and subjective wellbeing by EEG neurofeedback

Electroencephalographic (EEG) neurofeedback training has been shown to produce plastic modulations in salience network and default mode network functional connectivity in healthy individuals. In this study, we investigated whether a single session of neurofeedback training aimed at the voluntary reduction of alpha rhythm (8-12 Hz) amplitude would be related to differences in EEG network oscillations, functional MRI (fMRI) connectivity, and subjective measures of state anxiety and arousal in a group of individuals with post-traumatic stress disorder (PTSD). Twenty-one individuals with PTSD related to childhood abuse underwent 30 min of EEG neurofeedback training preceded and followed by a resting-state fMRI scan. Alpha desynchronizing neurofeedback was associated with decreased alpha amplitude during training, followed by a significant increase ('rebound') in resting-state alpha synchronization. This rebound was linked to increased calmness, greater salience network connectivity with the right insula, and enhanced default mode network connectivity with bilateral posterior cingulate, right middle frontal gyrus, and left medial prefrontal cortex. Our study represents a first step in elucidating the potential neurobehavioural mechanisms mediating the effects of neurofeedback treatment on regulatory systems in PTSD. Moreover, it documents for the first time a spontaneous EEG 'rebound' after neurofeedback, pointing to homeostatic/compensatory mechanisms operating in the brain.

The ages of anxiety—differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder

Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders, but its neural basis is relatively understudied. This study aims to characterize the functional connectivity in the default mode network (DMN) in GAD across the lifespan. Functional and structural magnetic resonance imaging data were collected with subjects at rest. We analyzed the resting state functional connectivity patterns in the DMN for 27 GAD participants and 39 non-anxious comparison participants. Using a two-way analysis of variance, we explored the interaction between age and GAD status on functional connectivity. In GAD participants, we analyzed the correlation of functional connectivity indices with the duration of illness and worry severity. The age-by-anxiety interaction showed a greater anxiety effect on the functional connectivity between the posterior cingulate seed and the medial prefrontal cortex for the older group relative to the younger participants. Longer duration of illness was positively correlated with greater functional connectivity between the posterior cingulate cortex and the insula. Worry severity was inversely correlated with the functional connectivity between the posterior cingulate cortex seed and the medial prefrontal cortex. The presence of GAD, longer duration of illness, and more severe worry exacerbate the effects of age on the functional connectivity in the DMN. These results support the need for tailored research and interventions in late-life anxiety.

Altered functional connectivity of the default mode network in diffuse gliomas measured with pseudo-resting state fMRI

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III–IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity.

Resting state functional connectivity and treatment response in late-life depression

Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment “frontalization” of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.

P.1.i.030 Default mode network functional connectivity in patients with temporal lobe epilepsy and comorbid depressive and anxiety symptoms

Background: The resting-state networks (RSNs) are sets of biological neuronal ensembles, demonstrating a synchronized low frequency BOLD (Blood Oxygenation Level Dependent) signal fluctuations (<0.08−0.1Hz). The Default Mode Network (DMN) is a RSN that is active when an individual is not focused on the outside world and the brain is at wakeful rest. It has been shown that DMN is involved in emotional processing and may play a significant role in the origin of affective symptoms. Affective symptoms (depression and anxiety) are common in temporal lobe epilepsy and DMN functional connectivity (FC) have been found to be altered in patients with this pathology. Aim: To investigate FC in TLE patients with and without comorbid anxiety-depressive symptoms. Materials and Methods: 28 patients with TLE, confirmed by EEG, aged between 18 and 50, without any significant brain alterations and history of other psychiatric disorders were included in this study. Affective symptoms were assessed during comprehensive psychiatric interview. Beck Depression Inventory, Hospital Anxiety Depressive Scale, Hamilton Anxiety Scale and Montgomery-Asberg Depressive Rating Scale were additionally used to quantify symptom severity. All subjects underwent routine MRI procedure and 9-min resting-state fMRI scanning session, during which they were asked to keep their eyes closed. The images were processed and analyzed using SPM8 and ‘GIFT’ toolbox. Independent component analysis was used to isolate DMN. The resulted maps were compared in groups using one-way ANOVA with post-hoc pairwise comparisons. The results were considered as statistically significant according to threshold of p< 0.005 with a 10-voxel cluster size [1]. Results: All patients were divided into three groups: patients with current affective symptoms and left-sided epileptic focus (left-sided ‘affective’ group (LSAG), n = 18), patients with current affective symptoms and right-sided focus (right-sided ‘affective’ group (RSAG), n = 18), and patients without affective symptoms (‘non-affective’ group (NAG), n = 18). In both groups with affective symptoms, a moderate level of depressive and anxiety symptoms was found, with higher ‘anxiety’ score in LSAG and higher ‘depressive’ score and ‘dysphoric’ symptoms in RSAG. ANOVA revealed significant group differences in the left insula, superior parietal and left frontal cortex. Post-hoc analysis identified increased FC in the right precuneus, parahippocampal and frontal cortex in RSAG compared to NAG. Higher FC in LSAG group demonstrated higher FC in the left insular and parietal cortex compared to RSAG. Conclusions: Increased insular and frontal FC, observed in LSAG, may determine more severe anxiety symptoms in this group. The results are consistent with the data from recent studies, indicating higher anxiety level in patients with left-sided epileptic focus localization. Increased FC in the right precuneus, parahippocampal and frontal area in RSAG may explain the presence of depressive symptoms in this groups and their association with impaired self-control and self-awareness. To finalize, TLE can be considered as a good model to investigate mechanisms underlying anxiety and depression not only in epilepsy, but also in many other neurological and psychiatric disorders.

Resting-State Functional Magnetic Resonance Imaging Analysis with Seed Definition Constrained by Regional Homogeneity

Researchers have recently focused their attention on the intrinsic functional connectivity (FC) in the brain using resting-state functional magnetic resonance imaging. Seed-based correlation analysis (SCAC), which correlates a predefined seed region with other voxels in the brain, is a common index for FC. However, definition of seed sizes and locations was ambiguous in previous studies and this may lead to spurious results for people with a unique functional anatomy. To address this issue, this study proposes a novel method (SCAReHo) that provides a data-driven seed selection (including sizes and locations) method by incorporating regional homogeneity (ReHo) in the SCAC method. The disparities between SCAC and SCAReHo methods among 12 healthy participants were evaluated in the FC of default mode network (DMN), task-positive network (TPN), and amygdala network. The SCAReHo method bypasses the seed-selection ambiguity and enhances the sensitivity in detecting FC of the DMN, TPN, and amygdala network. This study suggests that the SCAReHo method improves the sensitivity of FC analysis and reduces the uncertainty of seed selection. Thus, this method may be particularly useful for psychiatric and neurological investigations.

Impaired default network functional connectivity in autosomal dominant Alzheimer disease

To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.

Age-dependent default mode network functional connectivity in individuals with Down syndrome

Age-dependent default mode network functional connectivity in individuals with Down syndrome