Sub-regional anterior cingulate cortex functional connectivity revealed default network subsystem dysfunction in patients with major depressive disorder.

ObjectivesChildhood trauma (CT) is a known risk factor for major depressive disorder (MDD), but the mechanisms linking CT and MDD remain unknown. The purpose of this study was to examine the influence of CT and depression diagnosis on the subregions of the anterior cingulate cortex (ACC) in MDD patients.MethodsThe functional connectivity (FC) of ACC subregions was evaluated in 60 first-episode, drug-naïve MDD patients (40 with moderate-to-severe and 20 with no or low CT), and 78 healthy controls (HC) (19 with moderate-to-severe and 59 with no or low CT). The correlations between the anomalous FC of ACC subregions and the severity of depressive symptoms and CT were investigated.ResultsIndividuals with moderate-to severe CT exhibited increased FC between the caudal ACC and the middle frontal gyrus (MFG) than individuals with no or low CT, regardless of MDD diagnosis. MDD patients showed lower FC between the dorsal ACC and the superior frontal gyrus (SFG) and MFG. They also showed lower FC between the subgenual/perigenual ACC and the middle temporal gyrus (MTG) and angular gyrus (ANG) than the HCs, regardless of CT severity. The FC between the left caudal ACC and the left MFG mediated the correlation between the Childhood Trauma Questionnaire (CTQ) total score and HAMD-cognitive factor score in MDD patients.ConclusionFunctional changes of caudal ACC mediated the correlation between CT and MDD. These findings contribute to our understanding of the neuroimaging mechanisms of CT in MDD.

Objective To study the resting-state functional connectivity(FC) changes of anterior cingulate cortex(ACC) and amygdala in adolescent patients with medication-naive first-episode major depressive disorder(MDD). Methods Medication-naive first-episode MDD adolescents(n=30) and pair-wise matched healthy controls(HCs, n=29) underwent resting-state functional magnetic resonance images(fMRI). To study whether there were different in FC changes between amygdala and ACC and whole brain regions, and whether abnormal FC was related to clinical characteristics. Results Compared with HCs, the adolescent MDD patients showed decreased FC between the left amygdala and right thalamus(MNI x, y, z: 15, -21, 18)(t=-2.85)and increased FC between the left amygdala and the bilateral temporal middle gyrus, left occipital gyrus, right medial prefrontal cortex(MPFC)(MNI x, y, z: 9, 66, 15)(t=2.80). The right amygdale showed decreased FC with bilateral middle frontal gyrus, left caudate(MNI x, y, z: -15, -9, 21)(t=-2.53), right thalamus(MNI x, y, z: 12, -36, 12)(t=-3.01), right cerebellum(MNI x, y, z: 3, -84, -33)(t=-2.45) and increased FC with right temporal middle gyrus, right MPFC(MNI x, y, z: 6, 69, 12)(t=2.41). The left ACC showed decreased FC with left cerebellum(MNI x, y, z: 12, -87, -24)(t=-2.36), left frontal inferior triangle gyrus, right frontal inferior orbital gyrus and increased FC with right frontal middle orbital gyrus.The right ACC showed decreased FC with left caudate(MNI x, y, z: -15, 21, 6)(t=-2.29), right temporal middle gyrus, right MPFC(MNI x, y, z: 9, 54, 36)(t=-2.29), right frontal inferior orbital gyrus, right angular(MNI x, y, z: 45, -51, 21)(t=-3.01), left dorsolateral prefrontal cortex(MNI x, y, z: -21, 33, 36)(t=-2.61). The increased FC between the left amygdale and bilateral temporal middle gyrus showed positive correlation with the score of HAMD(r=0.50, P<0.05; r=0.45, P<0.05). And the FC between the right amygdale and right middle frontal gyrus was positive correlation with duration of disease(r=0.63, P<0.05). Conclusion There is widespread FC disorder in amygdala and ACC in adolescents patients with first-episode depression.Abnormal FC changes may be the neuropathological mechanism of depression. Key words: Adolescent major depressive disorder; Resting-state fMRI; Functional connectivity; Amygdala; Anterior cingulated cortex

Evidence of a Dissociation Pattern in Resting-State Default Mode Network Connectivity in First-Episode, Treatment-Naive Major Depression Patients

Objective: To study resting-state functional connectivity (FC) of default mode network (DMN) in adolescent patients with first-episode drug-naive major depressive disorder (MDD). Methods: We enrolled thirty first-episode and drug-naive adolescent MDD patients and twenty-nine adolescent healthy control (HC) participants in the First Affiliated Hospital of Zhengzhou University. There were no differences in age, sex, and education between the MDD and HC group. Resting-state functional magnetic resonance images (fMRI) was performed. We selected posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of DMN as regions of interests (ROI). The differences of these regions from the whole brain functional connectivity were analyzed. The relations between abnormalities in FCs of DMN and clinical variables were further investigated. Results: Compared to the HCs, the MDD patients had congruently reduced FCs between the PCC and cerebellum, temporal cortices, occipital cortices, fusiform, dorsolateral prefrontal cortex. MPFC not only had reduced FCs with fusiform, temporal cortices, anterior cingulate cortex, but also had enhanced FCs with occipital cortices, parietal cortices, and precentral gyrus. In addition, the increased FC between the right MPFC and right precentral gyrus was positive correlated with Hamilton Rating Scale for Depression (HAMD) scores (r=0.38, P=0.04). The reduced FC between the left middle temporal gyrus and left PCC as well as the enhanced FC between the right middle cingulum and right MPFC were positive correlated with the duration of depression since onset (r=0.39, P=0.03; r=0.38, P=0.04). Conclusions: These findings show dysfunctional DMN connectivity of adolescent MDD patients. Neurodevelopmental abnormalities in DMN may present in adolescent MDD.

Background: Previous neuroimaging studies have revealed that acupuncture modulates the default mode network (DMN) in healthy subjects and patients with certain disorder. However, few studies have been performed to investigate whether or not acupuncture might modulate the DMN in patients with major depressive disorder (MDD). Thereby, the aim of the present study was to assess alterations of the DMN induced by acupuncture stimulation in patients with first-episode, drug-naïve MDD.Materials and Methods: Twenty nine patients with first-episode, drug-naïve MDD and 29 healthy subjects were enrolled in this study. All the healthy subjects underwent 6-min resting-state functional magnetic resonance imaging (R-fMRI) scan. While patients underwent acupuncture stimulation for 20-min electro-acupuncture stimulation (EAS) at Baihui acupoint (GV20) and two 6-min R-fMRI scans before and after EAS. Based on the precuneus/posterior cingulate cortex (PC/PCC) as the seed region, functional connectivity (FC) method was adopted to examine abnormal DMN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the DMN in patients with MDD.Results: Compared to healthy subjects, MDD patients had abnormal DMN. Moreover, results showed that EAS at GV20 induced increased FC between the PC/PCC and bilateral anterior cingulate cortex (ACC), and decreased FC between the PC/PCC and left middle prefrontal cortex, left angualr gyrus and bilateral hippocampus/parahippocampus (HIPP/paraHIPP) in patients with MDD, which were the main brain regions showing significant differences between the patients and healthy subjects.Conclusion: Our findings provide imaging evidence to support that GV20-related acupuncture stimulation may modulate the DMN in patients with first-episode, drug-naïve MDD. This study may partly interpret the neural mechanisms of acupuncture at GV20 which is used to treat patients with MDD in clinical.

Objective To provide a new approach to further elucidate the underlying pathogenesis of major depressive disorder by using resting-state functional connectivity strengths(FCS) in unmedicated patients with major depressive disorder(MDD). Methods Thirty-three unmedicated patients with MDD and thirty-three normal controls underwent the resting-state functional magnetic resonance imaging(rs-fMRI).After preprocessing of rs-fMRI, the whole brain FCS values were constructed. Two-sample t-test was used to compare the FCS values of both groups to locate the regions with significant change. And correlation analysis was performed between the FCS values extracted from significantly different brain regions and Hamilton Depression Scale (HAMD24) scores. Results One sample t test had shown that high FCS values brain areas (hubs) of MDD patients and normal controls were mainly located in the default mode network (the prefrontal cortex, anterior cingulate gyrus, posterior cingulate gyrus, precuneus/cuneus, angular gyrus) and parietal cortex, lateral temporal cortex as well as occipital cortex. In comparison to the normal controls, the MDD patients had FCS values significantly decreased in the bilateral posterior cerebellar lobe (right posterior cerebellar t=-4.57, P<0.05; left posterior cerebellar t=-3.40,P<0.05), and FCS values increased in the right superior temporal gyrus (t=3.71,P<0.05) and left anterior insular lobe (t=3.91, P<0.05). There were no significant correlations between the HAMD24 scores and the FCS values in right/left posterior cerebellar (r=0.081, P=0.654; r=-0.028, P=0.877), right superior temporal gyrus (r=0.211, P=0.239) and left anterior insular lobe (r=-0.017,P=0.924). Conclusions These findings suggest abnormal functional connectivity in the bilateral posterior cerebellar lobe, right temporal lobe and left insular lobe in MDD. The FCS analysis may be used as a new research method to explore the pathogenesis of MDD. Key words: Depressive disorder; Resting state; Functional connectivity strengths

Modern neuroimaging research has recognized that major depressive disorder (MDD) is a connectome disorder, characterized by altered functional connectivity across large-scale brain networks. However, the clinical heterogeneity, likely stemming from diverse neurobiological disturbances, complicates findings from standard group comparison methods. This variability has driven the search for MDD subtypes using objective neuroimaging markers. In this study, we sought to identify potential MDD subtypes from subject-level abnormalities in functional connectivity, leveraging a large multi-site dataset of resting-state MRI from 1276 MDD patients and 1104 matched healthy controls. Subject-level extreme functional connections, determined by comparing against normative ranges derived from healthy controls using tolerance intervals, were used to identify biological subtypes of MDD. We identified a set of extreme functional connections that were predominantly between the visual network and the frontoparietal network, the default mode network and the ventral attention network, with the key regions in the anterior cingulate cortex, bilateral orbitofrontal cortex, and supramarginal gyrus. In MDD patients, these extreme functional connections were linked to age of onset and reward-related processes. Using these features, we identified two subtypes with distinct patterns of functional connectivity abnormalities compared to healthy controls (p < 0.05, Bonferroni correction). When considering all patients together, no significant differences were found. These subtypes significantly enhanced case-control discriminability and showed strong internal discriminability between subtypes. Furthermore, the subtypes were reproducible across varying parameters, study sites, and in untreated patients. Our findings provide new insights into the taxonomy and have potential implications for both diagnosis and treatment of MDD.

BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.MethodsWe examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.ResultsWe demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.ConclusionsWe demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

Decreased functional connectivity in patients with major depressive disorder and a history of childhood traumatization through experiences of abuse

Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex

Background: Major depressive disorder (MDD) is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS) to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS) in the treatment of MDD respond to rTMS, and whether functional connectivity (FC) measures can predict clinical response.Methods: rTMS (20 sessions) was administered to five MDD patients at the left-dorsolateral prefrontal cortex (L-DLPFC) over 4 weeks. Magnetoencephalography (MEG) recordings and Montgomery-Asberg depression rating scale (MADRS) assessments were acquired before, during and after treatment. Our primary measures, obtained with MEG source imaging, were changes in power spectral density (PSD) and changes in FC as measured using coherence.Results: Of the five patients, four met the clinical response criterion (40% or greater decrease in MADRS) after 4 weeks of treatment. An increase in gamma power at the L-DLPFC was correlated with improvement in symptoms. We also found that increases in delta band connectivity between L-DLPFC/amygdala and L-DLPFC/pregenual anterior cingulate cortex (pACC), and decreases in gamma band connectivity between L-DLPFC/subgenual anterior cingulate cortex (sACC), were correlated with improvements in depressive symptoms.Conclusions: Our results suggest that non-invasive intervention techniques, such as rTMS, modulate the ongoing activity of depressive circuits targeted for DBS, and that MEG can capture these changes. Gamma oscillations may originate from GABA-mediated inhibition, which increases synchronization of large neuronal populations, possibly leading to increased long-range FC. We postulate that responses to rTMS could provide valuable insights into early evaluation of patient candidates for DBS surgery.

BackgroundMild behavioral impairment (MBI) is a syndrome that uses later‐life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting‐state functional magnetic resonance imaging (rs‐fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI–).MethodsFrom two harmonized dementia‐free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI– individuals were identified (mean age: 71.7 years; 54.7% female). Seed‐based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p‐value of .05 considered significant.ResultsFor the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI–. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula.ConclusionMBI in dementia‐free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers.HighlightsResting‐state functional magnetic resonance imaging was completed in 95 dementia‐free persons from FAVR and COMPASS‐ND studies.Participants were stratified by informant‐rated Mild Behavioral Impairment Checklist (MBI‐C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early‐stage Alzheimer's disease.MBI may help identify persons with early‐stage neurodegenerative disease.

Childhood abuse and cortical gray matter volume in patients with major depressive disorder

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.