Multi-modal MRI measures reveal sensory abnormalities in major depressive disorder patients: A surface-based study

The hippocampus has been widely reported to be involved in the neuropathology of major depressive disorder (MDD). All the previous researches adopted group-level hippocampus subregions atlas to investigate abnormal functional connectivities in MDD in absence of capturing individual variability. In addition, the molecular basis of functional impairments of hippocampal subregions in MDD remains elusive. We aimed to reveal functional disruptions and recovery of individual hippocampal subregions in MDD patients before and after ECT and linked these functional connectivity differences to transcriptomic profiles to reveal molecular mechanism. we used group guided individual functional parcellation approach to define individual subregions of hippocampus for each participant. Resting-state functional connectivity (FC) analysis of individual hippocampal subregions was conducted to investigate functional disruptions and recovery in MDD patients before and after ECT. Spatial association between functional connectivity differences and transcriptomic profiles was employed to reveal molecular mechanism. MDD patients showed increased FCs of the left tail part of hippocampus with dorsolateral prefrontal cortex and middle temporal gyrus while decreased FC with primary visual cortex. These abnormal FCs in MDD patients were normalized after ECT. In addition, we found that functional disruptions of the left tail part of hippocampus in MDD were mainly related to synaptic signaling and transmission, ion transport, cell-cell signaling and neurogenesis. Our findings provide initial evidence for functional connectome disruption of individual hippocampal subregions and their molecular basis in MDD.

BackgroundEarly mild cognitive impairment (EMCI) represents a prodromal stage of dementia, and early detection is crucial for delaying dementia progression. However, accurately identifying its neuroimaging features remains challenging.ObjectiveTo comprehensively evaluate structural and functional neuroimaging changes in EMCI using multimodal magnetic resonance imaging (MRI) techniques.MethodsOne hundred and eleven participants were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 36 with cognitively normal (CN), 30 with EMCI, 32 with late mild cognitive impairment (LMCI), and 13 with Alzheimer's disease (AD). FreeSurfer software was employed to segment hippocampal and amygdala subregions. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity were processed using Data Processing & Analysis for Brain Imaging toolbox. Graph Theoretical Network Analysis toolbox was utilized to evaluate global functional network.ResultsThe volume of most hippocampal and amygdala subregions was decreased in AD group than those of EMCI group in structural MRI. Significant differences were found between EMCI and AD group in fALFF (right insula) and ReHo (bilateral caudate regions). EMCI group exhibited stronger functional connectivity between left hippocampus and right inferior temporal gyrus (compared to CN), left inferior temporal gyrus (compared to LMCI), and cerebellum crus 8 (compared to AD). EMCI group exhibited stronger connectivity between right hippocampus and left anterior cingulate gyrus compared to AD. Network metrics showed no significant differences among these groups, but all exhibited small-world properties.ConclusionsMultimodal MRI analysis revealed the neuroimaging characteristics of EMCI and promoted the understanding of the mechanisms underlying neuroimaging changes in EMCI.

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

We examined the functional connectivity of subcallosal cingulate gyrus (SCG), nucleus accumbens (NAc), and ventral caudate (VCa), the main target areas for the treatment of major depression disorder (MDD), using deep brain stimulation (DBS). MDD is one of the most common diseases in the world, and approximately 30% of MDD patients do not respond to common therapies, including psychotherapy and antidepressant medications. Alternatively, DBS has been recently used to treat MDD. Resting state fMRI was obtained from seventeen healthy subjects and seven MDD patients. The functional connectivity network of the brain was constructed for all subjects and measured by the `degree' value for each SCG, NAc, and VCa regions using the graph theory analysis. The results show that the degree values of VCa and the left SCG are higher in the MDD group than the healthy group. Furthermore, the patterns of the degree values were different for the right and left hemispheres in MDD patients. Our findings suggest that degree values and their patterns have a potential to be used as diagnosis tools to detect the brain areas with abnormal functional connectivity.

Haematological markers of inflammation in major depressive disorder (MDD) patients with suicidal behaviour: A systematic review and meta-analysis.

The impacts of anhedonia on brain functional alterations in patients with major depressive disorder: A resting-state functional magnetic resonance imaging study of regional homogeneity

Inflammation-related abnormal dynamic brain activity correlates with cognitive impairment in first-episode, drug-naïve major depressive disorder

Background: Major depressive disorder (MDD) patients are often associated with inhibition deficits in the visual cortex. Most previous research has focused on visual inhibition in MDD patients during acute and remission phases, with little research on first-episode and drug-naïve (FEDN) patients. To fill this gap, we psychophysically investigated the inhibitory process of visual motion in patients with FEDN MDD. Methods: Two psychophysical tasks: Center-Surround Suppression (CSS) and Motion Repulsion (MR) were utilized to investigate the presence of visual perceptual inhibition deficits in patients with FEDN MDD. We collected data from 74 patients with FEDN MDD and 68 healthy controls (HCs) matched for age, years of education, and gender. We also measured the Hamilton Depression Rating Scale, 17-item (HAMD-17) for each patient to assess the severity of depressive symptoms. Results: The results showed that CSS was significantly deteriorated in FEDN MDD patients (p=0.001), but it did not correlate with the HAMD score (p > 0.05). In addition, no significant differences were observed between the two groups of subjects in terms of gender, age, and education level (all p > 0.05). Analysis of two previously published datasets using the same CSS task involving MDD patients in different illness stages revealed that the levels of CSS reduction in our FEDN patients were also significantly distinguishable from those in acute and recovered MDD patients (all p < 0.01). This quantitative comparison indicates that CSS impairments are dynamic over the course of illness development. Moreover, the magnitudes of MR showed no significant differences between MDD patients and HCs (all p > 0.05). Conclusions: Our study was the first to demonstrate the deteriorated CSS in patients with FEDN MDD. Notably, inhibitory deficits in MDD are also highly specific, as MDD affects only the CSS, but not the MR. Therefore, the discrepancy between these two psychophysical tasks suggests CSS may serve as a feasible early marker in MDD. These findings offer new insights into the specific visual cortical deficits in patients with FEDN MDD. Limitation: The current study lacks imaging data to support the perceptual phenomenon we observed.

Amygdala is an important locus of dysfunction implicated in major depressive disorder(MDD). Aberrant amygdala networks(AN) had been reported in resting-state functional magnetic resonance imaging (rs-fMRI) study. The safety and efficacy of acupuncture treatment for MDD have been verified in previous clinical studies. This study is aimed to investigate whether acupuncture at GV20 could modulate the abnormal AN of patients with the first-episode, drug-naïve MDD by using rs-fMRI combined with functional connectivity (FC) method. Thirty MDD patient underwent 6-min rs-fMRI scans respectively before and after 20-min electro-acupuncture stimulate(EAS) at GV20. Twenty-nine healthy subjects underwent only a 6-min rs-fMRI scan. Based on the amygdala as the seed region, FC method was adopted to examine abnormal AN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the AN in patients with MDD. Compared to healthy subjects, MDD patients had aberrant intrinsic AN which mainly showed increased FC between amygdala and hippocampus, precuneus, precentral gyrus and angular gyrus, as well as decreased FC between amygdala and orbital frontal cortex(OFC). Moreover, our results indicated that EAS at GV20 induced increased/decreased FC between amygdala and certain regions in MDD patients. In addition, the intrinsic amygdala FC within other certain brain regions in MDD patients were regulated by EAS at GV20. The abnormal AN of MDD patients could be modulated by EAS at GV20. Our findings may further provide the potential imaging evidence to support the modulatory mechanisms of acupuncture on MDD.

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.

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.

Biogenetic temperament and character in insomnia and depression

Major depressive disorder (MDD) is one of the most common affective disorders which ranks among the top causes of worldwide disease burden and disability. Recent studies suggested that MDD resulted in the functional connectivity alteration in the resting state brain networks, such as the emotional circuit and the default mode network (DMN). In addition to these emotion-relevant networks, some other brain regions, such as cuneus gyrus, lingual gyrus and precuneus gyrus, were reported that the activity reduced while performing cognitive tasks. In this study, we examined three networks, i.e. the emotional circuit, the default mode network, and the whole brain network, derived from resting-state functional magnetic resonance imaging (fMRI) to investigate the difference between MDD patients and normal subjects. Furthermore, we explored whether there is another network affected by MDD. The functional MRI data was acquired from 22 healthy subjects and 20 patients with MDD. All images of each subject were parcellated into 90 cortical and sub-cortical regions which were defined as the nodes of the network. The functional relations between the 90 regions were estimated by the time-frequency normalized mutual information (TFNMI). We found that the functional connectivity between any pair of brain regions within each of the three networks was significantly decreased in MDD group by using the t test. The significantly decreased connectivity for MDD in emotional circuit was found in the frontal lobe and between the frontal cortex and limbic regions, and that in DMN exhibited between the frontal cortex and superior temporal cortex. However, in the whole brain network, the most significantly decreased connectivity was revealed in occipital lobe, parietal-occipital, and frontal-occipital regions. Our findings suggested that the functional brain network affected by MDD comprised not only the frontal and limbic regions but also the parts of the parietal and occipital lobe.

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