[Anatomic Abnormalities of Hippocampal Subfields in First-Episode Drug-Naïve Schizophrenia and Major Depressive Disorder: A Structural MRI Comparative Study].

Objective: To compare the structural changes along the longitudinal axis of hippocampus subfields between schizophrenia (SCZ) patients and major depressive disorder (MDD) patients in the early stage of their SCZ and MDD. Methods: Seventy-nine first-episode drug-naïve patients with SCZ, 48 first-episode drug-naïve patients with MDD, and 79 healthy controls (HC) were recruited and underwent assessment of clinical symptoms and magnetic resonance imaging (MRI) of the head. Following the calculation of hippocampal and subfield volumes with FreeSurfer, the volume of longitudinal subfields were summed up. Inter-group comparison of these indicators was made with the data of different groups and the correlation between clinical symptoms and the volumes of longitudinal subfields was analyzed. Results: Compared with HC, SCZ patients had smaller bilateral posterior hippocampus (left: t=－2.69, P=0.01; right: t=－2.90, P=0.004), while MDD patients exhibited no changes along the longitudinal axis of hippocampal subfields. In SCZ patients, the volume of bilateral posterior hippocampus was negatively correlated with the negative symptom scores of Positive and Negative Syndrome Scale (left: r=－0.29, P=0.01; right: r=－0.23, P=0.04). Conclusion: The smaller posterior hippocampus may be an imaging feature for distinguishing SCZ from MDD and may have contributed to the neuropathophysiological mechanism of SCZ in the early stage of the onset of the disease.

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study.

OBJECTIVES: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr. METHODS: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. RESULTS: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. DISCUSSION: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

NSCs promote hippocampal neurogenesis, metabolic changes and synaptogenesis in APP/PS1 transgenic mice.

Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12-month-old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H-MRS). The results showed that N-acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg-NSC mice compared with the Tg-PBS and Tg-AD mice 10 weeks after NSCs transplantation. NSC-induced an increase in expression of synaptophysin and postsynaptic protein-95, and the number of neurons with normal synapses was significantly increased in Tg-NSC mice. More doublecortin-, BrdU/NeuN- and Nestin-positive neurons were observed in the hippocampal DG and SVZ of the Tg-NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H-MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H-MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging.

BACKGROUND: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. METHODS: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. RESULTS: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. LIMITATIONS: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. CONCLUSION: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. METHODS: We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners' Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. RESULTS: Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. LIMITATIONS: This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. CONCLUSION: Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. METHODS: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. LIMITATIONS: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

Proton magnetic resonance spectroscopy revealed differences in the glutamate + glutamine/creatine ratio of the anterior cingulate cortex between healthy and pediatric post-traumatic stress disorder patients diagnosed after 2008 Wenchuan earthquake.

AIMS: Earthquakes always leave many surviving teenagers suffering from various mental problems, such as post-traumatic stress disorder (PTSD). We studied the metabolites in current and remitted pediatric PTSD patients and healthy controls after an earthquake, aiming to find the neurochemistry differences in these teenagers. METHODS: Proton magnetic resonance spectroscopy ((1) H-MRS) was performed in the anterior cingulate cortex (ACC) of 21 healthy, 10 PTSD and 23 remitted subjects. RESULTS: Significantly lower glutamate + glutamine/creatine (Glx/Cr) levels in the ACC (1.15 ± 0.14 vs 1.37 ± 0.08, P = 0.047) were found in PTSD subjects relative to remitted subjects; and significantly lower Glx/Cr levels in the ACC (1.37 ± 0.08 vs 1.59 ± 0.10, P = 0.045) were found in remitted subjects relative to healthy controls. CONCLUSIONS: Our findings imply that the Glx/Cr ratio in the ACC can be used to differentiate not only between healthy and pediatric PTSD patients, but also between the current and remitted phases of pediatric PTSD. The changes in the Glx/Cr ratio may be caused by brain dysfunction in the current phase and recovery in the remitted phase.

Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors.

A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors.

Brain structural plasticity in survivors of a major earthquake.

BACKGROUND: Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. METHODS: Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13-25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. RESULTS: We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). LIMITATIONS: Differences in the variance of survivor and control data could impact study findings. CONCLUSION: Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal-limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.

Resting-state fMRI study of treatment-naïve temporal lobe epilepsy patients with depressive symptoms.

BACKGROUND: Patients with temporal lobe epilepsy are at high risk for comorbid depression, and it is hypothesized that these two diseases are share common pathogenic pathways. We aimed to characterize regional brain activation in treatment-naïve temporal lobe epilepsy patients with depressive symptoms and compare the results to epilepsy patients without depressive symptoms and to healthy controls. SUBJECTS AND METHODS: We recruited 23 treatment-naïve patients (including anti-epilepsy drugs (AEDs) and antidepressants) and 17 matched healthy controls for this study. The patients were further divided into two groups: patients with depressive symptoms and patients without; the patients then used a self-rating depression scale (SDS) to assess their depression. All participants underwent resting functional magnetic resonance imaging (fMRI) scans using the Trio Tim magnetic resonance (MR) image system (3.0 T). The data were processed and analyzed using REST and SPSS11.5 software. RESULTS: The patients with depressive symptoms showed significantly higher activity in the bilateral thalamus, insula and caudate and right anterior cingulate compared with the two other groups (p<0.05, corrected). Brain network connectivity analysis revealed that connectivity decreased in the prefrontal-limbic system and increased within the limbic system and angular gyrus in patients with depressive symptoms (p<0.05, corrected). CONCLUSION: The epilepsy patients with depressive symptoms showed regional brain activity alterations and disruption of the mood regulation network at the onset of seizures. The present study offers further insight into the underlying neuropathophysiology of epilepsy with depressive symptoms.

Diffusion tensor imaging characterization of occult brain damage in relapsing neuromyelitis optica using 3.0T magnetic resonance imaging techniques.

Studies of relapsing neuromyelitis optica (RNMO) using advanced MRI techniques are limited compared with those done on multiple sclerosis (MS). The present study used diffusion tensor imaging (DTI) to investigate whether occult brain damage exists in RNMO patients. DTI scans using a 3.0T MRI scanner were performed in 24 clinically confirmed RNMO patients whose conventional brain MRI results were normal, and also in 24 age- and sex-matched healthy control subjects. DTI data were processed to generate fractional anisotropy (FA) and mean diffusivity (MD) maps, and region of interest (ROI) analyses were performed to obtain these parameters in white matter (including medulla oblongata, cerebral peduncle, optic radiation, genu of corpus callosum, splenium of corpus callosum, and internal capsule) and gray matter (including thalamus and putamen). Regional measures from patients at stable and acute phases were compared with healthy controls. Both acute and stable NMO patients had a higher average FA in ROIs of the thalamus and putamen. Acute NMO patients had significantly higher average MDs than controls in the genu of corpus callosum and optic radiation, and significantly lower average MDs in the medulla oblongata. Stable NMO patients had increased MDs in the genu of corpus callosum and optic radiation, but lower MDs in the medulla oblongata, internal capsule and thalamus. The DTI findings confirm the presence of occult tissue damage in normal-appearance white and gray matter, especially deep gray matter, in RNMO patients. This study adds further to the evidence that DTI is suitable as a tool for characterizing subtle brain tissue damage.

Longitudinal ¹H MRS assessment of the thalamus in a Coriaria lactone-induced rhesus monkey status epilepticus model.

Neurophysiological, biochemical and anatomical evidence implicates the thalamus as playing a role in epileptic seizures. Until recently, however, longitudinal characterization of in vivo thalamus dynamics had not been reported. In this study, we investigated the metabolism in the thalamus to identify the changes that occur following Coriaria lactone (CL)-induced status epilepticus (SE) and to observe whether the epileptiform discharges could present a difference between the left and right thalami. Five rhesus monkeys underwent whole-brain MRI and single-voxel MRS on a Siemens Trio Tim 3-T MR scanner with a 12-channel head coil. Spectra were processed using LCModel. Scans were performed in five animals before SE and at 1, 7, 21 and 42 days after the onset of SE. Statistical analysis of the data obtained demonstrated no significant difference in the bilateral thalamus of healthy macaques. Our MRS data showed symmetrical distributions of N-acetylaspartate in the right and left thalami after SE (p = 0.003). In addition, this longitudinal study demonstrated elevated glutamate/glutamine (p < 0.05) and reduced myo-inositol (p < 0.05) in the bilateral thalamus 1 day after SE, and all metabolites approached their baseline levels by the fifth scan. Our results demonstrate that metabolic changes occur in the thalamus during CL-induced SE in rhesus monkeys. The various metabolic changes may indicate that the left thalamus is more vulnerable to epileptic strike.

Gray matter atrophy in behavioral variant frontotemporal dementia: a meta-analysis of voxel-based morphometry studies.

BACKGROUND: Structural neuroimaging studies on behavioral variant frontotemporal dementia (bvFTD) using the voxel-based morphometry (VBM) method reported not entirely consistent findings. METHODS: A systematic review of VBM studies of bvFTD patients and healthy controls (HC) published in PubMed and Embase databases from 2000 to June 2011 was conducted. Meta-analysis was performed using a newly improved voxel-based meta-analytic tool, namely, effect size signed differential mapping, to quantitatively explore the gray matter (GM) changes between bvFTD patients and HC subjects. RESULTS: 11 VBM studies involving 237 bvFTD patients and 297 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the anterior medial frontal cortex (BA 9), extending to other frontal areas (BA 8, 10, 46, 24, 32), and other brain areas, such as the insula cortex, as well as the subcortical striatal regions in patients with bvFTD compared with HC subjects. The findings of the present study remain largely unchanged in the entire brain jackknife sensitivity analyses. CONCLUSIONS: The present meta-analysis provides evidence of GM changes in the frontal-striatal-limbic brain areas in patients with bvFTD. Furthermore, GM atrophy in the fron-toinsular cortex and anterior cingulate cortex may be important anatomical changes for the diagnosis of patients with bvFTD.

Facial perception bias in patients with major depression.

This study used a morphed categorical perception facial expression task to evaluate whether patients with depression demonstrated deficits in distinguishing boundaries between emotions. Forty-one patients with depression and 41 healthy controls took part in this study. They were administered a standardized set of morphed photographs of facial expressions with varying emotional intensities between 0% and 100% of the emotion, in 10% increments to provide a range of intensities from pleasant to unpleasant(e.g. happy to sad, happy to angry) and approach-avoidance (e.g. angry to fearful). Compared with healthy controls, the patients with depression demonstrated a rapid perception of sad expressions in happy-sad emotional continuum and demonstrated a rapid perception of angry expressions in angry-fearful emotional continuum. In addition, when facial expressions shifted from happy to angry, the depressed patients had a clear demarcation for the happy-angry continuum. Depressed patients had a perceptual bias towards unpleasant versus pleasant expressions and the hypersensitivity to angry facial signals might influence the interaction behaviors between depressed patients and others.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI.

Treatment-refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting-state functional MRI (rs-fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment-refractory (NDD) as comparison groups. Results were analyzed using a data-driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo-limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities.