Dataset Information

Ultra-High-Resolution Imaging of Amygdala Subnuclei Structural Connectivity in Major Depressive Disorder.

ABSTRACT:

Background

Major depressive disorder (MDD) is an increasingly common and disabling illness. As the amygdala has been reported to have pathological involvement in mood disorders, we aimed to investigate for the first time potential changes to structural connectivity of individual amygdala subnuclei in MDD using ultra-high-field 7T diffusion magnetic resonance imaging.

Methods

Twenty-four patients with MDD (11 women) and 24 age-matched healthy control participants (7 women) underwent diffusion-weighted imaging with a 1.05-mm isotropic resolution at 7T. Amygdala nuclei regions of interest were obtained through automated segmentation of 0.69-mm resolution T1-weighted images and 0.35-mm resolution T2-weighted images. Probabilistic tractography was performed on all subjects, with random seeding at each amygdala nucleus.

Results

The right lateral, basal, central, and centrocortical amygdala nuclei exhibited significantly increased connection density to the rest of the brain, whereas the left medial nucleus demonstrated significantly lower connection density (false discovery rate p < .05). Increased connection density in the right lateral and basal nuclei was driven by the stria terminalis, and the significant difference in the right central nucleus was driven by the uncinate fasciculus. Decreased connection density at the left medial nucleus did not appear to be driven by any individual white matter tract.

Conclusions

By exploiting ultra-high-resolution magnetic resonance imaging, structural hyperconnectivity was demonstrated involving the amygdaloid nuclei in the right hemisphere in MDD. To a lesser extent, impairment of subnuclei connectivity was shown in the left hemisphere.

SUBMITTER: Brown SSG

PROVIDER: S-EPMC7010542 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Ultra-High-Resolution Imaging of Amygdala Subnuclei Structural Connectivity in Major Depressive Disorder.

Brown Stephanie S G SSG Rutland John W JW Verma Gaurav G Feldman Rebecca E RE Schneider Molly M Delman Bradley N BN Murrough James M JM Balchandani Priti P

Biological psychiatry. Cognitive neuroscience and neuroimaging 20190813 2

<h4>Background</h4>Major depressive disorder (MDD) is an increasingly common and disabling illness. As the amygdala has been reported to have pathological involvement in mood disorders, we aimed to investigate for the first time potential changes to structural connectivity of individual amygdala subnuclei in MDD using ultra-high-field 7T diffusion magnetic resonance imaging.<h4>Methods</h4>Twenty-four patients with MDD (11 women) and 24 age-matched healthy control participants (7 women) underwen ...[more]

PMID: 31570286

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Project description:We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest.The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes.Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback regulation success.Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

Project description:BACKGROUND:Although dysfunction of amygdala-related circuits is centrally implicated in major depressive disorder (MDD), little is known about how this dysfunction differs between adult and adolescent MDD patients. METHODS:Voxel-wise meta-analyses of abnormal amygdala resting-state functional connectivity (rsFC) were conducted in adult and adolescent groups separately, followed by a quantitative meta-analytic comparison of the two groups. FINDINGS:Nineteen studies that included 665 MDD patients (392 adults and 273 adolescents) and 546 controls (341 adults and 205 adolescents) were identified in the current study. Adult-specific abnormal amygdala rsFC in MDD patients compared to that in controls was located mainly within the affective network, including increased connectivity with the right hippocampus/parahippocampus and bilateral ventromedial orbitofrontal cortex and decreased connectivity with the bilateral insula and the left caudate. Adolescent MDD patients specifically demonstrated decreased amygdala rsFC within the cognitive control network encompassing the left dorsolateral prefrontal cortex and imbalanced amygdala rsFC within the default mode network, which was manifested as hyperconnectivity in the right precuneus and hypoconnectivity in the right inferior temporal gyrus. Additionally, direct comparison between the two groups showed that adult patients had strengthened amygdala rsFC with the right hippocampus/parahippocampus as well as the right inferior temporal gyrus and weakened amygdala rsFC with the bilateral insula compared to that in adolescent patients. INTERPRETATION:Distinct impairments of amygdala-centered rsFC in adult and adolescent patients were related to different network dysfunctions in MDD. Adult-specific amygdala rsFC dysfunction within the affective network presumably reflects emotional dysregulation in MDD, whereas adolescent-specific amygdala rsFC abnormalities in networks involved in cognitive control might reflect the neural basis of affective cognition deficiency that is characteristic of adolescent MDD. FUND: This study was supported by a grant from the National Natural Science Foundation of China (81671669) and by a Sichuan Provincial Youth Grant (2017JQ0001).

Project description:BACKGROUND:In participants with major depressive disorder who are trained to upregulate their amygdalar hemodynamic responses during positive autobiographical memory recall with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. This study tested whether amygdalar rtfMRI-nf also changes emotional processing of positive and negative stimuli in a variety of behavioral and imaging tasks. METHODS:Patients with major depressive disorder completed two rtfMRI-nf sessions (18 received amygdalar rtfMRI-nf, 16 received control parietal rtfMRI-nf). One week before and following rtfMRI-nf training, participants performed tasks measuring responses to emotionally valenced stimuli including a backward-masking task, which measures the amygdalar hemodynamic response to emotional faces presented for traditionally subliminal duration and followed by a mask, and the Emotional Test Battery in which reaction times and performance accuracy are measured during tasks involving emotional faces and words. RESULTS:During the backward-masking task, amygdalar responses increased while viewing masked happy faces but decreased to masked sad faces in the experimental versus control group following rtfMRI-nf. During the Emotional Test Battery, reaction times decreased to identification of positive faces and during self-identification with positive words and vigilance scores increased to positive faces and decreased to negative faces during the faces dot-probe task in the experimental versus control group following rtfMRI-nf. CONCLUSIONS:rtfMRI-nf training to increase the amygdalar hemodynamic response to positive memories was associated with changes in amygdalar responses to happy and sad faces and improved processing of positive stimuli during performance of the Emotional Test Battery. These results may suggest that amygdalar rtfMRI-nf training alters responses to emotional stimuli in a manner similar to antidepressant pharmacotherapy.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Ultra-High-Resolution Imaging of Amygdala Subnuclei Structural Connectivity in Major Depressive Disorder.

Background

Methods

Results

Conclusions

Publications

Ultra-High-Resolution Imaging of Amygdala Subnuclei Structural Connectivity in Major Depressive Disorder.

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