Amygdala-pons connectivity is hyperactive and associated with symptom severity in depression.
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ABSTRACT:
SUBMITTER: Wong JJ
PROVIDER: S-EPMC9187701 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Amygdala-pons connectivity is hyperactive and associated with symptom severity in depression.
Wong Jing Jun JJ Wong Nichol M L NML Chang Dorita H F DHF Qi Di D Chen Lin L Lee Tatia M C TMC
Communications biology 20220610 1
Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinical ...[more]
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Project description:BackgroundThe incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents.MethodWe examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24).ResultsCompared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later.LimitationsOnly a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized.ConclusionsAdolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.
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Project description:BackgroundMajor depressive disorder (MDD) is associated with decreased function of cortico-limbic circuits, which play important roles in the pathogenesis of MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved in cortico-limbic circuits, has also been observed in MDD. However, little is known about connectivity alterations in late-onset depression (LOD) or whether disrupted connectivity is correlated with cognitive impairment in LOD.Methods and resultsA total of twenty-two LOD patients and twenty-two matched healthy controls (HC) underwent neuropsychological tests and resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI data between two groups. Compared with HC, LOD patients showed decreased ReHo in the right middle frontal gyrus and left superior frontal gyrus. In the LOD group, the left amygdala had decreased FC with the right middle frontal gyrus and the left superior frontal gyrus in the amygdala positive network, and it had increased FC with the right post-central gyrus in the amygdala negative network. However, significantly reduced FC with the right amygdala was observed in the right middle occipital gyrus in the amygdala negative network. Further correlative analyses revealed that decreased FC between the amygdala and the right middle occipital gyrus was negatively correlated with the verbal fluency test (VFT, r = -0.485, P = 0.022) and the digit span test (DST, r = -0.561, P = 0.007).ConclusionsOur findings of reduced activity of the prefrontal gyrus and abnormal FC with the bilateral amygdala may be key markers of cognitive dysfunction in LOD patients.
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Project description:ImportanceMajor depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships.ObjectiveTo examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions.Design, setting, and participantsA cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses.Main outcomes and measuresUsing a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala.ResultsAdolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls.Conclusions and relevanceImpaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.
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Project description:ObjectiveAdult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD.MethodA total of 51 children 7 through 11 years of age who had been prospectively studied since preschool age, completed resting state functional magnetic resonance imaging (fMRI) and were assigned to one of four groups: 1) C-MDD (N = 13), those children with a personal history of early-childhood-onset MDD; 2) M-MDD (N = 11), those with a maternal history of affective disorders; 3) CM-MDD (N = 13), those with both maternal and early-childhood-onset MDD; or 4) CON (N = 14), those without either a personal or maternal history of MDD. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in region-of-interest-based analyses of our child sample.ResultsWe found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when compared with CON, we found reduced connectivity between the amygdala and the "negative network" in children with C-MDD, M-MDD, and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the "positive network."ConclusionsOur finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD, suggesting developmental continuity of this alteration into early childhood.
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Project description:BackgroundFunctional movement disorders, a common cause of neurological disabilities, can occur with heterogeneous motor manifestations including functional weakness. However, the underlying mechanisms related to brain function and connectivity are unknown.ObjectiveTo identify brain connectivity alterations related to functional weakness we assessed network centrality changes in a group of patients with heterogeneous motor manifestations using task-free functional MRI in combination with different network centrality approaches.MethodsTask-free functional MRI was performed in 48 patients with heterogeneous motor manifestations including 28 patients showing functional weakness and 65 age- and sex-matched healthy controls. Functional connectivity differences were assessed using different network centrality approaches, i.e. global correlation, eigenvector centrality, and intrinsic connectivity. Motor symptom severity was assessed using The Simplified Functional Movement Disorders Rating Scale and correlated with network centrality.ResultsComparing patients with and without functional weakness showed significant network centrality differences in the left temporoparietal junction and precuneus. Patients with functional weakness showed increased centrality in the same anatomical regions when comparing functional weakness with healthy controls. Moreover, in the same regions, patients with functional weakness showed a positive correlation between motor symptom severity and network centrality. This correlation was shown to be specific to functional weakness with an interaction analysis, confirming a significant difference between patients with and without functional weakness.ConclusionsWe identified the temporoparietal junction and precuneus as key regions involved in brain connectivity alterations related to functional weakness. We propose that both regions may be promising targets for phenotype-specific non-invasive brain stimulation.
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