Altered Dynamic Functional Connectivity of Amygdala in Major Depressive Disorder
Lihua Qiu1,2, Mingrui Xia3, Yong He3, and Qiyong Gong2

1Radiology, The Second People's Hospital of Yibin, Yibin, China, People's Republic of, 2West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 3Beijing Normal University, Beijing, China, People's Republic of

Synopsis

Neuroimaging studies have shown that MDD is accompanied by functional abnormalities in amygdala and related connections; yet, little is known about amygdala subregion dynamic functional connectivity alterations of the whole-brain networks in MDD patients. In this work, general linear model analysis were used to assess the between-group differences of amygdalar subregion dynamic functional connectivity alterations in MDD patients. We found the altered amygdaloid projection were mainly in brainstem, cerebellum, thalamus, temporal and orbital cortical areas. These areas belong to limbic-thalamo-cortical circuitry which play important role in MDD and may associated with the impaired emotional modulation ability in MDD.

Purpose

Major depressive disorders (MDD) is the most disabling mental disorder and is one of the leading causes of disease burden worldwide.1 Neuroimaging studies have shown that MDD is accompanied by functional abnormalities in amygdala and related connections. However, previous study about the functional connectivity (FC) of amygdala with the whole brain have not taken into account the presence and potential of temporal variability which would reduce the rich temporal dynamics of the resting brain. In this work, the dynamic FC(dFC) based on resting state fMRI is estimated by computing correlations between component time courses2 using a series of sliding windows3 to investigate the amygdalar subregion dynamic functional connectivity alterations of the whole-brain networks in MDD patients.

Methods

In a cross-sectional study, 30 first-episode, drug naive MDD patients and 63 healthy controls(HC) underwent scanning using a gradient-echo echo-planar imaging sequence on a 3T MR system(GE Signa, Milwaukee, USA). Six subregions(including basolateral BL, centromedial CM and superficial SF) of bilateral amygdala were selected as seed areas. One-sample t tests on individual mean strength maps for each amygdalar subregion were used to examine the within-group functional connectivity patterns for the MDD and NC groups. General linear model (GLM) analysis were used to assess the between-group differences of the mean positive and negative connectivity strength of each amygdalar subregion with the entire brain by using age and gender as covariates.

Results

The within-group analysis revealed similar spatial dFC pattern of bilateral amygdalar subregions in the MDD and HC groups. The positive mean dFC of bilateral amygdalar subregions were mainly connected with the temporal lobe, sensorimotor cortex and subcortical areas of the brain, as well as the caudate, putamen, thalamus, brainstem and cerebellum. The negative mean dFC of bilateral amygdalar subregions were primarily connected with the frontal-parietal and occipital lobes of the brain(Figure 1). Compared with controls, MDD patients showed decreased positive mean dFC of bilateral CM and SF with the whole brain mainly in brainstem and cerebellum (Figure 2) as well as decreased positive mean dFC between left SF and left thalamus (mainly in mediodorsal thalamic nucleus) (corrected P<0.05). Additionally, the MDD-HC group differences in mean positive dFC strength between left SF and left thalamus showed a borderline significant trend of positive correlation with disease duration (r=0.38; uncorrected P < 0.05). MDD patients showed decreased negative mean dFC of left CM with the whole brain in right superior frontal gyrus and right CM with the whole brain in right medial temporal gyrus (corrected P<0.05) when compared with controls(Figure 3).

Discussion

Previous study have confirmed cerebellum plays a functional role in the regulation of HPA-axis which is an important node in the brain's stress circuit and suggested to play a role in several subtypes of depression.4 Thus, the decreased positive mean dFC connectivity between bilateral CM and SF with cerebellum may related with impaired stress circuit which may lead to depression. Animal experimental studies of amygdala connections confirmed a set of projections extends from the central amygdaloid nucleus to the brain stem, which appears to modulate visceral function in relation to emotional stimuli.5 Mediodorsal thalamic nucleus receives substantial subcortical inputs from the amygdala and also send direct (non thalamic) projections to the orbital and medial prefrontal cortex(OMPFC) which associated with mood, value assessment of objects, and stimulus-reward association.6 Our result of the decreased positive mean dFC between left SF and left thalamus might associated with the difficulty of ‘letting go’ of a negative mood in MDD. The decreased negative mean dFC of left CM with the right superior frontal gyrus and right CM with the right medial temporal gyrus may reflects the impaired projections of amygdaloid fibers to temporal and orbital cortical areas which might related with the behavioral responses to stressors and emotional stimuli in MDD.6

Conclusions

Our results revealed that the altered amygdaloid projection were mainly in brainstem, cerebellum, thalamus, temporal and orbital cortical areas. These areas belong to limbic-thalamo-cortical circuitry which play important role in MDD and the altered functional connection of amygdala may associated with the impaired emotional modulation ability in MDD. Future longitudinal studies are needed to clarify the episode-related functional connectivity alterations of amygdala, and the potential impact of therapeutic intervention on amygdaloid functional connection.

Acknowledgements

This study was supported by National Natural Science Foundation (Grant Nos.81030027, 81227002, 81222018 and 81220108013), National Key Technologies R&DProgram (Program No: 2012BAI01B03) and Program for Changjiang Scholars andInnovative Research Team in University (PCSIRT, Grant No. IRT1272) of China.

References

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2. Jafri, M.J., et al., A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage, 2008. 39(4): p. 1666-81.3.

3. Sakoglu, U., et al., A method for evaluating dynamic functional network connectivity and task-modulation: application to schizophrenia. MAGMA, 2010. 23(5-6): p. 351-66.4.

4. Schutter, D.J., The cerebello-hypothalamic-pituitary-adrenal axis dysregulation hypothesis in depressive disorder. Med Hypotheses, 2012. 79(6): p. 779-83.5.

5. Price, J.L., Comparative aspects of amygdala connectivity. Ann N Y Acad Sci, 2003. 985: p. 50-8.6.

6. Price, J.L. and W.C. Drevets, Neurocircuitry of mood disorders. Neuropsychopharmacology, 2010. 35(1): p. 192-216.

Figures

The within-group analysis of spatial dFC pattern of bilateral amygdalar subregions in the MDD and HC groups.

The MDD-HC group differences in mean positive dFC strength.

The MDD-HC group differences in mean negative dFC strength.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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