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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