Xinyu Hu1, Xi Yang2, Yanchun Yang2, Qiyong Gong1, and Xiaoqi Huang1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 2Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of
Synopsis
We analysis whole brain connectivity in a relatively large sample of drug-naive patients
with obsessive-compulsive disorder (OCD) using a novel graph-theory approach
known as functional connectivity strength (FCS) to identify brain regions displaying high-degree centrality of
connectivity. Based on the new
approach of FCS, our findings demonstrated obvious significant hyperactivity of
default mode network (DMN) in OCD patients at resting state. Furthermore, our results provided
evidence that besides the prevailing model of cortical–striatal–thalamic–cortical circuits in OCD, the disequilibrium between the DMN and the salience network (SN) might be associated with the pathophysiology of OCD.Target Audience
Those who are interested in
utilizing novel functional magnetic resonance imaging techniques in neuroscience
and psychiatry.
Purpose
Obsessive–compulsive disorder (OCD) is a
common, heritable neuropsychiatric disorder [1]. Resting-state fMRI (rs-fMRI) is a promising imaging technique that could
be used to detect abnormalities in spontaneous neuronal activity. Recent
advances in functional neuroimaging studies have
facilitated the models of OCD pathophysiology that encompass a
specific network of cortical–striatal–thalamic–cortical (CSTC) circuits [2]. Despite these advances, one important question that remains unanswered is
whether or not OCD-related functional changes occur only within the CSTC
circuits since most of the previous rs-fMRI studies in OCD have used a
seed-based approach, which is useful to detect regionally specific hypotheses
of brain function but has limited power to detect connectivity patterns not predicted
a priori [3]. Thus, the current study aims to analysis whole brain connectivity in a relatively
large sample of drug-naive OCD patients using a novel graph-theory approach
known as functional connectivity strength (FCS) [4] to identify brain regions displaying high-degree
centrality of connectivity, which represents cortical hubs in the whole brain
networks.
Methods
The study was approved
by the local ethical committee and written informed consent was obtained from
all subjects. A total of 68 drug-naive OCD patients and 68 age,
sex, handedness and years of education well matched healthy control subjects (HCS)
were recruited in current study. The diagnoses of OCD patients were determined
by using the structured clinical interview patient edition according to DSM-IV.
Clinical symptoms were evaluated using the Yale-Brown Obsessive-Compulsive
Scale (Y-BOCS).
The MRI examinations were performed via a 3-Telsa GE MRI system with an 8
channel phase array head coil. The rs-fMRI sensitized to changes in BOLD signal
levels were obtained via a GE-EPI sequence (TR/TE=2000/30msec, flip angle=90°, slice thickness=5mm
with no gap, 30 axial slices, 200 volumes in each run). Subjects were instructed to relax with
their eyes closed without falling asleep during MR examination. Image preprocessing was performed using
DPARSF software (http://www.restfmri.net) [5]. Whole-brain functional
connectivity analysis for FCS map calculation was implemented in REST (http://www.restfmri.net)
running under Matlab (Mathworks, 2010 release). Meanwhile, we selected the areas
with abnormal FCS values in OCD patients relative to HCS as regions of interest
(ROI) to conduct an additional seed-based interregional correlation analysis for
investigating more detailed connectivity alteration patterns associated with
the identified hubs. The statistic analyses of FCS and seed-based FC
maps between OCD patients and HCS were performed using the voxel-based
two-sample t-test in SPM8 (http://www.fil.ion.ucl.ac.uk/spm). Pearson
correlation analyses were conducted to identify the association between these functional
neural correlates and OCD symptom severity evaluated by Y-BOCS and subscale
scores.
Results
Relative to HCS, OCD patients showed higher FCS in the
posterior cingulate gyrus (PCC), anterior cingulate gyrus (ACC) and right
superior frontal gyrus (SFG) (P <
0.05, with AlphaSim correction) (Fig A). No
regions of FCS reduction were identified. FCS in the PCC was
positively correlated with Y-BOCS (r = 0.259; P = 0.033) (Fig B). Seed-based FC approach revealed
higher FC in the default mode
network (DMN) (including PCC and bilateral temporal cortex) and lower FC in the salience
network (SN) (including bilateral SFG and anterior insula) (P < 0.05, with AlphaSim correction) (Fig C).
Discussion and Conclusion
Using the new approach of FCS,
we demonstrated obvious significant hyperactivity of DMN (especially the PCC
region) in OCD patients at resting state.
Furthermore, our results also provided evidence that besides the prevailing
model of CSTC circuits in OCD, the disequilibrium between the DMN and the SN might be associated with the
pathophysiology of this disorder.
Acknowledgements
This study was supported by the National
Natural Science Foundation (Grant No. 81171488,
81227002, and 81220108013), the National Key Technologies Research
and Development Program of China (Program No. 2012BAI01B03) and Program for Changjiang Scholars and
Innovative Research Team in University (PCSIRT, Grant No. IRT1272) of China.
Dr. Qiyong Gong would like to acknowledge his Visiting Adjunct Professor
appointment in the Department of Psychiatry at the Yale School of Medicine,
Yale University, USA.
The authors reported no biomedical financial
interests or potential conflicts of interest
References
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[4] Buckner RL, et al. (2009). J Neurosci. 29:1860–1873.
[5] Yan CG, et al. (2010). Front Syst Neurosci. 4:13.