Altered whole brain functional connectivity in drug-naive patients with obsessive–compulsive disorder: A resting-state functional magnetic resonance imaging study
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

[1] Abramowitz JS, et al. (2009). Lancet 374:491-499.

[2] Menzies, L, et al. (2008). Neurosci Biobehav Rev. 32:525-549.

[3] Anticevic A, et al. (2014). Biol Psychiatry 75:595-605.

[4] Buckner RL, et al. (2009). J Neurosci. 29:1860–1873.

[5] Yan CG, et al. (2010). Front Syst Neurosci. 4:13.

Figures

Figure (A): Higher FCS in OCD patients compared with HCS. FCS increases are indicated in warm colors. No regions of FCS reduction were identified.

Figure (B): Pearson correlation exhibiting positive correlation between FCS in the PCC and Y-BOCS scores in the OCD group.

Figure (C): Locations of seed regions and their representative connectivity maps. The seed regions of interest (ROI) are displayed in green in the first column. The corresponding positive (warm) and negative (cool) functional connectivity maps of each of these seeds in OCD patients relative to the HCS are displayed in subsequent columns.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
4154