Quantitative prediction of symptom progression in drug-naive individuals with obsessive-compulsive disorder using resting-state functional magnetic resonance imaging
Xinyu Hu1, William Pettersson-Yeo2, Lizhou Chen1, Xi Yang3, Yanchun Yang 3, 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 Psychosis Studies, Institute of Psychiatry, King’s College London, London, United Kingdom, 3Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of

Synopsis

Neuroimaging techniques hold the promise that they may one day aid the clinical assessment of individual psychiatric patients. However, the vast majority of studies published so far have been based on average differences between groups. The current study aimed to apply a novel multivariate pattern analysis technique known as relevance vector regression to evaluating the potential of resting-state functional magnetic resonance imaging for making accurate predictions about symptom progression in a relatively large sample of drug-naive patients with obsessive-compulsive disorder.

Target Audience

Those who are interested in translational research of utilizing magnetic resonance imaging techniques in mental disorders.

Purpose

Obsessive-compulsive disorder (OCD) is a common, heritable and disabling neuropsychiatric disorder [1]. Recent advances in resting-state functional magnetic resonance imaging (rs-fMRI) have facilitated the models of OCD pathophysiology that encompass a specific network of cortico-striato-limbic regions [2]. However, the vast majority of these studies published so far have been based on average differences between groups. Whether functional neuroimaging could be used to inform the clinical assessment of individual OCD patients remains unclear. Thus, the aim of the current study was to apply a novel multivariate pattern analysis technique known as relevance vector regression (RVR) [3-5] to evaluating the potential of rs-fMRI for making accurate predictions about symptom progression in a relatively large sample of drug-naive patients with OCD.

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 the blood oxygen level dependent (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. The amplitude of low-frequency fluctuation (ALFF) maps were calculated using DPARSF software [6](http://www.restfmri.net). Initially, we performed a standard univariate analysis to explore alterations of regional neural function by comparing ALFF maps between OCD patients and HCS with the voxel-based two-sample t-test in SPM8 (http://www.fil.ion.ucl.ac.uk/spm). Pearson correlation analyses were performed to identify the association between functional neural correlates and OCD symptom severity evaluated by Y-BOCS and subscale scores. In addition, we examined the relationship between symptom scores and the ALFF using multivariate RVR as implemented in PRoNTo (http://www.mlnl.cs.ucl.ac.uk/pronto/) running under Matlab (Mathworks, 2010 release).

Results

Relative to HCS, OCD patients showed lower ALFF in the right middle temporal gyrus (MTG) and higher ALFF in the bilateral inferior frontal gyri extending to the anterior insula, bilateral middle frontal gyri, bilateral superior frontal gyri and the left anterior cingulate gyrus (P < 0.05, with family wise error correction) (Figure A). ALFF in right MTG was negatively correlated with compulsive subscale (r = -0.288, P = 0.017) (Figure B). Meanwhile, the application of RVR to rs-fMRI data allowed quantitative prediction of Y-BOCS scores with statistically significant accuracy (correlation = 0.38, P = 0.005; mean squared error = 25.93, P = 0.005) (Figure C). Accurate prediction was based on functional activation in a number of prefrontal, parietal, temporal and occipital regions (Figure D).

Discussion and Conclusion

Our study demonstrated the first evidence that functional neuroimaging techniques might inform the clinical assessment of OCD patients by providing an accurate and objective quantitative estimation of clinical scores. Furthermore, the contribution of posterior brain circuitry (including temporo-parieto-occipital associative areas) provided additional explanation to the well known frontal-subcortical mechanism of OCD.

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] Tipping ME, et al. (2001). J Mach Learn Res.1:211-244.

[4] Gong QY, et al. (2014). Neuropsychopharmacology 39:681-687.

[5] Tognin S, et al. (2014). Front Psychiatry 4:187.

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

Figures

Figure A: Altered ALFF in OCD patients compared with HCS. ALFF increases are indicated in warm colors while ALFF reductions are indicated in cool colors.

Figure B: Pearson correlation exhibiting negative correlation between ALFF in the right MTG and compulsive subscale scores in the OCD group.

Figure C: Scatter plot showing the predicted Y-BOCS score for each OCD subject derived from their rs-fMRI data using RVR, vs. their actual Y-BOCS score.

Figure D: Multivariate map showing the weight of each voxel indicating its relative contribution to the regression function in the context of all other voxels.



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