**4.4 The limbic lobe**

In the present study, VoR with PTSD had significant increases in GMD in the right posterior cingulate cortex compared to HC. Meta-analyses have revealed that the prominent themes in the posterior cingulate cortex are episodic memory retrieval and pain (Nielsen et al., 2005), visuospatial processing and assessment of threat (Nemeroff et al., 2006), as well as fear conditioning (Doronbekov et al., 2005). Comparison of connectivity maps by functional connectivity analyses (Lanius et al., 2004) reveals that subjects with PTSD showed greater correlations in interregional brain activity than subjects without PTSD in the right posterior cingulate cortex (BA 29). Functional neuroimaging studies have found increased activation in the posterior cingulate cortex in victims with PTSD compared to victims without PTSD and to healthy controls (Bremner et al., 1999a, b, 2003; Doronbekov et al., 2005; Sachinvala et al., 2000). These indicate that dysfunction in the posterior cingulate cortex may underlie pathological symptoms provoked by traumatic reminders of sexual assault among VoR with PTSD.

### **4.5 The cerebellum**

We found that the density of cerebellum, which plays an important role in motor and cognition (Mandolesi et al., 2001; Bischoff-Grethe et al., 2002; Vokaer et al., 2002; Claeys et al., 2003; Guenther et al., 2005; Allen et al., 2005; Konarski et al., 2005; Schmahmann & Caplan, 2006; Gianaros et al., 2007; Schweizer et al., 2007), was increased in patients with PTSD. Combination of early studies about structural abnormal (Leroi et al., 2002; Liszewski et al., 2004; Bellis & Kuchibhatla, 2006) and functional abnormal (Bonne et al., 2003; Molina et al., 2010; Gianaros et al., 2007; Liotti et al., 2000; Phan et al., 2002) in the cerebellum in PTSD patients, the finding is consistent with our hypothesis that the cerebellum was involved in the neuropathology of cognitive processing and emotional processing in PTSD patients. Furthermore, the density increased in the cerebellum while decreased in the prefrontal cortex. According to the anatomical studies that the cerebellum interacts with the prefrontal cortex via the thalamus (Middleton & Strick, 2001; Zhu et al., 2006), and the functional studies that the cerebellum influences several areas of the prefrontal cortex via the thalamus (Middleton & Strick, 2001) and exhibits a pattern similar to the frontal cortex during semantic decisions (Gold & Buckner, 2002), the findings suggest that the cerebellum

Abnormal Brain Density in Victims of Rape with PTSD in Mainland

different subgroups of PTSD patients.

Vol. 11, pp. 805-821

(2009CB918303, 2006CB5000800 to Lingjiang Li).

**6. Acknowledgments** 

**7. References** 

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8, pp. 171-186

China: A Voxel-Based Analysis of Magnetic Resonance Imaging Study 387

symptoms. In addition, the findings of this study need to be confirmed in the future and in

We acknowledge support from grant from the National Natural Science Foundation of China (30830046 to Lingjiang Li and Shuangge Sui), the National Science and Technology Program of China (2007BAI17B02 to Lingjiang Li), and the National 973 Program of China

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may be involved in the functional compensation for the pathological changes in the neurocircuitry of PTSD.

Earlier studies in the cerebellum of PTSD patients found correlations with abnormal blood flow and glucose absorption (Bonne et al., 2003; Molina et al., 2010) and abnormal volume (Bellis & Kuchibhatla, 2006) in the cerebellum also. This study extends the literature on cerebellum structure involvement in PTSD. This finding, if replicated in larger patient samples, may serve as a marker of brain dysfunction in PTSD, and thus allows for the study of cerebellum pathophysiology before and throughout the course and treatment of PTSD. It should be noted that whilst the sample size (11 VoR with PTSD) of this study meets the threshold of research reported in the literature (Jatzko et al., 2006a; Hou et al., 2007), it was nevertheless limited in terms of its statistical power. A further limitation is the potential for selection bias in both the VoR Group and HC. Given the social stigma attached to VoR in the Chinese cultural context that often results in sexual shame, fear and anxiety over disclosure of the rape, guilt over derogating family honor, self-scrutiny and self-blame after the fact, and even blame of the victim, contribute to the potential selection bias in the VoR Group. Regarding the selection bias in HC, it was not our intention for this group (12 HC) to be representative of the general population, nor were the 65-pooled controls. This group was particularly designed to match the VoR with PTSD regarding the major demographic characteristics. However, given the fact that HC were recruited from healthy workers, selection bias from the healthy-worker effect should be borne in mind.

The use of a cross-sectional design is another significant limitation of this study. The shared variance estimated between variables in a cross-sectional design does not allow for a critical examination of causal relationships among them. Consequently, we cannot state categorically whether changes in brain density were the cause or the effect of trauma exposure/PTSD.
