Surface-based regional homogeneity in bipolar disorder: A resting-state fMRI study
Introduction
Bipolar disorder (BD) is one of the most challenging psychiatric disorders to manage, with both periods of depression and elevated mood. BD patients without a history of mania are frequently misdiagnosed, leading to inadequate treatment (Parker, 2000). Furthermore, the pathophysiology underlying BD remains unclear.
Resting-state functional magnetic resonance imaging (rfMRI) evaluates regional interactions in the brain that occur when an individual is not performing an explicit task (Biswal, 2012). Several recent studies have reported functional abnormalities in patients with BD using rfMRI (Minuzzi et al., 2017, Wang et al., 2017). Among several functional homogeneity measures of rfMRI, regional homogeneity (ReHo) is the most widely used to provide information about local activity within a small region of the brain (Zang et al., 2004) and is strongly recommended as an algorithm for BD studies (Vargas et al., 2013).
As such, ReHo has been widely used to investigate BD within the past decade (Gao et al., 2014, Liang et al., 2013, Liu et al., 2012). To our knowledge, all previous fMRI studies examining ReHo in BD patients to determine local synchronization of spontaneous neuronal activity have done so via three-dimensional (3D) ReHo (Lin et al., 2018, Wei et al., 2018). Despite variation among different research designs, results consistently suggest extensive brain regions with altered local synchronization of spontaneous neuronal activity exist in patients with BD (Gao et al., 2014, Lim et al., 2013, Syan et al., 2018). Altered regional brain activity presents evidence for abnormality in BD during a resting state, providing fresh insights into the possible pathophysiological mechanisms underlying BD, as well as potential treatment options. However, voxels close to the boundaries between gray and white matter show remarkable partial volume effects. It has been demonstrated that compared with 3dReHo, two-dimensional (2d) ReHo is more specific to the intrinsic functional organization of the cortical mantle and has higher test-retest reliability at the cost of restricting analyses to the cortical mantle (Jiang and Zuo, 2016).
In the present study, two-dimensional regional homogeneity (2dReHo) was used to detect abnormalities of local functional synchronization of spontaneous neuronal activity in BD. We compared the resting-state local functional homogeneity of patients with BD to those of healthy participants. As ReHo serves as an index to demonstrate the temporal synchronization of regional blood oxygen level dependent (BOLD) signals and reflect the coordination of local neuronal activity, we hypothesized that patients with BD would demonstrate abnormal local synchronization of spontaneous neuronal activity across the global cortex mantle, if a global difference existed. However, if a local cluster difference was observed, this would imply that the specific region may be involved in the neuropathophysiological mechanisms underlying BD. Specifically, 2dReHo has been associated with some phenotypic variables, such as age (Jiang et al., 2015). Previous correlation studies have demonstrated that the normal aging process may disrupt local homogeneity at the millimeter scale (Fair et al., 2009, Lopez-Larson et al., 2011, Wu et al., 2007); however, the exact correlation between age and ReHo still remains unclear. Therefore, the present study also aimed to detect the correlation tendency between ReHo and age, both for patients with BD and healthy controls (HC).
Section snippets
Participants
The Ethics Committee of the First Hospital of China Medical University approved this study. A total of 184 individuals were enrolled in the present study, including 71 patients with BD (49 subjects with BD type I, 22 subjects with BD type II) who were recruited from the outpatient facility of the Department of Psychiatry, in the Mental Health Center of the Shenyang and the First Affiliated Hospital of China Medical University. The BD diagnosis for adult patients was individually determined by
Demographic data
Demographic data are shown in Table 1. BD and HC groups were well-matched in age and gender. Moreover, medication status, age of illness onset, YMRS, HAMD, and HAMA score of BD patients are also included in Table 1.
Surface-based regional homogeneity differences between BD and HC
In comparison with HC at the global level, BD patients showed reduced surface-based ReHo across the cortical surface (Fig. 1). At the cluster level, patients with BD showed lower 2dReHo than HC in the left ventral visual stream (VVS) cortex (Fig. 2). Results of the independent sample
Discussion
ReHo is defined as a local measure for quantifying functional synchronizations between neighboring vertices, which is distinct from remote functional-connectivity measures (Jiang and Zuo, 2016). Abnormal ReHo suggests that there are changes in spontaneous neuronal activity at the local level, or that there are atypical patterns of neuronal synchrony across global networks. With its ability to detect unpredicted hemodynamic responses, ReHo could help us to better understand highly complex brain
Limitations
Several limitations should be considered in the interpretation of the findings. First, 45 patients were medicated in the present study, despite their clinically stable mood status, for the MRI scanning. While considering possible effects of medication on ReHo, future studies should focus on mixed-medication effects. Second, our present surface-based ReHo analysis focused only on the cortex rather than subcortical regions, the latter of which has been proven to be crucial in emotional processing
Conclusion
In the present study, patients with BD demonstrated decreased surface-based ReHo across the cortical surface at the global level and lower surface-based ReHo in the left VVS cortex. The abnormal activity in the left VVS cortex may participate in the pathogenesis of BD. As such, surface-based ReHo may be a useful index to explore the pathophysiology of BD.
Acknowledgments
The authors would like to thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
Funding
This work was supported by grants from the National Natural Science Foundation of China (81271499 and 81571331 to Yanqing Tang, and 81571331 to Fei Wang), Liaoning Pandeng Scholar (to Fei Wang), the National Key Research and Development Program (2016YFC 0904300 to Fei Wang), the National High Tech Development Plan (863) (2015AA020513 to Fei Wang), and the National Key Research and Development Program (2016YFC1306900 to Yanqing Tang). This research did not receive any specific grant from funding
Conflict of interest
The authors declare that there are no conflicts of interest.
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