Research reportFrequency-dependent alterations in regional homogeneity in major depression
Introduction
Major depressive disorder (MDD) is a common mental disorder that is characterized by persistent depressed mood, anxiety and dysphoria, psychomotor changes, alterations of motivation and social behavior, and sleep abnormalities [3]. MDD is often accompanied by deficits in cognitive control and abnormal emotional processing [5]. Advanced noninvasive neuroimaging technology, such as functional magnetic resonance imaging (fMRI), allows us to observe the functional brain abnormalities associated with MDD, and resting-state fMRI has been widely used in recent years to investigate abnormal spontaneous neural activity in MDD [6], [9], [11], [19], [29], [40].
In contrast to task-based fMRI, resting-state fMRI does not require complex experimental designs that can remove some stimuli or task-related confounds. It provides a reliable measure of “baseline” brain activity and connectivity [14]. Regional homogeneity (ReHo) has been shown to be an effective index to measure spontaneous neural activity in resting-state fMRI analysis [36]. ReHo reflects the neural coherence of a given voxel with its nearest voxels in a voxel-wise analysis, which has been interpreted as “localized connectivity” [17], [19]. Numerous studies that have explored spontaneous brain activity in MDD using the ReHo method have provided some evidence of brain abnormalities in MDD during rest [10], [11], [12], [19], [20], [22], [29], [31], [35]. For example, Guo et al. [11] found abnormal ReHo in regions of limbic-cortical networks in MDD, while Liu et al. [22] found decreased ReHo in the insula and cerebellum in MDD. Wu et al. [29] found that MDD patients showed high ReHo within temporo-limbic regions and low ReHo in the frontal, parietal, and fusiform cortex and the caudate. Moreover, a meta-analysis by Iwabuchi et al. [17] found that the medial prefrontal cortex (mPFC) showed the most reliable abnormalities in MDD.
Previous resting-state studies have examined MDD-related neural activity in the typical low frequency band (0.01–0.08 Hz). However, whether the abnormal ReHo in MDD is related to a specific frequency band is largely unknown. The aim of the present study was to investigate frequency-dependent alterations in ReHo in MDD. The main reason why we focused on frequency-dependent alterations was that different neural signals within different frequency bands might be generated by distinct oscillators that have specific properties and physiological functions [4], [24]. The low frequency band can be subdivided into several bands: slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz), and slow-2 (0.198–0.25 Hz)] [4], [24]. The slow-2 and slow-3 bands mainly reflect high-frequency physiological noise and white-matter signals, whereas the slow-4 and slow-5 bands reflect gray-matter signals [20], [41]. Recently, Xue et al. [30] systematically explored the different characteristics of the slow-4 and slow-5 bands at regional and network levels. They found the slow-4 band exhibited higher ReHo in the superior frontal cortex, anterior cingulate cortex (ACC), the fusiform gyrus, and other areas, and the slow-5 band exhibited higher ReHo in the bilateral inferior frontal gyrus (IFG) and some midline structures, including the medial frontal cortex (mPFC) and the supplementary motor area (SMA). In addition, Wei et al. (2014) found that low frequency fluctuations in specific bands were associated with personality traits, which might imply that spontaneous brain activity is frequency-dependent. On the other hand, using this approach to investigate the neural activity of specific frequency bands (slow-4 and slow-5 bands) has been successful in detecting local abnormalities in different psychiatric disorders, such as Alzheimer’s disease [21], schizophrenia [33], [34], social anxiety [39], mild cognitive impairment [15], and Parkinson’s disease [16], [39]. To the best of our knowledge, no study has investigated specific frequency bands in MDD. Therefore, it would be useful to differentiate the frequency band specificity associated with MDD.
We sought to address this issue by examining the frequency-dependent neural activity in MDD during the resting-state. This is the first study, to our knowledge, to use ReHo as an index to investigate the spontaneous neural activity of specific frequency bands (slow-4 and slow-5 band) in MDD. We hypothesized that MDD patients would show abnormal ReHo in regions associated with cognitive control and emotional processing, and that these abnormalities would be associated with specific frequency bands. In addition, we also investigated ReHo in the typical frequency band (0.01–0.08 Hz) to identify potential frequency-dependent changes [34].
Section snippets
Participants
This investigation recruited thirty-one depressed patients (eighteen female) who were outpatients at a Chongqing Medical University affiliated hospital. Thirty-one age-, gender-, and education-matched healthy subjects were recruited from students, government retirees, hospital staff, logistics staff, and other persons. Detailed demographic and clinical characteristics of the samples are shown in Table 1. All patients were diagnosed as suffering from MDD using the following criteria: (1) they
ReHo analysis in the typical frequency band (0.01–0.08 Hz)
The MDD patients showed significantly higher ReHo in the typical frequency band (0.01–0.08 Hz), relative to the healthy controls, in the dorsal lateral prefrontal cortex (dlPFC), while lower ReHo was observed in the fusiform and postcentral gyrus (Table 2 and Figs. 1 a and 2 ).
Main effect of groups and frequency bands
The ANOVA found a main effect of groups on ReHo, which is shown in Table S1 and Fig. S1. Compared to the controls, the MDD patients exhibited significantly higher ReHo in the middle occipital gyrus (MOG), medial frontal
Discussion
The present study used the ReHo method to explore spontaneous neural activity during the resting state in three different frequency bands (the slow-4, slow-5, and typical bands). Our results showed that MDD patients exhibited abnormal ReHo in the frontal and temporal regions in the typical band. We also found that widespread brain regions showed significant differences in ReHo between MDD patients and healthy controls, and between the slow-4 and slow-5 bands. Importantly, we found that many
Conclusions
This is the first study to examine differences in spontaneous neural activity in specific frequency bands between MDD patients and healthy controls. Our results indicate that abnormal ReHo in MDD may be associated with these frequency bands. The findings implied that future studies should take frequency band effects into account when examining spontaneous neural activity.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (31070900; 31271087), the Program for New Century Excellent Talents in University (2011) by the Ministry of Education and the Fundamental Research Funds for the Central Universities (SWU1209101), and the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning (CNLYB1310). The authors declare no competing interests.
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2019, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :There are several reports mentioning the ReHo alterations in depression, such as lower ReHo values in the regions related to the top-down regulation (Huang et al., 2014)., reduced ReHo values in frontal regions (Guo et al., 2015; Wang et al., 2014; Xue et al., 2016), alterations in anterior cingulate cortex (ACC) (Lai and Wu, 2016a; Spati et al., 2015). According to this, the frontal regions (including the ACC) play a significant role for MDD pathophysiology in depression.