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Abnormalities of intrinsic regional brain activity at resting state in schizophrenia: a meta-analysis of resting-state functional MRI1Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China, 2Department of Radiology, Six Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 3Department of Applied Psychology, Guangdong University of Foreign Studies, Guangzhou, China, 4School of Psychology, Institute of Brain Research and Rehabilitation (IBRR), Center for the Study of Applied Psychology & MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, South China Normal University, Guangzhou, China
Synopsis
Evidences of abnormal intrinsic brain activity in schizophrenia (SZ) are inconsistent demonstrated by previous studies. A meta-analysis that explored the differences of the ALFF between SZ patients (including first episode [FE] and chronic patients) and healthy controls were conducted. FE patients demonstrated decreased ALFF in the DMN and increased in the putamen, VN (visual network). Chronic patients showed decreased ALFF in the DMN, sensorimotor network, and VN and increased in the salience network, frontotemporal regions. Aberrant regional brain activity during the initial stage and widespread damage with the progression of disease contributes to understand the progressive pathophysiology feature of SZ.
Introduction
Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided numerous evidences of abnormal intrinsic regional spontaneous brain activity in schizophrenia (SZ) 1-5. However, the inconsistent results have hindered our understanding of the exact neuropathology related to SZ.Methods
A meta-analysis of whole-brain rs-fMRI studies that explored differences of the amplitude of low-frequency fluctuation (ALFF) between SZ patients (including first episode [FE] and chronic patients) and healthy controls (HCs) were performed. In this work, a well-established and validated meta-analytic tool, Seed-based d Mapping (SDM) software package, was applied due to its widely usage in neuroimaging studies 6-8. Meta-regression was used to explore the effects of clinical characteristics. We searched PubMed, Embase, Web of Science, SinoMed, CNKI, and WanFang databases using the keywords “schizophrenia” OR “schizoaffective disorder”; AND “amplitude of low frequency fluctuation” OR “ALFF” OR “low frequency fluctuation” OR “LFF” OR “amplitude of low frequency oscillation” OR “LFO” for eligible whole-brain rs-fMRI studies that measured ALFF differences between patients with SZ and HCs published from January 1st, 2000 until April 24th, 2018. A flow diagram of the identification and exclusion of studies is presented in Figure 1.Results
Twenty-four studies reporting 28 datasets, comparing 1249 SZ patients (583 FE patients and 666 chronic patients with SZ; 721 males and 528 females; mean age = 28.93 years; mean illness duration = 70.23 months) and 1179 HCs (636 males and 543 females; mean age = 29.80 years), were included in the meta-analysis. No significant differences were observed between patients with SZ and HCs with respect to age (standardized mean difference [SMD] = ∼0; 95% confidence interval [CI] = -4.066 to 3.082, t = -0.276, p = 0.783) or gender distribution (relative risk [RR] = 1.087, 95% CI = 1.011 to 1.169, z = 2.243, p = 0.249). As illustrated in Figure 2, the meta-analytic brain map showed both decreased and increased ALFF in SZ patients relative to HCs. Compared to HCs, all SZ patients displayed decreased ALFF in the bilateral postcentral gyrus, bilateral precuneus, left inferior parietal gyri (IPG), and right occipital lobe and increased ALFF in the right putamen, right inferior frontal gyrus (IFG), left inferior temporal gyrus (ITG), and right anterior cingulate cortex (ACC). In the subgroup analysis, the FE patients with SZ demonstrated decreased ALFF in the bilateral IPG, right precuneus, and left medial prefrontal cortex (mPFC) and increased ALFF in the bilateral putamen and bilateral occipital gyrus; the chronic patients with SZ showed decreased ALFF in the bilateral postcentral gyrus, left precuneus, and right occipital gyrus and increased ALFF in the bilateral IFG, bilateral superior frontal gyrus, left amygdala, left ITG, right ACC and left insula. The results from the SDM analysis are summarized in Table 1. A meta-regression analysis demonstrated that for all patients with SZ and chronic patients, ALFF alterations involving putamen, superior occipital gyrus, IFG, ACC, and ITG were correlated with the positive and negative syndrome scale total score. The results of the meta-regression analyses are presented in Table 2.Discussion and Conclusion
Our comprehensive meta-analysis suggests that during the initial stages of SZ, that is FE patients, aberrant regional intrinsic brain activity predominantly involved the default mode network (DMN), visual network (VN), and putamen. With the progression of the disease, brain activity abnormalities progress over time after illness onset. The chronic patients demonstrate much more widespread brain functional damage, including the DMN, salience network, sensorimotor network, VN, putamen, and frontotemporal regions, which contributes to understand the progressive pathophysiology feature of SZ.Acknowledgements
No acknowledgement found.References
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