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Coordinate-based meta-analyses (CBMA) are very useful for summarizing the large number of voxel-based neuroimaging studies of normal brain functions and brain abnormalities in neuropsychiatric disorders. However, current CBMA methods do not conduct common voxelwise tests, but rather a test of convergence, which relies on some spatial assumptions that data may seldom meet, and has lower statistical power when there are multiple effects. Here we present a new algorithm that can use standard voxelwise tests and, importantly, conducts a standard permutation of subject images (PSI). Its main steps are: a) multiple imputation of study images; b) imputation of subject images; and c) subject-based permutation test to control the familywise error rate (FWER). The PSI algorithm is general and we believe that developers might implement it for several CBMA methods. We present here an implementation of PSI for seed-based d mapping (SDM) method, which additionally benefits from the use of effect sizes, random-effects models, Freedman-Lane-based permutations and threshold-free cluster enhancement (TFCE) statistics, among others. Finally, we also provide an empirical validation of the control of the FWER in SDM-PSI, which showed that it might be too conservative. We hope that the neuroimaging meta-analytic community will welcome this new algorithm and method. •We present a new algorithm for coordinate-based meta-analyses (CBMA) methods.•Opposed to current methods, it conducts common permutation tests.•It may be implemented in several CBMA methods.•We detail and validate its implementation for seed-based d mapping (SDM).

•Visual working memory recruits a frontoparietal-inferotemporal network during delay.•Sustained delay-period activity is not evident in early visual cortex.•Patterns of delay activity depend on different aspects of visual working memory. Visual working memory refers to the temporary maintenance and manipulation of task-related visual information. Recent debate on the underlying neural substrates of visual working memory has focused on the delay period of relevant tasks. Persistent neural activity throughout the delay period has been recognized as a correlate of working memory, yet regions demonstrating sustained hemodynamic responses show inconsistency across individual studies. To develop a more precise understanding of delay-period activations during visual working memory, we conducted a coordinate-based meta-analysis on 30 fMRI experiments involving 515 healthy adults with a mean age of 25.65 years. The main analysis revealed a widespread frontoparietal network associated with delay-period activity, as well as activation in the right inferior temporal cortex. These findings were replicated using different meta-analytical algorithms and were shown to be robust against between-study heterogeneity and publication bias. Further meta-analyses on different subgroups of experiments with specific task demands and stimulus types revealed similar delay-period networks, with activations distributed across the frontal and parietal cortices. The roles of prefrontal regions, posterior parietal regions, and inferior temporal areas are reviewed and discussed in the context of content-specific storage. We conclude that cognitive operations that occur during the unfilled delay period in visual working memory tasks can be flexibly expressed across a frontoparietal-temporal network depending on experimental parameters.

Childhood maltreatment has been suggested to have an adverse impact on neurodevelopment, including microstructural brain abnormalities. Existing neuroimaging findings remain inconsistent and heterogeneous. We aim to explore the most prominent and robust cortical thickness (CTh) and gray matter volume (GMV) alterations associated with childhood maltreatment. A systematic search on relevant studies was conducted through September 2022. The whole-brain coordinate-based meta-analysis (CBMA) on CTh and GMV studies were conducted using the seed-based d mapping (SDM) software. Meta-regression analysis was subsequently applied to investigate potential associations between clinical variables and structural changes. A total of 45 studies were eligible for inclusion, including 11 datasets on CTh and 39 datasets on GMV, consisting of 2550 participants exposed to childhood maltreatment and 3739 unexposed comparison subjects. Individuals with childhood maltreatment exhibited overlapped deficits in the median cingulate/paracingulate gyri simultaneously revealed by both CTh and GM studies. Regional cortical thinning in the right anterior cingulate/paracingulate gyri and the left middle frontal gyrus, as well as GMV reductions in the left supplementary motor area (SMA) was also identified. No greater regions were found for either CTh or GMV. In addition, several neural morphology changes were associated with the average age of the maltreated individuals. The median cingulate/paracingulate gyri morphology might serve as the most robust neuroimaging feature of childhood maltreatment. The effects of early-life trauma on the human brain predominantly involved in cognitive functions, socio-affective functioning and stress regulation. This current meta-analysis enhanced the understanding of neuropathological changes induced by childhood maltreatment.

Coordinate-based meta-analyses (CBMA) methods, such as Activation Likelihood Estimation (ALE) and Seed-based d Mapping (SDM), have become an invaluable tool for summarizing the findings of voxel-based neuroimaging studies. However, the progressive sophistication of these methods may have concealed two particularities of their statistical tests. Common univariate voxelwise tests (such as the t/z-tests used in SPM and FSL) detect voxels that activate, or voxels that show differences between groups. Conversely, the tests conducted in CBMA test for “spatial convergence” of findings, i.e., they detect regions where studies report “more peaks than in most regions”, regions that activate “more than most regions do”, or regions that show “larger differences between groups than most regions do”. The first particularity is that these tests rely on two spatial assumptions (voxels are independent and have the same probability to have a “false” peak), whose violation may make their results either conservative or liberal, though fortunately current versions of ALE, SDM and some other methods consider these assumptions. The second particularity is that the use of these tests involves an important paradox: the statistical power to detect a given effect is higher if there are no other effects in the brain, whereas lower in presence of multiple effects. •The statistical tests of coordinate-based meta-analyses (CBMA) have particularities.•Differently from what common voxelwise tests do, they test for spatial convergence.•Violation of their spatial assumptions may make results either conservative or liberal.•They have lower statistical power in the presence of multiple effects.

The impact of prolonged sports training on athletes’ brain functional activity remains inconclusive. A systematic review and coordinate-based meta-analysis of resting-state functional magnetic resonance imaging (rs-MRI) is necessary to identify functional connectivity changes induced by prolonged sports training. A total of 31 studies were included in the systematic review, and 18 studies with 347 non-athletes and 327 athletes were analyzed using coordinate-based activation likelihood estimation (ALE) and seed-based d mapping with permutation of subject images (SDM-PSI) meta-analysis. Results revealed that greater functional connectivity in athletes in the paracentral lobule, medial frontal gyrus, precuneus, inferior parietal lobule, supramarginal gyrus, inferior frontal gyrus, Rolandic operculum, and median cingulate/paracingulate gyri (DCG). Consistent changes in the DCG were identified in closed-skill sports athletes. Furthermore, increased regional functional activity was observed in the posterior cingulate gyrus, lingual gyrus and cerebellum. Both meta-analytical methods emphasize altered functional activity within the default mode network (DMN), cerebellar network (CBN), ventral attention network (VAN), visual network (VA), and sensorimotor network (SMN). These findings suggest that long-term sport training optimizes connection strength and efficiency in brain regions associated with visual attention, cognitive and motor control in athletes. Overall, our study reveals shared neural adaptations across different types of athletes, offering new insights into the effects of long-term specific training on brain functional connectivity in specialists.

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age ≤ 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.

Background: Voxel-based morphometry (VBM) has been widely used to investigate structural alterations in amnesia mild cognitive impairment (aMCI). However, inconsistent results have hindered our understanding of the exact neuropathology related to aMCI. Objectives: Our aim was to systematically review the literature reporting VBM on aMCI to elucidate consistent gray matter alterations, their functional characterization, and corresponding co-activation patterns. Methods: The PubMed, Web of Science, and EMBASE databases were searched for VBM studies on aMCI published from inception up to June 2020. Peak coordinates were extracted from clusters that showed significant gray matter differences between aMCI patients and healthy controls (HC). Meta-analysis was performed using seed-based d mapping with the permutation of subject images (SDM-PSI), a newly improved meta-analytic method. Functional characterization and task-based co-activation patterns using the BrainMap database were performed on significant clusters to explore their functional roles. Finally, VBM was performed based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to further support the findings. Results: A total of 31 studies with 681 aMCI patients and 837 HC were included in this systematic review. The aMCI group showed significant gray matter atrophy in the left amygdala and right hippocampus, which was consistent with results from the ADNI dataset. Functional characterization revealed that these regions were mainly associated with emotion, cognition, and perception. Further, meta-regression analysis demonstrated that gray matter atrophy in the left inferior frontal gyrus and the left angular gyrus was significantly associated with cognitive impairment in the aMCI group. Conclusions: The findings of gray matter atrophy in the left amygdala and right hippocampus are highly consistent and robust, and not only offer a better understanding of the underlying neuropathology but also provide accurate potential biomarkers for aMCI.

The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate‐based meta‐analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD.

There is an urgent need for a meta-analysis that characterizes the brain states of major depression disorder (MDD) patients and potentially provides reliable biomarkers, because heterogeneity in the results of resting-state functional neuroimaging has been observed between studies, with some patients not showing the consistent changes, or even opposite patterns. Thus, we evaluated consistent regional brain activity alterations in medication-naive patients with first-episode unipolar MDD and compared the results with those in healthy controls (HCs). A systematic database search was conducted (in PubMed, Ovid, and Web of Knowledge) between January 1984 and July 2016 to select resting-state functional activity studies with a voxel-wise analysis in MDD. We used anisotropic effect size-signed differential mapping to perform a whole-brain meta-analysis, comparing functional alterations between first-episode medication-naive unipolar MDD patients and HCs by integrating the studies. In addition, subgroup meta-analysis was conducted to control for the MRI analysis method. Moreover, the meta-regression analyses were performed to examine the potential effects of mean age, education duration, illness duration, and severity of depressive symptoms. A total of 12 studies were included, comparing 313 MDD patients with 283 HCs. The pooled and subgroup meta-analysis found that the MDD patients showed hyperactivity in the left parahippocampal gyrus, left supplementary motor area, left amygdala, left hippocampus, and left middle frontal gyrus (MFG; orbital part), and hypoactivity in the left lingual gyrus, left middle occipital gyrus, right cuneus cortex, right MFG (orbital part), and left cerebellum. In the meta-regression analyses, the mean illness duration was positively associated with hyper-activation in the left parahippocampal gyrus and hypoactivation in the hemispheric lobule IV/V of the left cerebellum. This meta-analysis indicated that MDD patients had significant and robust resting-state brain activity alteration in amygdala, left hippocampus and other regions, which implicated this finding in the pathophysiology of cognitive and emotional impairment in MDD patients.

Functional gastrointestinal disorders (FGIDs) are characterized by complex interactions between the gut and brain, leading to altered brain function and symptom manifestation. We used neuroimaging meta-analytic techniques in order to analyze the correlation between FGIDs and aberrant brain activity. A systematic review was performed to ascertain resting-state functional magnetic resonance imaging (rs-fMRI) studies examining brain function in FGIDs. Pooled meta-analyses by seed-based d mapping with permutation of subject images (SDM-PSI) were performed to assess variations in regional brain activity, and sensitivity analyses were applied to evaluate the robustness of findings. Meta-regression analyses were then carried out to examine possible links between demographic factors and neuroimaging changes. Our meta-analysis revealed significant changes in regional brain activities among FGIDs patients compared to healthy controls (HC). Increased brain activation was observed in several regions including the postcentral gyrus, calcarine fissure/surrounding cortex, superior frontal gyrus, and insula, while decreased activity was noted in the left posterior cingulate gyrus, right median cingulate/paracingulate gyri, and the left caudate nucleus. Furthermore, meta-regression analyses indicated negative associations between disease duration and alterations in specific brain regions. These findings underscored the intricate interplay between gut dysfunction and aberrant brain activity in FGIDs. Early intervention and multidisciplinary approaches addressing both gastrointestinal symptoms and associated emotional distress are crucial for improving the quality of life of the patients.