Effect-size Signed Differential Mapping Research Articles

Shared and distinct abnormalities of brain magnetization transfer ratio in schizophrenia and major depressive disorder: a comparative voxel-based meta-analysis.

Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.

A meta-analysis of brain morphometric aberrations in adolescents who experienced childhood trauma.

Childhood trauma is known to have dramatic effects on the risks for developing psychiatric disorders and increased suicidality. We conducted a meta-analysis of whole brain voxel-based morphometry (VBM) correlates of childhood trauma in adolescents exposed to childhood maltreatment (N = 379) and unexposed controls (N = 348). Anisotropic effect size-signed differential mapping (AES-SDM) was utilized to synthesize the studies. We observed increased volume amongst adolescents with a history of childhood trauma in regions that are involved in motor functions and language production: left precentral gyrus, including part of the left inferior frontal gyrus, left fibers of the body of corpus callosum, and left postcentral gyrus. We observed decreased volume amongst adolescents with a history of childhood trauma in regions that are involved in language processing and/or sensory processing: bilateral cerebellum, bilateral middle temporal gyrus, left rostrum of corpus callosum, and bilateral supramarginal gyrus. We suggest that these morphometric differences may be reflective of impaired motor development and increased sensory sensitivity and hypervigilance in adolescents with experiences of childhood trauma. Our results differ from meta-analytical findings in adults with history of childhood trauma and may contribute to a better understanding of neural mechanisms of childhood trauma, prediction of neurodevelopmental outcomes, and development of more effective and personalized therapies.

A systematic review and meta-analysis of voxel-based morphometric studies of migraine.

To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine. Neuroimaging studies published from origin to August 1, 2021 were searched in six databases including PubMed, Web of Science, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP. Study selection, quality assessment, and data extraction were conducted by two independent researchers. Anisotropic effect size-signed differential mapping (AES-SDM) and activation likelihood estimation (ALE) were used to perform the meta-analysis of available studies reporting whole-brain gray matter (GM) structural data in migraine patients. Clinical variables correlation analysis and migraine subgroup analysis were also conducted. 40 articles were included after the strict screening, containing 1616 migraine patients and 1681 matched healthy subjects (HS) in total. Using the method of AES-SDM, migraine patients showed GM increase in the bilateral amygdala, the bilateral parahippocampus, the bilateral temporal poles, the bilateral superior temporal gyri, the left hippocampus, the right superior frontal gyrus, and the left middle temporal gyrus, as well as GM decrease in the left insula, the bilateral cerebellum (hemispheric lobule IX), the right dorsal medulla, the bilateral rolandic operculum, the right middle frontal gyrus, and the right inferior parietal gyrus. Using the method of ALE, migraine patients showed GM increase in the left parahippocampus and GM decrease in the left insula. The results of correlation analysis showed that many of these brain regions were associated with migraine headache frequency and migraine disease duration. Migraine patients in different subtypes (such as migraine without aura (MwoA), migraine with aura (MwA), episodic migraine (EM), chronic migraine (CM), vestibular migraine (VM), etc.), and in different periods (in the ictal and interictal periods) presented not entirely consistent GM alterations. Migraine patients have GM alterations in multiple brain regions associated with sensation, affection, cognition, and descending modulation aspects of pain. These changes might be a consequence of repeated migraine attacks. Further studies are required to determine how these GM changes can be used to diagnose, monitor disease progression, or exploit potential therapeutic interventions for migraine patients.

Identify aberrant white matter microstructure in ASD, ADHD and other neurodevelopmental disorders: A meta-analysis of diffusion tensor imaging studies

BackgroundNeurodevelopmental disorders (NDDs) usually present overlapping symptoms. Abnormal white matter (WM) microstructure has been found in these disorders. Identification of common and unique neural abnormalities across NDDs could provide further insight into the underlying pathophysiological mechanisms. MethodsWe performed a voxel-based meta-analysis of whole-brain diffusion tensor imaging (DTI) studies in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and other NDDs. A systematic literature search was conducted through March 2020 to identify studies that compared measures of WM microstructure between patients with NDDs and neurotypical controls. Peak voxel coordinates were meta-analyzed via anisotropic effect size-signed differential mapping (AES-SDM) as well as activation likelihood estimation (ALE). ResultsOur final sample included a total of 4137 subjects from 66 studies across five NDDs. Fractional anisotropy (FA) reductions were found in the splenium of the CC in ADHD, and the genu and splenium of CC in ASD. And mean diffusivity (MD) increases were shown in posterior thalamic radiation in ASD. No consistent abnormalities were detected in specific learning disorder, motor disorder or communication disorder. Significant differences between child/adolescent and adult patients were found within the CC across NDDs, reflective of aberrant neurodevelopmental processes in NDDs. ConclusionsThe current study demonstrated atypical WM patterns in ASD, ADHD and other NDDs. Microstructural abnormalities in the splenium of the CC were possibly shared among ASD and ADHD.

Microstructural Abnormalities of White Matter Across Tourette Syndrome: A Voxel-Based Meta-Analysis of Fractional Anisotropy

Introduction: Tourette syndrome (TS) is a neuropsychiatric disorder with multiple motor and vocal tics whose neural basis remains unclear. Diffusion tensor imaging (DTI) studies have demonstrated white matter microstructural alternations in TS, but the findings are inconclusive. In this study, we aimed to elucidate the most consistent white matter deficits in patients with TS.Method: By systematically searching online databases up to December 2020 for all DTI studies comparing fractional anisotropy (FA) between patients with TS and healthy controls (HCs), we conducted anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis to investigate FA differences in TS, as well as performed meta-regression analysis to explore the effects of demographics and clinical characteristics on white matter abnormalities among TS.Results: A total of eight datasets including 168 patients with TS and 163 HCs were identified. We found that TS patients showed robustly decreased FA in the corpus callosum (CC) and right inferior longitudinal fasciculus (ILF) compared with HCs. These two regions preserved significance in the sensitivity analysis. No regions of increased FA were reported. Meta-regression analysis revealed that age, sex, tic severity, or illness duration of patients with TS were not linearly correlated with decreased FA.Conclusion: Patients with TS display deficits of white matter microstructure in the CC and right ILF known to be important for interhemispheric connections as well as long association fiber bundles within one hemisphere. Because the results reported in the primary literature were highly variable, future investigations with large samples would be required to support the identified white matter changes in TS.

Differential mirror neuron system (MNS) activation during action observation with and without social-emotional components in autism: a meta-analysis of neuroimaging studies

BackgroundImpaired imitation has been found to be an important factor contributing to social communication deficits in individuals with autism spectrum disorder (ASD). It has been hypothesized that the neural correlate of imitation, the mirror neuron system (MNS), is dysfunctional in ASD, resulting in imitation impairment as one of the key behavioral manifestations in ASD. Previous MNS studies produced inconsistent results, leaving the debate of whether “broken” mirror neurons in ASD are unresolved.MethodsThis meta-analysis aimed to explore the differences in MNS activation patterns between typically developing (TD) and ASD individuals when they observe biological motions with or without social-emotional components. Effect size signed differential mapping (ES-SDM) was adopted to synthesize the available fMRI data.ResultsES-SDM analysis revealed hyperactivation in the right inferior frontal gyrus and left supplementary motor area in ASD during observation of biological motions. Subgroup analysis of experiments involving the observation of stimuli with or without emotional component revealed hyperactivation in the left inferior parietal lobule and left supplementary motor during action observation without emotional components, whereas hyperactivation of the right inferior frontal gyrus was found during action observation with emotional components in ASD. Subgroup analyses of age showed hyperactivation of the bilateral inferior frontal gyrus in ASD adolescents, while hyperactivation in the right inferior frontal gyrus was noted in ASD adults. Meta-regression within ASD individuals indicated that the right cerebellum crus I activation increased with age, while the left inferior temporal gyrus activation decreased with age.LimitationsThis meta-analysis is limited in its generalization of the findings to individuals with ASD by the restricted age range, heterogeneous study sample, and the large within-group variation in MNS activation patterns during object observation. Furthermore, we only included action observation studies which might limit the generalization of our results to the imitation deficits in ASD. In addition, the relatively small sample size for individual studies might also potentially overestimate the effect sizes.ConclusionThe MNS is impaired in ASD. The abnormal activation patterns were found to be modulated by the nature of stimuli and age, which might explain the contradictory results from earlier studies on the “broken mirror neuron” debate.

Altered white matter microarchitecture in Parkinson's disease: a voxel-based meta-analysis of diffusion tensor imaging studies.

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson's disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size-signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with 30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses.

Failure of activation of striatum during the performance of executive function tasks in adult patients with bipolar disorder.

Although numerous studies have used functional neuroimaging to identify executive dysfunction in patients with bipolar disorder (BD), the findings are not consistent. The aim of this meta-analysis is to identify the most reliable functional anomalies in BD patients during performance of Executive Function (EF) tasks. A web-based search was performed on publication databases to identify functional magnetic resonance imaging studies of BD patients performing EF tasks and a voxel-based meta-analytic method known as anisotropic Effect Size Signed Differential Mapping (ES-SDM) was used to identify brain regions which showed anomalous activity in BD patients compared with healthy controls (HC). Twenty datasets consisting of 463 BD patients and 484 HC were included. Compared with HC, BD patients showed significant hypo-activation or failure of activation in the left striatum (p = 0.00007), supplementary motor area (BA 6, p = 0.00037), precentral gyrus (BA 6, p = 0.0014) and cerebellum (BA 37, p = 0.0019), and hyper-activation in the left gyrus rectus (BA 11, p ≈ 0) and right middle temporal gyrus (BA 22, p = 0.00031) during performance of EF tasks. Sensitivity and subgroup analyses showed that the anomaly of left striatum is consistent across studies and present in both euthymic and BD I patients. Patients with BD consistently showed abnormal activation in the cortico-striatal system during performance of EF tasks compared with HC. Failure of activation of the striatum may be a reliable marker for impairment in performance of especially inhibition tasks by patients with BD.

Brain regions responding to acupuncture stimulation of Zusanli (ST36) in healthy subjects analyzed on the basis of spontaneous brain activity

To determine the attributes of responses of the higher nerve center to acupuncture stimulation of Zusanli (ST36) on the basis of spontaneous brain activity, so as to explore the synchronization level of different brain rejoins after acupuncture. All studies using fMRI to investigate the effect of acupuncture stimulation of ST36 and/or other acupoints on the human brain (at least 10 healthy subjects or patients in one group) published in journals from January of 1995 to January of 2018 were searched from databases of CNKI and PubMed by using keywords of acupuncture, electroacupuncture, and resting-state functional magnetic resonance images (rs-fMRI) or regional homogeneity (ReHo). Brain functional image data of acupuncture stimulation of ST36 and/or other acupoints were collected and analyzed with anisotropic effect size-signed differential mapping (AES-SDM) software (Meta-analysis), and those of acupuncture of simple ST36 analyzed as a subgroup. A total of 229 papers in Chinese and 109 in English were collected. According to our inclusive and exclusive standards, 11 papers containing 235 subjects were brought into analysis at last. Meta-analysis of brain image data of acupuncture at ST36 and/or other acupoints (comparison between pre- and post-acupuncture) revealed that the same brain regions (generality) which showed a significant increase in ReHo, are the right and left anterior cingulated gyrus, right caudate, left superior frontal gyrus, right middle frontal gyrus, and the right paracentral lobe, and those which showed a marked decrease of ReHo are the left mid-inferior occipital gyrus, left and right precentral and postcentral gyrus. The brain regions responding to acupuncture at ST36 only (specificity) are the right inferior parietal lobe, left middle inferior gyrus, right posterior lobe of cerebellum, and the left angular gyrus which displayed an increase of ReHo, and the right middle superior frontal gyrus which showed a decrease in ReHo. After acupuncturing at ST36, the relative generality and specificity of the central response in healthy subjects reflected as the location of the affected brain regions and the difference in the synchronization level of the corresponding spontaneous brain activities.

A Quantitative Meta-analysis of Neuroimaging Studies of Pragmatic Language Comprehension: In Search of a Universal Neural Substrate

Pragmatics may be defined as the ability to communicate by expressing and recognizing intentions. The objective of this meta-analysis was to identify neural substrates for comprehension of pragmatic content in general, as well as the differences between pragmatic forms, and to describe if there is differential recruitment of brain areas according to natural language. This meta-analysis included 48 functional magnetic resonance imaging studies that reported pragmatic versus literal language contrasts. The pragmatic forms were speech acts, metaphors, idioms, and irony. Effect Size-Signed Differential Mapping software was used to calculate the mean for all contrasts as well as for each pragmatic form, and make comparisons among all forms. Due to variations in pragmatic content configuration such as natural language, stimulus modality, and writing systems, these variations were also analyzed with subgroups’ analyses. The analyses found a highly reproducible bilateral fronto-temporal and medial prefrontal cortex network for pragmatic comprehension. Each pragmatic form showed a specific convergence pattern within this bilateral network. Natural language analyses showed that fronto-temporal regions were recruited by Germanic languages, while only left frontal areas were recruited by Romance languages, and right medial prefrontal cortex by Japanese. In conclusion, pragmatic language comprehension involves classical language areas in bilateral perisylvian regions, along with the medial prefrontal cortex, an area involved in social cognition. Together, these areas could represent the “pragmatic language network”. Nonetheless, when proposing a universal neural substrate for all forms of pragmatic language, the diversity among studies in terms of pragmatic form, and configuration, must be taken into consideration.

Altered Resting-State Functional Activity in Patients With Autism Spectrum Disorder: A Quantitative Meta-Analysis.

Background: There is accumulating evidence showing that patients with autism spectrum disorder (ASD) have obvious changes in resting-state functional brain activity. So far, there have been no meta-analyses of the resting-state brain activity alterations in patients with ASD. We attempted to explore the resting-state functional activity changes in patients with ASD, possibly providing a new perspective for investigating the pathophysiology of patients with ASD.Methods: We screened relevant studies published before August 2017 in PubMed, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wan-fang database. Fifteen resting-state functional neural activity datasets (including 382 patients and 348 healthy controls) were included. Through the use of the effect-size signed differential mapping (ES-SDM) method, we carried out a meta-analysis of resting-state functional activity studies of patients with ASD.Results: Compared with healthy controls, patients with ASD showed hyperactivity in the right supplementary motor area, middle frontal gyrus, inferior frontal gyrus, the left precentral gyrus, and the bilateral cerebellum hemispheric lobule (VIII/IX), and hypoactivity in the right middle temporal gyrus, superior temporal gyrus, and the left precuneus, posterior cingulate cortex, median cingulate cortex, and bilateral cerebellum (crus I).Conclusion: This meta-analysis indicates that patients with ASD have significant and robust resting-state brain activity alterations in the language comprehension network, inferior-posterior cerebellum, default mode network (DMN), and cerebellar crus I. These brain regions may serve as specific regions of interest for further studies of ASD, which will allow us to further clarify the neurobiological mechanisms in patients with ASD.

Functional Connectivity of the Corticobasal Ganglia-Thalamocortical Network in Parkinson Disease: A Systematic Review and Meta-Analysis with Cross-Validation.

Purpose To quantitatively summarize the functional connectivity (FC) feature of the corticobasal ganglia-thalamocortical (CBTC) network in patients with Parkinson disease (PD) by means of a meta-analysis with cross-validation. Materials and Methods For this prospective study, a systematic literature search in the PubMed and EMBASE databases was performed for resting-state functional magnetic resonance (MR) imaging studies of PD published between January 2000 and May 2017. Then, a coordinate-based meta-analysis was conducted by Effect Size-Signed Differential Mapping. A cross-validation analysis was performed by using an independent resting-state functional MR imaging data set that contained 25 patients with PD and 19 age-, sex-, and education-matched healthy control participants. Two-sample t test was performed on FC maps between PD and control groups. Results Thirty studies with 854 patients with PD and 831 control participants were included in this meta-analysis. The main meta-analysis found increased FC in the left pre- and postcentral gyrus in patients with PD compared with healthy control participants (z = 2.6; P < .001). The abnormality of the postcentral gyrus was further confirmed by subgroup meta-analyses on medication-naive (n = 25; z = 2.2; P < .001) and medication-off (n = 11; z = 1.5; P < .001) experiments, which suggested that the finding was unaffected by medication. The abnormality of the postcentral gyrus was cross-validated by the independent data set (t = 5.0; P < .05), which suggested a high reproducibility and generalizability. Conclusion This meta-analysis emphasizes the left postcentral gyrus as a critical region in PD, which may become a potential target for clinical intervention. © RSNA, 2018 Online supplemental material is available for this article.

Altered white matter microarchitecture in amyotrophic lateral sclerosis: A voxel-based meta-analysis of diffusion tensor imaging.

BackgroundThe results of recent diffusion tensor imaging (DTI) studies on amyotrophic lateral sclerosis (ALS) are inconclusive and controversial. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS.MethodsA systematic search was conducted for relevant studies that used voxel-wise analyses of WM microarchitecture in patients with ALS. Anisotropic effect size-signed differential mapping (AES-SDM) was applied to analyze fractional anisotropy (FA) differences between ALS patients and healthy controls. Meta-regression analysis was used to explore the effects of clinical characteristics on WM integrity in patients with ALS.ResultsA total of 14 studies with 16 datasets that included 396 patients and 360 healthy controls were identified. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The largest cluster exhibited a peak coordinate in the left corona radiata, extending to the body and splenium of the corpus callosum, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus. The other cluster exhibited decreased FA in the right corticospinal tract that extended to the right cerebral peduncle. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Mean age and illness duration were not linearly correlated with the FA reductions.ConclusionsThis study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract but also includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

Voxel-Wise Meta-Analysis of Gray Matter Changes in Amyotrophic Lateral Sclerosis.

Background: Increasing neuroimaging studies have revealed gray matter (GM) anomalies of several brain regions by voxel-based morphometry (VBM) studies in patients with amyotrophic lateral sclerosis (ALS). A voxel-wise meta-analysis was conducted to integrate the reported studies to determine the consistent GM alterations in ALS based on VBM methods.Methods: Ovid Medline, Pubmed, Emabase, and BrainMap database were searched for relevant studies.Data were extracted by two independent researchers. Voxel-wise meta-analysis was performed using the effect-size signed differential mapping (ES-SDM) software.Results: Twenty-nine VBM studies comprising 638 subjects with ALS and 622 healthy controls (HCs) met inclusion criteria.The global GM volumes of ALS patients were significantly decreased compared with those of HCs. GM reductions in patients were mainly located in the right precentral gyrus, the left Rolandic operculum, the left lenticular nucleus and the right anterior cingulate/paracingulate gyri. The right precentral gyrus and the left inferior frontal gyrus might be potential anatomical biomarkers to evaluate the severity of the disease, and longer disease duration was associated with more GM atrophy in the left frontal aslant tract and the right precentral gyrus in ALS patients.Conclusion: The results support that ALS is a complex degenerative disease involving multisystems besides the motor system.The mechanism of asymmetric atrophy of the motor cortex and the implication of Rolandic operculum involvement in ALS need to be further elucidated in future studies.

Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics

White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.

Gray matter abnormalities in cocaine versus methamphetamine-dependent patients: a neuroimaging meta-analysis

Background: Voxel-based morphometry has been used to explore gray matter alterations in cocaine and methamphetamine dependence. However, the results of this research are inconsistent. Objectives: The current study meta-analytically examined neuroimaging findings of all studies published before 2014 using the Anisotropic Effect-Size Signed Differential Mapping (ES-SDM). Methods: Independent investigators searched four major databases for relevant neuroimaging studies involving cocaine and methamphetamine dependence. Nine cocaine and four methamphetamine studies met inclusion criteria. Results: Results indicated that cocaine- and methamphetamine-dependent patients share overlapping regional gray matter abnormalities compared to healthy controls. However, subgroup analysis showed some regional differences; with methamphetamine showing more prominent reductions in the left superior temporal gyrus and the right inferior parietal lobe. Reductions in the right insula and the left superior frontal gyrus were more prominent in cocaine dependence. Moderator analyses indicated that with longer use, cocaine is associated with reductions in the right hippocampus, right middle temporal gyrus, and right inferior frontal gyrus, while methamphetamine is associated with reductions in the left precentral gyrus and the right supramarginal gyrus. Conclusion: These findings indicate that cocaine and methamphetamine dependence are significantly and differentially associated with gray matter abnormalities. Results also point to possible gray matter recovery after abstinence from methamphetamine. Although the sample size was adequate, these findings should be considered preliminary and analyses should be revisited with additional primary research focusing on long or short-term duration of use, as well as the length of abstinence.

Voxel-based meta-analysis of grey matter changes in Alzheimer's disease.

BackgroundVoxel-based morphometry (VBM) using structural brain MRI has been widely used for the assessment of impairment in Alzheimer’s disease (AD), but previous studies in VBM studies on AD remain inconsistent.ObjectiveWe conducted meta-analyses to integrate the reported studies to determine the consistent grey matter alterations in AD based on VBM method.MethodsThe PubMed, ISI Web of Science, EMBASE and Medline database were searched for articles between 1995 and June 2014. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters with significant grey matter difference between AD patients and healthy controls (HC). Meta-analysis was performed using a new improved voxel-based meta-analytic method, Effect Size Signed Differential Mapping (ES-SDM).ResultsThirty data-sets comprising 960 subjects with AD and 1195 HC met inclusion criteria. Grey matter volume (GMV) reduction at 334 coordinates in AD and no GMV increase were found in the current meta-analysis. Significant reductions in GMV were robustly localized in the limbic regions (left parahippocampl gyrus and left posterior cingulate gyrus). In addition, there were GM decreases in right fusiform gyrus and right superior frontal gyrus. The findings remain largely unchanged in the jackknife sensitivity analyses.ConclusionsOur meta-analysis clearly identified GMV atrophy in AD. These findings confirm that the most prominent and replicable structural abnormalities in AD are in the limbic regions and contributes to the understanding of pathophysiology underlying AD.

White matter abnormalities in long-term heroin users: a preliminary neuroimaging meta-analysis

Background: Diffusion tensor imaging has been used to explore white matter changes in heroin-dependent patients; however, results have been inconsistent. Objectives: The current study meta-analytically examines the neuroimaging findings of all studies published before 2014 using the novel technique of Effect Size Signed Differential Mapping (ES-SDM). Methods: Two independent investigators searched three databases for whole-brain voxel-based fractional anisotropy morphometric studies involving heroin use without comorbid polysubstance abuse. Of 59 initial primary studies, four met stringent inclusion criteria. Results: Results from this preliminary analysis indicate that heroin abusers may have significant reductions in fractional anisotropy in the bilateral frontal sub-gyral regions extending from the limbic structures to the prefrontal association cortices, implicating damage to the cingulum and superior longitudinal fasciculus. Exploratory moderator analyses indicate that the potential damage in the left cingulate gyrus may increase with longer use and decrease after long-term abstinence. Conclusion: These preliminary findings suggest that heroin abuse is significantly associated with damage to white matter integrity. These results are considered preliminary and analyses should be revisited with more primary studies focusing on either long- or short-term abuse as well as abstinence.

Meta-analytic Comparison Between PIB-PET and FDG-PET Results in Alzheimer’s Disease and MCI

We conducted a meta-analysis of positron emission tomography (PET) findings in Alzheimer's disease (AD) and mild cognitive impairment (MCI) to clarify the changes underpinning these conditions. All studies that utilised the PET tracers Pittsburgh Compound-B (PIB) or 2-[18F]fluoro-2-deoxy-D-glucose (FDG) to investigate patients with MCI or AD, were considered for the meta-analysis. Meta-analyses of PIB-PET and FDG-PET changes between patients and controls were undertaken with the effect-size signed differential mapping (ES-SDM) voxel-based meta-analytic method. A total of 24 studies were included involving 728 AD patients, 211 MCI patients and 658 healthy controls. Individuals with AD showed a significant PIB retention in bilateral precuneus and temporal, supramarginal, cingulate and fusiform gyri, as well as right insula and putamen. In addition, AD patients showed significant glucose hypometabolism in bilateral precuneus and temporal, supramarginal, cingulate, fusiform, angular, inferior parietal and middle frontal gyri, as well as left precentral and parahippocampal gyri and right superior frontal gyrus and thalamus. An exploratory meta-analysis of the few studies on MCI showed mildly decreased glucose metabolism with a similar regional distribution than in patients with AD. We suggest that our results can be used for further region-of-interest studies of AD and MCI patients.