A multimodal meta-analysis of regional functional and structural brain abnormalities in obsessive-compulsive disorder.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.

Functional and structural brain abnormalities in substance use disorder: A multimodal meta-analysis of neuroimaging studies.

INTRODUCTION: Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta-analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV). METHODS: A whole-brain meta-analysis on resting-state functional imaging and VBM studies was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD. RESULTS: In this meta-analysis, 39 independent studies with 47 datasets related to resting-state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting-state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta-analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex. CONCLUSIONS: This multimodal meta-analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.

Functional and structural brain differences in bipolar disorder: a multimodal meta-analysis of neuroimaging studies.

BACKGROUND: Numerous studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed differences in specific brain regions of patients with bipolar disorder (BD), but the results have been inconsistent. METHODS: A whole-brain voxel-wise meta-analysis was conducted on resting-state functional imaging and VBM studies that compared differences between patients with BD and healthy controls using Seed-based d Mapping with Permutation of Subject Images software. RESULTS: A systematic literature search identified 51 functional imaging studies (1842 BD and 2190 controls) and 83 VBM studies (2790 BD and 3690 controls). Overall, patients with BD displayed increased resting-state functional activity in the left middle frontal gyrus, right inferior frontal gyrus (IFG) extending to the right insula, right superior frontal gyrus and bilateral striatum, as well as decreased resting-state functional activity in the left middle temporal gyrus extending to the left superior temporal gyrus and post-central gyrus, left cerebellum, and bilateral precuneus. The meta-analysis of VBM showed that patients with BD displayed decreased VBM in the right IFG extending to the right insula, temporal pole and superior temporal gyrus, left superior temporal gyrus extending to the left insula, temporal pole, and IFG, anterior cingulate cortex, left superior frontal gyrus (medial prefrontal cortex), left thalamus, and right fusiform gyrus. CONCLUSIONS: The multimodal meta-analyses suggested that BD showed similar patterns of aberrant brain activity and structure in the insula extending to the temporal cortex, fronto-striatal-thalamic, and default-mode network regions, which provide useful insights for understanding the underlying pathophysiology of BD.

Structural and functional brain alterations in anorexia nervosa:A multimodal meta-analysis of neuroimaging studies.

Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel-based morphometry (VBM) and resting-state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole-brain meta-analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting-state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting-state functional imaging studies, patients with AN displayed decreased resting-state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting-state functional activity in the right parahippocampal gyrus. This multimodal meta-analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.

Altered brain function in persistent postural perceptual dizziness: A study on resting state functional connectivity.

This study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I-IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.

Brain network alteration in patients with temporal lobe epilepsy with cognitive impairment.

The aims of this study were to investigate the brain network alternation in patients with temporal lobe epilepsy (TLE) with and without cognitive impairment (CI) using functional magnetic resonance imaging (fMRI) and to further explore the potential mechanisms of epilepsy-induced CI. Forty patients with TLE and nineteen healthy controls (HCs) were recruited for this study. All participants received the Montreal Cognitive Assessment (MoCA) test, and the patients were divided into CI (n=21) and cognitive nonimpairment (CNI) groups (n=19) according to MoCA performance. Functional connectivity (FC) differences of resting state networks (RSNs) were compared among the CI, CNI, and HC groups. Correlation between FC and MoCA scores was also observed. When compared with the HC group, significantly decreased FC between medial visual network (mVN) and left frontoparietal network (lFPN) as well as between visuospatial network (VSN) and the anterior default mode network (aDMN) were revealed in both CI and CNI groups. In addition, significantly decreased FC between lFPN and executive control network (ECN) and increased FC between ECN and sensorimotor-related network (SMN) were found in CNI and CI groups, respectively. When compared with the CNI group, the CI group exhibited significant increased FC between ECN and lFPN as well as between ECN and SMN. Moreover, in the CI group, FC between ECN and lFPN showed negative correlation with attention scores. Our findings suggested that cognitive networks are different from epileptic networks, and the increased FC between RSNs closely related to cognitive function changes may help us to further understand the mechanism of CI in TLE.

Compensation patterns and altered functional connectivity in alcohol use disorder with and without Korsakoff's syndrome.

Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff's syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff's syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff's syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff's syndrome compared to alcohol use disorder without Korsakoff's syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff's syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff's syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff's syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients' overall lower cognitive performance. Korsakoff's syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder.

BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Meta-analysis of structural and functional brain abnormalities in early-onset schizophrenia.

Background: Previous studies based on resting-state functional magnetic resonance imaging(rs-fMRI) and voxel-based morphometry (VBM) have demonstrated significant abnormalities in brain structure and resting-state functional brain activity in patients with early-onset schizophrenia (EOS), compared with healthy controls (HCs), and these alterations were closely related to the pathogenesis of EOS. However, previous studies suffer from the limitations of small sample sizes and high heterogeneity of results. Therefore, the present study aimed to effectively integrate previous studies to identify common and specific brain functional and structural abnormalities in patients with EOS. Methods: The PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were systematically searched to identify publications on abnormalities in resting-state regional functional brain activity and gray matter volume (GMV) in patients with EOS. Then, we utilized the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software to conduct a whole-brain voxel meta-analysis of VBM and rs-fMRI studies, respectively, and followed by multimodal overlapping on this basis to comprehensively identify brain structural and functional abnormalities in patients with EOS. Results: A total of 27 original studies (28 datasets) were included in the present meta-analysis, including 12 studies (13 datasets) related to resting-state functional brain activity (496 EOS patients, 395 HCs) and 15 studies (15 datasets) related to GMV (458 EOS patients, 531 HCs). Overall, in the functional meta-analysis, patients with EOS showed significantly increased resting-state functional brain activity in the left middle frontal gyrus (extending to the triangular part of the left inferior frontal gyrus) and the right caudate nucleus. On the other hand, in the structural meta-analysis, patients with EOS showed significantly decreased GMV in the right superior temporal gyrus (extending to the right rolandic operculum), the right middle temporal gyrus, and the temporal pole (superior temporal gyrus). Conclusion: This meta-analysis revealed that some regions in the EOS exhibited significant structural or functional abnormalities, such as the temporal gyri, prefrontal cortex, and striatum. These findings may help deepen our understanding of the underlying pathophysiological mechanisms of EOS and provide potential biomarkers for the diagnosis or treatment of EOS.

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis.

Background: Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. Objectives: To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Design: Single-center retrospective cross-sectional study. Methods: Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-ß and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3 Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. Results: In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network. Conclusion: Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Functional connectivity of the cerebellar vermis in bipolar disorder and associations with mood.

Purpose: Studies of the neural underpinnings of bipolar type I disorder have focused on the emotional control network. However, there is also growing evidence for cerebellar involvement, including abnormal structure, function, and metabolism. Here, we sought to assess functional connectivity of the cerebellar vermis with the cerebrum in bipolar disorder and to assess whether connectivity might depend on mood. Methods: This cross-sectional study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed a 3 T magnetic resonance imaging (MRI) study, which included anatomical as well as resting state Blood Oxygenation Level Dependent (BOLD) imaging. Functional connectivity of the cerebellar vermis to all other brain regions was assessed. Based on quality control metrics of the fMRI data, 109 participants with bipolar disorder and 79 controls were included in the statistical analysis comparing connectivity of the vermis. In addition, the data was explored for the potential impacts of mood, symptom burden, and medication in those with bipolar disorder. Results: Functional connectivity between the cerebellar vermis and the cerebrum was found to be aberrant in bipolar disorder. The connectivity of the vermis was found to be greater in bipolar disorder to regions involved in motor control and emotion (trending), while reduced connectivity was observed to a region associated with language production. In the participants with bipolar disorder, past depression symptom burden affected connectivity; however, no effects of medication were observed. Functional connectivity between the cerebellar vermis and all other regions revealed an inverse association with current mood ratings. Conclusion: Together the findings may suggest that the cerebellum plays a compensatory role in bipolar disorder. The proximity of the cerebellar vermis to the skull may make this region a potential target for treatment with transcranial magnetic stimulation.

Changes in resting-state functional brain activity are associated with waning cognitive functions in HIV-infected children.

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment.

Longitudinal evaluation of resting-state connectivity, white matter integrity and cortical thickness in stable HIV infection: Preliminary results.

Purpose The objectives of this study were to determine if HIV-infected patients treated with highly active antiretroviral therapy (HAART), without dementia, suffer from longitudinal gray matter (GM) volume loss, changes in white matter (WM) integrity and deterioration in functional connectivity at rest, in an average interval of 30 months. Methods Clinically stable HIV-positive patients (on HAART, CD4 + T lymphocyte > 200 cells/µl, and viral loads <50 copies/µl) were recruited. None of them had HIV-associated dementia. Each patient underwent two scans, performed in a 1.5-T magnetic resonance imaging (MRI) scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of GM structures. WM integrity was assessed using tract-based spatial statistics to post-process diffusion tensor imaging data, and FMRIB's Software Library tools were used to post-process resting-state functional magnetic resonance imaging (RS-fMRI). Results There were no significant differences in cortical thickness, deep GM volumes, or diffusivity parameters between the scans at the two time points. Five resting-state networks were identified in our patients. In the second MRI, HIV-positive patients presented increased areas of functional connectivity in visual pathways, frontoparietal and cerebellar networks, compared with the first MRI (considering p < 0.05). Conclusions RS-fMRI revealed potentially compensatory longitudinal alterations in the brains of HIV-positive patients, attempting to compensate for brain damage related to the infection.