Specific cortico-striato-thalamic circuits are hypothesised to mediate the symptoms of obsessive-compulsive disorder (OCD), but structural neuroimaging studies have been inconsistent.
To conduct a ...meta-analysis of published and unpublished voxel-based morphometry studies in OCD.
Twelve data-sets comprising 401 people with OCD and 376 healthy controls met inclusion criteria. A new improved voxel-based meta-analytic method, signed differential mapping (SDM), was developed to examine regions of increased and decreased grey matter volume in the OCD group v. control group. Results No between-group differences were found in global grey matter volumes. People with OCD had increased regional grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, as well as decreased volumes in bilateral dorsal medial frontal/anterior cingulate gyri. A descriptive analysis of quartiles, a sensitivity analysis as well as analyses of subgroups further confirmed these findings. Meta-regression analyses showed that studies that included individuals with more severe OCD were significantly more likely to report increased grey matter volumes in the basal ganglia. No effect of current antidepressant treatment was observed. Conclusions The results support a dorsal prefrontal-striatal model of the disorder and raise the question of whether functional alterations in other brain regions commonly associated with OCD, such as the orbitofrontal cortex, may reflect secondary compensatory strategies. Whether the reported differences between participants with OCD and controls precede the onset of the symptoms and whether they are specific to OCD remains to be established.
Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not ...fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
We meta-analyzed imaging studies on theory of mind and formed individual task groups based on stimuli and instructions. Overlap in brain activation between all task groups was found in the mPFC and ...in the bilateral posterior TPJ. This supports the idea of a core network for theory of mind that is activated whenever we are reasoning about mental states, irrespective of the task- and stimulus-formats (Mar, 2011). In addition, we found a number of task-related activation differences surrounding this core-network. ROI based analyses show that areas in the TPJ, the mPFC, the precuneus, the temporal lobes and the inferior frontal gyri have distinct profiles of task-related activation. Functional accounts of these areas are reviewed and discussed with respect to our findings.
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).
ObjectiveChildhood maltreatment acts as a severe stressor that produces a cascade of physiological and neurobiological changes that lead to enduring alterations in brain structure. However, ...structural neuroimaging findings have been inconsistent. The authors conducted a meta-analysis of published whole-brain voxel-based morphometry studies in childhood maltreatment to elucidate the most robust volumetric gray matter abnormalities relative to comparison subjects to date.MethodTwelve data sets were included, comprising 331 individuals (56 children/adolescents and 275 adults) with a history of childhood maltreatment and 362 comparison subjects (56 children/adolescents and 306 adults). Anisotropic effect size-signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of smaller and larger gray matter volumes in maltreated individuals relative to comparison subjects.ResultsRelative to comparison subjects, individuals exposed to childhood maltreatment exhibited significantly smaller gray matter volumes in the right orbitofrontal/superior temporal gyrus extending to the amygdala, insula, and parahippocampal and middle temporal gyri and in the left inferior frontal and postcentral gyri. They had larger gray matter volumes in the right superior frontal and left middle occipital gyri. Deficits in the right orbitofrontal-temporal-limbic and left inferior frontal regions remained in a subgroup analysis of unmedicated participants. Abnormalities in the left postcentral and middle occipital gyri were found only in older maltreated individuals relative to age-matched comparison subjects.ConclusionsThe findings demonstrate that the most consistent gray matter abnormalities in individuals exposed to childhood maltreatment are in relatively late-developing ventrolateral prefrontal-limbic-temporal regions that are known to mediate late-developing functions of affect and cognitive control, which are typically compromised in this population.
Abstract Objective Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped/repetitive and compulsive ...behaviours, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions. Methods A comparative meta-analysis of 62 voxel-based morphometry (VBM) and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing grey matter volume (GMV) and activation abnormalities between ASD (sMRI:911;fMRI:188) and OCD (sMRI:928;fMRI:247) patients versus controls. Multimodal meta-analysis compared groups across VBM and fMRI. Results Both disorders shared reduced function and structure in rostral/dorsomedial prefrontal cortex including anterior cingulate. OCD had disorder-specific increase in structure and function of left basal ganglia (BG)/insula relative to controls and ASD, who had reduced right BG/insula volumes versus OCD. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, while OCD patients showed temporo-parietal underactivation. Conclusions The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. While rostro-dorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG/insula in OCD, but a reduction in ASD, presumably reflecting a disorder-specific fronto-striato-insular dysregulation in OCD in the form of poor frontal control over overactive BG, and a fronto-striato-insular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in ASD and OCD.
This meta-analysis of brain imaging studies confirmed that gray matter volume deficits are less abnormal for patients taking stimulants and for adults with the disorder. The latter finding suggests ...that development may “catch up” as the patient ages.
Objective:Structural neuroimaging studies in attention-deficit hyperactivity disorder (ADHD) have been relatively inconsistent and have mainly been conducted with pediatric samples. Furthermore, there is evidence that stimulant medication may have an effect on brain structure. The authors conducted a meta-analysis of voxel-based morphometry studies in children and adults with ADHD and examined the potential effects of age and stimulant medication on regional gray matter volumes.
Method:The PubMed, ScienceDirect, Web of Knowledge, and Scopus databases were searched for articles published between 2001 and 2011. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters of significant gray matter difference between ADHD patients and healthy comparison subjects. Metaregression methods were used to explore potential age and stimulant medication effects.
Results:Fourteen data sets comprising 378 patients with ADHD and 344 healthy subjects met inclusion criteria. The ADHD group had global reductions in gray matter volumes, which were robustly localized in the right lentiform nucleus and extended to the caudate nucleus. Both increasing age and percentage of patients taking stimulant medication were found to be independently associated with more normal values in this region. Patients also had slightly greater gray matter volumes in the left posterior cingulate cortex.
Conclusions:These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.
Along with the increased interest in and volume of social cognition research, there has been higher awareness of a lack of agreement on the concepts and taxonomy used to study social processes. Two ...central concepts in the field, empathy and Theory of Mind (ToM), have been identified as overlapping umbrella terms for different processes of limited convergence. Here, we review and integrate evidence of brain activation, brain organization, and behavior into a coherent model of social-cognitive processes. We start with a meta-analytic clustering of neuroimaging data across different social-cognitive tasks. Results show that understanding others' mental states can be described by a multilevel model of hierarchical structure, similar to models in intelligence and personality research. A higher level describes more broad and abstract classes of functioning, whereas a lower one explains how functions are applied to concrete contexts given by particular stimulus and task formats. Specifically, the higher level of our model suggests 3 groups of neurocognitive processes: (a) predominantly cognitive processes, which are engaged when mentalizing requires self-generated cognition decoupled from the physical world; (b) more affective processes, which are engaged when we witness emotions in others based on shared emotional, motor, and somatosensory representations; (c) combined processes, which engage cognitive and affective functions in parallel. We discuss how these processes are explained by an underlying principal gradient of structural brain organization. Finally, we validate the model by a review of empathy and ToM task interrelations found in behavioral studies.
Public Significance Statement
Empathy and Theory of Mind are important human capacities for understanding others. Here, we present a meta-analysis of neuroimaging data from 4,207 participants, which shows that these abilities can be deconstructed into specific and partially shared neurocognitive subprocesses. Our findings provide systematic, large-scale support for the hypothesis that understanding others' mental states can be described by a multilevel model of hierarchical structure, similar to models in intelligence and personality research.
Attention-deficit hyperactivity disorder (ADHD) is associated with deficits in timing functions with, however, inconclusive findings on the underlying neurofunctional deficits. We therefore conducted ...a meta-analysis of 11 functional magnetic resonance imaging (fMRI) studies of timing in ADHD, comprising 150 patients and 145 healthy controls. Peak coordinates were extracted from significant case-control activation differences as well as demographic, clinical, and methodological variables. In addition, meta-regression analyses were used to explore medication effects. The most consistent deficits in ADHD patients relative to controls were reduced activation in typical areas of timing such as left inferior prefrontal cortex (IFC)/insula, cerebellum, and left inferior parietal lobe. The findings of left fronto-parieto-cerebellar deficits during timing functions contrast with well documented right fronto-striatal dysfunctions for inhibitory and attention functions, suggesting cognitive domain-specific neurofunctional deficits in ADHD. The meta-regression analysis showed that right dorsolateral prefrontal cortex (DLPFC) activation was reduced in medication-naïve patients but normal in long-term stimulant medicated patients relative to controls, suggesting potential normalization effects on the function of this prefrontal region with long-term psychostimulant treatment.
Abstract Background Identification of white matter microstructure differences and similarities between major depression and bipolar disorder is a necessary step to better understand the underlying ...brain abnormalities in affective disorders and target more effective treatments. However, research has not yet yielded robust conclusions. We report here a meta-analysis of diffusion tensor imaging studies in these conditions. Methods A comprehensive literature search was conducted up to 2014 to identify studies comparing fractional anisotropy (FA) between patients and control subjects. Results were combined to identify white matter abnormalities in major depression (736 patients vs. 668 control subjects) and bipolar disorder (536 patients vs. 489 control subjects). Effect size comparison and conjunction analysis allowed identification of similarities and differences between the disorders. Results A significant decrease in FA in the genu of the corpus callosum characterized both conditions. The comparison between unipolar and bipolar disorders revealed a greater decrease in FA in the left posterior cingulum in bipolar disorder. Studies that adopted tract-based spatial statistics methodology showed more pronounced reductions in these regions compared with voxel-based analyses. Conclusions Major depression and bipolar disorder are characterized by abnormalities in white matter tracts of the genu of the corpus callosum that connect the two hemispheres of the prefrontal cortex implicated in mood regulation. Bipolar disorder was associated with reduced white matter integrity in the left posterior cingulum, which may contribute to cognitive impairment described in this condition. Tract-based spatial statistics may be a more sensitive technique to detect white matter abnormalities in these regions compared with voxel-based analyses.
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