Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety ...disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understood. Here we provide a comprehensive meta-analysis of human fear-conditioning studies carried out with functional magnetic resonance imaging (fMRI), yielding a pooled sample of 677 participants from 27 independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from the authors of 13 of these studies. Our primary analyses demonstrate that human fear conditioning is associated with a consistent and robust pattern of neural activation across a hypothesized genuine network of brain regions resembling existing anatomical descriptions of the 'central autonomic-interoceptive network'. This finding is discussed with a particular emphasis on the neural substrates of conscious fear processing. Our associated meta-analysis of functional deactivations-a scarcely addressed dynamic in fMRI fear-conditioning studies-also suggests the existence of a coordinated brain response potentially underlying the 'safety signal' (that is, non-threat) processing. We attempt to provide an integrated summary on these findings with the view that they may inform ongoing studies of fear-conditioning processes both in healthy and clinical populations, as investigated with neuroimaging and other experimental approaches.
Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available ...structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment.
Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk HR) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and "signed differential mapping" voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables.
Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results.
Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.
While multiple studies have examined the brain functional correlates of reward, meta-analyses have either focused on studies using the monetary incentive delay (MID) task, or have adopted a broad ...strategy, combining data from studies using both monetary and non-monetary reward, as probed using a wide range of tasks. To meta-analyze fMRI studies that used monetary reward and in which there was a definable cue-reward contingency. Studies were limited to those using monetary reward in order to avoid potential heterogeneity from use of other rewards, especially social rewards. Studies using gambling or delay discounting tasks were excluded on the grounds that reward anticipation is not easily quantifiable. Ovid, Medline and PsycInfo, from 2000 to 2020, plus checking of review articles and meta-analyses. Pooled data from 45 studies of reward anticipation revealed activations in the ventral striatum, the middle cingulate cortex/supplementary motor area and the insula. Pooled data from 28 studies of reward delivery again revealed ventral striatal activation, plus cortical activations in the anterior and posterior cingulate cortex. There was relatively little evidence of publication bias. Among moderating variables, only whether the task was pre-learnt exerted an influence. According to this meta-analysis monetary reward anticipation and delivery both activate the ventral but not the dorsal striatum, and are associated with different patterns of cortical activation.
Structure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are ...available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions.
Cognitive-behavioural therapy (CBT) is considered to be effective for the symptoms of schizophrenia. However, this view is based mainly on meta-analysis, whose findings can be influenced by failure ...to consider sources of bias.
To conduct a systematic review and meta-analysis of the effectiveness of CBT for schizophrenic symptoms that includes an examination of potential sources of bias.
Data were pooled from randomised trials providing end-of-study data on overall, positive and negative symptoms. The moderating effects of randomisation, masking of outcome assessments, incompleteness of outcome data and use of a control intervention were examined. Publication bias was also investigated.
Pooled effect sizes were -0.33 (95% CI -0.47 to -0.19) in 34 studies of overall symptoms, -0.25 (95% CI -0.37 to -0.13) in 33 studies of positive symptoms and -0.13 (95% CI -0.25 to -0.01) in 34 studies of negative symptoms. Masking significantly moderated effect size in the meta-analyses of overall symptoms (effect sizes -0.62 (95% CI -0.88 to -0.35) v. -0.15 (95% CI -0.27 to -0.03), P = 0.001) and positive symptoms (effect sizes -0.57 (95% CI -0.76 to -0.39) v. -0.08 (95% CI -0.18 to 0.03), P<0.001). Use of a control intervention did not moderate effect size in any of the analyses. There was no consistent evidence of publication bias across different analyses.
Cognitive-behavioural therapy has a therapeutic effect on schizophrenic symptoms in the 'small' range. This reduces further when sources of bias, particularly masking, are controlled for.
•Anterior cingulate and insular cortices are activated by extinction and reappraisal.•Activation in sensory and emotion processing regions is observed in fear extinction.•Cognitive reappraisal ...recruits the dorsal fronto-parietal network.•Reappraisal differences with extinction partially depend on the regulation strategy.
Cognitive reappraisal and fear extinction learning represent two different approaches to emotion regulation. While their respective neural correlates have been widely studied with functional magnetic resonance imaging (fMRI), few direct comparisons between these processes have been conducted. We conducted a meta-analysis of fMRI studies of reappraisal and fear extinction, with the aim of examining both commonalities and differences in their neural correlates. We also conducted independent analyses that focused on specific reappraisal strategies (reinterpretation, distancing). Overall, we observed that the dorsal anterior cingulate cortex (dACC) and the bilateral anterior insular cortex (AIC) were similarly consistently engaged by reappraisal and extinction. Extinction was more consistently linked to activation of sensory and emotion processing regions, whereas reappraisal was more consistently associated with activation of a dorsal fronto-parietal network. Interestingly, the amygdala was preferentially deactivated by distancing. These results suggest that the dACC and the AIC are involved in domain-general regulatory networks. Differences between extinction and reappraisal could be explained by their relative processing demands on visual perceptual versus higher cognitive neural systems.
We conducted a meta-analysis of voxel-based morphometry (VBM) studies in autism spectrum disorder (ASD) to clarify the changes in regional white-matter volume underpinning this condition, and ...generated an online database to facilitate replication and further analyses by other researchers.
PubMed, ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002 (the date of the first white-matter VBM study in ASD) and 2010. Manual searches were also conducted. Authors were contacted to obtain additional data. Coordinates were extracted from clusters of significant white-matter difference between patients and controls. A new template for white matter was created for the signed differential mapping (SDM) meta-analytic method. A diffusion tensor imaging (DTI)-derived atlas was used to optimally localize the changes in white-matter volume.
Thirteen datasets comprising 246 patients with ASD and 237 healthy controls met inclusion criteria. No between-group differences were found in global white-matter volumes. ASD patients showed increases of white-matter volume in the right arcuate fasciculus and also in the left inferior fronto-occipital and uncinate fasciculi. These findings remained unchanged in quartile and jackknife sensitivity analyses and also in subgroup analyses (pediatric versus adult samples).
Patients with ASD display increases of white-matter volume in tracts known to be important for language and social cognition. Whether the results apply to individuals with lower IQ or younger age and whether there are meaningful neurobiological differences between the subtypes of ASD remain to be investigated.
Meta-analyses are essential to summarize the results of the growing number of neuroimaging studies in psychiatry, neurology and allied disciplines. Image-based meta-analyses use full image ...information (i.e. the statistical parametric maps) and well-established statistics, but images are rarely available making them highly unfeasible. Peak-probability meta-analyses such as activation likelihood estimation (ALE) or multilevel kernel density analysis (MKDA) are more feasible as they only need reported peak coordinates. Signed-differences methods, such as signed differential mapping (SDM) build upon the positive features of existing peak-probability methods and enable meta-analyses of studies comparing patients with controls. In this paper we present a new version of SDM, named Effect Size SDM (ES-SDM), which enables the combination of statistical parametric maps and peak coordinates and uses well-established statistics. We validated the new method by comparing the results of an ES-SDM meta-analysis of studies on the brain response to fearful faces with the results of a pooled analysis of the original individual data. The results showed that ES-SDM is a valid and reliable coordinate-based method, whose performance might be additionally increased by including statistical parametric maps. We anticipate that ES-SDM will be a helpful tool for researchers in the fields of psychiatry, neurology and allied disciplines.
Grey matter (GM) damage in Multiple Sclerosis (MS) occurs largely independent of white matter (WM) lesions and shows stronger correlation with clinical parameters than WM damage but no clear pattern ...of GM atrophy distribution has emerged in the literature. We used Signed Differential Mapping (SDM), a novel neuroimaging meta-analytical method, to assess global and regional GM volume differences in MS. Meta-regression methods were used to explore potential effects of disease duration and degree of functional disability. We found a highly localized pattern of regional GM volume loss in Relapsing Remitting MS involving bilateral thalamus, basal ganglia structures, pre/postcentral regions and cingulate gyrus. These results remained largely unchanged after subgroup and sensitivity analyses. Furthermore, GM volume loss in left pre/postcentral regions correlated with increasing functional disability in MS. These results demonstrate that GM atrophy occurs as a regional rather than global process in MS, and that functional disability is specifically associated with atrophy of the left pre/post central gyrus. Further investigation is needed to determine whether these structures are targeted by neurodegenerative processes and to establish their clinical and neurocognitive correlates.
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