•Reports a set of meta-analyses of human fMRI fear extinction studies involving over 1300 participants.•Human fear extinction learning and extinction recall are consistently distinct in their neural ...correlates.•The contribution of prefrontal cortical subregions to extinction appears to be more nuanced than what is currently suggested.
The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices. An overlapping anatomical result was obtained from the meta-analysis of extinction recall studies, except when studies directly compared an extinguished threat stimulus to an unextinguished threat stimulus (instead of a safety stimulus). In this latter instance, more consistent activation was observed in dorsolateral and ventromedial prefrontal cortex regions, together with other areas including the hippocampus. While our results partially support the notion of a shared neuroanatomy between human and rodent models of extinction processes, they also encourage an expanded account of the neural basis of human fear extinction.
Electroconvulsive therapy (ECT) is considered the most effective treatment for major depressive disorder (MDD). In recent years, the pursuit of the neurobiological mechanisms of ECT action has ...generated a significant amount of functional magnetic resonance imaging (fMRI) research.
In this systematic review, we integrated all fMRI research in patients with MDD receiving ECT and, importantly, evaluated the level of convergence and replicability across multiple fMRI metrics.
While according to most studies changes in patients with MDD after ECT appear to be widely distributed across the brain, our multimetric review revealed specific changes involving functional connectivity increases in the superior and middle frontal gyri as the most replicated and across-modality convergent findings. Although this modulation of prefrontal connectivity was associated to ECT outcome, we also identified fMRI measurements of the subgenual anterior cingulate cortex as the fMRI signals most significantly linked to clinical response.
We identified specific prefrontal and cingulate territories which activity and connectivity with other brain regions is modulated by ECT, critically accounting for its mechanism of action.
•Multimetric reviews are the optimal approach for detecting neurofunctional findings.•Electroconvulsive therapy consistently modulates prefrontal functional connectivity.•Cingulate function is the best electroconvulsive therapy response biomarker.
Despite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive-compulsive disorder (OCD) remains controversial. In the context of neuroimaging ...studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings.
To assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm.
Cross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls.
The severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions.
Amygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.
Individuals with psychopathy present deficits in the recognition of facial emotional expressions. However, the nature and extent of these alterations are not fully understood. Furthermore, available ...data on the functional neural correlates of emotional face recognition deficits in adult psychopaths have provided mixed results. In this context, emotional face morphing tasks may be suitable for clarifying mild and emotion-specific impairments in psychopaths. Likewise, studies exploring corresponding anatomical correlates may be useful for disentangling available neurofunctional evidence based on the alleged neurodevelopmental roots of psychopathic traits. We used Voxel-Based Morphometry and a morphed emotional face expression recognition task to evaluate the relationship between regional gray matter (GM) volumes and facial emotion recognition deficits in male psychopaths. In comparison to male healthy controls, psychopaths showed deficits in the recognition of sad, happy and fear emotional expressions. In subsequent brain imaging analyses psychopaths with better recognition of facial emotional expressions showed higher volume in the prefrontal cortex (orbitofrontal, inferior frontal and dorsomedial prefrontal cortices), somatosensory cortex, anterior insula, cingulate cortex and the posterior lobe of the cerebellum. Amygdala and temporal lobe volumes contributed to better emotional face recognition in controls only. These findings provide evidence suggesting that variability in brain morphometry plays a role in accounting for psychopaths' impaired ability to recognize emotional face expressions, and may have implications for comprehensively characterizing the empathy and social cognition dysfunctions typically observed in this population of subjects.
The notion of a "default mode of brain function" has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show ...prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during (i) eyes-closed spontaneous rest, (ii) activation by moral dilemma, and (iii) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.
Imaging studies on neuronal network formation provide relevant information as to how the brain matures during adolescence. We used a novel imaging approach combining well-established MRI measures of ...local functional connectivity that jointly provide qualitatively different information relating to the functional structure of the cerebral cortex. To investigate the adolescent transition into adulthood, we comparatively assessed 169 preadolescents aged 8–12 years and 121 healthy adults. Whole-brain functional connectivity maps were generated using multi-distance measures of intracortical neural activity coupling defined within iso-distant local areas. Such Iso-Distant Average Correlation (IDAC) measures therefore represent the average temporal correlation of a given brain unit, or voxel, with other units situated at increasingly separated iso-distant intervals. The results indicated that between-group differences in the functional structure of the cerebral cortex are extensive and implicate part of the lateral prefrontal cortex, a medial frontal/anterior cingulate region, the superior parietal lobe extending to the somatosensory strip and posterior cingulate cortex, and local connections within the visual cortex, hippocampus, amygdala and insula. We thus provided detail of the cerebral cortex functional structure maturation during the transition to adulthood, which may serve to establish more accurate links between adolescent performance gains and cerebral cortex maturation. Remarkably, our study provides new information as to the cortical maturation processes in prefrontal areas relevant to executive functioning and rational learning, medial frontal areas playing an active role in the cognitive appraisal of emotion and anxiety, and superior parietal cortices strongly associated with bodily self-consciousness in the context of body image formation.
Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective neuromodulation therapies for treatment-resistant depression (TRD). While ECT is generally ...considered the most effective antidepressant, rTMS is less invasive, better tolerated and leads to more durable therapeutic benefits. Both interventions are established device antidepressants, but it remains unknown if they share a common mechanism of action. Here we aimed to compare the brain volumetric changes in patients with TRD after right unilateral (RUL) ECT versus left dorsolateral prefrontal cortex (lDLPFC) rTMS.
We assessed 32 patients with TRD before the first treatment session and after treatment completion using structural magnetic resonance imaging. Fifteen patients were treated with RUL ECT and seventeen patients received lDLPFC rTMS.
Patients receiving RUL ECT, in comparison with patients treated with lDLPFC rTMS, showed a greater volumetric increase in the right striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. However, ECT- or rTMS-induced brain volumetric changes were not associated with the clinical improvement.
We evaluated a modest sample size with concurrent pharmacological treatment and without neuromodulation therapies randomization.
Our findings suggest that despite comparable clinical outcomes, only RUL ECT is associated with structural change, while rTMS is not. We hypothesize that structural neuroplasticity and/or neuroinflammation may explain the larger structural changes observed after ECT, whereas neurophysiological plasticity may underlie the rTMS effects. More broadly, our results support the notion that there are multiple therapeutic strategies to move patients from depression to euthymia.
•RUL 0.3-0.5 ms pulse width ECT and 10 Hz lDLPFC rTMS may have comparable clinical antidepressant efficacy.•ECT and rTMS induce different patterns of structural change: rTMS did not induce significant changes, while RUL ECT did.•Temporal, subcortical and cingulate volume increases are greater after ECT than rTMS.•Generally, results suggest there are multiple circuit-level antidepressant strategies.
Posttraumatic stress disorder (PTSD) is a highly disabling psychiatric condition that may arise after exposure to acute and severe trauma. It is a highly prevalent mental disorder worldwide, and the ...current treatment options for these patients remain limited due to low effectiveness. The time window right after traumatic events provides clinicians with a unique opportunity for preventive interventions against potential deleterious alterations in brain function that lead to PTSD. Some studies pointed out that PTSD patients present an abnormal function of the hypothalamic-pituitary-adrenal axis that may contribute to a vulnerability toward PTSD. Moreover, glucocorticoids have arisen as a promising option for preventing the disorder's development when administered in the aftermath of trauma. The present work compiles the recent findings of glucocorticoid administration for the prevention of a PTSD phenotype, from human studies to animal models of PTSD. Overall, glucocorticoid-based therapies for preventing PTSD demonstrated moderate evidence in terms of efficacy in both clinical and preclinical studies. Although clinical studies point out that glucocorticoids may not be effective for all patients' subpopulations, those with adequate traits might greatly benefit from them. Preclinical studies provide precise insight into the mechanisms mediating this preventive effect, showing glucocorticoid-based prevention to reduce long-lasting behavioral and neurobiological abnormalities caused by traumatic stress. However, further research is needed to delineate the precise mechanisms and the extent to which these interventions can translate into lower PTSD rates and morbidity.
This article is part of the Special Issue on 'Fear, Anxiety and PTSD'.
•PTSD may be prevented by interventions implemented immediately after a trauma.•Vulnerable individuals may benefit from glucocorticoid-based prevention of PTSD.•Glucocorticoids prevent behavioral and biological effects induced in animal models.•Larger studies are necessary for glucocorticoid prevention of PTSD.
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