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Objective: Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities., Methods: This coordinate-based meta-analysis included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies of blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy, increased function, and decreased function in patients with major depression relative to healthy control subjects. In secondary meta-analyses, the data were grouped across primary categories, and in tertiary analyses, by medication status and absence of psychiatric comorbidity. Activation likelihood estimation was used for all analyses., Results: A total of 92 publications reporting 152 experiments were identified, collectively representing 2,928 patients with major depressive disorder. The primary analyses detected no convergence across studies. The secondary analyses identified portions of the subgenual cingulate cortex, hippocampus, amygdala, and putamen as demonstrating convergent abnormalities. The tertiary analyses (clinical subtypes) showed improved convergence relative to the secondary analyses., Conclusions: Coordinate-based meta-analysis identified spatially convergent structural (VBM) and functional (VBP) abnormalities in major depression. The findings suggest replicable neuroimaging features associated with major depression, beyond the transdiagnostic effects reported in previous meta-analyses, and support a continued research focus on the subgenual cingulate and other selected regions' role in depression.

Personality is associated with variation in all kinds of mental faculties, including affective, social, executive, and memory functioning. The intrinsic dynamics of neural networks underlying these mental functions are reflected in their functional connectivity at rest (RSFC). We, therefore, aimed to probe whether connectivity in functional networks allows predicting individual scores of the five-factor personality model and potential gender differences thereof. We assessed nine meta-analytically derived functional networks, representing social, affective, executive, and mnemonic systems. RSFC of all networks was computed in a sample of 210 males and 210 well-matched females and in a replication sample of 155 males and 155 females. Personality scores were predicted using relevance vector machine in both samples. Cross-validation prediction accuracy was defined as the correlation between true and predicted scores. RSFC within networks representing social, affective, mnemonic, and executive systems significantly predicted self-reported levels of Extraversion, Neuroticism, Agreeableness, and Openness. RSFC patterns of most networks, however, predicted personality traits only either in males or in females. Personality traits can be predicted by patterns of RSFC in specific functional brain networks, providing new insights into the neurobiology of personality. However, as most associations were gender-specific, RSFC-personality relations should not be considered independently of gender.

Many neuroimaging studies have investigated the neural correlates of face processing. However, the location of face-preferential regions differs considerably between studies, possibly due to the use of different stimuli or tasks. By using Activation likelihood estimation meta-analyses, we aimed to a) delineate regions consistently involved in face processing and b) to assess the influence of stimuli and task on convergence of activation patterns. In total, we included 77 neuroimaging experiments in healthy subjects comparing face processing to a control condition. Results revealed a core face-processing network encompassing bilateral fusiform gyrus (FFG), inferior occipital (IOG) gyrus, superior temporal sulcus/middle temporal gyrus (STS/MTG), amygdala, inferior frontal junction (IFJ) and gyrus (IFG), left anterior insula as well as pre-supplementary motor area (pre-SMA). Furthermore, separate meta-analyses showed, that while significant convergence across all task and stimuli conditions was found in bilateral amygdala, right IOG, right mid-FFG, and right IFG, convergence in IFJ, STS/MTG, right posterior FFG, left FFG and pre-SMA differed between conditions. Thus, our results point to an occipito-frontal-amygdalae system that is involved regardless of stimulus and attention, whereas the remaining regions of the face-processing network are influenced by the task-dependent focus on specific facial characteristics as well as the type of stimuli processed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Formal thought disorder (FTD) refers to a psychopathological dimension characterized by disorganized and incoherent speech. Whether symptoms of FTD arise from aberrant processing in language-related regions or more general cognitive networks, however, remains debated. Here, we addressed this question by a quantitative meta-analysis of published functional neuroimaging studies on FTD. The revised Activation Likelihood Estimation (ALE) algorithm was used to test for convergent aberrant activation changes in 18 studies (30 experiments) investigating FTD, of which 17 studies comprised schizophrenia patients and one study healthy subjects administered to S-ketamine. Additionally, we analyzed task-dependent and task-independent (resting-state) functional connectivity (FC) of brain regions showing convergence in activation changes. Subsequent functional characterization was performed for the initial clusters and the delineated connectivity networks by reference to the BrainMap database. Consistent activation changes were found in the left superior temporal gyrus (STG) and two regions within the left posterior middle temporal gyrus (p-MTG), ventrally (vp-MTG) and dorsally (dp-MTG). Functional characterization revealed a prominent functional association of ensuing clusters from our ALE meta-analysis with language and speech processing, as well as auditory perception in STG and with social cognition in dp-MTG. FC analysis identified task-dependent and task-independent networks for all three seed regions, which were mainly related to language and speech processing, but showed additional involvement in higher order cognitive functions. Our findings suggest that FTD is mainly characterized by abnormal activation in brain regions of the left hemisphere that are associated with language and speech processing, but also extend to higher order cognitive functions. Hum Brain Mapp 38:4946-4965, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto-occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Importance: During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings., Objective: To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing., Data Sources: Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop., Study Selection: Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected., Data Extraction and Synthesis: Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated., Main Outcomes and Measures: Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases., Results: In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results., Conclusions and Relevance: Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches.

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Functional neuroimaging research on the neural basis of social evaluation has traditionally focused on face perception paradigms. Thus, little is known about the neurobiology of social evaluation processes based on auditory cues, such as voices. To investigate the top-down effects of social trait judgments on voices, hemodynamic responses of 44 healthy participants were measured during social trait (trustworthiness [TR] and attractiveness [AT]), emotional (happiness, HA), and cognitive (age, AG) voice judgments. Relative to HA and AG judgments, TR and AT judgments both engaged the bilateral inferior parietal cortex (IPC; area PGa) and the dorsomedial prefrontal cortex (dmPFC) extending into the perigenual anterior cingulate cortex. This dmPFC activation overlapped with previously reported areas specifically involved in social judgments on 'faces.' Moreover, social trait judgments were expected to share neural correlates with emotional HA and cognitive AG judgments. Comparison of effects pertaining to social, social-emotional, and social-cognitive appraisal processes revealed a dissociation of the left IPC into 3 functional subregions assigned to distinct cytoarchitectonic subdivisions. In total, the dmPFC is proposed to assume a central role in social attribution processes across sensory qualities. In social judgments on voices, IPC activity shifts from rostral processing of more emotional judgment facets to caudal processing of more cognitive judgment facets., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Schizophrenia is characterized by marked deficits in executive and psychomotor functions, as demonstrated for goal-directed actions in the antisaccade task. Recent studies, however, suggest that this deficit represents only one manifestation of a general deficit in stimulus-response integration and volitional initiation of motor responses. We here used functional magnetic resonance imaging to investigate brain activation patterns during a manual stimulus-response compatibility task in 18 schizophrenic patients and 18 controls. We found that across groups incongruent vs. congruent responses recruited a bilateral network consisting of dorsal fronto-parietal circuits as well as bilateral anterior insula, dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (preSMA). When testing for the main-effect across all conditions, patients showed significantly lower activation of the right DLPFC and, in turn, increased activation in a left hemispheric network including parietal and premotor areas as well as the preSMA. For incongruent responses patients showed significantly increased activation in a similar left hemispheric network, as well as additional activation in parietal and premotor regions in the right hemisphere. The present study reveals that hypoactivity in the right DLPFC in schizophrenic patients is accompanied by hyperactivity in several fronto-parietal regions associated with task execution. Impaired top-down control due to a dysfunctional DLPFC might thus be partly compensated by an up-regulation of task-relevant regions in schizophrenic patients.

Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and midcingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients did not show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group., (© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Emotion in daily life is often expressed in a multimodal fashion. Consequently emotional information from one modality can influence processing in another. In a previous fMRI study we assessed the neural correlates of audio-visual integration and found that activity in the left amygdala is significantly attenuated when a neutral stimulus is paired with an emotional one compared to conditions where emotional stimuli were present in both channels. Here we used dynamic causal modelling to investigate the effective connectivity in the neuronal network underlying this emotion presence congruence effect. Our results provided strong evidence in favor of a model family, differing only in the interhemispheric interactions. All winning models share a connection from the bilateral fusiform gyrus (FFG) into the left amygdala and a non-linear modulatory influence of bilateral posterior superior temporal sulcus (pSTS) on these connections. This result indicates that the pSTS not only integrates multi-modal information from visual and auditory regions (as reflected in our model by significant feed-forward connections) but also gates the influence of the sensory information on the left amygdala, leading to attenuation of amygdala activity when a neutral stimulus is integrated. Moreover, we found a significant lateralization of the FFG due to stronger driving input by the stimuli (faces) into the right hemisphere, whereas such lateralization was not present for sound-driven input into the superior temporal gyrus. In summary, our data provides further evidence for a rightward lateralization of the FFG and in particular for a key role of the pSTS in the integration and gating of audio-visual emotional information., (Copyright © 2011 Elsevier Inc. All rights reserved.)