Network and state specificity in connectivity-based predictions of individual behavior.

Predicting individual behavior from brain functional connectivity (FC) patterns can contribute to our understanding of human brain functioning. This may apply in particular if predictions are based on features derived from circumscribed, a priori defined functional networks, which improves interpretability. Furthermore, some evidence suggests that task-based FC data may yield more successful predictions of behavior than resting-state FC data. Here, we comprehensively examined to what extent the correspondence of functional network priors and task states with behavioral target domains influences the predictability of individual performance in cognitive, social, and affective tasks. To this end, we used data from the Human Connectome Project for large-scale out-of-sample predictions of individual abilities in working memory (WM), theory-of-mind cognition (SOCIAL), and emotion processing (EMO) from FC of corresponding and non-corresponding states (WM/SOCIAL/EMO/resting-state) and networks (WM/SOCIAL/EMO/whole-brain connectome). Using root mean squared error and coefficient of determination to evaluate model fit revealed that predictive performance was rather poor overall. Predictions from whole-brain FC were slightly better than those from FC in task-specific networks, and a slight benefit of predictions based on FC from task versus resting state was observed for performance in the WM domain. Beyond that, we did not find any significant effects of a correspondence of network, task state, and performance domains. Together, these results suggest that multivariate FC patterns during both task and resting states contain rather little information on individual performance levels, calling for a reconsideration of how the brain mediates individual differences in mental abilities.

The heterogeneity of the left dorsal premotor cortex evidenced by multimodal connectivity-based parcellation and functional characterization.

Despite the common conception of the dorsal premotor cortex (PMd) as a single brain region, its diverse connectivity profiles and behavioral heterogeneity argue for a differentiated organization of the PMd. A previous study revealed that the right PMd is characterized by a rostro-caudal and a ventro-dorsal distinction dividing it into five subregions: rostral, central, caudal, ventral and dorsal. The present study assessed whether a similar organization is present in the left hemisphere, by capitalizing on a multimodal data-driven approach combining connectivity-based parcellation (CBP) based on meta-analytic modeling, resting-state functional connectivity, and probabilistic diffusion tractography. The resulting PMd modules were then characterized based on multimodal functional connectivity and a quantitative analysis of associated behavioral functions. Analyzing the clusters consistent across all modalities revealed an organization of the left PMd that mirrored its right counterpart to a large degree. Again, caudal, central and rostral modules reflected a cognitive-motor gradient and a premotor eye-field was found in the ventral part of the left PMd. In addition, a distinct module linked to abstract cognitive functions was observed in the rostro-ventral left PMd across all CBP modalities, implying greater differentiation of higher cognitive functions for the left than the right PMd.

Correlations Between Personality and Brain Structure: A Crucial Role of Gender.

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 Right Dorsal Premotor Mosaic: Organization, Functions, and Connectivity.

The right dorsal premotor cortex (PMd) of humans has been reported to be involved in a broad range of motor and cognitive functions. We explored the basis of this behavioral heterogeneity by performing a connectivity-based parcellation using meta-analytic approach applied to PMd coactivations. We compared our connectivity-based parcellation results with parcellations obtained through resting-state functional connectivity and probabilistic diffusion tractography. Functional connectivity profiles and behavioral decoding of the resulting PMd subregions allowed characterizing their respective behavior profile. These procedures divided the right PMd into 5 distinct subregions that formed a cognitive-motor gradient along a rostro-caudal axis. In particular, we found 1) a rostral subregion functionally connected with prefrontal cortex, which likely supports high-level cognitive processes, such as working memory, 2) a central subregion showing a mixed behavioral profile and functional connectivity to parietal regions of the dorsal attention network, and 3) a caudal subregion closely integrated with the motor system. Additionally, we found 4) a dorsal subregion, preferentially related to hand movements and connected to both cognitive and motor regions, and 5) a ventral subregion, whose functional profile fits the concept of an eye movement-related field. In conclusion, right PMd may be considered as a functional mosaic formed by 5 subregions.

Neural correlates of formal thought disorder: An activation likelihood estimation meta-analysis.

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.

On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification.

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.

Sex differences in the functional connectivity of the amygdalae in association with cortisol.

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.

ANIMA: A data-sharing initiative for neuroimaging meta-analyses.

Meta-analytic techniques allow cognitive neuroscientists to pool large amounts of data across many individual task-based functional neuroimaging experiments. These methods have been aided by the introduction of online databases such as Brainmap.org or Neurosynth.org, which collate peak activation coordinates obtained from thousands of published studies. Findings from meta-analytic studies typically include brain regions which are consistently activated across studies for specific contrasts, investigating cognitive or clinical hypotheses. These regions can be subsequently used as the basis for seed-based connectivity analysis, or formally compared to neuroimaging data in order to help interpret new findings. To facilitate such approaches, we have developed a new online repository of meta-analytic neuroimaging results, named the Archive of Neuroimaging Meta-analyses (ANIMA). The ANIMA platform consists of an intuitive online interface for querying, downloading, and contributing data from published meta-analytic studies. Additionally, to aid the process of organizing, visualizing, and working with these data, we present an open-source desktop application called Volume Viewer. Volume Viewer allows users to easily arrange imaging data into composite stacks, and save these sessions as individual files, which can also be uploaded to the ANIMA database. The application also allows users to perform basic functions, such as computing conjunctions between images, or extracting regions-of-interest or peak coordinates for further analysis. The introduction of this new resource will enhance the ability of researchers to both share their findings and incorporate existing meta-analytic results into their own research.

Imbalance in subregional connectivity of the right temporoparietal junction in major depression.

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.

Neural correlates of explicit social judgments on vocal stimuli.

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.

Psychosocial versus physiological stress - Meta-analyses on deactivations and activations of the neural correlates of stress reactions.

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.

Comparison of Vaginal Pessaries to Standard Care or Pelvic Floor Muscle Training for Treating Postpartum Urinary Incontinence: a Pragmatic Randomized Controlled Trial.

Introduction: To compare three conservative treatment options, standard care, pelvic floor muscle training (PFMT), and vaginal pessaries, for postpartum urinary incontinence (UI) that are accessible to most patients and practitioners in a generalizable cohort. Materials and Methods: A multicenter, open-label, parallel group, pragmatic randomized controlled clinical trial comparing standard care, PFMT, and vaginal cube pessary for postpartum urinary incontinence was conducted in six outpatient clinics. Sample size was based on large treatment effects (Cramers' V > 0.35) with a power of 80% and an alpha of 0.05 for a 3 × 3 contingency table, 44 patients needed to be included in the trial. Outcomes were analyzed according to the intention-to-treat principle. Group comparisons were made using analysis of variance (ANOVA), Kruskal-Wallis, and chi-square test as appropriate. P < 0.05 was considered statistically significant. Results: Of the 516 women screened, 111 presented with postpartum UI. Of these, 52 were randomized to one of three treatment groups: standard care (n = 17), pelvic floor muscle training (n = 17), or vaginal cube pessary (n = 18). After 12 weeks of treatment, treatment success, as measured by patient satisfaction, was significantly higher in the vaginal pessary group (77.8%, n = 14/18), compared to the standard care group (41.2%, n = 7/17), and the PFMT (23.5%, n = 4/17; χ 2 2,n = 52  = 14.55; p = 0.006, Cramer-V = 0.374). No adverse events were reported. SUI and MUI accounted for 88.4% of postpartum UI. Conclusion: Vaginal pessaries were superior to standard care or PFMT to satisfyingly reduce postpartum UI symptoms. No complications were found.

The effect of task complexity on the neural network for response inhibition: An ALE meta-analysis.

Response inhibition is classically investigated using the go/no-go (GNGT) and stop-signal task (SST), which conceptually measure different subprocesses of inhibition. Further, different task versions with varying levels of additional executive control demands exist, making it difficult to identify the core neural correlates of response inhibition independent of variations in task complexity. Using neuroimaging meta-analyses, we show that a divergent pattern of regions is consistently involved in the GNGT versus SST, arguing for different mechanisms involved when performing the two tasks. Further, for the GNGT a strong effect of task complexity was found, with regions of the multiple demand network (MDN) consistently involved particularly in the complex GNGT. In contrast, both standard and complex SST recruited the MDN to a similar degree. These results complement behavioral evidence suggesting that inhibitory control becomes automatic after some practice and is performed without input of higher control regions in the classic, standard GNGT, but continues to be implemented in a top-down controlled fashion in the SST.

Socio-cognitive, expertise-based and appearance-based accounts of the other-'race' effect in face perception: A label-based systematic review of neuroimaging results.

Two competing theories explain the other-'race' effect (ORE) either by greater perceptual expertise to same-'race' (SR) faces or by social categorization of other-'race' (OR) faces at the expense of individuation. To assess expertise and categorization contributions to the ORE, a promising-yet overlooked-approach is comparing activations for different other-'races'. We present a label-based systematic review of neuroimaging studies reporting increased activity in response to OR faces (African, Caucasian, or Asian) when compared with the SR of participants. Hypothetically, while common activations would reflect general aspects of OR perception, 'race'-preferential ones would represent effects of 'race'-specific visual appearance. We find that several studies report activation of occipito-temporal and midcingulate areas in response to faces across different other-'races', presumably due to high demand on the visual system and category processing. Another area reported in response to all OR faces, the caudate nucleus, suggests the involvement of socio-affective processes and behavioural regulation. Overall, our results support hybrid models-both expertise and social categorization contribute to the ORE, but they provide little evidence for reduced motivation to process OR faces. Additionally, we identify areas preferentially responding to specific OR faces, reflecting effects of visual appearance.

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior.

Stress is an important factor in the development, triggering, and maintenance of psychotic symptoms. Still, little is known about the neural correlates of cognitively regulating stressful events in schizophrenia. The current study aimed at investigating the cognitive down-regulation of negative, stressful reactions during a neuroimaging psychosocial stress paradigm (non-regulated stress versus cognitively regulated stress). In a randomized, repeated-measures within-subject design, we assessed subjective reactions and neural activation in schizophrenia patients (SZP) and matched healthy controls in a neuroimaging psychosocial stress paradigm. In general, SZP exhibited an increased anticipation of stress compared to controls (p = 0.020). During non-regulated stress, SZP showed increased negative affect (p = 0.033) and stronger activation of the left parietal operculum/posterior insula (p < 0.001) and right inferior frontal gyrus/anterior insula (p = 0.005) than controls. Contrarily, stress regulation compared to non-regulated stress led to increased subjective reactions in controls (p = 0.003) but less deactivation in SZP in the ventral anterior cingulate cortex (p = 0.027). Our data demonstrate stronger reactions to and anticipation of stress in patients and difficulties with cognitive stress regulation in both groups. Considering the strong association between mental health and stress, the investigation of cognitive regulation in individuals vulnerable to stress, including SZP, has crucial implications for improving stress intervention trainings.

Stressor-Specific Sex Differences in Amygdala-Frontal Cortex Networks.

Females and males differ in stress reactivity, coping, and the prevalence rates of stress-related disorders. According to a neurocognitive framework of stress coping, the functional connectivity between the amygdala and frontal regions (including the dorsolateral prefrontal cortex (dlPFC), ventral anterior cingulate cortex (vACC), and medial prefrontal cortex (mPFC)) plays a key role in how people deal with stress. In the current study, we investigated the effects of sex and stressor type in a within-subject counterbalanced design on the resting-state functional connectivity (rsFC) of the amygdala and these frontal regions in 77 healthy participants (40 females). Both stressor types led to changes in subjective ratings, with decreasing positive affect and increasing negative affect and anger. Females showed higher amygdala-vACC and amygdala-mPFC rsFC for social exclusion than for achievement stress, and compared to males. Whereas a higher amygdala-vACC rsFC indicates the activation of emotion processing and coping, a higher amygdala-mPFC rsFC indicates feelings of reward and social gain, highlighting the positive effects of social affiliation. Thus, for females, feeling socially affiliated might be more fundamental than for males. Our data indicate interactions of sex and stressor in amygdala-frontal coupling, which translationally contributes to a better understanding of the sex differences in prevalence rates and stress coping.

Network and State Specificity in Connectivity-Based Predictions of Individual Behavior.

Predicting individual behavior from brain functional connectivity (FC) patterns can contribute to our understanding of human brain functioning. This may apply in particular if predictions are based on features derived from circumscribed, a priori defined functional networks, which improves interpretability. Furthermore, some evidence suggests that task-based FC data may yield more successful predictions of behavior than resting-state FC data. Here, we comprehensively examined to what extent the correspondence of functional network priors and task states with behavioral target domains influences the predictability of individual performance in cognitive, social, and affective tasks. To this end, we used data from the Human Connectome Project for large-scale out-of-sample predictions of individual abilities in working memory (WM), theory-of-mind cognition (SOCIAL), and emotion processing (EMO) from FC of corresponding and non-corresponding states (WM/SOCIAL/EMO/resting-state) and networks (WM/SOCIAL/EMO/whole-brain connectome). Using root mean squared error and coefficient of determination to evaluate model fit revealed that predictive performance was rather poor overall. Predictions from whole-brain FC were slightly better than those from FC in task-specific networks, and a slight benefit of predictions based on FC from task versus resting state was observed for performance in the WM domain. Beyond that, we did not find any significant effects of a correspondence of network, task state, and performance domains. Together, these results suggest that multivariate FC patterns during both task and resting states contain rather little information on individual performance levels, calling for a reconsideration of how the brain mediates individual differences in mental abilities.

Testosterone and the Amygdala's Functional Connectivity in Women and Men.

The amygdala contains androgen receptors and is involved in various affective and social functions. An interaction between testosterone and the amygdala's functioning is likely. We investigated the amygdala's resting-state functional connectivity (rsFC) network in association with testosterone in 94 healthy young adult women and men (final data available for analysis from 42 women and 39 men). Across the whole sample, testosterone was positively associated with the rsFC between the right amygdala and the right middle occipital gyrus, and it further predicted lower agreeableness scores. Significant sex differences appeared for testosterone and the functional connectivity between the right amygdala and the right superior frontal gyrus (SFG), showing higher testosterone levels with lower connectivity in women. Sex further predicted the openness and agreeableness scores. Our results show that testosterone modulates the rsFC between brain areas involved in affective processing and executive functions. The data indicate that the cognitive control of the amygdala via the frontal cortex is dependent on the testosterone levels in a sex-specific manner. Testosterone seems to express sex-specific patterns (1) in networks processing affect and cognition, and (2) in the frontal down-regulation of the amygdala. The sex-specific coupling between the amygdala and the frontal cortex in interaction with the hormone levels may drive sex-specific differences in a variety of behavioral phenomena that are further associated with psychiatric illnesses that show sex-specific prevalence rates.

Crossmodal interactions in audiovisual emotion processing.

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.