Markus Heinrichs’s research while affiliated with University of Freiburg and other places

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18–49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho‐physiological interaction) to fear, angry, and happy facial stimuli using an emotional face‐matching task. All amygdala subregions responded to all stimuli ( p ‐FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala ( p ‐FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala ( p ‐FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face‐processing network.

Social anxiety disorder (SAD) is a prevalent and disabling mental health condition, characterized by excessive fear and anxiety in social situations. Resting-state functional magnetic resonance imaging (fMRI) paradigms have been increasingly used to understand the neurobiological underpinnings of SAD in the absence of threat-related stimuli. Previous studies have primarily focused on the role of the amygdala in SAD. However, the amygdala consists of functionally and structurally distinct subregions, and recent studies have highlighted the importance of investigating the role of these subregions independently. Using multiband fMRI, we analyzed resting-state data from 135 participants (42 SAD, 93 healthy controls). By employing voxel-wise permutation testing, we examined group differences of fMRI connectivity and associations between fMRI connectivity and social anxiety symptoms to further investigate the classification of SAD as a categorical or dimensional construct. Seed-to-whole brain functional connectivity analysis using multiple ‘seeds’ including the amygdala and its subregions and the precuneus, revealed no statistically significant group differences. However, social anxiety severity was significantly negatively correlated with functional connectivity of the precuneus - perigenual anterior cingulate cortex and positively correlated with functional connectivity of the amygdala (specifically the superficial subregion) - parietal/cerebellar areas. Our findings demonstrate clear links between symptomatology and brain connectivity in the absence of diagnostic differences, with evidence of amygdala subregion-specific alterations. The observed brain-symptom associations did not include disturbances in the brain’s fear circuitry (i.e., disturbances in connectivity between amygdala - prefrontal regions) likely due to the absence of threat-related stimuli.

Deep brain stimulation (DBS) of the supero-lateral medial forebrain bundle (slMFB) is associated with rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Beyond that, improvements in social functioning have been reported. However, it is unclear whether social skills, the basis of successful social functioning, are systematically altered following slMFB DBS. Therefore, the current study investigated specific social skills (affective empathy, compassion, and theory of mind) in patients with TRD undergoing slMFB DBS in comparison to healthy subjects. 12 patients with TRD and 12 age- and gender-matched healthy subjects (5 females) performed the EmpaToM, a video-based naturalistic paradigm differentiating between affective empathy, compassion, and theory of mind. Patients were assessed before and three months after DBS onset and compared to an age- and gender-matched sample of healthy controls. All data were analyzed using non-parametric Mann-Whitney U tests. DBS treatment significantly affected patients’ affective responsiveness towards emotional versus neutral situations (i.e. affective empathy): While their affective responsiveness was reduced compared to healthy subjects at baseline, they showed normalized affective responsiveness three months after slMFB DBS onset. No effects occurred in other domains with persisting deficits in compassion and intact socio-cognitive skills. Active slMFB DBS resulted in a normalized affective responsiveness in patients with TRD. This specific effect might represent one factor supporting the resumption of social activities after recovery from chronic depression. Considering the small size of this unique sample as well as the explorative nature of this study, future studies are needed to investigate the robustness of these effects.

Disclosure: C. Atila: None. F. Holze: None. R. Murugesu: None. N. Rommers: None. N. Hutter: None. N. Varghese: None. C.O. Sailer: None. A. Eckert: None. M. Heinrichs: None. M. Liechti: None. M. Christ-crain: None. Introduction: Despite adequate treatment, patients with arginine vasopressin deficiency (AVP-D), known as central diabetes insipidus (cDI), often report psychological symptoms such as heightened anxiety levels, difficulties describing emotions, and depressed mood. Given the anatomical proximity, disruptions of the hypothalamic-pituitary axis causing an AVP-D could also disturb the oxytocin (OXT) system. OXT regulates socio-emotional functioning, including fear reduction, attachment, emotion recognition, and empathy. Therefore, these psychological symptoms may be caused by an additional OXT deficiency. However, OXT deficiency has not been established as a pituitary entity, as no provocation test for OXT is currently available. Here, we aimed to investigate the OXT system stimulator 3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) as a novel biochemical and psychoactive provocation test to reveal an OXT deficiency in patients with cDI. Methods: Randomized, placebo-controlled, double-blind, cross-over study in 15 patients with cDI and 15 matched healthy controls. Participants underwent a psychological baseline evaluation, including the assessment of anxiety levels using the State-Trait Anxiety Inventory (STAI), mood using the Beck’s Depression Inventory (BDI), and alexithymia using the Toronto Alexithymia Scale (TAS). Participants were randomized to receive either a single oral dose of MDMA (100 mg) or placebo first. OXT samples were collected at 0, 90, 120, 150, 180, and 300 minutes after drug intake. Subjective effects in response to MDMA were assessed throughout the experiment. The primary outcome was the area under the plasma OXT concentration curve (AUC) after MDMA intake. Results: Already at baseline, patients compared with healthy controls, showed significantly higher scores in anxiety (STAI: 41 points [IQR 34-48] vs. 28 points [24-31]; p=0.02), alexithymia (TAS: 47 points [38-59] vs. 30 points [29-37; p=0.04), and depression symptoms (BDI: 6 points [3-17] vs. 1 point [0-2]; p=0.04). In response to MDMA stimulation, in patients, there was only a minimal OXT change with 66 pg/ml [16-94], while in healthy controls, OXT increased by 658 pg/ml [355-914]. The AUC was 15.8 times (1485%), i.e., 85,678 pg/ml (95%-CI [-10,800 to -63,356], p<0.001), lower in patients compared with healthy controls. This lack of OXT in patients was associated with lower subjective effects such as ‘good drug effect,’ ‘feeling high,’ ‘satisfaction,’ ‘happy,’ ‘trust,’ ‘talkative,’ ‘openness,’ and ‘fear reduction’ compared with healthy controls. Conclusion: These results lay the groundwork for OXT deficiency as a hypothalamic-pituitary entity. In patients with cDI, this lack in OXT was associated with reduced pro-social, empathic, and anxiolytic effects. Presentation: Saturday, June 17, 2023

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by “eyeballing” of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Psychosocial stress is increasing in society, impacting our lives in all social domains. However, the conditions under which stress facilitates ("tend-and-befriend") or hinders ("fight-or-flight") social approach remain elusive. We tested whether previous heterogeneous findings might be resolved by accounting for individual differences in social performance under stress. For that purpose, we introduce the novel Trier Social Stress Test (TSST) social performance index that was aggregated across ratings from two independent observers. Moreover, we apply an innovative setup enabling electroencephalographic (EEG) data to be measured inside an electrically-shielded cabin during stress, namely the TSST-EEG. Relying on a sample of 59 healthy male participants, we collected behavioral (i.e., sharing resources with others) and cognitive (i.e., detecting facial emotional expressions) approach patterns while participants experienced either acute psychosocial stress (n = 31) or no stress (control condition; n = 28) and while EEG was being recorded. During stress exposure, high-performing participants behaved more prosocially, and differentiated better between happy and neutral emotions on both behavioral and neurophysiological levels (revealed by intensity differences in a N170-like response). Overall, our findings demonstrate the added value of both the novel TSST social performance index and the novel TSST-EEG setup. By showing that high social performance during the TSST is associated with behavioral, cognitive, and neurophysiological approach patterns, our study offers valuable insights into adaptive or maladaptive psychobiological mechanisms in coping with psychosocial stress. Future stress research should address the role of social performance differences during stress in social interaction to better understand the behavioral consequences of psychosocial stress in humans.

Nonverbal expressions are essential to regulating social communication and interaction. Impaired emotion recognition from facial expressions has been linked to various psychiatric conditions characterized by severe social deficits such as autism. As body expressions as an additional source of social-emotional information have attracted little research attention, little is known about whether emotion recognition impairments are specific to faces, or extend to body expressions. This study explored and compared emotion recognition from face versus body expressions in autism spectrum disorder. We compared 30 men with autism spectrum disorder to 30 male age- and IQ-matched control participants in their ability to recognize angry, happy, and neutral expressions from dynamic face and body expressions. Participants with autism spectrum disorder showed impaired recognition of angry expressions from both faces and bodies, while there were no group differences in recognizing happy and neutral expressions. In autism spectrum disorder, recognizing angry face expressions was inversely predicted by gaze avoidance, while recognizing angry body expressions was inversely predicted by impairments in social interaction and autistic traits. These findings suggest that distinct mechanisms may underlie the impaired emotion recognition from face and body expressions in autism spectrum disorder, respectively. Overall, our study demonstrates that emotion-specific recognition difficulties in autism spectrum disorder are not limited to face expressions but extend to emotional body expressions.