Search

Across species, the neuropeptide oxytocin has been associated with affiliative and social approach behavior. It has been suggested to exert its effects by modulating neural circuitry underlying anxiety, affiliative motivation, and social salience. The present study aims to investigate differences in subregional amygdala resting-state connectivity in healthy adult carriers of different genotypes of the oxytocin receptor (OXTR) gene polymorphism rs2268498. Previous studies have associated this polymorphic locus with social cognitive and affiliative phenotypes. The amygdala qualifies as a reasonable target due to its broad implication in emotional and social cognitive processing as well as its key role in mediating the behavioral effects of oxytocin. Whole brain seed-based functional connectivity analyses for the basolateral, centromedial and superficial amygdala revealed stronger resting-state connectivity of all amygdala subregions to the fusiform and inferior occipital gyrus in TT-carriers compared to C-allele carriers. Additional modulations were found for the centromedial amygdala which showed stronger resting-state connectivity to inferior frontal regions and the insula in C-allele carriers and to brainstem regions in TT-carriers. Our findings not only show the importance of oxytocin functioning in amygdalar neuronal signaling but also emphasize the need to investigate the amygdalar subregions individually instead of the amygdala as a whole. In summary, the present study is the first to characterize the impact of genetic variation of the OXTR gene with known functional consequences on widespread changes in a functional brain network originating from the amygdala.

The hypothalamic neuropeptide oxytocin (OT) has received increasing attention for its role in modulating social-emotional processes across species. Previous studies on using intranasal-OT in humans point to a crucial engagement of the amygdala in the observed neuromodulatory effects of OT under task and rest conditions. However, the amygdala is not a single homogenous structure, but rather a set of structurally and functionally heterogeneous nuclei that show distinct patterns of connectivity with limbic and frontal emotion-processing regions. To determine potential differential effects of OT on functional connectivity of the amygdala subregions, 79 male participants underwent resting-state fMRI following randomized intranasal-OT or placebo administration. In line with previous studies OT increased the connectivity of the total amygdala with dorso-medial prefrontal regions engaged in emotion regulation. In addition, OT enhanced coupling of the total amygdala with cerebellar regions. Importantly, OT differentially altered the connectivity of amygdala subregions with distinct up-stream cortical nodes, particularly prefrontal/parietal, and cerebellar down-stream regions. OT-induced increased connectivity with cerebellar regions were largely driven by effects on the centromedial and basolateral subregions, whereas increased connectivity with prefrontal regions were largely mediated by right superficial and basolateral subregions. OT decreased connectivity of the centromedial subregions with core hubs of the emotional face processing network in temporal, occipital and parietal regions. Preliminary findings suggest that effects on the superficial amygdala-prefrontal pathway were inversely associated with levels of subclinical depression, possibly indicating that OT modulation may be blunted in the context of increased pathological load. Together, the present findings suggest a subregional-specific modulatory role of OT on amygdala-centered emotion processing networks in humans.

Interactions between oxytocin and the basal ganglia are central in current overarching conceptualizations of its broad modulatory effects on behavior. Whereas evidence from animal models emphasizes the critical role of the ventral striatum in the behavioral effects of oxytocin, region-specific contributions of the basal ganglia have not been systematically explored in humans. The present study combined the randomized placebo-controlled administration of oxytocin versus placebo in healthy men (n = 144) with fMRI-based resting-state functional connectivity to determine the modulatory role of oxytocin on the major basal ganglia pathways. Oxytocin specifically increased connectivity between ventral striatal and pallidal nodes with upstream frontal regions, whereas it decreased the strengths of downstream pathways between the dorsal striatum and posterior cerebellum. These pathways have previously been implicated in salience, reward and behavioral flexibility, thus shaping goal-directed behavior. Given the importance of aberrant striatal intrinsic organization in autism, addiction and schizophrenia the present findings may suggest new mechanistic perspectives for the therapeutic potential of oxytocin in these disorders.

Background Vicarious embarrassment (VE) is an emotion triggered by the observation of others' pratfalls or social norm violations. Several explanatory approaches have been suggested to explain the source of this phenomenon, including perspective taking abilities or ingroup identification. Knowledge about its biological bases, however, is scarce. To gain a better understanding, the present study investigated neural activation patterns in response to video clips from reality TV shows. Reality TV is well known for presenting social norm violations, flaws and pratfalls of its protagonists in real life situations thereby qualifying as an ecological valid trigger for VE. Methods N = 60 healthy participants viewed stand stills from previously watched video clips taken from German reality TV-shows while undergoing functional magnetic resonance imaging. The clips were preselected for high versus low VE content in a pilot study. Besides the investigation of differences in brain activation elicited by VE versus control stand stills (blocked design contrast), we performed additional exploratory functional connectivity analyses (psychophysiological interaction; PPI) to detect VE related brain networks. Results Compared to the low VE condition, participants in the high VE condition showed a higher activation in the middle temporal gyrus, the supramarginal gyrus, the right inferior frontal gyrus and the gyrus rectus. Functional connectivity analyses confirmed increased connectivity of these regions with the anterior cingulate in the VE condition. Moreover, self-ratings of VE and brain activity were correlated positively. Conclusion Reality TV formats with high VE content activate brain regions associated with Theory of Mind, but also with empathic concern and social identity. Therefore, our results support the idea that the ability to put oneself in other person's shoes is a major prerequisite for VE.

Dopaminergic activity is modulated by acetylcholine with relevance for cognitive functioning, as shown by pharmacological work in a rodent model. In humans, the two transmitter systems' joint effort on cognition has been described on the molecular genetic level: DRD2 rs6277, a single nucleotide polymorphism (SNP) on the dopamine D2 receptor gene and CHRNA4 rs1044396, a SNP on the nicotinic acetylcholine receptor gene interact on visuo-spatial and phonological working memory. The present study uses structural MRI and voxel based morphometry to extend this behavioral work to an intermediate phenotype on the neural level. We found significantly reduced gray matter volume in the right putamen in carriers of the DRD2 C/C and CHRNA4 T/T groups. This genotype combination has previously proven to be beneficial for working memory capacity. Results are in line with the idea that the two genes jointly influence the gating signals from subcortical structures to the prefrontal cortex.

Dopaminergic neurotransmission in the mesocortical system is crucial for higher order cognition. Common variation on the dopamine D2 receptor (DRD2) gene has been linked to individual differences in dopaminergic signaling and was also repeatedly associated to cognitive markers. The relationship between dopaminergic genetic variants and neurostructural properties of the mesocortical system, however, has received little attention so far. Recently, the direction of a dopaminergic manipulation was predicted from the integrity of fiber tracts between subcortical areas and the frontal lobes. Fiber tract integrity was therefore proposed as an indicator of baseline dopamine activity. This raises the question whether DRD2 variants that relate to dopamine turnaround are also linked to fiber tract integrity. In the present study we assessed associations between the DRD2 rs6277 polymorphism and subcortical connections from connectome maps derived from diffusion weighted imaging in n=105 healthy volunteers (43 males and 62 females). Carriers of the CC genotype who are characterized by elevated striatal dopamine turnaround showed higher integrity in terms of fractional anisotropy on fiber tracts between the basal ganglia and frontal regions compared to carriers of the CT and TT variant. Our results indicate that structural connectivity could serve as a conceptual link between genetically determined individual differences in dopaminergic activity and effects of dopamine challenges on executive functioning.

According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality.

The proneness to minor errors and slips in everyday life as assessed by the Cognitive Failures Questionnaire (CFQ) constitutes a trait characteristic and is reflected in stable features of brain structure and function. It is unclear, however, how dynamic interactions of large-scale brain networks contribute to this disposition. To address this question, we performed a high model order independent component analysis (ICA) with subsequent dual regression on resting-state fMRI data from 71 subjects to extract temporal time courses describing the dynamics of 17 resting-state networks (RSN). Dynamic network interactions between all 17 RSN were assessed by linear correlations between networks' time courses. On this basis, we investigated the relationship between subject-level RSN interactions and the susceptibility to everyday cognitive failure. We found that CFQ scores were significantly correlated with the interplay of the cingulo-opercular network (CON) and a posterior parietal network which unifies clusters in the posterior cingulate, precuneus, intraparietal lobules and middle temporal regions. Specifically, a higher positive functional connectivity between these two RSN was indicative of higher proneness to cognitive failure. Both the CON and posterior parietal network are implicated in cognitive functions, such as tonic alertness and executive control. Results indicate that proper checks and balances between the two networks are needed to protect against cognitive failure. Furthermore, we demonstrate that the study of temporal network dynamics in the resting state is a feasible tool to investigate individual differences in cognitive ability and performance.