There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.
Abstract Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 ( TPH2 ), and transgenic animal models suggest that TPH2 -gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.
Abstract Background Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique with promising therapeutic potential in the context of epilepsy, pain, and depression and which may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. Objective In order to investigate the impact of taVNS on social cognition we have studied its effects on gaze towards emotional faces using an eye-tracking task and also on release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. Methods A total of fifty-four subjects were enrolled in a sham-controlled, participant-blind crossover experiment, consisting of two treatment sessions, separated by one week. In one session participants received 30-min taVNS (tragus), and in the other, they received 30-min sham (earlobe) stimulation with the treatment order counterbalanced across participants. Gaze duration towards the faces and facial features (eyes, nose, and mouth) were measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Results Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased fixation time on the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Conclusion Our findings suggest that taVNS biases visual attention towards socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.
Graph neural networks (GNNs) have received increasing interest in the medical imaging field given their powerful graph embedding ability to characterize the non-Euclidean structure of brain networks based on magnetic resonance imaging (MRI) data. However, previous studies are largely node-centralized and ignore edge features for graph classification tasks, resulting in moderate performance of graph classification accuracy. Moreover, the generalizability of GNN model is still far from satisfactory in brain disorder [e.g., autism spectrum disorder (ASD)] identification due to considerable individual differences in symptoms among patients as well as data heterogeneity among different sites. In order to address the above limitations, this study proposes a novel adversarial learning-based node-edge graph attention network (AL-NEGAT) for ASD identification based on multimodal MRI data. First, both node and edge features are modeled based on structural and functional MRI data to leverage complementary brain information and preserved in the constructed weighted adjacent matrix for individuals through the attention mechanism in the proposed NEGAT. Second, two AL methods are employed to improve the generalizability of NEGAT. Finally, a gradient-based saliency map strategy is utilized for model interpretation to identify important brain regions and connections contributing to the classification. Experimental results based on the public Autism Brain Imaging Data Exchange I (ABIDE I) data demonstrate that the proposed framework achieves a classification accuracy of 74.7% between ASD and typical developing (TD) groups based on 1007 subjects across 17 different sites and outperforms the state-of-the-art methods, indicating satisfying classification ability and generalizability of the proposed AL-NEGAT model. Our work provides a powerful tool for brain disorder identification.
Long-term wellbeing monitoring is an underlying theme in many local and national policies and procedures outlined by governments and health care services. Natural, efficacious, and trustworthy monitoring by using wearable sensors is necessary for researchers to find and establish the interrelationships of affective computing, body sensor networks (BSNs), social signal processing, and physical mental health. Specially, Giancarlo Fortino has an outstanding contribution for applying BSNs on health monitoring. This paper investigated how technology can help to objectively monitor an individual's wellbeing in a naturalistic environment. For this purpose, we designed and implemented a wearable device with the integration of multi-sensors which consist of audio sensing, behavior monitoring, environment, and physiological sensing. In order to avoid privacy issues, four audio-wellbeing features are embedded into a wearable hardware platform to automatically evaluate speech information without preserving raw audio data. In addition, four weeks of long-term monitoring experiment studies have been conducted in conjunction with a series of wellbeing questionnaires in a group of students. The relationships between physical and mental health were investigated objectively by utilizing data from speech, behavioral activities and ambient factors in a completely natural daily situation.
ABSTRACT Real-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity or connectivity, with demonstrated feasibility in experimental and therapeutic applications. The crucial role of the insula in emotional and salience processing makes it a popular target in rtfMRI studies although there is no systematic review of their efficacy. To promote our understanding of mechanisms underlying insula regulation and thereby facilitate therapeutic translation, the present review identified 22 preclinical and clinical studies and found that rtfMRI-based NF training is efficient for modulating insula activity (> 86%) and its associated behavioral and neural changes. Based on findings, continuous feedback for multiple training sessions, specific strategies validated before application, inclusion of a practice session, and choosing appropriate localization strategies are suggested as guidelines. We also recommend standardization of training protocol design, statistical analyses and results reports for future studies. In summary, the present review informs both fundamental research and therapeutic translation of NF training as an intervention in mental disorders, particularly those with insula dysfunction.
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