"Listen to your heart": A novel interoceptive strategy for real-time fMRI neurofeedback training of anterior insula activity.

Real-time fMRI (rt-fMRI) neurofeedback (NF) training is a novel non-invasive technique for volitional brain modulation. Given the important role of the anterior insula (AI) in human cognitive and affective processes, it has become one of the most investigated regions in rt-fMRI studies. Most rt-fMRI insula studies employed emotional recall/imagery as the regulation strategy, which may be less effective for psychiatric disorders characterized by altered emotional processing. The present study thus aimed to examine the feasibility of a novel interoceptive strategy based on heartbeat detection in rt-fMRI guided AI regulation and its associated behavioral changes using a randomized double-blind, sham feedback-controlled between-subject design. 66 participants were recruited and randomly assigned to receive either NF from the left AI (LAI) or sham feedback from a control region while using the interoceptive strategy. N = 57 participants were included in the final data analyses. Empathic and interoceptive pre-post training changes were collected as behavioral measures of NF training effects. Results showed that participants in the NF group exhibited stronger LAI activity than the control group with LAI activity being positively correlated with interoceptive accuracy following NF training, although there were no significant increases of LAI activity over training sessions. Importantly, ability of LAI regulation could be maintained in a transfer session without feedback. Successful LAI regulation was associated with strengthened functional connectivity of the LAI with cognitive control, memory and learning, and salience/interoceptive networks. The present study demonstrated for the first time the efficacy of a novel regulation strategy based on interoceptive processing in up-regulating LAI activity. Our findings also provide proof of concept for the translational potential of this strategy in rt-fMRI AI regulation of psychiatric disorders characterized by altered emotional processing.

Oxytocin administration enhances pleasantness and neural responses to gentle stroking but not moderate pressure social touch by increasing peripheral concentrations.

Background: Social touch constitutes a key component of human social relationships, although in some conditions with social dysfunction, such as autism, it can be perceived as unpleasant. We have previously shown that intranasal administration of oxytocin facilitates the pleasantness of social touch and activation of brain reward and social processing regions, although it is unclear if it influences responses to gentle stroking touch mediated by cutaneous C-touch fibers or pressure touch mediated by other types of fibers. Additionally, it is unclear whether endogenous oxytocin acts via direct entry into the brain or by increased peripheral blood concentrations. Methods: In a randomized controlled design, we compared effects of intranasal (direct entry into the brain and increased peripheral concentrations) and oral (only peripheral increases) oxytocin on behavioral and neural responses to social touch targeting C-touch (gentle-stroking) or other (medium pressure without stroking) cutaneous receptors. Results: Although both types of touch were perceived as pleasant, intranasal and oral oxytocin equivalently enhanced pleasantness ratings and responses of reward, orbitofrontal cortex, and social processing, superior temporal sulcus, regions only to gentle-stroking not medium pressure touch. Furthermore, increased blood oxytocin concentrations predicted the pleasantness of gentle stroking touch. The specificity of neural effects of oxytocin on C-touch targeted gentle stroking touch were confirmed by time-course extraction and classification analysis. Conclusions: Increased peripheral concentrations of oxytocin primarily modulate its behavioral and neural responses to gentle social touch mediated by C-touch fibers. Findings have potential implications for using oxytocin therapeutically in conditions where social touch is unpleasant. Funding: Key Technological Projects of Guangdong Province grant 2018B030335001. Clinical trial number: NCT05265806.

Transcutaneous auricular vagus nerve stimulation increases eye-gaze on salient facial features and oxytocin release.

Non-invasive, transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) via the ear is used therapeutically in epilepsy, pain, and depression, and 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. To investigate the impact of taVNS on social cognition we have studied its effects on gaze toward emotional faces in combination with eye-tracking and on the release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. A total of 54 subjects were enrolled (49 were included in the final analysis) in a sham-controlled, participant-blind, crossover experiment, consisting of two treatment sessions 1 week apart. 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. The proportion of time spent viewing the faces and facial features (eyes, nose, and mouth) was measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased time spent viewing the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Our findings suggest that taVNS biases visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.