Identifying neural biomarkers of pain has long been a central theme in pain neuroscience. Here, we review the state-of-the-art candidates for neural biomarkers of acute and chronic pain. We classify these potential neural biomarkers into five categories based on the nature of their target variables, including neural biomarkers of (1) within-individual perception, (2) between-individual sensitivity, and (3) discriminability for acute pain, as well as (4) assessment and (5) prospective neural biomarkers for chronic pain. For each category, we provide a synthesized review of candidate biomarkers developed using neuroimaging techniques including functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), and electroencephalography (EEG). We also discuss the conceptual and practical challenges in developing neural biomarkers of pain. Addressing these challenges, optimal biomarkers of pain can be developed to deepen our understanding of how the brain represents pain and ultimately help alleviate patients' suffering and improve their well-being.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive technique with potential beneficial effects on human emotion and cognition, including cortical arousal and alertness. However, it remains unclear how taVNS could improve cortical arousal and alertness, which are crucial for consciousness and daily task performance. Here, we aimed to estimate the modulatory effect of taVNS on cortical arousal and alertness and to reveal its underlying neural mechanisms. Sixty subjects were recruited and randomly assigned to either the taVNS group (receiving taVNS for 20 min) or the control group (receiving taVNS for 30 s). The effects of taVNS were evaluated behaviorally using a cue-target pattern task, and neurologically using a resting-state electroencephalogram (EEG). We found that taVNS facilitated the reaction time for the targets requiring right-hand responses and attenuated high-frequency alpha oscillations under the close-eye resting state. Importantly, taVNS-modulated alpha oscillations were positively correlated with the facilitated target detection performance, i.e., reduced reaction time. Furthermore, microstate analysis of the resting-state EEG when the eyes were closed illustrated that taVNS reduced the mean duration of microstate C, which has been proven to be associated with alertness. Altogether, this work provided novel evidence suggesting that taVNS could be an enhancer of both cortical arousal and alertness.

Background: Music is sometimes used as an adjunct to pain management. However, there is limited understanding of by what means music modulates pain perception and how the brain responds to nociceptive inputs while listening to music, because clinical practice typically involves the coexistence of multiple therapeutic interventions. To address this challenge, laboratory studies with experimental and control conditions are needed. Methods: In the present investigation, we delivered nociceptive laser stimuli on 30 participants under three conditions – participants were sitting in silence, listening to their preferred music, or listening to white noise. Differences among conditions were quantified by self-reports of pain intensity and unpleasantness, and brain activity sampled by electroencephalography (EEG). Results: Compared with the noise and silence conditions, participants in the music condition reported lower ratings on pain unpleasantness, as reflected by reduced brain oscillations immediately prior to the nociceptive laser stimulus at frequencies of 4–15 Hz in EEG. In addition, participants showed smaller P2 amplitudes in laser-evoked potentials (LEPs) when they were listening to music or white noise in comparison to sitting in silence. These findings suggest that a general modulation effect of sounds on pain, with a specific reduction of pain unpleasantness induced by the positive emotional impact. Conclusion: Music may serve as a real-time regulator to modulate pain unpleasantness. Results are discussed in view of current understandings of music-induced analgesia.

Females are considered the more empathic sex. This conventional view, however, has been challenged in the past few decades with mixed findings. These heterogeneous findings could be caused by the fact that empathy is a complex and multifaceted construct. To clarify whether sex differences exist in certain dimensions of empathy and whether they are associated with specific neural bases, this study measured trait empathy using the interpersonal reactivity index (IRI) and collected brain structural and functional magnetic resonance imaging data in a large sample of healthy participants (206 males vs. 302 females). We found that females scored higher in the personal distress (PD) subscale than males, but they were comparable to males in other IRI subscales. Sex difference in PD was encoded by brain structural (e.g. gray matter volume in left anterior insula [AI]) and functional (e.g. resting-state functional connectivity between left AI and temporoparietal junction/inferior frontal gyrus) characteristics. Notably, the relationship between sex and PD was indirect-only and serially mediated by AI-associated structural and functional characteristics. Altogether, our results suggested that sex difference existed in self-oriented affective empathy (i.e. PD) and highlighted the importance of the AI, both structurally and functionally, in mediating the sex difference in trait empathy.

Music not only regulates mood but also promotes the development and maintenance of empathy and social understanding. Since empathy is crucial for well-being and indispensable in social life, it is necessary to develop strategies to improve empathy and prosocial behaviors. To fulfill this aim, researchers have extensively investigated the effect of intensive musical training on the development of empathy. Here, we first summarize evidence showing the powerful influence of musical training on the development of empathy and then discuss psychological mechanisms responsible for those observations. The conclusions drawn from most previous studies were mainly based on behavioral measurements, while the neural basis of musical training in the development of the empathic brain is still unclear. Fortunately, brain imaging research has contributed greatly to our understanding of the neural underpinnings associated with musical training and its possible connection to the development of the empathic brain. One of the most distinctive signatures of musical training is structural and functional changes of multiple brain regions, and such changes might be related to some of the empathic behaviors observed in musically trained children. Therefore, intensive musical training in childhood may increase levels of empathy, and applied research is required to optimize the training strategy before implementing music education in empathy regulation. Moreover, future longitudinal studies are needed to better understand neural mechanisms underlying the causal effect of musical training on empathy development. These findings have important implications for understanding the development of the empathic brain and for improving prosocial behaviors.