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Objectives Traditional moxibustion might be not safe due to the excessive heat stimulation or toxic chemical components involved. Electric moxibustion (EM), which has been recently developed as an alternative, offers adjustable and constant heat stimulation. This study aimed to investigate the psychophysical and psychophysiological responses to EM heat stimulation. Methods Twenty-seven healthy volunteers received two different levels of heat stimulation using EM. High-temperature (HT) and medium-temperature (MT) heat stimulations were randomly delivered at the TE5 acupoint on the left or right arm. Participants rated the intensity and the spatial information of the heat sensations immediately after each EM stimulation. Local blood flow around the acupoint was measured with Laser Doppler perfusion imaging before and after heat stimulation. Results Both HT-EM and MT-EM induced considerable heat sensations and enhanced local blood flow around the acupoints. HT-EM resulted in greater heat sensation compared to MT-EM. HT-EM induced a higher increase in local blood flow around the stimulation site compared to MT-EM. No remarkable adverse effects were noted. Conclusion Two different levels of EM heat stimulation induced two different levels of heat sensations and enhanced local blood flow. This preliminary study suggests that the newly developed EM can be further applied to examine the effectiveness of moxibustion in clinical trials.

The operant conditioning has been less studied than the classical conditioning as a mechanism of placebo-like effect, and two distinct learning mechanisms have never been compared to each other in terms of their neural activities. Twenty-one participants completed cue-learning based pain rating tasks while their brain responses were measured using functional magnetic resonance imaging. After choosing (instrumental) or viewing (classical) one of three predictive cues (low- and high-pain cues with different level of certainty), they received painful stimuli according to the selected cues. Participants completed the same task during the test session, except that they received only a high pain stimulus regardless of the selected cues to identify the effects of two learning paradigms. While receiving a high pain stimulation, low-pain cue significantly reduced pain ratings compared to high-pain cue, and the overall ratings were significantly lower under operant than under classical conditioning. Operant behavior activated the temporoparietal junction significantly more than the passive behavior did, and neural activity in the primary somatosensory cortex was significantly reduced during pain in instrumental as compared with classical conditioning trials. The results suggest that pain modulation can be induced by classical and operant conditioning, and mechanisms of attention and context change are involved in instrumental learning.

Faces can be categorized in various ways, for example as male or female or as belonging to a specific biogeographic ancestry (race). Here we tested the importance of the main facial features for race perception. We exchanged inner facial features (eyes, mouth or nose), face contour (everything but those) or texture (surface information) between Asian and Caucasian faces. Features were exchanged one at a time, creating for each Asian/Caucasian face pair ten facial variations of the original face pair. German and Korean participants performed a race classification task on all faces presented in random order. The results show that eyes and texture are major determinants of perceived biogeographic ancestry for both groups of participants and for both face types. Inserting these features in a face of another race changed its perceived biogeographic ancestry. Contour, nose and mouth, in that order, had decreasing and much weaker influence on race perception for both participant groups. Exchanging those features did not induce a change of perceived biogeographic ancestry. In our study, all manipulated features were imbedded in natural looking faces, which were shown in an off-frontal view. Our findings confirm and extend previous studies investigating the importance of various facial features for race perception.

The classification of Alzheimer’s disease (AD) using deep learning methods has shown promising results, but successful application in clinical settings requires a combination of high accuracy, short processing time, and generalizability to various populations. In this study, we developed a convolutional neural network (CNN)-based AD classification algorithm using magnetic resonance imaging (MRI) scans from AD patients and age/gender-matched cognitively normal controls from two populations that differ in ethnicity and education level. These populations come from the Seoul National University Bundang Hospital (SNUBH) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). For each population, we trained CNNs on five subsets using coronal slices of T1-weighted images that cover the medial temporal lobe. We evaluated the models on validation subsets from both the same population (within-dataset validation) and other population (between-dataset validation). Our models achieved average areas under the curves of 0.91–0.94 for within-dataset validation and 0.88–0.89 for between-dataset validation. The mean processing time per person was 23–24 s. The within-dataset and between-dataset performances were comparable between the ADNI-derived and SNUBH-derived models. These results demonstrate the generalizability of our models to different patients with different ethnicities and education levels, as well as their potential for deployment as fast and accurate diagnostic support tools for AD.

We investigated whether enhanced interoceptive bodily states of fear would facilitate recognition of the fearful faces. Participants performed an emotional judgment task after a bodily imagery task inside a functional magnetic resonance imaging scanner. In the bodily imagery task, participants were instructed to imagine feeling the bodily sensations of two specific somatotopic patterns: a fear-associated bodily sensation (FBS) or a disgust-associated bodily sensation (DBS). They were shown faces expressing various levels of fearfulness and disgust and instructed to classify the facial expression as fear or disgust. We found a stronger bias favoring the “fearful face” under the congruent FBS condition than under the incongruent DBS condition. The brain response to fearful versus intermediate faces increased in the fronto-insular-temporal network under the FBS condition, but not the DBS condition. The fearful face elicited activity in the anterior cingulate cortex and extrastriate body area under the FBS condition relative to the DBS condition. Furthermore, functional connectivity between the anterior cingulate cortex/extrastriate body area and the fronto-insular-temporal network was modulated according to the specific bodily sensation. Our findings suggest that somatotopic patterns of bodily sensation provide informative access to the collective visceral state in the fear processing via the fronto-insular-temporal network.

The discovery that pleasant touch is coded by C-tactile fibers has generated considerable research interest and increased understanding of the skin as a channel for social information via cutaneous senses. However, no study has differentiated between the pleasant response to visual and tactile non-human stimulations. Our study investigated pleasant touch in which the visual and haptic touch information was obtained from an affective, but non-social experience, by a custom-built non-human device. Participants (n=19) received soft brush strokes on their lower left arm delivered by a rotary tactile stimulator (physical session) or watched a video of an arm being stroked by a rotary tactile stimulator (visual session). The brush strokes were delivered at the same velocities (0.3, 1, 3, 10, 30cm/s) and force (0.4N) in both sessions. After each trial, participants rated the pleasantness of the touch. Analysis of variance was used to assess the effects of velocity and modality (visual touch vs. physical touch) on the pleasantness rating. Participants rated strokes between 1 and 10cm/s as most pleasant under both conditions. The pleasantness rating patterns differed significantly among velocities; however, no significant differences were found between modalities. Visual and physical (without human-to-human interaction) touch elicited similar behavioral responses, including an inverted U-shaped perception of pleasantness. These findings suggest that the pleasantness of touch is influenced by the velocity of the strokes in both visual and physical touch with a non-human stimulation.

Objective: The optimal acupoints for a particular disease can be determined by analysis of diagnosis patterns. The objective of this study was to reveal the association between such patterns and the acupoints prescribed in clinical practice using medical data extracted from case reports. Methods: This study evaluated online virtual diagnoses made by currently practicing Korean medical doctors (N = 80). The doctors were presented with 10 case reports published in Korean medical journals and were asked to diagnose the patients and prescribe acupoints accordingly. A network analysis and the term frequency-inverse document frequency (tf-idf) method were used to analyse and quantify the relationship between diagnosis patterns and prescribed acupoints. Results: The network analysis showed that ST36, LI4, LR3, and SP6 were the most frequently used acupoints across all diagnoses. The tf-idf values showed the acupoints used for specific diseases, such as BL40 for bladder disease and LU9 for lung disease. Conclusions: The associations between diagnosis patterns and prescribed acupoints were identified using an online virtual diagnosis modality. Network and text mining analyses revealed commonly applied and disease-specific acupoints in both qualitative and quantitative terms.

The present study applied multivoxel pattern analysis to decode spatial discrimination in pain perception to acupuncture needle from brain functional magnetic resonance image. Fourteen participants were stimulated by acupuncture needles at two adjacent body parts on their left forearm (PC6 vs. HT7). We trained support vector machines on the spatial information from the whole-brain functional magnetic resonance imaging data and projected the support vector machine weight to the brain image space to represent the effect of each voxel on the classifier output. Using region-of-interest masks in individual brains, we trained and tested a linear support vector machine classifier on the accuracy of spatial discrimination in trial-wise functional magnetic resonance imaging data. A classical univariate general linear model analysis testing for differences between the two different locations did not reveal any significant differences. Multivoxel pattern analysis revealed that the brain regions for the prediction of sensory discrimination in pain perceptions to two different points were in the primary somatosensory cortex, primary motor cortex, and supramarginal gyrus, anterior and posterior insula, anterior and posterior cingulate cortex, ventromedial prefrontal cortex, and inferior parietal lobule. Our findings suggest that spatial localizations of pain perceptions to acupuncture needle can be predicted by the neural response patterns in the somatosensory areas and the frontoparietal areas.

Growing evidence indicates that neuropathic pain is frequently accompanied by cognitive impairments, which aggravate the quality of life of chronic pain patients. Here, we investigated whether acupuncture treatments can improve cognitive dysfunction as well as allodynia induced by neuropathic pain in mice. One week after the left partial sciatic nerve ligation (PSNL), acupuncture treatments on the acupoints GB30-GB34 (AP1), HT7-GV20 (AP2), or control points (CP) were performed for 4 weeks. Notably, the significant attenuations of mechanical allodynia and cognitive impairment were observed in the AP1 group, but not in PSNL, AP2, or CP groups. A random decision forest classifier based on the pain and cognitive functions displayed that the acupuncture group was clearly segregated from the other groups. We also demonstrated that acupuncture restored the reduced field excitatory post-synaptic potentials and was able to elevate the expression levels of glutamate receptors (NR2B and GluR1) in the hippocampus. Moreover, the expressions of Ca2+/calmodulin-dependent protein kinase II and synaptic proteins (pPSD-95 and pSyn-1) were enhanced by acupuncture treatment. These results suggest that acupuncture can enhance hippocampal long-term action through the regulation of the synaptic efficacy and that acupuncture may provide a viable option for managing both pain and cognitive functions associated with chronic neuropathic pain.

The experience of pain relief arises from physiological and psychological factors, and attributes such as the commercial features of analgesic treatments have been shown to influence placebo analgesia by affecting treatment expectations. Therefore, treatment valuation from price information should influence the placebo analgesic effect. This hypothesis was tested in a functional magnetic resonance imaging study in which healthy subjects were enrolled in a 2-day experiment. On day 1, the participants (n = 19) had treatment experiences with 2 different placebo creams during a conditioning session without receiving information on treatment price. On day 2, placebo analgesia was tested after providing price information (high vs low) while functional magnetic resonance imaging was performed. The results showed that the higher priced placebo treatment leads to enhanced pain relief. Placebo analgesia in response to the higher priced treatment was associated with activity in the ventral striatum, ventromedial prefrontal cortex, and ventral tegmental area. The behavioral results indicate that the experience of pain was influenced by treatment valuation from price. Our findings reveal that the context of values in pain control is associated with activity in expectation- and reward-related circuitry. Perspective Treatment with higher price was associated with enhanced placebo analgesia, and this effect was influenced by activities in expectation and reward processing brain areas. The context of value such as medical cost influences cognitive evaluation processes to modulate pain. Our study may help evaluate a patient's preference toward high-priced drugs.

Previous studies have suggested that acupuncture is effective for ameliorating itch intensity. However, factors associated with the antipruritic effects of acupuncture have yet to be clarified. In a randomized, sham-controlled, crossover trial, we investigated the antipruritic effects of acupuncture against histamine-induced itch in healthy volunteers. Autonomic changes using heart rate variability (HRV) and brain connectivity using functional magnetic resonance imaging (fMRI) were also assessed to identify physiological factors associated with the acupuncture response. Acupuncture significantly reduced itch intensity and skin blood perfusion as assessed by laser Doppler perfusion imaging compared to sham control, indicating the antipruritic effects of acupuncture. In responder and non-responder analysis, the power of normalized high frequency (HF norm) was significantly higher, while the power of normalized low frequency (LF norm) and LF/HF ratio were significantly lower in responders compared to non-responders, suggesting the acupuncture response involved parasympathetic activation. In fMRI analysis, the putamen and the posterior part of the midcingulate cortex (pMCC) were positively connected to itch and negatively correlated with itch intensity in responders. These results suggest that parasympathetic activity and functional connectivity of the putamen and pMCC could be associated with antipruritic response to acupuncture.

Emotional perception can be shaped by inferences about bodily states. Here, we investigated whether exteroceptive inferences about bodily sensations in the chest area influence the perception of fearful faces. Twenty-two participants received pseudo-electrical acupuncture stimulation at three different acupoints: CV17 (chest), CV23 (chin), and PC6 (left forearm). All stimuli were delivered with corresponding visual cues, and the control condition included visual cues that did not match the stimulated body sites. After the stimulation, the participants were shown images with one of five morphed facial expressions, ranging from 100% fear to 100% disgust, and asked to classify them as fearful or disgusted. Brain activity was measured using functional magnetic resonance imaging during the facial expression classification task. When the participants expected that they would receive stimulation of the chest (CV17), the ratio of fearful to non-fearful classifications decreased compared to the control condition, and brain activities within the periaqueductal gray and the default mode network decreased when they viewed fearful faces. Our findings suggest that bodily sensations around the chest, but not the other tested body parts, were selectively associated with fear perception and that altering external inferences inhibited the perception of fearful faces.

Objective. Attempts to understand the emotion have evolved from the perspective of an independent cognitive system of the mind to that of an interactive response involving the body. This study aimed to quantify and visualize relationships between different emotions and bodily organ systems from the perspective of East Asian medicine. Methods. Term frequency-inverse document frequency (tf-idf) method was used to quantify the significance of Five Viscera and the gallbladder relative to seven different emotions through the classical medical text of DongUiBoGam. Bodily organs that corresponded to different emotions were visualized using a body template. Results. The emotions had superior tf-idf values with the following bodily organs: anger with the liver, happiness with the heart, thoughtfulness with the heart and spleen, sadness with the heart and lungs, fear with the kidneys and the heart, surprise with the heart and the gallbladder, and anxiety with the heart and the lungs. Specific patterns between the emotions and corresponding bodily organ systems were identified. Conclusion. The present findings will further the current understanding of the relationship between the mind and body from the perspective of East Asian medicine. Western medicine characterizes emotional disorders using “neural” language while East Asian medicine uses “somatic” language.

The brain actively interprets sensory inputs by integrating top-down and bottom-up information. Humans can make inferences on somatosensation based on prior experiences and expectations even without the actual stimulation. We used functional magnetic resonance imaging to investigate the neural substrates of the expectations of the sensory experience of cutaneous electrical stimulation on acupoint without actual stimuli. This study included 22 participants who wore sticker-type electrodes attached on three different acupoints on different body regions: CV17 (chest), CV23 (chin), and left PC6 (arm). Participants evaluated de qi sensations after they expected electrical stimulation on those points in random order without actual stimulation. All stimuli were presented with corresponding visual information of the stimulation sites. The control condition included the same visual information but outside the body. The expectations of cutaneous electrical stimuli without actual stimulation on three acupoints resulted in greater de qi sensation compared to the control condition. Cognitive components of cutaneous electrical stimulation exhibited greater brain activation in the anterior insula, pre-supplementary motor area, and secondary somatosensory area. The expectations of acupuncture stimulation exhibited a distinct experience of somatosensation as well as brain activations in insula and pre-supplementary motor area. Our findings suggest that the sensory experience of the pseudo-cutaneous stimulation may be derived from the predictive role of the salience network in monitoring internal and external body states., Highlights • The pseudo-cutaneous stimulation can elicit remarkable somatic sensations. • Insula and pre-SMA are involved in the expectations of sensory experience. • Somatic sensation from pseudo-stimulation is influenced by top-down information.

The brain can only attend to a fraction of all the information that is entering the visual system at any given moment. One way of overcoming the so-called bottleneck of selective attention (e.g., J. M. Wolfe, Vo, Evans, & Greene, 2011) is to make use of redundant visual information and extract summarized statistical information of the whole visual scene. Such ensemble representation occurs for low-level features of textures or simple objects, but it has also been reported for complex high-level properties. While the visual system has, for example, been shown to compute summary representations of facial expression, gender, or identity, it is less clear whether perceptual input from all parts of the visual field contributes equally to the ensemble percept. Here we extend the line of ensemble-representation research into the realm of race and look at the possibility that ensemble perception relies on weighting visual information differently depending on its origin from either the fovea or the visual periphery. We find that observers can judge the mean race of a set of faces, similar to judgments of mean emotion from faces and ensemble representations in low-level domains of visual processing. We also find that while peripheral faces seem to be taken into account for the ensemble percept, far more weight is given to stimuli presented foveally than peripherally. Whether this precision weighting of information stems from differences in the accuracy with which the visual system processes information across the visual field or from statistical inferences about the world needs to be determined by further research.

Ye-Seul Lee,1 Won-Mo Jung,1 Hyunchul Jang,2 Sanghyun Kim,2 Sun-Yong Chung,3 Younbyoung Chae1 1Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 2Mibyeong Research Center, Korean Institute of Oriental Medicine, Daejeon, 3Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea Objectives: Recently, there has been increasing interest in preventing and managing diseases both inside and outside medical institutions, and these concerns have supported the development of the individual Personal Health Record (PHR). Thus, the current study created a mobile platform called “Mind Mirror” to evaluate psychological and physical conditions and investigated whether PHRs would be a useful tool for assessment of the dynamic relationship between the emotional and physical conditions of an individual.Methods: Mind Mirror was used to collect 30days of observational data about emotional valence and the physical states of pain and fatigue from 20 healthy participants, and these data were used to analyze the dynamic relationship between emotional and physical conditions. Additionally, based on the cross-correlations between these three parameters, a multilevel multivariate regression model (mixed linear model [MLM]) was implemented.Results: The strongest cross-correlation between emotional and physical conditions was at lag 0, which implies that emotion and body condition changed concurrently. In the MLM, emotional valence was negatively associated with fatigue (β =-0.233, P

Magnetic resonance (MR) imaging plays a highly important role in radiotherapy treatment planning for the segmentation of tumor volumes and organs. However, the use of MR is limited, owing to its high cost and the increased use of metal implants for patients. This study is aimed towards patients who are contraindicated owing to claustrophobia and cardiac pacemakers, and many scenarios in which only computed tomography (CT) images are available, such as emergencies, situations lacking an MR scanner, and situations in which the cost of obtaining an MR scan is prohibitive. From medical practice, our approach can be adopted as a screening method by radiologists to observe abnormal anatomical lesions in certain diseases that are difficult to diagnose by CT. The proposed approach can estimate an MR image based on a CT image using paired and unpaired training data. In contrast to existing synthetic methods for medical imaging, which depend on sparse pairwise-aligned data or plentiful unpaired data, the proposed approach alleviates the rigid registration of paired training, and overcomes the context-misalignment problem of unpaired training. A generative adversarial network was trained to transform two-dimensional (2D) brain CT image slices into 2D brain MR image slices, combining the adversarial, dual cycle-consistent, and voxel-wise losses. Qualitative and quantitative comparisons against independent paired and unpaired training methods demonstrated the superiority of our approach.

The emotion-associated bodily sensation map is composed of a specific topographical distribution of bodily sensations to categorical emotions. The present study investigated whether or not interoceptive accuracy was associated with topographical changes in this map following emotion-induced bodily sensations. This study included 31 participants who observed short video clips containing emotional stimuli and then reported their sensations on the body map. Interoceptive accuracy was evaluated with a heartbeat detection task and the spatial patterns of bodily sensations to specific emotions, including anger, fear, disgust, happiness, sadness, and neutral, were visualized using Statistical Parametric Mapping (SPM) analyses. Distinct patterns of bodily sensations were identified for different emotional states. In addition, positive correlations were found between the magnitude of sensation in emotion-specific regions and interoceptive accuracy across individuals. A greater degree of interoceptive accuracy was associated with more specific topographical changes after emotional stimuli. These results suggest that the awareness of one's internal bodily states might play a crucial role as a required messenger of sensory information during the affective process.

Every acupoint has specific indications for acupuncture treatment. These indications, primarily established based on the meridian system, have spatial patterns of symptoms on the human body. We investigated the associations between acupoints and symptom locations in 75 patients with chronic pain who were asked to sketch the localization of their symptoms on body schemes using the bodily sensation map (BSM) system. Combining the BSM and clinical information, we estimated the statistical parameters of relationships between acupoints and spatial information on symptoms. We further visualized spatial patterns of indications of the representative acupoints on the human body template using a Z score. Using a statistical parametric map method, we observed significant activation patterns of 12 acupoint indications with spatial patterns. The 1st group of patterns was distant from the acupoint locus and was strongly associated with the route of the corresponding meridian. The 2nd group was found around the acupoint locus, the majority of which was located at the trunk or back areas. Intensive investigations of the spatial patterns of acupoint indications would be a novel paradigm to explain point specificity of acupuncture treatment based on the original concept of the meridian system. Future studies should include more meaningful clinical data with larger sample sizes.

Placebo analgesia can be primarily explained by the Pavlovian conditioning paradigm in which a passively applied cue becomes associated with less pain. In contrast, instrumental conditioning employs an active paradigm that might be more similar to clinical settings. In the present study, an instrumental conditioning paradigm involving a modified trust game in a simulated clinical situation was used to induce placebo analgesia. Additionally, Bayesian modeling was applied to predict the placebo responses of individuals based on their choices. Twenty-four participants engaged in a medical trust game in which decisions to receive treatment from either a doctor (more effective with high cost) or a pharmacy (less effective with low cost) were made after receiving a reference pain stimulus. In the conditioning session, the participants received lower levels of pain following both choices, while high pain stimuli were administered in the test session even after making the decision. The choice-dependent pain in the conditioning session was modulated in terms of both intensity and uncertainty. Participants reported significantly less pain when they chose the doctor or the pharmacy for treatment compared to the control trials. The predicted pain ratings based on Bayesian modeling showed significant correlations with the actual reports from participants for both of the choice categories. The instrumental conditioning paradigm allowed for the active choice of optional cues and was able to induce the placebo analgesia effect. Additionally, Bayesian modeling successfully predicted pain ratings in a simulated clinical situation that fits well with placebo analgesia induced by instrumental conditioning.