Exploratory research on genetic polymorphisms associated with positive empathy and trait forgivingness among the Japanese.

OBJECTIVES: Previous studies have indicated that good human relationships contribute significantly to subjective well-being. We recently focused on two important ways of developing good interpersonal relationships: positive empathy, which focuses on the happiness of other people, and trait forgivingness, a tendency to forgive others. We novelly conducted an exploratory genome-wide association study (GWAS) to identify candidate gene polymorphisms associated with positive empathy and trait forgivingness among the Japanese. MATERIAL AND METHODS: We for the first time identified several genetic polymorphisms associated with positive empathy and trait forgivingness through the GWAS based on a small sample population and relatively low threshold. We subsequently validated three genetic polymorphisms from these candidate genes using a real-time polymerase chain reaction system. RESULTS: The results demonstrated that polymorphism in the vomeronasal type-1 receptor 1 (VN1R1) (rs61744949), a putative human pheromone receptor, is associated with positive empathy. In addition, genetic polymorphisms in the 5-hydroxytryptamine (serotonin) receptor 7 (HTR7: rs77843021) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon (YWHAE: rs9908013), which are associated with dopamine and serotonin biosynthesis, are associated with trait forgivingness. CONCLUSION: This study novelly illustrated the influence of the genetic polymorphism in VN1R1 on positive empathy and that of genetic polymorphisms in HTR7 and YWHAE on trait forgivingness. It identified a relationship between previously unreported genetic polymorphisms and the necessary abilities for developing good human relationships. This will significantly impact future research on positive psychology and social psychology.

Association between internet addiction, brain structure, and social capital in adolescents.

Of late, internet addiction among adolescents has become a serious problem, with increased internet use. Previous research suggests that the more people become addicted to the internet, the more they isolate themselves from society. Conversely, it has been suggested that abundant social capital (the networks of relationships among people who live and work in a particular society) protects people from becoming addicted to the internet. This study focused on the brain structure of typical adolescents (10-18 years of age) and hypothesized that the size of the left dorsolateral prefrontal cortex (DLPFC), which is thought to be associated with self-control ability, is associated with both internet addiction and social capital. Voxel-based morphometry analysis indicated that left DLPFC volume was negatively correlated with the severity of internet addiction and positively correlated with social capital. Furthermore, correlation analysis demonstrated that the severity of internet addiction and social capital were negatively correlated. The statistical association between them was no longer significant when left DLPFC volume was used as a control variable. These results suggest that the left DLPFC may mediate the relationship between social capital and internet addiction in adolescents.

Changes in the sleeping habits of Japanese university students during the COVID-19 pandemic: a 3-year follow-up study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly changed our daily life. Owing to the imposed restrictions, many educational facilities have introduced remote teaching. This study aims to clarify the association between remote teaching and Japanese university students' sleeping habits. METHODS: The participants were medical students at Aichi Medical University. We used data from an ongoing longitudinal sleeping habits survey. For the participants who enrolled in the university during 2018-2020, multilevel analyses of sleep duration during weekdays and weekends across 3 years were conducted, adjusting for sex, grade, place of stay, sleep problems and lifestyle habits. RESULTS: Among the students enrolled in the university, the data of 677 in 2018, 657 in 2019, and 398 in 2020 was available for analysis. The mean sleep duration during weekdays (in minutes) was 407.6 ± 60.3 in 2018, 406.9 ± 63.0 in 2019, and 417.3 ± 80.9 in 2020. The mean sleep duration during weekends (in minutes) was 494.5 ± 82.5 in 2018, 488.3 ± 87.9 in 2019, and 462.3 ± 96.4 in 2020. Multilevel analysis conducted for the 684 participants who enrolled during 2018-2020 showed that sleep duration during weekdays was associated with the place of stay and survey year. Moreover, students reported significantly longer sleep duration during weekdays in 2020 than in 2019, but no significant difference in sleep duration was found between 2018 and 2019. The other multilevel analysis found sleep duration during weekends to be associated with the survey year, sex and always doing something before going to bed. Sleep duration during weekends was shorter in 2020 than in 2019 and longer for male students and students who always do something before going to bed. Ten students were reported to have a delayed sleep phase in 2020. CONCLUSIONS: Students' sleep duration increased during weekdays and decreased during weekends in 2020. This difference could be explained by the COVID-19 pandemic and the introduction of remote teaching.

Elevated ratio of serum anandamide to arachidonic acid intake in community-dwelling women with high depressive symptoms.

OBJECTIVES: The purpose of the present study was to investigate the serum levels of endocannabinoids (eCBs; anandamide: AEA and 2-arachidonoylglycerol: 2-AG) and daily intake of polyunsaturated fatty acids (PUFAs; arachidonic acid: ARA, docosahexaenoic acid: DHA, and eicosapentaenoic acid: EPA) among subjects with high and low depressive symptoms. METHODS: The participants comprised female community-dwellers aged 40 years or older in Japan. Among 208 females, fourteen participants with high depressive symptoms and ten participants with low depressive symptoms were selected for this study. The depressive symptoms were measured by the Japanese version of the Centre for Epidemiologic Studies Depression Scale (CES-D). The daily intake of PUFAs were assessed utilising the brief-type self-administered diet history questionnaire. The blood samples were analysed for AEA, 2-AG, and the CB receptor 1 gene (CNR1) single nucleotide polymorphism (SNP) rs806377. RESULTS: The ratio of AEA serum level to ARA intake (AEA/ARA) in high depressive participants was significantly higher compared with those in low depressive participants even after controlling for confounders, whereas there were no significant differences in the serum concentrations of eCBs, daily intake of PUFAs, as well as the CNR1 SNP (rs806377) between the high and low CES-D scored groups. CONCLUSION: The elevated level of AEA/ARA among high depressive participants suggests that the conversion rate of ARA to AEA may be accelerated in depressive individuals.

Association between salivary oxytocin levels and the amygdala and hippocampal volumes.

Salivary oxytocin levels have been widely measured and studied in relation to social behavior because of procedural simplicity and noninvasiveness. Although the relationship between oxytocin levels in the blood and the hippocampus and amygdala is now becoming clear with reliable blood oxytocin studies, few studies have examined the relationship between salivary oxytocin and the brain function and structure. This study aimed to investigate whether the salivary oxytocin level is associated with the volume of the amygdala and hippocampus in 178 adults (92 women and 86 men) in their third to seventh decade of life. We performed volumetric analysis of the amygdala and hippocampus using FreeSurfer and measured salivary oxytocin levels using enzyme-linked immunosorbent assay. The results showed contradictory effects of the salivary oxytocin level on the amygdala volume by sex and no significant effect on the hippocampal volume. Specifically, men showed a positive correlation between the salivary oxytocin level and amygdala volume, whereas women showed a negative correlation between the salivary oxytocin level and amygdala volume. The present study's finding of sex differences in the association between salivary oxytocin and brain structure supports previous findings that there are sex differences in the oxytocin system.

Is oxytocin a trust hormone? Salivary oxytocin is associated with caution but not with general trust.

Studies on the association between trust and oxytocin, a neuropeptide of the central nervous system, have not reached a consensus, thereby challenging the possibility of a direct association between the two. However, previous studies have not examined how oxytocin is correlated with trust, based on its categorization into different factors in the field of social science. For instance, based on Yamagishi's trust theory, trust can be categorized into two factors: general trust and caution. General trust refers to beliefs about the trustworthiness of others, whereas caution refers to the belief that caution is needed when dealing with high social uncertainty. In this study, to examine the relationship between these two factors and oxytocin, we analyzed data of 197 adults (men = 98, women = 99; mean age = 41.7 years; standard deviation for age = 10.4 years) and examined the relationships between these two factors of trust and endogenous salivary oxytocin levels. We found that oxytocin was positively correlated with caution rather than with general trust thereby suggesting that oxytocin plays a role in regulating caution rather than general trust among the components of trust. The present study demonstrated that salivary oxytocin level can act as a biomarker that partially predicts one's trust, especially as reflected by caution.

A Genetic Variation in the Y Chromosome Among Modern Japanese Males Related to Several Physiological and Psychological Characteristics.

Previous studies in population genetics have proposed that the Y-chromosomal (Y-DNA) haplogroup D ancestor likely originated from Africa. The haplogroup D branch next started Out-of-Africa migration, rapidly expanded across Eurasia, and later diversified in East Asia. Y-DNA haplogroup D-M55, one of the branches of haplogroup D, is only found in modern Japanese males, suggesting that individuals with Y-DNA haplogroup D migrated from the Eurasian continent. Based on previous observations, Y-DNA haplogroup D is expected to be associated with some male characteristics including personality. Therefore, this study investigated whether the Y-DNA haplogroup D-M55 is associated with several physiological and psychological characteristics, including exploratory motivation and human relationship-related perception. We recruited Japanese young adult males and females and investigated the association between Y-DNA haplogroup D-M55, physiological [body mass index (BMI)], and several psychological parameters [perceived number of close friends, behavioral inhibition system/behavioral activation system (BIS/BAS), perceived happiness, and perceived loneliness]. The results indicated that males with haplogroup D-M55 had a higher BMI and more close friends, compared with non-carrier males. Additional multiple regression analyses, which tested the hypothesis that haplogroup D-M55 predicts BMI and perceived number of close friends, confirmed our hypothesis, even after controlling for the potentially confounding variables of age and sex. We also analyzed the gene-gene interaction between haplogroup D-M55 and an autosomal gene polymorphism associated with BMI and human relationships, such as the dopamine D2 receptor gene (DRD2: rs1800497). Results showed gene-gene interactions between haplogroups D-M55 and DRD2 in BMI. Based on these findings, it is demonstrated that Y-DNA haplogroup D is associated with human personality.

Cultural differences in social support seeking: The mediating role of empathic concern.

Prior research has found that East Asians are less willing than Westerners to seek social support in times of need. What factors account for this cultural difference? Whereas previous research has examined the mediating effect of relational concern, we predicted that empathic concern, which refers to feeling sympathy and concern for people in need and varies by individuals from different cultures, would promote support seeking. We tested the prediction in two studies. In Study 1, European Canadians reported higher empathic concern and a higher frequency of support seeking, compared to the Japanese participants. As predicted, cultural differences in social support seeking were influenced by empathic concern. In Study 2, both empathic concern and relational concern mediated cultural differences in support seeking. Japanese with lower empathic concern but higher relational concern were more reluctant than European Americans to seek social support during stressful times. Finally, loneliness, which was more prevalent among the Japanese than among the European Americans, was partially explained by social support seeking.

Salivary Oxytocin Is Negatively Associated With Religious Faith in Japanese Non-Abrahamic People.

Spirituality and religiosity have a significant impact on one's well-being. Although previous studies have indicated that the neuropeptide hormone oxytocin is associated with spirituality/religiosity, existing findings remain inconsistent. Some studies have reported a positive relationship between oxytocin and spirituality/religiosity, while other studies have reported a negative association. Herein, we examined the association between endogenous oxytocin and spirituality/religiosity in 200 non-Abrahamic Japanese individuals (102 females, mean age ± standard deviation = 41.53 ± 10.46) by measuring the level of salivary oxytocin and spiritual/religious faith. We found that the level of salivary oxytocin was negatively associated with spiritual/religious faith. Individuals with higher levels of salivary oxytocin tend to have more negative spiritual/religious faith compared with those with low oxytocin levels (e.g., "Spirituality/religiosity makes people passive and clinging."). Moreover, this tendency was only significant in individuals who were not interested in a specific religion. The uniqueness of spirituality/religiosity in Japan could help interpret the current findings.

Investigation of plant leaf-derived graphene quantum dot clusters via magnetic force microscopy.

Magnetic force microscopy (MFM) is utilized to characterize the magnetic moment in nanostructured plant leaf-derived graphene quantum dot clusters (GQDCs). The MFM signal reveals that the magnetic response of the GQDCs depends on the height and width of the GQDCs. However, individual GQDs, and smaller clusters with widths of less than 20 nm, have not shown any observable magnetic signal. Importantly, experimental analyses suggest that the magnetic signal of GQDCs distributed in a plane can be effectively detected at room temperature. These results could pave the way for future graphene-based magnetic storage media and spin manipulation quantum devices.

Omega-3 Eicosapentaenoic Acid Is Related to Happiness and a Sense of Fulfillment-A Study among Female Nursing Workers.

Background: Omega (ω) 3 fatty acid (FA) is a polyunsaturated FA (PUFA) that can modulate some mental statuses. However, most studies have not considered the functional differences between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We investigated associations among happiness, a sense of fulfillment and serum ω3 PUFA levels. Methods: Participants were 133 female staff from a hospital and nursing homes. Happiness was measured using the Japanese version of the subjective happiness scale (SHS); a sense of fulfillment was assessed using a visual analogue scale. Serum FA concentrations were measured. A partial correlation test and a regression model were applied. Results: The SHS scores showed significantly positive correlations with a sense of fulfillment, DHA% and EPA% (p < 0.05, < 0.05 and < 0.005, respectively), after controlling for age, BMI, menopause, snacking habits and leisure-time physical activities. A sense of fulfillment was significantly negatively correlated with α-linoleic acid%, and positively correlated with DHA% and EPA% (p < 0.05, < 0.05 and < 0.005, respectively), after controlling for the confounders. A regression model showed that a sense of fulfillment, EPA, and not stopping menstruation explained happiness (standardised beta, B = 0.18, p < 0.05; B = 0.24, p < 0.01; and B = 0.32, and p < 0.05, respectively), whereas age, BMI and snacking habits could not. Simultaneously, a regression model could not explain the association between DHA and happiness. Conclusion: Happiness was related with serum EPA%, a sense of fulfillment, and premenopause.

Role of the Orbitofrontal Cortex in the Computation of Relationship Value.

This research investigated whether the medial orbitofrontal cortex (OFC), which is known to code the value of various rewards, is involved in the relationship value recalibration process. Previous research suggests that people upregulate the relationship value of a specific friend in response to the friend's commitment signals. In a functional magnetic resonance imaging study (Study 1), participants imagined receiving high-cost commitment signals, low-cost commitment signals, or no signals from a particular friend. Participants' subjective rating of the relationship value upregulation was positively correlated with medial OFC activity. Subtraction analyses showed that high-cost commitment signals engaged the medial OFC more than did signal failures. An auxiliary analysis revealed that medial OFC activity in response to low-cost commitment signals was negatively correlated with loneliness. To follow-up these findings, we conducted an online vignette study (Study 2), in which participants rated the relationship value of a real friend before and after imagining receiving a series of low-cost commitment signals from that friend. Corroborating the upregulation hypothesis, perceived relationship value significantly increased after imagining a series of commitment signals. This effect was weaker among individuals high in loneliness.

Oxytocin Receptor Gene (OXTR) and Childhood Adversity Influence Trust.

Early-life environments have been associated with various social behaviors, including trust, in late adolescence and adulthood. Given that the oxytocin receptor gene polymorphism (OXTR rs53576) moderates the impact of childhood experience on social behaviors, in the present study, we examined the main effect of childhood adversity through a self-report measure and its interactions with OXTR rs53576 on general trust among 203 Japanese and 200 European Canadian undergraduate students. After controlling for the effect of culture, the results indicated that childhood adversity had a negative association with general trust, and that OXTR rs53576 moderated the impact of childhood adversity on general trust. Specifically, the negative association between childhood adversity and general trust is only significant among homozygote A-allele carriers. These findings demonstrated that OXTR rs53576 moderated the relations between childhood experiences and social functioning in early adulthood.

Costly group apology communicates a group's sincere "intention".

Groups, such as governments and organizations, apologize for their misconduct. In the interpersonal context, the forgiveness-fostering effect of apologies is pronounced when apologizing entails some cost (e.g., compensating damage, canceling a favorite activity to prioritize the apology) because costly apologies tend to be perceived as more sincere than non-costly apologies (e.g., merely saying "sorry"). Since groups lack a mental state (e.g., sincere intention), this could arguably render a group apology ineffective. This research investigated the possibility that people ascribe intention to group agents and that offering a costly group apology is an effective means of fostering perceived sincerity. A vignette study (Pilot Study) showed that costly group apologies tend to be perceived as more sincere than non-costly group apologies. A subsequent functional magnetic resonance imaging study revealed that costly group apologies engaged the bilateral temporoparietal junction and precuneus more so than non-costly group apologies and no apology did. The bilateral temporoparietal junction and precuneus have been implicated in the reasoning of social/communicative intention. Therefore, these results suggest that although a group mind does not exist, people ascribe a mental state (i.e., sincere intention) to a group especially when the group issues a costly apology after committing some transgression.

Serum IL-6 levels and oxidation rate of LDL cholesterol were related to depressive symptoms independent of omega-3 fatty acids among female hospital and nursing home workers in Japan.

BACKGROUND: Chronic low-grade inflammation and oxidative stress are commonly observed in persons with depression or depressive symptoms. We explored the degree of depressive symptoms under psychological stress in relation to serum LDL oxidation, inflammatory markers, and fatty acid (FA) distribution among female population. The purpose of this study was to identify peripheral factors that are related to depressive symptoms, and to assess how each factor is related to depressive symptoms. METHODS: 133 female workers in a hospital and nursing homes were recruited in Japan. Depressive symptoms were assessed using the Japanese version of the Centre for Epidemiologic Studies Depression Scale (CES-D), and perceived stress was assessed using the visual analogue scale. Cytokine levels and oxidation rate of LDL cholesterol (ox-LDL/LDL) were measured as indices of inflammation and oxidation. Omega-3 FA distribution was also measured. Path analysis and hierarchical regression analysis were used to determine if each factor was predictive of depressive symptoms. RESULTS: It was identified that serum ox-LDL/LDL was positively connected with depressive symptoms, but was more strongly related to perceived psychological stress. Elevated serum IL-6 was positively correlated with depressive symptoms, though the effect was partly transmitted via ox-LDL/LDL. Additionally, serum ω3 PUFAs were inversely associated with depressive symptoms independently of IL-6 or ox-LDL/LDL. CONCLUSION: Although this study is unlikely to fully explain the causes of depressive symptoms, it suggests that psychological stress and somatic factors such as inflammation, oxidation and nutrition are related to depressive symptoms. These findings suggest the therapeutic potential of lifestyle targets to alleviate the identified depression risk factors, anti-oxidative therapies, anti-inflammatory therapies and nutritional interventions to prevent depression.

Culture and cannabinoid receptor gene polymorphism interact to influence the perception of happiness.

Previous studies have shown that a cytosine (C) to thymine (T) single nucleotide polymorphism (SNP) of the human cannabinoid receptor 1 (CNR1) gene is associated with positive emotional processing. C allele carriers are more sensitive to positive emotional stimuli including happiness. The effects of several gene polymorphisms related to sensitivity to emotional stimuli, such as that in the serotonin transporter gene-linked polymorphic region (5HTTLPR), on emotional processing have been reported to differ among cultures-e.g., between those that are independent and interdependent. Thus, we postulated that the effects of the CNR1 genotype on happiness might differ among different cultures because the concept of happiness varies by culture. We recruited healthy male and female young adults in Japan, where favorable external circumstances determine the concept of happiness, and Canada, where the concept of happiness centers on positive inner feelings, and compared the effects of the CNR1 genotype on both subjective happiness levels (self-evaluation as being a happy person) and situation-specific happiness (happy feelings accompanying various positive events) by using a questionnaire. We found that the effect of CNR1 on subjective happiness was different between the Japanese and Canadian groups. The subjective happiness level was the highest in Japanese individuals with the CC genotype, whereas in Canadian participants, it was the highest in individuals with the TT genotype. Furthermore, the effects of CNR1 genotype on situation-specific happiness were also different between the groups. Happiness accompanied with being surrounded by happy people was the highest among Japanese individuals with the CC genotype, whereas among Canadian individuals, it was the highest in TT genotype carriers. These findings suggest that culture and CNR1 polymorphism interact to influence the perception of happiness.

Elevated Levels of Serum IL-17A in Community-Dwelling Women with Higher Depressive Symptoms.

Recent studies indicate that patients with depression have increased concentrations of serum pro-inflammatory cytokines. However, studies of IL-17 and studies on community-dwellers are few. The purpose of this study was to investigate serum cytokine levels, especially IL-17A, among subjects with high and low depressive symptoms of a general population. The participants comprised 20 female community-dwellers aged 40 years or older who contributed to a Shika study in Ishikawa, Japan. Ten participants who showed higher and ten who showed lower depressive symptoms among 208 females assessed by the Japanese version of the Centre for Epidemiologic Studies Depression Scale (CES-D) were selected for this study. Serum samples were analyzed for TNF-alpha, IL-6, IL-10, IL-12, and IL-17A using a multiplex Luminex analysis. For the comparison between the high and low depressive groups statistically, linear regression analyses were applied. The serum level of IL-17A was significantly higher among the high depressive participants (p < 0.05) even after controlling possible confounders, whereas there were no differences in TNF-alpha, IL-6, IL-10, or IL-12 between the high and low depressive groups. Our findings supported an association between serum IL-17A levels and depressive symptoms. Peripheral IL-17A immune response may be a preventive and treatment target for depression.

Confocal Raman microscopy reveals changes in chemical composition of wood surfaces exposed to artificial weathering.

Weathering leads to rapid depolymerization and modification of wood chemical components. The present study aims to assess the structural and distributional changes in the main wood polymers, such as lignin and polysaccharides, located in the surface layers during weathering exposure. A confocal Raman microscopic technique, which is useful for evaluating the structure of molecules with a high spatial resolution, was utilized to examine the effects of weathering on the chemical composition of wood surfaces at the cellular level. Raman spectra showed that lignin degradation during weathering proceeds with the formation of o- and p-quinones, carbonyl groups, and certain types of CC double bonds such as stilbene derivatives. Comparing the weathering conditions between light only and light plus water exposure, it was found that weathering in the presence of water significantly enhances the degradation of lignin. The Raman images exhibited that the degree of lignin degradation by light only exposure is according to the depth. However, in the case of light plus water exposure, lignin degradation in the outermost cell walls proceeded from both the exposed surface side and the lumen side of the cell walls. This study is expected to potentially promote development of more effective and efficient methods to protect wood surfaces against weathering.

Effects of movement music therapy with a percussion instrument on physical and frontal lobe function in older adults with mild cognitive impairment: a randomized controlled trial.

OBJECTIVES: We tested the hypothesis that performing a rhythmic physical task accompanied by a cognitive task, such as multitask movement music therapy (MMT) involving repetitive rhythmic movement with a musical instrument (the Naruko clapper), may improve pre-frontal cortex (PFC) function and cognitive performance. METHOD: Forty-five older adult participants with MCI (74.62 ± 5.05 years) participated in this randomized, controlled, single-blind intervention trial. 35 were assigned to the MMT group and 10 to the control STT group. Before and after the 12-week exercise program, we administered six physical function tests, the Frontal Assessment Battery (FAB), and measured relative oxyhemoglobin concentrations using 45-multichannel functional near-infrared spectroscopy as a reflection of hemodynamic responses in the PFC. RESULTS: We observed significant improvements in FAB scores only in the MMT group. Cerebral blood flow (CBF) in the PFC during the exercise was significantly increased in the MMT group compared with the STT group. The CBF increase was significantly correlated among various channels in the MMT group. CONCLUSIONS: The MMT program appeared to stimulate the PFC and improve cognitive performance in our older adult participants with MCI, suggesting that the repetitive, rhythmic movements of MMT can activate the prefrontal area in older adults. TRIAL REGISTRATION: Clinical Trial Registry Numbers: R000026130, UMIN000022671 (2016/06/08) [(University Hospital Medical Information Network (UMIN) Center] retrospectively registered.

An interactive sports video game as an intervention for rehabilitation of community-living patients with schizophrenia: A controlled, single-blind, crossover study.

Hypofrontality is a state of decreased cerebral blood flow in the prefrontal cortex during executive function performance; it is commonly observed in patients with schizophrenia. Cognitive dysfunction, as well as the psychological symptoms of schizophrenia, influences the ability of patients to reintegrate into society. The current study investigated the effects of an interactive sports video game (IVG; Nintendo Wii™ Sports Resort) on frontal lobe function of patients with schizophrenia. A sample of eight patients (6 male and 2 female; mean age = 46.7 years, standard deviation (SD) = 13.7) engaged in an IVG every week for 3 months in a controlled, single-blind, crossover study. Before and after the intervention we examined frontal lobe blood-flow volume using functional near-infrared spectroscopy (fNIRS), and assessed functional changes using the Frontal Assessment Battery, Health-Related Quality of Life scale, and behaviorally-assessed physical function tests. fNIRS revealed that prefrontal activity during IVG performance significantly increased in the IVG period compared with the control period. Furthermore, significant correlations between cerebral blood flow changes in different channels were observed during IVG performance. In addition, we observed intervention-related improvement in health-related quality of life following IVG. IVG intervention was associated with increased prefrontal cortex activation and improved health-related quality of life performance in patients with schizophrenia. Patients with chronic schizophrenia are characterized by withdrawal and a lack of social responsiveness or interest in others. Interventions using IVG may provide a useful low-cost rehabilitation method for such patients, without the need for specialized equipment.