Perceiving humanness across ages: neural correlates and behavioral patterns.

Humanness perception, which attributes fundamental and unique human characteristics to other objects or people, has significant consequences for people's interactions. Notably, the failure to perceive humanness in older adults can lead to prejudice. This study investigates the effect of a target's age on humanness perception in terms of two dimensions: agency (the ability to act and do) and experience (the ability to feel and sense). We also examined brain activity using a magnetic resonance imaging (MRI) scanner in order to understand the underlying neural mechanisms. Healthy university students viewed the facial images of older and younger individuals and judged the humanness of each individual in terms of agency and experience while inside the MRI scanner. The results indicated that older adults were rated higher on experience, and no difference was found in ratings for agency between younger and older face images. Analysis of brain imaging data indicated that positive functional connectivity between the ventral and dorsal regions of the medial prefrontal cortex (mPFC) was greater when judging the humanness of younger faces than older faces. We also found that the negative functional connectivity between the left inferior frontal gyrus and postcentral gyrus was greater when judging the humanness of older faces as compared to that of younger faces. Although the current study did not show distinct brain activities related to humanness perception, it suggests the possibility that different brain connectivities are related to humanness perception regarding targets belonging to different age groups.

Neuroregulatory Effects of Microcone Patch Stimulation on the Auricular Branch of the Vagus Nerve and the Prefrontal Cortex: A Feasibility Study.

Background: The primary purpose of this study was to preliminarily examine the effects of autonomic nervous system activity on the dorsolateral prefrontal cortex. Recent studies have examined approaches to modulating autonomic activity using invasive and non-invasive methods, but the effects of changes in autonomic activity during cognitive tasks on the dorsolateral prefrontal cortex have not been fully investigated. The purpose of this preliminary investigation was to examine changes in autonomic activity and blood oxygen saturation in the dorsolateral prefrontal cortex during reading tasks induced by vagus nerve stimulation using a microcone patch. Methods: A cohort of 40 typically developing adults was enrolled in this study. We carefully examined changes in autonomic nervous system activity and blood oxygen saturation in the dorsolateral prefrontal cortex during a reading task in two conditions: with and without microcone patch stimulation. Results: Significant changes in brain activation in the dorsolateral prefrontal cortext due to microcone patch stimulation were confirmed. In addition, hierarchical multiple regression analysis revealed specific changes in reading task-related blood oxygen saturation in the dorsolateral prefrontal region during microcone patch stimulation. Conclusions: It should be recognized that this study is a preliminary investigation and does not have immediate clinical applications. However, our results suggest that changes in autonomic nervous system activity induced by external vagal stimulation may affect activity in specific reading-related regions of the dorsolateral prefrontal cortex. Further research and evaluation are needed to fully understand the implications and potential applications of these findings.

Right amygdala and caudate activation patterns predict implicit attitudes toward people with autism spectrum disorders and physical disabilities, respectively.

Attitudes toward people with disabilities tend to be negative, regardless of the visibility of the disorder traits. Individuals with autism spectrum disorder (ASD) experience stigmatization that is rooted in negative attitudes or prejudice toward them because of their social awkwardness. The neural underpinnings of attitudes toward people with disabilities remain unclear. In this study, we focused on implicit attitudes toward people with ASD and physical disabilities, which are more visible than ASD, and investigated whether implicit attitudes were predicted by using neural activity with multivoxel pattern analysis (MVPA) in the prejudice network. Thirty-six, right-handed, Japanese, university students without disabilities participated. Two implicit association tests (IAT) toward people with ASD and physical disabilities revealed negative implicit attitudes. In the MRI scanner, participants performed a one-back task by using the same picture sets of IATs to examine their neural responses toward people with ASD and physical disabilities. According to the MVPA results, activation patterns of the right amygdala and right caudate significantly predicted implicit attitudes toward people with ASD and physical disabilities, respectively. These results suggest that implicit attitudes toward ASD and physical disabilities can be predicted by using neural signals from different regions within the prejudice network.

Brain Activation and Functional Connectivity of Reappraisal and Acceptance for Anxious Events.

Despite the significant health consequences of anxiety, the neural basis of regulation for personal anxious events is not well understood. We examined brain activity and functional connectivity during cognitive emotion regulation strategies (reappraisal and acceptance) for personal anxious events. Functional MRI (fMRI) data were obtained while 35 college students were thinking about (the control condition), reappraising, or accepting their own anxiety-provoking situations. Although reappraisal and acceptance decreased anxiety, no statistically significant differences were observed in the brain activation levels between cognitive emotion regulation strategies and the control condition. However, acceptance decreased activation in the posterior cingulate cortex and precuneus more than reappraisal. Moreover, functional connectivity with the amygdala and ventral anterior insula distinguished the emotion regulation strategies for anxiety. Reappraisal showed stronger negative functional connectivity with the amygdala and cognitive control regions than other strategies. In addition, reappraisal had negative functional coupling between the ventral anterior insula and temporal pole compared with acceptance. In contrast, acceptance showed stronger positive functional coupling between the ventral anterior insula and precentral and postcentral gyrus compared with the control condition. Our findings contribute to the understanding of emotion regulation processes by revealing the brain activity and functional connectivity patterns in reappraisal and acceptance for personal anxious events.

The Effect of Cognitive Training with Neurofeedback on Cognitive Function in Healthy Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive training aims to improve cognitive function through cognitive tasks or training games. Neurofeedback is a technique to monitor brain signals with either visual or auditory feedback. Previous studies suggest that a combination of cognitive training and neurofeedback has a superior effect on cognitive functions compared with cognitive training alone. However, no systematic reviews and meta-analyses of the benefits of cognitive training with neurofeedback (CTNF) exist. The purpose of this study was to examine the beneficial effects of CTNF in healthy adults using a systematic review and multilevel meta-analysis. METHODS: PubMed, Scopus, PsychoINFO, and MEDLINE were searched for research papers reporting the results of interventions using CTNF. RESULTS: After an initial screening of 234 records, three studies using near-infrared spectroscopy (NIRS) and one study using electroencephalography were extracted from the database. We performed a multi-level meta-analysis with three NIRS studies including 166 participants (mean ages ranged from 21.43 to 65.96 years). A multi-level meta-analysis revealed that CTNF has a beneficial effect on the episodic, long-term, and working memory domains. CONCLUSIONS: Although three studies were included in the systematic review and meta-analysis, our results indicate that CTNF using NIRS would lead to improvements in memory functioning.

Academic achievements and brain volume development in children and adolescents.

Children are expected to acquire both basic and numeric skills. Achievement of higher levels of reading, writing, arithmetic, and vocabulary are favorable and desirable. The relationship between each literacy skill and neural development has been investigated; however, association between brain development and the 4 literacy skills has not been examined. This longitudinal, structural, neuroimaging study explored the contribution of higher academic achievement in reading, writing, arithmetic, and vocabulary to neural development. The brain volumes of children and adolescents aged 9-16 years were measured in the first test. Approximately 2.6 years later, the brain volumes and 4 academic achievement scores of 77 participants were measured in the second test. Changes in the gray matter volume in the left fusiform gyrus were associated with vocabulary scores, whereas those in the left striatum were associated with arithmetic scores. The reading and writing scores showed no statistically significant relationship with changes in brain volume. The current vocabulary score correlated with current gray matter volume, while brain volumes in the first test showed no association with any achievement scores. These results suggest that academic achievement may modulate brain plasticity in various ways.

Does the eight-factor "power to live" in disaster exist since childhood?

Background: Studies on the survivors of the 2011 Great East Japan earthquake and tsunami have revealed eight factors, called power to live, which are closely related to resilience and effective coping after intense and prolonged stress. However, whether the eight factors, which were examined in adults, are applicable to children is unclear. The purpose of this study is to evaluate whether the eight-factor structure of power to live was present since late childhood. Method: A 34-item power to live questionnaire was filled by middle- to upper-grade elementary (n = 378) and junior high school students (n = 456). Moreover, because elementary school students may lack introspective ability, their power to live was evaluated through a parental assessment (n = 358). Additionally, we examined the relationship between each power to live factor and questions regarding disaster prevention awareness among 25 elementary school students. Results: The results from confirmatory factor analysis for factor structure revealed generally acceptable fit indices. The reports from elementary school students and their parents significantly positively correlated with each power to live factor. Although reliability indices for factors such as stubbornness, etiquette, self-transcendence, and active well-being were not good for elementary school students, the reliability indices for all factors, excluding stubbornness, increased in junior high school students. Moreover, we identified a correlation between problem-solving, altruism, and emotional regulation and questionnaire items regarding awareness of disaster prevention in elementary school students. Conclusion: Our results suggest that although factors common to adults, such as leadership, problem-solving, altruism, and emotional regulation, were identified at the elementary school stage, some factors, such as stubbornness, are in the process of being formed. Future studies should examine the developmental changes assumed to underlie these factors and their relationship to experience and neurodevelopmental basis.

Common and distinct neural bases of multiple positive emotion regulation strategies: A functional magnetic resonance imaging study.

Appropriate emotion regulation is crucially involved in mental and physical health. The neural basis of negative but not positive emotion regulation has been well investigated. Several strategies should be compared to elucidate the neural correlates of positive emotion regulation. However, there are no studies on multiple positive emotion regulation strategies. We aimed to investigate the neural correlates of positive emotion regulation with multiple emotion regulation strategies and identify common and differential brain areas involved in positive emotion upregulation. We acquired functional magnetic resonance imaging data from healthy college student volunteers while they upregulated positive emotions through instructed strategies or by viewing positive pictures. The instructed strategies included Attentional Deployment, Cognitive Change, and Response Modulation. These strategies increased subjective positive emotions and activation of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Region of interest analysis revealed greater activation of the ventral striatum during positive emotion regulation. There are different networks involved in Cognitive Change and Response Modulation. Our findings indicate that multiple strategies for positive emotion upregulation involve common (e.g., PFC, ACC, and ventral striatum) and unique networks.

Auditory Cognitive Training Improves Brain Plasticity in Healthy Older Adults: Evidence From a Randomized Controlled Trial.

The number of older adults is increasing globally. Aging is associated with cognitive and sensory decline. Additionally, declined auditory performance and cognitive function affect the quality of life of older adults. Therefore, it is important to develop an intervention method to improve both auditory and cognitive performances. The current study aimed to investigate the beneficial effects of auditory and cognitive training on auditory ability and cognitive functions in healthy older adults. Fifty healthy older adults were randomly divided into four training groups-an auditory-cognitive training group (AC training; n = 13), an auditory training group (A training; n = 13), a cognitive training group (C training; n = 14), and an active control group (n = 12). During the training period, we reduced the sound intensity level in AC and A training groups and increase training task difficulty in AC, A, and C training groups based on participants' performance. Cognitive function measures [digit-cancelation test (D-CAT); logical memory (LM); digit span (DS)], auditory measures [pure-tone audiometry (PTA)], and magnetic resonance imaging (MRI) scans were performed before and after the training periods. We found three key findings. First, the AC training group showed difference between other training groups (A, C, and active control training groups) in regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex, the left inferior temporal gyrus (L. ITG), the left superior frontal gyrus, the left orbitofrontal cortex, the right cerebellum (lobule 7 Crus 1). Second, the auditory training factor groups (ATFGs, the AC and A training groups) improved auditory measures and increased the rGMV and functional connectivity (FC) in the left temporal pole compared to the non-ATFGs (the C training group and active control group). Third, the cognitive training factor groups (CTFGs; the AC and C training groups) showed statistically significant improvement in cognitive performances in LM and D-CAT compared to the non-CTFGs (the A training group and active control group). Therefore, the auditory training factor and cognitive training factor would be useful in enhancing the quality of life of older adults. The current AC training study, the plasticity of the brain structure was observed after 4 weeks of training.

Benefits of VR Physical Exercise on Cognition in Older Adults with and without Mild Cognitive Decline: A Systematic Review of Randomized Controlled Trials.

It is well known that physical exercise has beneficial effects on cognitive function in older adults. Recently, several physical exercise programs with virtual reality (VR) have been proposed to support physical exercise benefits. However, it is still unclear whether VR physical exercise (VR-PE) has positive effects on cognitive function in older adults. The purpose of this study was to conduct a systematic review (SR) of the effects of VR-PE on cognitive function in older adults with and without cognitive decline. We used academic databases to search for research papers. The criteria were intervention study using any VR-PE, participants were older adults with and without mild cognitive decline (not dementia), and cognitive functions were assessed. We found that 6 of 11 eligible studies reported the significant benefits of the VR-PE on a wide range of cognitive functions in aging populations. The SR revealed that VR-PE has beneficial effects on the inhibition of executive functions in older adults with and without mild cognitive decline. Moreover, VR-PE selectively leads to improvements in shifting and general cognitive performance in healthy older adults. The SR suggests that VR-PE could be a successful approach to improve cognitive function in older adults with and without cognitive decline.

Intrinsic hippocampal functional connectivity underlying rigid memory in children and adolescents with autism spectrum disorder: A case-control study.

LAY ABSTRACT: Atypical learning and memory in early life can promote atypical behaviors in later life. Specifically, less relational learning and inflexible retrieval in childhood may enhance restricted and repeated behaviors in patients with autism spectrum disorder. The purpose of this study was to elucidate the mechanisms of atypical memory in children with autism spectrum disorder. We conducted picture-name pair learning and delayed-recognition tests with two groups of youths: one group with high-functioning autism spectrum disorder children (aged 7-16, n = 41) and one group with typically developing children (n = 82) that matched the first group's age, sex, and full-scale IQ. We examined correlations between successful recognition scores and neural connectivity during resting in the magnetic resonance imaging scanner without thinking about anything. Although both learning and retrieval performances were comparable between the two groups, we observed significantly fewer memory gains in the autism spectrum disorder group than in the typically developing group. The memory network was involved in successful memory retrieval in youths with typically developing, while the other memory systems that do not depend to a great degree on networks may be involved in successful memory in youths with autism spectrum disorder. Context-independent and less relational memory processing may be associated with fewer memory gains in autism spectrum disorder. In other words, autism spectrum disorder youths might benefit from non-relational memory. These atypical memory characteristics in autism spectrum disorder may exaggerate their inflexible behaviors in some situations, or-vice versa-their atypical behaviors may result in rigid and less connected memories.

DNA damage response and its clinicopathological relationship in appendiceal tumors.

BACKGROUND: Appendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors. METHODS: Chk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining. RESULTS: Chk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC. CONCLUSIONS: The current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.

Whipple disease diagnosed with PCR using formalin-fixed paraffin-embedded specimens of the intestinal mucosa.

We herein present the case of a 54-year-old Japanese woman with Whipple disease diagnosed with polymerase chain reaction (PCR) using formalin-fixed paraffin-embedded (FFPE) specimens. The patient complained of weight loss, diarrhea and arthralgia. An endoscopic examination revealed swollen villi in the duodenum and ileum. Pathology demonstrated the presence of numerous macrophages filled with diastase-resistant PAS-positive particles. PCR using FFPE specimens amplified a fragment of 16S rDNA from Tropheryma whipplei. After the administration of ceftriaxone followed by trimethoprim/sulfamethoxazole, no signs of recurrence were observed for two years. The use of FFPE specimens for PCR should be considered for the prompt diagnosis and prevention of disease progression.

Hepatocellular carcinoma with portal vein tumor thrombosis: clinical characteristics, prognosis, and patient survival analysis.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a poor prognosis. New therapeutic modalities, such as continuous hepatic arterial infusion chemotherapy (CHAIC), have recently been reported to be promising strategies. The aim of this study was to evaluate the clinical characteristics, prognosis, and survival of patients with PVTT according to treatment regimen. One hundred ninety-three patients with HCC complicated with PVTT at the time of diagnosis were included in this study. All patients were newly diagnosed to have HCC and were observed from January 1992 to December 2003. CHAIC was performed using an implanted drug delivery system with low-dose cisplatin and 5-fluorouracil. Clinical characteristics, prognosis, and patient survival were analyzed by the Kaplan-Meier method and Cox's proportional hazards model. The mean age of the patients complicated with PVTT was 64.3+/-10.3 years (range, 20-88 years). The survival of the 193 patients with PVTT was 37.5%, 24.0%, 18.9%, and 8.3% at 1, 2, 3, and 5 years, respectively. According to treatment, the survival of patients who underwent surgical treatment was the best, followed by CHAIC, transcatheter arterial infusion/embolization, and supportive care. The 3-year survivals for each treatment regimen were 53.0%, 19.3%, 15.0%, and 4.0%, respectively. Although the survival of patients who received surgical treatment was best, such patients were restricted. There was no difference in survival between treated and untreated patients demonstrating Child-Pugh grade C. In Child B patients, treatment for HCC significantly increased survival (P<0.01). Cox's proportional hazards model revealed the Child-Pugh classification to be an independent prognostic factor for patients with HCC and PVTT (P<0.01). We conclude that the prognosis of HCC with PVTT was quite poor. The treatment did not improve the survival of Child C patients. As a result, the prevention, early diagnosis, and development of new treatment strategies are required.

[A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer].

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.

Hepatocellular carcinoma in young adults: the clinical characteristics, prognosis, and findings of a patient survival analysis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20-39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.

Hepatocellular carcinoma in extremely elderly patients: an analysis of clinical characteristics, prognosis and patient survival.

AIM: To identify the clinical and prognostic features of patients with hepatocellular carcinoma (HCC) aged 80 years or more. METHODS: A total of 1310 patients with HCC were included in this study. Ninety-one patients aged 80 years or more at the time of diagnosis of HCC were defined as the extremely elderly group. Two hundred and thirty-four patients aged > or = 50 years but less than 60 years were regarded as the non-elderly group. RESULTS: The sex ratio (male to female) was significantly lower in the extremely elderly group (0.90:1) than in the non-elderly group (3.9:1, P < 0.001). The positive rate for HBsAg was significantly lower in the extremely elderly group and the proportion of patients negative for HBsAg and HCVAb obviously increased in the extremely elderly group (P < 0.001). There were no significant differences in the following parameters: diameter and number of tumors, Child-Pugh grading, tumor staging, presence of portal thrombosis or ascites, and positive rate for HCVAb. Extremely elderly patients did not often receive surgical treatment (P < 0.001) and they were more likely to receive conservative treatment (P < 0.01). There were no significant differences in survival curves based on the Kaplan-Meier methods in comparison with the overall patients between the two groups. However, the survival curves were significantly worse in the extremely elderly patients with stage I/II, stage I/II and Child-Pugh grade A cirrhosis in comparison with the non-elderly group. The causes of death did not differ among the patients, and most cases died of liver-related diseases even in the extremely elderly patients. CONCLUSION: In the patients with good liver functions and good performance status, aggressive treatment for HCC might improve the survival rate, even in the extremely elderly patients.

Severe manifestation of acute hepatitis A recently found in Gunma, Japan.

BACKGROUND: The incidence of acute hepatitis A infection in Japan peaked 10 years ago and has been decreasing since then. However, an increase in severe cases of the disease has been documented recently. We experienced an outbreak in 1998-1999, and compared the clinical features of the disease in 1998-1999 (recent outbreak) and in 1987-1988 (past outbreak) in our prefecture (Gunma). METHODS: Forty patients with acute hepatitis A were admitted to nine Gunma hospitals from October 1998 to September 1999. Their clinical features were compared with those of 100 patients with acute hepatitis A admitted to the same hospitals in 1987-1988. RESULTS: Both outbreaks occurred mostly during the winter-spring season. Secondary familial infection was significantly decreased in the recent outbreak. Patients in the recent outbreak were 7 years older than those in the past outbreak. Laboratory findings, such as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and prothrombin time, were worse in the recent than in the past outbreak. Severe-type hepatitis and fulminant hepatitis occurred in 5 patients (12.5%) in the recent outbreak but in only 2 patients (2.0%) in the past outbreak. CONCLUSIONS: Clinical data and manifestations were more severe in the recent outbreak than in the past outbreak of acute hepatitis A. It is important to be aware of hepatitis A virus infection and to take into account the available vaccination against hepatitis A virus in Japan.