Neural and behavioral effects of parent training on emotion recognition in mothers rearing children with attention-deficit/hyperactivity disorder.

This randomized controlled study examined neurological changes in socioemotional processing skills through parent training in caregivers of children with attention-deficit/hyperactivity disorder. Thirty mothers of children with attention-deficit/hyperactivity disorder were stratified into parent training and non-parent training groups. Functional magnetic resonance imaging was performed during the "Reading the Mind in the Eyes" test, and parenting difficulties were evaluated using the Parenting Stress Index and the Parenting Scale, twice (before and after parent training). Only mothers in the parent training group showed a significant decrease in Parenting Stress Index and Parenting Scale scores. They also demonstrated increased activity in the left occipital fusiform gyrus during the task of estimating emotions from facial pictures. We presumed that these changes might reflect the potential impact of enrollment in parent training in reducing stress, which might have increased activation of the fusiform gyrus.

[Two-chambered Right Ventricle Diagnosed in Adulthood:Report of a Case].

A 64-year-old female without symptoms of heart failure was diagnosed with a two-chambered right ventricle (TCRV) during examination of a heart murmur and cardiac enlargement, for which surgery was performed. Under cardiopulmonary bypass and cardiac arrest, we first performed a right atrium and pulmonary artery incision and observed the right ventricle through the tricuspid and pulmonary valves, although we could not obtain a sufficient view of the right ventricular outflow tract. After subsequently incising the right ventricular outflow tract and the anomalous muscle bundle, the right ventricular outflow tract was patch-enlarged using a bovine cardiovascular membrane. After weaning from cardiopulmonary bypass, disappearance of the pressure gradient in the right ventricular outflow tract was confirmed. The patient's postoperative course was uneventful without any complications including arrhythmia.

[Metastatic Right Ventricular Tumor Eleven-year after Nephrectomy for Renal Cell Carcinoma].

Metastatic heart tumors make up the majority of heart tumors and are 20 to 40 times more frequent than primary heart tumors. Cardiac metastasis of renal cell carcinoma is often asymptomatic until advanced stage, and there are few reports of surgical tumor resection for metastatic heart tumors at very late term. We experienced a case of metastatic right ventricular tumor eleven-year after nephrectomy for renal cell carcinoma. Tumor resection was performed under cardiopulmonary bypass and cardiac arrest, but the tumor on the free wall of the right ventricle trabeculae could not be completely resected. After surgery, the patient underwent chemotherapy for residual tumor, which is growing.

Beneficial Effects of Behavioral Parent Training on Inhibitory Control in Children With Attention-Deficit/Hyperactivity Disorder: A Small-Scale Randomized Controlled Trial.

The purpose of this study was to examine whether the beneficial effects of behavioral parent training (BPT), as an indirect type of psychosocial treatment, are extended to cognitive manifestations beyond behavioral symptoms of attention-deficit/hyperactivity disorder (ADHD). Although previous studies of community families have shown an association between parenting quality and a child's cognitive functions, little is known about the effects of BPT on cognitive manifestations in children with ADHD. In this study, we focused on inhibitory control among cognitive domains, which is considered to be the most malleable to direct types of psychosocial treatment for ADHD. We hypothesized that inhibitory control is affected by BPT, which uses parents as the primary agents of change to help their children. Thirty school-age children (6-12 years old) with ADHD and their parents (mothers) participated and were randomly assigned to either the standard BPT or waitlist control group. Using two objective laboratory-based tasks of inhibitory control (i.e., go/no-go and single response selection tasks), we assessed baseline and post-treatment response inhibition to suppress task-irrelevant responses and response selection to select task-relevant responses. In addition to decreased ADHD symptoms and negative parenting, the BPT group exhibited significantly improved performance in the single response selection task, but not in the go/no-go task, compared with the waitlist control group. Although tentative, these findings partially support our hypothesis that BPT has beneficial effects on the cognitive inhibitory control of ADHD, highlighting the potential for supportive environmental modifications to advance cognitive development in children with ADHD.

Epigenetic Clock Deceleration and Maternal Reproductive Efforts: Associations With Increasing Gray Matter Volume of the Precuneus.

Reproductive efforts, such as pregnancy, delivery, and interaction with children, make maternal brains optimized for child-rearing. However, extensive studies in non-human species revealed a tradeoff between reproductive effort and life expectancy. In humans, large demographic studies have shown that this is the case for the most part; however, molecular marker studies regarding aging remain controversial. There are no studies simultaneously evaluating the relationship between reproductive effort, aging, and brain structures. We therefore examined the associations between reproductive efforts (parity status, number of deliveries, motherhood period, and cumulative motherhood period), DNA methylation age (mAge) acceleration (based on Horvath's multi-tissue clock and the skin & blood clock), and the regional gray matter volumes (obtained through brain magnetic resonance imaging (MRI) using voxel-based morphometry) in 51 mothers aged 27-46 years of children in early childhood. We found that increasing reproductive efforts were significantly associated with decelerated aging in mothers with one to four children, even after adjusting for the confounding effects in the multiple linear regression models. We also found that the left precuneus gray matter volume was larger as deceleration of aging occurred; increasing left precuneus gray matter volume, on the other hand, mediates the relationship between parity status and mAge deceleration. Our findings suggest that mothers of children in early childhood, who have had less than four children, may benefit from deceleration of aging mediated via structural changes in the precuneus.

A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents.

Child maltreatment dysregulates the brain's oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5-8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.

Increased resting-state activity in the cerebellum with mothers having less adaptive sensory processing and trait anxiety.

Child-rearing mothers with high levels of trait anxiety have a tendency for less adaptive sensory processing, which causes parenting stress. However, the neural mechanisms underlying this sensory processing and trait anxiety remain unclear. We aimed to determine the whole-brain spontaneous neural activity and sensory processing characteristics in mothers with varying parenting stress levels. Using resting-state functional magnetic resonance imaging, we assessed mothers caring for more than one preschool aged (2-5 years) child and presenting with varying levels of sensory processing, trait anxiety, and parenting stress. Spontaneous neural activities in select brain regions were evaluated by whole-brain correlation analyses based on the fractional amplitude of low-frequency fluctuations (fALFF). We found significant positive correlations between levels of sensory processing with trait anxiety and parenting stress. Mothers having less adaptive sensory processing had significantly increased resting-state network activities in the left lobule VI of the cerebellum. Increased fALFF values in the left lobule VI confirmed the mediation effect on the relationship between trait anxiety and sensory processing. A tendency for less adaptive sensory processing involving increased brain activity in lobule VI could be an indicator of maternal trait anxiety and the risk of parenting stress.

RETRACTED: Epigenetic modification of the oxytocin gene is associated with gray matter volume and trait empathy in mothers.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The Editor has concluded that the acceptance of this article was partly based upon the positive advice of an unreliable reviewer report. The report was provided to the journal by a reviewer suggested by the authors, and there were inappropriate communications between the authors and reviewer during the peer-review process. The Editor has therefore concluded that the review was not appropriate or independent. This manipulation of the peer-review process represents a clear violation of the fundamentals of peer review, our publishing policies, and publishing ethics standards. Apologies are offered to the readers of the journal that this deception was not detected during the submission process.

The Neural Correlates of Semantic and Grammatical Encoding During Sentence Production in a Second Language: Evidence From an fMRI Study Using Structural Priming.

Japanese English learners have difficulty speaking Double Object (DO; give B A) than Prepositional Object (PO; give A to B) structures which neural underpinning is unknown. In speaking, syntactic and phonological processing follow semantic encoding, conversion of non-verbal mental representation into a structure suitable for expression. To test whether DO difficulty lies in linguistic or prelinguistic process, we conducted functional magnetic resonance imaging. Thirty participants described cartoons using DO or PO, or simply named them. Greater reaction times and error rates indicated DO difficulty. DO compared with PO showed parieto-frontal activation including left inferior frontal gyrus, reflecting linguistic process. Psychological priming in PO produced immediately after DO and vice versa compared to after control, indicated shared process between PO and DO. Cross-structural neural repetition suppression was observed in occipito-parietal regions, overlapping the linguistic system in pre-SMA. Thus DO and PO share prelinguistic process, whereas linguistic process imposes overload in DO.

Association of Epigenetic Differences Screened in a Few Cases of Monozygotic Twins Discordant for Attention-Deficit Hyperactivity Disorder With Brain Structures.

The present study examined the relationship between DNA methylation differences and variations in brain structures involved in the development of attention-deficit hyperactivity disorder (ADHD). First, we used monozygotic (MZ) twins discordant (2 pairs of 4 individuals, 2 boys, mean age 12.5 years) for ADHD to identify candidate DNA methylation sites involved in the development of ADHD. Next, we tried to replicate these candidates in a case-control study (ADHD: N = 18, 15 boys, mean age 10.0 years; Controls: N = 62, 40 boys, mean age 13.9 years). Finally, we examined how methylation rates at those sites relate to the degree of local structural alterations where significant differences were observed between cases and controls. As a result, we identified 61 candidate DNA methylation sites involved in ADHD development in two pairs of discordant MZ twins, among which elevated methylation at a site in the sortilin-related Vps10p domain containing receptor 2 (SorCS2) gene was replicated in the case-control study. We also observed that the ADHD group had significantly reduced gray matter volume (GMV) in the precentral and posterior orbital gyri compared to the control group and that this volume reduction was positively associated with SorCS2 methylation. Furthermore, the reduced GMV regions in children with ADHD are involved in language processing and emotional control, while SorCS2 methylation is also negatively associated with emotional behavioral problems in children. These results indicate that SorCS2 methylation might mediate a reduced GMV in the precentral and posterior orbital gyri and therefore influence the pathology of children with ADHD.

Neural Mechanisms of Parental Communicative Adjustments in Spoken Language.

During cultural transmission, caregivers typically adjust their form of speech according to the presumed characteristics of an infant/child, a phenomenon known as infant/child directed speech (IDS/CDS) or "parentese." Although ventromedial prefrontal cortex (vmPFC) damage was previously found to be associated with failure in adjusting non-verbal communicative behaviors, little is known about the neural mechanisms of verbal communicative adjustments, such as IDS/CDS. In the current study, 30 healthy mothers with preschool-age children underwent functional magnetic resonance imaging (fMRI) while performing a picture naming task which required them to name an object for either a child or an adult. In the picture naming task, mothers exhibited a longer naming duration in the toward-child condition than the toward-adult control condition. Naming an object for a child, compared with naming it for an adult, resulted in greater involvement in the vmPFC and other regions (e.g., cerebellum) in the global caregiving network. In particular, the vmPFC exhibited task-related deactivation and decreased functional connectivity with the supplementary motor, precentral, postcentral, and supramarginal regions. These findings suggest that the vmPFC, which is included in the default mode network, is involved in optimizing communicative behaviors for the inter-generational transmission of knowledge. This function of the vmPFC may be considered as a prosocial drive to lead to prosocial communicative behaviors depending on the context. This study provides a better understanding of the neural mechanisms involved in communicative adjustments for children and insight into related applied research fields such as parenting, pedagogy, and education.

White matter changes in children and adolescents with reactive attachment disorder: A diffusion tensor imaging study.

Childhood maltreatment is associated with altered brain structure and function and is a major risk factor for psychopathology, including reactive attachment disorder (RAD). However, whether changes to white matter microstructural integrity are associated with RAD is unclear. We used diffusion tensor imaging (DTI) to assess group differences in fractional anisotropy (FA) in patients with RAD (n = 25; mean age = 13.2) to typically developing (TD) controls (n = 33; mean age = 13.0). To further interpret differences in FA, additional parameters such as mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were assessed. We found that FA values in the body of corpus callosum (CC) and in the projection and thalamic pathways, including the posterior limb of the internal capsule and corona radiata (anterior, posterior, and superior), were significantly higher in the RAD than in the TD group. Additionally, RAD group showed significantly lower RD values in the body of the CC and abovementioned pathways than TD group. Our findings indicate that RAD is associated with altered structure of the CC and projection and thalamic pathways, which may play a role in emotion regulation. The aberrant development of these tracts in RAD may reflect stress-related psychophysiological responses.

Less efficient detection of positive facial expressions in parents at risk of engaging in child physical abuse.

BACKGROUND: Parental physical punishment (e.g., spanking) of children can gradually escalate into child physical abuse (CPA). According to social-information processing (SIP) models of aggressive behaviors, distorted social cognitive mechanisms can increase the risk of maladaptive parenting behaviors by changing how parents detect, recognize, and act on information from their social environments. In this study, we aimed to identify differences between mothers with a low and high risk of CPA regarding how quickly they detect positive facial expressions. METHODS: Based on their use of spanking to discipline children, 52 mothers were assigned to a low- (n = 39) or high-CPA-risk group (n = 13). A single-target facial emotional search (face-in-the-crowd) task was used, which required participants to search through an array of faces to determine whether a target emotional face was present in a crowd of non-target neutral faces. Search efficiency index was computed by subtracting the search time for target-present trials from that for target-absent trials. RESULTS: The high-CPA-risk group searched significantly less efficiently for the happy, but not sad, faces, than did the low-CPA-risk group; meanwhile, self-reported emotional ratings (i.e., valence and arousal) of the faces did not differ between the groups. CONCLUSIONS: Consistent with the SIP models, our findings suggest that low- and high-CPA-risk mothers differ in how they rapidly detect positive facial expressions, but not in how they explicitly evaluate them. On a CPA-risk continuum, less efficient detection of positive facial expressions in the initial processes of the SIP system may begin to occur in the physical-discipline stage, and decrease the likelihood of positive interpersonal experiences, consequently leading to an increased risk of CPA.

Oxytocin receptor DNA methylation and alterations of brain volumes in maltreated children.

Although oxytocin (OXT) plays an important role in secure attachment formation with a primary caregiver, which is impaired in many children with childhood maltreatment (CM), epigenetic regulation in response to CM is a key factor in brain development during childhood. To address this issue, we first investigated differences in salivary DNA methylation of the oxytocin receptor (OXTR) between CM and Non-CM groups of Japanese children (CM: n = 44; Non-CM: n = 41) and its impact on brain structures in subgroup analysis using brain imaging and full clinical data (CM: n = 24; Non-CM: n = 31). As a result, we observed that the CM group showed higher CpG 5,6 methylation than did the Non-CM group and confirmed negative correlations of gray matter volume (GMV) in the left orbitofrontal cortex (OFC) with CpG 5,6 methylation. In addition, the CM group showed significantly lower GMV in the left OFC than did the Non-CM group. Furthermore, as a result of examining the relationship between GMV in the left OFC and psychiatric symptoms in CM, we observed a negative association with insecure attachment style and also confirmed the mediation effect of left-OFC GMV reduction on the relationship between OXTR methylation and insecure attachment style. These results suggest that any modulation of the oxytocin signaling pathway induced by OXTR hypermethylation at CpG 5,6 leads to atypical development of the left OFC, resulting in distorted attachment formation in children with CM.

Local-to-distant development of the cerebrocerebellar sensorimotor network in the typically developing human brain: a functional and diffusion MRI study.

Sensorimotor function is a fundamental brain function in humans, and the cerebrocerebellar circuit is essential to this function. In this study, we demonstrate how the cerebrocerebellar circuit develops both functionally and anatomically from childhood to adulthood in the typically developing human brain. We measured brain activity using functional magnetic resonance imaging while a total of 57 right-handed, blindfolded, healthy children (aged 8-11 years), adolescents (aged 12-15 years), and young adults (aged 18-23 years) (n = 19 per group) performed alternating extension-flexion movements of their right wrists in precise synchronization with 1-Hz audio tones. We also collected their diffusion MR images to examine the extent of fiber maturity in cerebrocerebellar afferent and efferent tracts by evaluating the anisotropy-sensitive index of hindrance modulated orientational anisotropy (HMOA). During the motor task, although the ipsilateral cerebellum and the contralateral primary sensorimotor cortices were consistently activated across all age groups, the functional connectivity between these two distant regions was stronger in adults than in children and adolescents, whereas connectivity within the local cerebellum was stronger in children and adolescents than in adults. The HMOA values in cerebrocerebellar afferent and efferent tracts were higher in adults than in children (some were also higher than in adolescents). The results indicate that adult-like cerebrocerebellar functional coupling is not completely achieved during childhood and adolescence, even for fundamental sensorimotor brain function, probably due to anatomical immaturity of cerebrocerebellar tracts. This study clearly demonstrated the principle of "local-to-distant" development of functional brain networks in the human cerebrocerebellar sensorimotor network.

Histone deacetylase inhibitor targets CD123/CD47-positive cells and reverse chemoresistance phenotype in acute myeloid leukemia.

Chemoresistance may be due to the survival of leukemia stem cells (LSCs) that are quiescent and not responsive to chemotherapy or lie on the intrinsic or acquired resistance of the specific pool of AML cells. Here, we found, among well-established LSC markers, only CD123 and CD47 are correlated with AML cell chemosensitivities across cell lines and patient samples. Further study reveals that percentages of CD123+CD47+ cells significantly increased in chemoresistant lines compared to parental cell lines. However, stemness signature genes are not significantly increased in resistant cells. Instead, gene changes are enriched in cell cycle and cell survival pathways. This suggests CD123 may serve as a biomarker for chemoresistance, but not stemness of AML cells. We further investigated the role of epigenetic factors in regulating the survival of chemoresistant leukemia cells. Epigenetic drugs, especially histone deacetylase inhibitors (HDACis), effectively induced apoptosis of chemoresistant cells. Furthermore, HDACi Romidepsin largely reversed gene expression profile of resistant cells and efficiently targeted and removed chemoresistant leukemia blasts in xenograft AML mouse model. More interestingly, Romidepsin preferentially targets CD123+ cells, while chemotherapy drug Ara-C mainly targeted fast-growing, CD123- cells. Therefore, Romidepsin alone or in combination with Ara-C may be a potential treatment strategy for chemoresistant patients.

Role of the right anterior insular cortex in joint attention-related identification with a partner.

Understanding others as intentional agents is critical in social interactions. We perceive others' intentions through identification, a categorical judgment that others should work like oneself. The most primitive form of understanding others' intentions is joint attention (JA). During JA, an initiator selects a shared object through gaze (initiative joint attention, IJA), and the responder follows the direction of the initiator's gaze (reactive joint attention, RJA). Therefore, both participants share the intention of object selection. However, the neural underpinning of shared intention through JA remains unknown. In this study, we hypothesized that JA is represented by inter-individual neural synchronization of the intention-related activity. Additionally, JA requires eye contact that activates the limbic mirror system; therefore, we hypothesized that this system is involved in shared attention through JA. To test these hypotheses, participants underwent hyperscanning fMRI while performing JA tasks. We found that IJA-related activation of the right anterior insular cortex of participants was positively correlated with RJA-related activation of homologous regions in their partners. This area was activated by volitional selection of the target during IJA. Therefore, identification with others by JA is likely accomplished by the shared intentionality of target selection represented by inter-individual synchronization of the right anterior insular cortex.

[Papillary Fibroelastoma Arising from Chordae Tendineae of the Mitral Valve Chordae;Report of a Case].

Cardiac papillary fibroelastoma is a rare primary cardiac tumor arising from any part of the endocardium. In particular, papillary fibroelastoma originating from the mitral valve chordae is very rare. A 66-year-old man was hospitalized for a left ventricular tumor. Echocardiography revealed a high echoic mass of the mitral valve chordae with grade I mitral regurgitation. Under cardiopulmonary bypass, we performed excision of the mass and the marginal chordae of the mitral valve, and decided there was no need of valvuloplasty. Pathological diagnosis indicated the tumor was papillary fibroelastoma. The postoperative course was uneventful and echocardiography showed no progression of mitral valve regurgitation.