Repetitive transcranial magnetic stimulation decreased effortful frontal activity for shifting in patients with major depressive disorder.

Patients with major depressive disorder (MDD) exhibit several clinical symptoms including difficulties in flexible thinking. Flexible thinking mainly relies on a cognitive ability called shifting; however, the mechanisms underlying shifting in patients with MDD have not yet been clarified. Therefore, we conducted a preliminary intervention study to clarify the association between depression and shifting ability. We examined the hemodynamic responses in the frontal regions during the shifting task using functional near-infrared spectroscopy (fNIRS) in 21 patients with MDD who were treated using high-frequency repetitive transcranial magnetic stimulation (rTMS). Behavioral performance on the shifting task did not change between pre- and posttreatments, whereas patients who responded well to rTMS treatment showed a significant decrease in hemodynamic responses posttreatment. On the other hand, the poor responders did not show significant changes in the hemodynamic responses between pre- and posttreatments. These results suggest that the good responders were successfully remedied with rTMS treatment and did not need effortful activity in frontal regions for shifting, which made their brain activity more efficient.

Response of tomatoes primed by mycorrhizal colonization to virulent and avirulent bacterial pathogens.

Most plants interact with arbuscular mycorrhizal fungi, which enhance disease resistance in the host plant. Because the effects of resistance against bacterial pathogens are poorly understood, we investigated the effects of mycorrhizal colonization on virulent and avirulent pathogens using phytopathological and molecular biology techniques. Tomato plants colonized by Gigaspora margarita acquired resistance not only against the fungal pathogen, Botrytis cinerea, but also against a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000 (Pst). In G. margarita-colonized tomato, salicylic acid (SA)- and jasmonic acid (JA)-related defense genes were expressed more rapidly and strongly compared to those in the control plants when challenged by Pst, indicating that the plant immunity system was primed by mycorrhizal colonization. Gene expression analysis indicated that primed tomato plants responded to the avirulent pathogen, Pseudomonas syringae pv. oryzae, more rapidly and strongly compared to the control plant, where the effect on the JA-mediated signals was stronger than in the case with Pst. We found that the resistance induced by mycorrhizal colonization was effective against both fungal and bacterial pathogens including virulent and avirulent pathogens. Moreover, the activation of both SA- and JA-mediated signaling pathways can be enhanced in the primed plant by mycorrhizal colonization.

Sudden Unexpected Death of Infantile Dilated Cardiomyopathy with JPH2 and PKD1 Gene Variants.

A Japanese girl with polycystic kidney disease (PKD) developed normally, but at 8 months of age, she was hospitalized for acute onset dyspnea. On the day after admission to hospital, her general condition suddenly became worse. An echocardiogram showed left ventricular dilatation with thin walls, severe mitral valve regurgitation, and a reduced ejection fraction. She died of acute cardiac failure 3 hours after the sudden change. Postmortem analysis with light microscopy showed disarray of cardiomyocytes without obvious infiltration of lymphocytes, and we diagnosed her heart failure as idiopathic dilated cardiomyopathy (DCM). Clinical exome sequencing showed compound heterozygous variants in JPH2 (p.T237A/p.I414L) and a heterozygous nonsense mutation in PKD1 (p.Q4193*). To date, several variants in the JPH2 gene have been reported to be pathogenic for adult-onset hypertrophic cardiomyopathy or DCM in an autosomal dominant manner and infantile-onset DCM in an autosomal recessive manner. Additionally, autosomal dominant polycystic kidney disease is a systemic disease associated with several extrarenal manifestations, such as cardiomyopathy. Here we report a sudden infant death case of DCM and discuss the genetic variants of DCM and PKD.

Executive dysfunction in medication-naïve children with ADHD: A multi-modal fNIRS and EEG study.

OBJECTIVE: Children with attention deficit hyperactivity disorder (ADHD) exhibit deficits in executive function. Since there are no clear biomarkers for the disorder, this study aimed to investigate the neurophysiological biomarkers for deficits in executive function in children with ADHD using functional near-infrared spectroscopy (fNIRS) and electroencephalography. METHODS: Twenty patients diagnosed with ADHD and 19 typically developing children (TDC; 8-11 years old) were included. Event related potentials (ERPs) were recorded using an electroencephalogram (EEG) and oxygenated hemoglobin concentrations (Oxy-Hb) were recorded using fNIRS during a colored Go/NoGo task, simultaneously. Latencies and amplitudes of NoGo-N2 and NoGo/Go-P3 tasks were measured using EEG. RESULTS: Children with ADHD showed significantly decreased Oxy-Hb in the right frontal cortex as well as longer NoGo-P3 latencies and a decreased NoGo/Go-P3 amplitude. There was a significant positive correlation between the Oxy-Hb and NoGo/Go-P3 amplitude. CONCLUSIONS: These results suggest that children with ADHD experience executive dysfunction. Hemodynamic and electrophysiological findings during the Go/NoGo task might be useful as a biomarker of executive function. SIGNIFICANCE: These findings have key implications for understanding the pathophysiology of deficits in executive function in ADHD.

Discrepancy between musical ability and language skills in children with Williams syndrome.

BACKGROUND: Children with Williams syndrome (WS) show a marked interest in music, a characteristic often explored in clinical settings. However, the actual musical abilities of patients with WS remain debatable due to some of the relevant data being derived from experimental tasks that require a verbal response, despite the known language impairments in WS. The present study aimed to examine musical ability in children with WS using a newly invented pitch discrimination task with minimal involvement of language and clarify its relationship with language skill. METHODS: Eleven children with WS participated in the study. We used a novel pitch discrimination task that required minimal language use. Two piano tones were presented sequentially, and children were asked to give a non-verbal response as to whether the second tone was higher than, lower than, or the same as the first tone. RESULTS: Pitch discrimination performance in children with WS was lower than the level predicted for their chronological age (CA), even in the non-verbal task. Pitch discrimination ability and verbal mental age (VMA) were shown to be dissociated, such that children with WS with a lower skill level for language showed an unexpectedly higher level of pitch discrimination ability and vice versa. CONCLUSIONS: Our results indicated reduced musical ability with respect to CA in children with WS. The dissociation between musical ability and language skills may indicate unique developmental relationships that differ from those in normal children. These findings provide new evidence to support the importance of assessing actual musical ability in WS prior to implementing interventional music therapy.

Predictive factors of success in neurofeedback training for children with ADHD.

INTRODUCTION: Neurofeedback (NF) training aims the enhancement of self-regulation over brain activities. While it is largely recognized as an effective treatment for attention deficit hyperactivity disorder (ADHD), the existence of non-learners has also been reported. The present study explored pre-training assessment indices that could predict learners prior to NF training. METHODS: Twenty-two children with ADHD participated in slow cortical potential (SCP) NF training and completed pre- and post-training assessments. Participants were classified into learners or non-learners based on their progress in the SCP regulation, and pre-training indices that differentiate the two groups were examined by decision tree analysis. RESULTS AND DISCUSSION: The learner rate in NF training was 45.5%. Learners were predicted by pre-training cognitive and neurophysiological measures regarding Stroop tasks, which suggested relatively intact executive function as their characteristics. Given that NF training is not universally effective for children with ADHD, further studies are necessary to establish application criteria.

Applicability of the Movement Assessment Battery for Children-Second Edition (MABC-2) for Japanese Children Aged 3-6 Years: A Preliminary Investigation Emphasizing Internal Consistency and Factorial Validity.

This study investigated the applicability of the Movement Assessment Battery for Children - Second Edition (MABC-2) for 3- to 6-year-old Japanese children, particularly addressing its internal consistency and factorial validity. The MABC-2 test set for 3- to 6-year-old children was administered to 252 children. Differences between Japanese children and those of the original normative sample (i.e. United Kingdom children) were investigated along with sex differences. The Japanese children aged 3-6 years were found to have higher Manual Dexterity and Balance component scores than children of the normative sample. Girls scored higher than boys on the Balance component. Results of several analyses showed good internal consistency of the MABC-2. Confirmatory factor analysis revealed that a theoretical three-component model of the MABC-2 was not fitted to Japanese children aged 3-6 years. Instead, a new three-component model was postulated and discussed. The new three-component model of the MABC-2, with Manual Dexterity, Static Balance and Ball Skills, and Dynamic Balance, has high factorial validity in Japanese children aged 3-6 years.

Right prefrontal cortex specialization for visuospatial working memory and developmental alterations in prefrontal cortex recruitment in school-age children.

OBJECTIVE: The right prefrontal cortex (PFC) plays an essential role in active processing within visuospatial working memory (VSWM). The aim of this study was to examine developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks in school-age participants. METHODS: We recruited 80 school-age children who were classified into three age groups: 7- to 8-year-old, 9- to 10-year-old, and 11- to 12-year-old children. We used near infrared spectroscopy (NIRS) to measure PFC activity during visuospatial memory task. Memory stimuli were presented either sequentially or simultaneously. RESULTS: In all three groups, right-lateralized PFC activity was observed during sequential presentation, suggesting specialization of the right PFC for VSWM. During simultaneous presentation, right-lateralized PFC activity was not observed in 7- to 8-year-old children or 9- to 10-year-old children. In contrast, PFC activity was right-lateralized in 11- to 12-year-old children. CONCLUSIONS: We suggest that specialization of the right PFC for VSWM is already present before school-age, but widely distributed activity in response to visuospatial memory tasks changes to more focal activity in VSWM-specific regions during the early school years. SIGNIFICANCE: Using NIRS, we showed developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks.

The relationship between the superior frontal cortex and alpha oscillation in a flanker task: Simultaneous recording of electroencephalogram (EEG) and near infrared spectroscopy (NIRS).

Activity in the alpha band of the electroencephalogram (EEG) reflects functional inhibition of the cerebral cortex. The superior frontal cortex (SFC) is known to control alpha activity. Based on this relationship between SFC and alpha, we hypothesized that SFC controlled alpha mediates proactive control over interference. In this study, we examined the relationship between SFC and alpha in the flanker task by simultaneously recording EEG and near infrared spectroscopy (NIRS). Forty participants performed a flanker task with occasional (compatible 75%, incompatible 25%) and successive (incompatible 100%) conditions. In the occasional condition, larger SFC activity was related to pre-stimulus alpha enhancement under occipital electrodes. This is consistent with a model in which SFC enhances pre-stimulus alpha activity, leading to proactive control over interference. However, we could not detect a correlation between SFC activity and alpha activity in the successive condition. Active inhibition may have been reduced by a need to continuously inhibit brain regions associated with the irrelevant information. This may have reduced the role of the SFC in controlling alpha activity. Based on these findings, we postulate that there are two cerebral mechanisms of proactive control over interference.

Abscisic acid modulates salicylic acid biosynthesis for systemic acquired resistance in tomato.

Among the regulatory mechanisms of systemic acquired resistance (SAR) in tomato, antagonistic interaction between salicylic acid (SA) and abscisic acid (ABA) signaling pathways was investigated. Treatment with 1,2-benzisothiazol-3(2H)-one1,1-dioxide (BIT) induced SAR in tomato thorough SA biosynthesis. Pretreatment of ABA suppressed BIT-induced SAR including SA accumulation, suggesting that ABA suppressed SAR by inhibiting SA biosynthesis.

Pure and Short-Term Phonics-Training Improves Reading and Print-Specific ERP in English: A Case Study of a Japanese Middle School Girl.

Although phonics is the most frequently used approach in treating students with reading difficulties, its effects have not been fully clarified at either a behavioral or neurophysiological level. The present case study administered pure and short-term (i.e., 10 minutes per day for five weeks) phonics-training to a 13-year-old Japanese girl with severe difficulty in learning English. As a result, a drastic improvement in reading accuracy was associated with the enhancement of print-specific N170 in event-related potentials (ERPs) elicited by the trained words. The present finding indicates that phonics training can, by itself, remediate English reading and affect its neurophysiological bases.

Excessive hemodynamic activity in the superior frontal cortex during the flanker task in children with attention deficit hyperactivity disorder.

Near-infrared spectroscopy studies in children with attention deficit hyperactivity disorder (ADHD) have shown excessive prefrontal activity responsible for coping with interference. However, it is possible that the previous results were influenced by verbal, reading, and memory developments. The flanker task is an interference task that does not require a verbal response, reading, or memorization. We examined activity in the superior frontal cortex (SFC) during the flanker task in 12 children with ADHD and 14 children with typical development using near-infrared spectroscopy. SFC activity was significantly greater in children with ADHD than in those with typical development. The results showed excessive interference coping activity in children with ADHD irrespective of verbal, reading, and memory development. Moreover, SFC activity was positively correlated with the inattention subscale score of the ADHD rating scale. We suggest that children with ADHD need greater SFC activation to cope with interference, and the inefficient mechanism is demanding and hard to sustain, which causes inattention symptoms of children with ADHD.

Effects of colonization of a bacterial endophyte, Azospirillum sp. B510, on disease resistance in tomato.

A plant growth-promoting bacteria, Azospirillum sp. B510, isolated from rice, can enhance growth and yield and induce disease resistance against various types of diseases in rice. Because little is known about the interaction between other plant species and this strain, we have investigated the effect of its colonization on disease resistance in tomato plants. Treatment with this strain by soil-drenching method established endophytic colonization in root tissues in tomato plant. The endophytic colonization with this strain-induced disease resistance in tomato plant against bacterial leaf spot caused by Pseudomonas syringae pv. tomato and gray mold caused by Botrytis cinerea. In Azospirillum-treated plants, neither the accumulation of SA nor the expression of defense-related genes was observed. These indicate that endophytic colonization with Azospirillum sp. B510 is able to activate the innate immune system also in tomato, which does not seem to be systemic acquired resistance.

Print-specific N170 involves multiple subcomponents for Japanese Hiragana.

Print-specific N170 in event-related potentials is generally considered to reflect relatively automatic processing for letter strings, which is crucial for fluent reading. However, our previous studies demonstrated that print-specific N170 for transparent Japanese Hiragana script consists of at least two subcomponents under rapid stimulus presentation: an attention-related left-lateralized N170 and a bilateral N170 associated with more automatic orthographic processes (Okumura, Kasai & Murohashi, 2014, 2015). The present study aimed to confirm the latter component by controlling presentation frequency of letters and nonlinguistic visual controls (i.e., symbols), but found a quite different pattern of results; an enhanced occipito-temporal positivity for words (80-120ms poststimulus) followed by the typical left-lateralized N170 and an enhanced parietal negativity for nonwords (150-200ms). These results should provide further insights into the interaction processes between attention and early stages of print processing.

Spatial working memory encoding type modulates prefrontal cortical activity.

Spatial working memory (SWM) involves both simultaneous and sequential encoding, but the differences in their neural correlates are unclear. We investigated the differences in prefrontal cortex activity related to these SWM encoding types. We also examined the patterns of brain activity influencing individual visuospatial abilities (VSA). We conducted SWM tasks with two different conditions, sequential and simultaneous encoding, and examined hemodynamic activity in 39 healthy adults using near-infrared spectroscopy. The bilateral dorsolateral prefrontal cortex was activated more strongly in the sequential condition compared with the simultaneous condition. This suggests that prefrontal cortex activity underlying SWM is modulated by the type of encoding. We also found that individuals with high VSA showed weaker activation in the right-dorsolateral prefrontal cortex compared with those with lower VSA during the simultaneous condition. This hypoactivation is thought to reflect neural efficiency in the individuals with high ability. These findings are expected to lead to a better understanding of neural substrates for SWM.

Attention that covers letters is necessary for the left-lateralization of an early print-tuned ERP in Japanese hiragana.

Extensive experience with reading develops expertise in acquiring information from print, and this is reflected in specific enhancement of the left-lateralized N170 component in event-related potentials. The N170 is generally considered to reflect visual/orthographic processing; while modulations of its left-lateralization related to phonological processes have also been indicated. However, in our previous study, N170-like response to Hiragana strings lacked left-lateralization when the stimuli were completely task-irrelevant in rapid-presentation sequences [Okumura et al. (2014). Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings. Neuroreport 25, 410-414]. This suggests that, despite the highly transparent character-to-syllable correspondence, the phonological mapping of Hiragana strings requires some kind of attention toward print. To verify this notion, the present study examined ERPs under the same experimental condition as in the previous study, except that the task required attention to a stimulus attribute (i.e., color). As a result, Hiragana words and nonwords elicited left-lateralized negative deflection in the occipito-temporal region during 130-170ms post-stimulus in comparison to symbol strings, but only when the print had a narrow intercharacter spacing. Moreover, we observed the enhancement of very early occipital ERP in response to words during 70-100ms. The present results suggest that visual attention plays a role in early print processing, which may contribute to our understanding of the mechanisms that underlie expert as well as impaired reading.

Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

The role of apelin on the alleviative effect of Angiotensin receptor blocker in unilateral ureteral obstruction-induced renal fibrosis.

BACKGROUND: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. METHODS: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model. RESULTS: WE OBTAINED THE FOLLOWING RESULTS: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. CONCLUSION: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.

Serum and urinary neutrophil gelatinase-associated lipocalin levels in children with chronic renal diseases.

BACKGROUND: Recent studies showed that serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for early detection of acute kidney injury. However, the clinical significance of measuring serum and urinary NGAL on chronic renal diseases remains unclear. METHODS: In this study, we measured serum and urinary NGAL levels in patients with several common pediatric renal diseases such as renal dysfunction (estimated glomerular filtration rate < 90 mL/min/1.73 m(2)), proliferative glomerulonephritis, steroid-resistant and steroid-sensitive nephrotic syndrome, and tubular dysfunction. RESULTS: Urinary NGAL level was significantly increased compared with the control in all of these disease groups except in patients with a remission stage of steroid-sensitive nephrotic syndrome, although a significant increase in serum NGAL level was observed in the renal dysfunction group only. Both serum and urinary NGAL levels showed significant inverse correlations with an estimated glomerular filtration rate in the analysis with total subjects, and also in the analysis with the renal dysfunction group in urinary NGAL. In proteinuric patients, the extent of proteinuria significantly correlated with urinary NGAL level. In patients with tubular dysfunction, the increase of urinary NGAL level was remarkable compared with the other disease groups. CONCLUSION: These results indicated that urinary NGAL level is a better biomarker for chronic renal diseases in children than serum NGAL level, although multiple pathological mechanisms should be considered in evaluating these NGAL values.