Quality of life of children with neurodevelopmental disorders and their parents during the COVID-19 pandemic: a 1-year follow-up study.

This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.

Psychological Status Associated With Low Quality of Life in School-Age Children With Neurodevelopmental Disorders During COVID-19 Stay-At-Home Period.

Background: This study seeks to ascertain how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders (NDDs) who had experienced sleep schedules alteration and clarify what psychological status predicted low QOL in children with and without altered sleep patterns. Materials and Methods: Study participants were 86 children between 8 and 17 years of age (mean age, 11.7 years; 70 boys, 16 girls; mean intellectual quotient, 83.6). QOL was evaluated using the self-assessment KINDLR. Participants answered questions regarding depression and anxiety on a visual analog scale (VAS) for temporary mood. Their parents answered questionnaires regarding their maladaptive behaviors and differences in sleep patterns before and during the COVID-19 pandemic. The student's t-test was performed to examine the presence or absence of sleep changes in the children, which affected QOL, temporary mood, and maladaptive behaviors. Multiple or simple linear regression analyses were also performed to identify the psychogenic factors that significantly affected decreased QOL for each group with and without changes in sleep schedule. Results: During the COVID-19 stay-at-home period, 46.5% of participants experienced changes in sleep patterns. These changes were associated with decreased QOL as well as internalized symptoms. The decreased QOL of children with sleep patterns changed was predicted by a high level of depression. In addition, low QOL in children with unchanged sleep patterns was predicted by a high level of depression and low current mood status. Conclusions: Almost half of the participants experienced a poor sleep schedule during the stay-at-home period. These alterations in sleep patterns were associated with a low QOL. The QOL of children with a stable life schedule was affected not only by depressive tendencies but also temporary moods. Therefore, they need to live a fulfilling life to maintain their QOL. However, the QOL of children with poor sleep patterns was affected only by depressive tendencies. Hence, clinicians need to ensure that children with NDDs are well-diagnosed with depression and treated for sleep problems.

Age dependency and lateralization in the three branches of the human superior longitudinal fasciculus.

The superior longitudinal fascicle/fasciculus (SLF) is a major white matter tract connecting the frontal and parietal cortices in humans. Although the SLF has often been analyzed as a single entity, several studies have reported that the SLF is segregated into three distinct branches (SLF I, II, and III). They have also reported the right lateralization of the SLF III volume and discussed its relationship with lateralized cortical functions in the fronto-parietal network. However, to date, the homogeneity or heterogeneity of the age dependency and lateralization properties of SLF branches have not been fully clarified. Through this study, we aimed to clarify the age dependency and lateralization of SLF I-III by analyzing diffusion-weighted MRI (dMRI) and quantitative R1 (qR1) map datasets collected from a wide range of age groups, mostly comprising right-handed children, adolescents, adults, and seniors (6 to 81 years old). The age dependency in dMRI measurement (fractional anisotropy, FA) was heterogeneous among the three SLF branches, suggesting that these branches are regulated by distinct developmental and aging processes. Lateralization analysis on SLF branches revealed that the right SLF III was larger than the left SLF III in adults, replicating previous reports. FA measurement also suggested that, in addition to SLF III, SLF II was lateralized to the right hemisphere in adolescents and adults. We further found a left lateralization of SLF I in qR1 data, a microstructural measurement sensitive to myelin levels, in adults. These findings suggest that the SLF sub-bundles are distinct entities in terms of age dependency and lateralization.

De novo ATP1A3 variants cause polymicrogyria.

Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.

The quality of life of children with neurodevelopmental disorders and their parents during the Coronavirus disease 19 emergency in Japan.

This study aimed to reveal how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders and their parents and to identify possible factors that enabled them to maintain their QOL. We enrolled 136 school-aged children (intellectual quotient ≥ 50) and their parents and administered QOL questionnaires to assess the maladaptive behavior of the children; depression, anxiety, and stress of the parents; and activities of their daily lives. The relationship between their QOL and clinical features was examined. The decrease in QOL of children and parents was associated with the mother's limited job flexibility. Decreased QOL was also associated with changes in the sleep rhythms of the children. Maladaptive behaviors in children were associated with parental stress. However, maintained QOL of some families who faced these same conditions of job stress and sleep disorders was associated with less parental stress, less parental depression and anxiety, and milder maladaptive behavior in children. Both mothers with limited job flexibility and changes in the sleep rhythm of children were associated with reduced QOL of children and their parents. Low parental stress was associated with decreased maladaptive behavior in children and with maintained QOL of the family.

Neurological and behavioral features of locomotor imagery in the blind.

In people with normal sight, mental simulation (motor imagery) of an experienced action involves a multisensory (especially kinesthetic and visual) emulation process associated with the action. Here, we examined how long-term blindness influences sensory experience during motor imagery and its neuronal correlates by comparing data obtained from blind and sighted people. We scanned brain activity with functional magnetic resonance imaging (fMRI) while 16 sighted and 14 blind male volunteers imagined either walking or jogging around a circle of 2 m radius. In the training before fMRI, they performed these actions with their eyes closed. During scanning, we explicitly instructed the blindfolded participants to generate kinesthetic motor imagery. After the experimental run, they rated the degree to which their motor imagery became kinesthetic or spatio-visual. The imagery of blind people was more kinesthetic as per instructions, while that of the sighted group became more spatio-visual. The imagery of both groups commonly activated bilateral frontoparietal cortices including supplementary motor areas (SMA). Despite the lack of group differences in degree of brain activation, we observed stronger functional connectivity between the SMA and cerebellum in the blind group compared to that in the sighted group. To conclude, long-term blindness likely changes sensory emulation during motor imagery to a more kinesthetic mode, which may be associated with stronger functional coupling in kinesthetic brain networks compared with that in sighted people. This study adds valuable knowledge on motor cognition and mental imagery processes in the blind.

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.

[Parietal Cortices and Body Information].

Proprioceptive signals originating from skeletal muscles and joints contribute to the formation of both the human body schema and the body image. In this chapter, we introduce various types of bodily illusions that are elicited by proprioceptive inputs, and we discuss distinct functions implemented by different parietal cortices. First, we illustrate the primary importance of the motor network in the processing of proprioceptive (kinesthetic) signals originating from muscle spindles. Next, we argue that the right inferior parietal cortex, in concert with the inferior frontal cortex (both regions connected by the inferior branch of the superior longitudinal fasciculus-SLF III), may be involved in the conscious experience of body image. Further, we hypothesize other functions of distinct parietal regions: the association between internal hand motor representation with external object representation in the left inferior parietal cortex, visuo-kinesthetic processing in the bilateral posterior parietal cortices, and the integration of somatic signals from different body parts in the higher-order somatosensory parietal cortices. Our results indicate that a distinct parietal region, in concert with its anatomically and functionally connected frontal regions, probably plays specialized roles in the processing of body-related information.

Importance of human right inferior frontoparietal network connected by inferior branch of superior longitudinal fasciculus tract in corporeal awareness of kinesthetic illusory movement.

It is generally believed that the human right cerebral hemisphere plays a dominant role in corporeal awareness, which is highly associated with conscious experience of the physical self. Prompted by our previous findings, we examined whether the right frontoparietal activations often observed when people experience kinesthetic illusory limb movement are supported by a large-scale brain network connected by a specific branch of the superior longitudinal fasciculus fiber tracts (SLF I, II, and III). We scanned brain activity with functional magnetic resonance imaging (MRI) while nineteen blindfolded healthy volunteers experienced illusory movement of the right stationary hand elicited by tendon vibration, which was replicated after the scanning. We also scanned brain activity when they executed and imagined right hand movement, and identified the active brain regions during illusion, execution, and imagery in relation to the SLF fiber tracts. We found that illusion predominantly activated the right inferior frontoparietal regions connected by SLF III, which were not substantially recruited during execution and imagery. Among these regions, activities in the right inferior parietal cortices and inferior frontal cortices showed right-side dominance and correlated well with the amount of illusion (kinesthetic illusory awareness) experienced by the participants. The results illustrated the predominant involvement of the right inferior frontoparietal network connected by SLF III when people recognize postural changes of their limb. We assume that the network bears a series of functions, specifically, monitoring the current status of the musculoskeletal system, and building-up and updating our postural model (body schema), which could be a basis for the conscious experience of the physical self.

Body representations in the human brain revealed by kinesthetic illusions and their essential contributions to motor control and corporeal awareness.

The human brain can generate a continuously changing postural model of our body. Somatic (proprioceptive) signals from skeletal muscles and joints contribute to the formation of the body representation. Recent neuroimaging studies of proprioceptive bodily illusions have elucidated the importance of three brain systems (motor network, specialized parietal systems, right inferior fronto-parietal network) in the formation of the human body representation. The motor network, especially the primary motor cortex, processes afferent input from skeletal muscles. Such information may contribute to the formation of kinematic/dynamic postural models of limbs, thereby enabling fast online feedback control. Distinct parietal regions appear to play specialized roles in the transformation/integration of information across different coordinate systems, which may subserve the adaptability and flexibility of the body representation. Finally, the right inferior fronto-parietal network, connected by the inferior branch of the superior longitudinal fasciculus, is consistently recruited when an individual experiences various types of bodily illusions and its possible roles relate to corporeal awareness, which is likely elicited through a series of neuronal processes of monitoring and accumulating bodily information and updating the body representation. Because this network is also recruited when identifying one's own features, the network activity could be a neuronal basis for self-consciousness.

Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures.

OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures. The pathogenesis of AESD is considered to be fever-induced seizure susceptibility and excitotoxicity, which may be caused by sodium channel dysfunction in some cases. Here we studied whether mutations in genes encoding sodium channels, SCN1A and SCN2A, predispose children to AESD. METHODS: We recruited 92 AESD patients in a nationwide survey of acute encephalopathy in Japan from 2008 to 2011. We collected their genomic DNA samples, and sequenced the entire coding region of SCN1A and SCN2A. RESULTS: Five out of 92 patients (5.4%) had missense mutations either in SCN1A or SCN2A. After a preceding infection with fever, all the patients showed status epilepticus at the onset. Hemiconvulsion-hemiplegia was recognized in three patients during the acute/subacute phase. One patient had taken theophylline for the treatment of bronchial asthma just before the onset of AESD. Familial history was not remarkable except one patient with a SCN1A mutation (G1647S) whose mother had a similar episode of AESD in her childhood. A different substitution (G1674R) at the same amino acid position, as well as two other SCN1A mutations found in this study, had previously been reported in Dravet syndrome. Another SCN1A mutation (R1575C) had been detected in other types of acute encephahlitis/encephalopathy. One patient had SCN2A mutation, F328V, which had previously been reported in Dravet syndrome. Another SCN2A mutation, I172V, was novel. None of the patients were diagnosed with Dravet syndrome or genetic (generalized) epilepsy with febrile seizure plus in the following-up period. CONCLUSIONS: Mutations in SCN1A and SCN2A are a predisposing factor of AESD. Altered channel activity caused by these mutations may provoke seizures and excitotoxic brain damage.

Clinical and genetic features of acute encephalopathy in children taking theophylline.

BACKGROUND: Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD. METHODS: We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD. RESULTS: Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patient died, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene. CONCLUSIONS: Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD.

Distinct neural mechanisms of tonal processing between musicians and non-musicians.

OBJECTIVE: Both behavioral and neural responses to deviant melody endings can be enhanced through musical training. Yet it is unknown whether there are any differences in the neural responses of musicians and non-musicians given no difference in their behavioral responses. It is also unknown whether the melody preceding the fixed final tone influences the sense of completion. METHODS: We recorded neuromagnetic responses in ten musicians and ten non-musicians while they were evaluating the sense of completion associated with melodies. RESULTS: The sense of a melody's completion was influenced by the combination of the preceding melody and the ending tones. The N1 had shorter latency in musicians, while the sustained field had larger amplitudes in non-musicians. CONCLUSIONS: Musicians and non-musicians rated the sense of completion similarly, yet neural responses differed between the groups. SIGNIFICANCE: These findings suggest that neural processes in musicians and non-musicians may be distinct even when the sense of completion is assessed similarly in both groups. In other words, there might be specific tonal processing available to non-musicians which can compensate for their lack of musical training.

Mutations of the SCN1A gene in acute encephalopathy.

PURPOSE: Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthema subitum. It occurs worldwide, but is most prevalent in East Asia. Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation. To determine whether SCN1A mutations are a predisposing factor of acute encephalopathy, we sought to identify SCN1A mutations in a large case series of acute encephalopathy including various syndromes. METHODS: We analyzed the SCN1A gene in 87 patients with acute encephalopathy, consisting of 20 with acute necrotizing encephalopathy (ANE), 61 with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and six with nonspecific (unclassified) acute encephalopathy. KEY FINDINGS: Three patients had distinct point mutations. Two of them had epileptic seizures prior to acute encephalopathy. Clinical and neuroradiologic findings of acute encephalopathy were diverse among the three patients, although all had a prolonged and generalized seizure at its onset. The first patient with V982L had partial epilepsy and AESD. The second patient with M1977L had febrile seizures and nonspecific acute encephalopathy. The third patient with R1575C had no seizures until the onset of ANE. M1977L was a novel mutation, whereas the remaining two, V982L and R1575C, have previously been reported in cases of Dravet syndrome and acute encephalopathy, respectively. SIGNIFICANCE: These findings provide further evidence that SCN1A mutations are a predisposing factor for the onset of various types of acute encephalopathy.

Magnetoencephalographic study of the neural responses in body perception.

A fundamental trait of human beings is the ability to discern information communicated by others. The human body is one of the important sources of such information. To date, several researchers have reported two body-selective regions in the brain-the extrastriate body area (EBA) and fusiform body area. As compared to the number of studies on spatial distribution, studies on the temporal processing of body perception are few. The electroencephalography (EEG) findings of a recent study indicate that observation of the human body induces a remarkable response leading to the generation of event-related-potentials that peak at 190 ms. However, source localization by using EEG has limitations. The advantage of magnetoencephalography (MEG) is that it enables localization of cortical activities and has excellent temporal resolution. In this study, we used MEG to measure the neural responses underlying the perception of the human body. Our results suggest that cortical activation induced by body images was observed in the bilateral EBA region with a latency of 190 ms and right-hemispheric dominance. Our study revealed the regions involved and the latency differences between these regions in body perception. Further, our results show the usefulness of MEG for body perception studies and suggest that like the face, the body plays a unique role in the human recognition process.

Effects of motor imagery on intermanual transfer: a near-infrared spectroscopy and behavioural study.

Intermanual transfer is the ability that previous studies by one limb promote the later learning by the other limb. This ability has been demonstrated in various effectors and types of training. Motor imagery, the mental simulation of motor execution, is believed to be strongly associated with the cognitive aspects of motor execution, and the pattern of brain activity during motor imagery is similar to that of motor execution, although the activation pattern is smaller, and the level is lower. If the cognitive component of motor execution strongly contributes to transfer, the training effect of motor imagery would be expected to transfer to the contralateral limb. In the present study, we used the tapping sequence paradigm to evaluate the occurrence of intermanual transfer through motor imagery and to compare differences of transfer effects to motor execution learning. We divided participants into three groups: an execution group, a motor imagery group and a no-training control group. Before and after a nondominant left hand training session, ipsilateral hand tests were conducted. After the post-test, a contralateral right-hand test was also conducted. In order to investigate the relationship between transfer effect and neural activation during the learning phase, we measured motor-related brain area activity using near-infrared spectroscopy (NIRS). Execution was effective especially for trained movement, imagery was effective for both trained movement and intermanual transfer. Brain activity suggesting predictive transfer differed between two groups, suggesting that motor execution and motor imagery training have different behavioural effects and neural contributions.

Mild influenza encephalopathy with biphasic seizures and late reduced diffusion.

Two Japanese infants with influenza A infection presented with a brief febrile seizure, followed by secondary seizures and disturbance of consciousness on day 5. Magnetic resonance imaging revealed reduced subcortical diffusion around day 5. Both were diagnosed with mild form of acute encephalopathy syndrome characterized by biphasic seizures and late reduced diffusion. It is important for clinicians in Asian countries to recognize and to inform parents that secondary progression may occur even after a brief febrile seizure with influenza.