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Akemi Tomoda

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11 papers

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YNIMG Journal 2025 Journal Article

White-Matter fiber tract and resting-state functional connectivity abnormalities in young children with autism spectrum disorder

Jia Wang
Natasha Y.S. Kawata
Xuan Cao
Jie Zhang
Takashi X. Fujisawa
Xinyi Zhang
Lili Fan
Wei Xia

Autism spectrum disorder (ASD) is a complex developmental disorder characterized by difficulties in social interaction and communication and repetitive behaviors. Although abnormal brain development has been shown to exist in children with ASD, the link between structural brain abnormalities and resting-state functional connectivity (rsFC) disruptions in children with ASD remains understudied. To address this limitation, we utilized the population-based bundle-to-region connectome, providing a detailed understanding of the connectivity between cortical regions and white matter (WM) tracts. By precisely indexing WM-Gray Matter (GM) interactions, we investigated the rsFC of the cortex-associated ROIs to explore the association between structural and rsFC abnormalities and clinical symptoms in young children with ASD. This MRI study identified significant differences in WM structure and rsFC between children with ASD (n = 34) and typically developing children (TD, n = 43). Our results showed that decreased fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD WM tracts compared to TD, particularly in left hemisphere tracts (anterior thalamic radiation [ATR], cingulum, inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF], and uncinate fasciculus [UF]). Abnormal rsFC was observed in GM areas connected by ATR, cingulum, IFOF, ILF, and SLF. Furthermore, abnormalities in the structural and functional connectivity index (SFCI) within the SLF and cingulum were identified. An association has been observed between these abnormalities and clinical symptoms. Specifically, SLF structural and functional connectivity appear to be associated with repetitive and restrictive behavior (RRB), while cingulum connectivity is associated with communication abilities. In conclusion, young children with ASD exhibit abnormal WM tract structures and associated rsFC abnormalities. These differences highlight significant disruptions in rsFC mapped from WM tracts to cortical areas in ASD, correlating with the severity of ASD symptoms, and suggest the importance of multi-modal imaging in capturing these variations.

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YNIMG Journal 2024 Journal Article

Brain structures and functional connectivity in neglected children with no other types of maltreatment

Natasha Y.S. Kawata
Shota Nishitani
Akiko Yao
Shinichiro Takiguchi
Yoshifumi Mizuno
Sakae Mizushima
Kai Makita
Shoko Hamamura

Child maltreatment can adversely affect brain development, leading to vulnerabilities in brain structure and function and various psychiatric disorders. Among the various types of child maltreatment, neglect has the highest incidence rate (76.0%); however, data on its sole adverse influence on the brain remain limited. This case-control brain magnetic resonance imaging (MRI) study identified the changes in gray matter structure and function that distinguish neglected children with no other type of maltreatment (Neglect group, n = 23) from typically developing children (TD group, n = 140), and investigated the association between these structural and functional differences and specific psychosocial phenotypes observed in neglected children. Our results showed that the Neglect group had a larger right and left anterior cingulate cortex (R/L.ACC) and smaller left angular gyrus (L.AG) gray matter volume. The larger R/L.ACC was associated with hyperactivity and inattention. Resting-state functional analysis showed increased functional connectivity (FC) between the left supramarginal gyrus (L.SMG) in the salience network (SN) and the right middle frontal gyrus (R.MFG) simultaneously with a decrease in FC with the L.ACC for the same seed. The increased FC for the R.MFG was associated with difficulty in peer problems and depressive symptoms; a mediating effect was evident for depressive symptoms. These results suggest that the structural atypicality of the R/L.ACC indirectly contributes to the disturbed FCs within the SN, thereby exacerbating depressive symptoms in neglected children. In conclusion, exposure to neglect in childhood may lead to maladaptive brain development, particularly neural changes associated with depressive symptoms.

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YNIMG Journal 2022 Journal Article

Methylphenidate remediates aberrant brain network dynamics in children with attention‐deficit/hyperactivity disorder: A randomized controlled trial

Yoshifumi Mizuno
Weidong Cai
Kaustubh Supekar
Kai Makita
Shinichiro Takiguchi
Akemi Tomoda
Vinod Menon

Methylphenidate is a widely used first-line treatment for attention deficit/hyperactivity disorder (ADHD), but the underlying circuit mechanisms are poorly understood. Here we investigate whether a single dose of osmotic release oral system methylphenidate can remediate attention deficits and aberrancies in functional circuit dynamics in cognitive control networks, which have been implicated in ADHD. In a randomized placebo-controlled double-blind crossover design, 27 children with ADHD were scanned twice with resting-state functional MRI and sustained attention was examined using a continuous performance task under methylphenidate and placebo conditions; 49 matched typically-developing (TD) children were scanned once for comparison. Dynamic time-varying cross-network interactions between the salience (SN), frontoparietal (FPN), and default mode (DMN) networks were examined in children with ADHD under both administration conditions and compared with TD children. Methylphenidate improved sustained attention on a continuous performance task in children with ADHD, when compared to the placebo condition. Children with ADHD under placebo showed aberrancies in dynamic time-varying cross-network interactions between the SN, FPN and DMN, which were remediated by methylphenidate. Multivariate classification analysis confirmed that methylphenidate remediates aberrant dynamic brain network interactions. Furthermore, dynamic time-varying network interactions under placebo conditions predicted individual differences in methylphenidate-induced improvements in sustained attention in children with ADHD. These findings suggest that a single dose of methylphenidate can remediate deficits in sustained attention and aberrant brain circuit dynamics in cognitive control circuits in children with ADHD. Findings identify a novel brain circuit mechanism underlying a first-line pharmacological treatment for ADHD, and may inform clinically useful biomarkers for evaluating treatment outcomes.

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YNICL Journal 2018 Journal Article

Type and timing of childhood maltreatment and reduced visual cortex volume in children and adolescents with reactive attachment disorder

Takashi X. Fujisawa
Koji Shimada
Shinichiro Takiguchi
Sakae Mizushima
Hirotaka Kosaka
Martin H. Teicher
Akemi Tomoda

Reactive attachment disorder (RAD) is a severe social functioning disorder associated with early childhood maltreatment where the child displays emotionally withdrawn/inhibited behaviors toward caregivers. Brain regions develop at different rates and regions undergoing rapid change may be particularly vulnerable during these times to stressors or adverse experiences. The aim of this study was to investigate the effect of type and timing of childhood adversities on structural alterations in regional gray matter (GM) volume in maltreated children with RAD. High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12. 76 years) and typically developing (TD) control subjects (n = 22; mean age = 12. 95 years). Structural images were analyzed using a whole-brain voxel-based morphometry approach and the type and timing of maltreatment, which may be more strongly associated with structural alterations, was assessed using random forest regression with conditional inference trees. Our findings revealed that there is a potential sensitive period between 5 and 7 years of age for GM volume reduction of the left primary visual cortex (BA17) due to maltreatment. We also found that the number of types of maltreatment had the most significant effect on GM volume reduction and that the second most significant variable was exposure to neglect. The present study provides the first evidence showing that type and timing of maltreatment have an important role in inducing structural abnormalities in children and adolescents with RAD.

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YNICL Journal 2016 Journal Article

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Kei Mizuno
Junko Kawatani
Kanako Tajima
Akihiro T. Sasaki
Tetsuya Yoneda
Masanori Komi
Toshinori Hirai
Akemi Tomoda

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

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YNICL Journal 2015 Journal Article

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

Kei Mizuno
Masaaki Tanaka
Hiroki C. Tanabe
Takako Joudoi
Junko Kawatani
Yoshihito Shigihara
Akemi Tomoda
Teruhisa Miike

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

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YNICL Journal 2015 Journal Article

Reduced visual cortex grey matter volume in children and adolescents with reactive attachment disorder

Koji Shimada
Shinichiro Takiguchi
Sakae Mizushima
Takashi X. Fujisawa
Daisuke N. Saito
Hirotaka Kosaka
Hidehiko Okazawa
Akemi Tomoda

Child maltreatment increases the risk for psychiatric disorders throughout childhood and into adulthood. One negative outcome of child maltreatment can be a disorder of emotional functioning, reactive attachment disorder (RAD), where the child displays wary, watchful, and emotionally withdrawn behaviours. Despite its clinical importance, little is known about the potential neurobiological consequences of RAD. The aim of this study was to elucidate whether RAD was associated with alterations in grey matter volume (GMV). High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n = 22; mean age = 12.95 years). Using a whole-brain voxel-based morphometry approach, structural images were analysed controlling for age, gender, full scale intelligence quotient, and total brain volume. The GMV was significantly reduced by 20.6% in the left primary visual cortex (Brodmann area 17) of the RAD group compared to the TD group (p = .038, family-wise error-corrected cluster level). This GMV reduction was related to an internalising problem measure of the Strength and Difficulties Questionnaire. The visual cortex has been viewed as part of the neurocircuit regulating the stress response to emotional visual images. Combined with previous studies of adults with childhood maltreatment, early adverse experience (e.g. sensory deprivation) may affect the development of the primary visual system, reflecting in the size of the visual cortex in children and adolescents with RAD. These visual cortex GMV abnormalities may also be associated with the visual emotion regulation impairments of RAD, leading to an increased risk for later psychopathology.

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YNICL Journal 2013 Journal Article

Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder

Kei Mizuno
Tetsuya Yoneda
Masanori Komi
Toshinori Hirai
Yasuyoshi Watanabe
Akemi Tomoda

Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.

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YNIMG Journal 2011 Journal Article

Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus

Akemi Tomoda
Yi-Shin Sheu
Keren Rabi
Hanako Suzuki
Carryl P. Navalta
Ann Polcari
Martin H. Teicher

Objective Exposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology. Methods Optimized voxel-based morphometry was performed on 21 unmedicated, right-handed subjects (18–25years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV) – covaried by age, gender, parental education, financial stress, and total GMV – were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner). Results GMV was increased by 14. 1% in the left superior temporal gyrus (STG, BA 22) (P =0. 004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal ( ß =0. 544, P <0. 0001) and paternal ( ß =0. 300, P <0. 02) verbal aggression and inversely associated with parental education ( ß =−0. 577, P <0. 0001). Conclusion Previous studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke's and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally abusive language.

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YNIMG Journal 2009 Journal Article

Metabolic dysfunction and circadian rhythm abnormalities in adolescents with sleep disturbance

Akemi Tomoda
Junko Kawatani
Takako Joudoi
Akinobu Hamada
Teruhisa Miike

Background Sleep disturbance attributable to circadian rhythm abnormalities frequently occurs in previously healthy children and adolescents who often complain of gastrointestinal discomfort after meals. Methods Glucose metabolism, autonomic function, and human clock gene expression in whole blood cells were investigated in 18 adolescent patients with circadian rhythm sleep disorder. Results Glucose tolerance was significantly lower in the patients than in normal controls: the mean sigma blood glucose level was significantly higher (P <0. 05) and the insulinogenic index was significantly lower (P <0. 05) in the patient group than in controls. Messenger ribonucleic acid level of hPer2 was significantly higher at 6: 00 in the control subjects, but in only 3 of the 18 patients. Component analysis of cardiographic R–R interval revealed that high-frequency component peaks were suppressed significantly in the patient group compared to the controls (P <0. 001). Conclusions Metabolic and endocrine dysfunctions were identified in adolescents with sleep disturbance as decreased glucose tolerance and absence of human clock gene regulation in whole blood cells. Their brain dysfunction attributable to sleep disturbances might cause such peripheral autonomic imbalance and carbohydrate metabolic dysfunction.

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YNIMG Journal 2009 Journal Article

Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment

Akemi Tomoda
Hanako Suzuki
Keren Rabi
Yi-Shin Sheu
Ann Polcari
Martin H. Teicher

Objective Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). Methods 1455 young adults (18–25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. Results GMV was reduced by 19. 1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P =0. 037, corrected cluster level), by 14. 5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P =0. 015, uncorrected cluster level) and by 16. 9% in the right anterior cingulate gyrus (BA24) (P <0. 001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. Conclusions Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.

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