Supplemental Digital Content is Available in the Text. Using magnetic resonance spectroscopy in vivo, we show GABA and glutamate alterations in children aged 7 to 13 years with migraine, which are associated with migraine characteristics.

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The inhibitory neurotransmitter γ-Aminobutyric acid (GABA) plays a crucial role in cortical development. Therefore, characterizing changes in GABA levels during development has important implications for the study of healthy development and developmental disorders. Brain GABA levels can be measured non-invasively using GABA-edited magnetic resonance spectroscopy (MRS). However, the most commonly used editing technique to measure GABA results in contamination of the GABA signal with macromolecules (MM). Therefore, GABA measured using this technique is often referred to as GABA+ . While few in number, previous studies have shown GABA+ levels increase with age during development. However, these studies are unable to specify whether it is specifically GABA that is increasing or, instead, if levels of MM increase. In this study, we use a GABA-editing technique specifically designed to suppress the MM signal (MM-supp GABA). We find no relationship between MM-supp GABA and age in healthy children aged 7–14 years. These findings suggest that the relationship between GABA+ and age is driven by changes in MM levels, not by changes in GABA levels. Moreover, these findings highlight the importance of accounting for MM levels in MRS quantification.

Many long-term survivors of childhood cancer (LTSCCs) experience late-and long-term effects from their treatments, including pain. Yet, pain is poorly understood among LTSCCs. The current study aims to 1a) identify rates and patterns of chronic pain 1b) describe multiple dimensions of pain, and 2) test predictors of chronic pain in LTSCCs. Survivors [n=140; 48.6% male, Mage=17.3 years (SD=4.9)] were recruited from across Canada. Participants completed the

Tactile perception plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. A better understanding of how tactile function improves with age from early childhood to adulthood is fundamental in understanding atypical tactile experiences in childhood-onset neurodevelopmental disorders, including autism spectrum disorder. In this study, one hundred and forty-two children and adults aged 3–23 years completed a vibrotactile testing battery consisting of five tasks, which rely on different cortical mechanisms. The battery was designed to be suitable for testing in young children and was used to investigate tactile perception from early childhood to adulthood. Our results show a general pattern of rapid, age-related improvements in tactile perception (lower discrimination threshold = greater sensitivity) across early childhood (ages 3–6 years). However, differences in the rate of change across tasks were observed, with tactile performance reaching adult-like levels earlier on same tasks than others. These findings highlight that early childhood is a period of rapid changes in tactile perception, and that the different underlying cortical, physical and cognitive development processes likely develop at different rates. Further, we are the first to show the feasibility of vibrotactile testing in an early childhood sample, which has important clinical implications for examining developmental disorders with altered tactile function and our results can be used as a reference.

BackgroundAdolescent and young adult (AYA; 13 to 39 years) survivors of childhood cancer may be especially vulnerable to physical health and mental health concerns during the pandemic. We investigated the impact of COVID-19 on the mental health status of AYA survivors (Aim 1) and shared tailored, evidence-based health-related information on COVID-19 (Aim 2).MethodsBetween May and June 2020, participants completed a cross-sectional online survey assessing their cancer history, current mental health status, and their COVID-19 information needs.ResultsNinety-four participants (78 females, 13 males, 2 non-binary) with a mean age of 26.9 years (SD = 6.2) were included in the final sample. Participants reported residing from 10 countries and 94% identified as White. Nearly half of the participants (49%) described their mental health status as worse now than before the pandemic. Thirty-nine participants (41%) that indicated their current mental health status was tied to fears/worries about their past cancer and treatment experienced a higher level of anxiety and PTSS than those who did not report the same. Most participants (77%) had not received any information related to the potential risks of COVID-19 and expressed an interest in receiving this information. In response, an infographic detailing recommended strategies for coping with mental health problems in the pandemic, along with preliminary study findings, was developed.DiscussionAYA survivors reporting their mental health status was linked to their past cancer experienced poorer mental health. There is a value to educating survivors on their potential health risks, but accounting for their perceived mental health vulnerabilities should be considered when disseminating knowledge. The use of an infographic is a unique contribution towards the development of innovative and personalized means of sharing health education to this vulnerable yet resilient group. This research on the mental health status of AYA survivors very early in the pandemic informs continued initiatives investigating the rapidly changing nature of how COVID-19 may impact AYA survivors today and in the future.

Despite migraine being one of the top five most prevalent childhood diseases, a lack of knowledge about pediatric migraine limits effective treatment strategies; standard adult pharmaceutical therapies are less effective in children and can carry undesirable side-effects. Non-pharmacological therapies have shown some success in adults; however, to appropriately apply these in children we need to understand pediatric migraine's underlying biology. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions. Although there is indirect evidence of abnormal excitability in pediatric migraine, GABA and glutamate levels have yet to be assessed.The purpose of this study was to measure levels of GABA and glutamate in the thalamus, sensorimotor cortex and visual cortex of children with migraine using MRS. We found that children with migraine and aura had significantly lower glutamate levels in the visual cortex as compared to control children, opposite to results seen in adults. Additionally, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with a higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to paediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in the development of more effective treatments.

Background Migraine affects roughly 10% of youth aged 5–15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. Methods Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7–15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. Results We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. Conclusions We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.