Region-specific changes in brain glutamate and gamma-aminobutyric acid across the migraine attack in children and adolescents.

ABSTRACT: In patients with migraine, an excitation-inhibition imbalance that fluctuates relative to attack onset has been proposed to contribute to the underlying pathophysiology of migraine, but this has yet to be explored in children and adolescents. This prospective, observational, cohort study examined glutamate and gamma-aminobutyric acid (GABA) levels across the phases of a migraine attack and interictally in children and adolescents using magnetic resonance spectroscopy. Macromolecule-suppressed GABA (sensorimotor cortex and thalamus) and glutamate (occipital cortex, sensorimotor cortex, and thalamus) were measured in children and adolescents (10-17 years) with a migraine diagnosis with or without aura 4 times over 2 weeks. Linear mixed-effects models examined changes in glutamate and GABA during the 72 hours leading up to, and after the onset of an attack. We found significant region-specific changes in glutamate and GABA. Specifically, sensorimotor GABA significantly increased leading up to the headache phase, whereas glutamate significantly decreased following the headache onset in the occipital cortex and the thalamus. Post hoc analyses examined the 24 hours leading up to or following the onset of the headache phase. In the 24 hours before the headache onset, sensorimotor glutamate, occipital glutamate, and thalamic GABA decreased. In the 24 hours post headache onset, sensorimotor glutamate continued to decrease. Our results suggest changes in glutamate and GABA that are consistent with the thalamocortical dysrhythmia hypothesis. These findings provide insight into developmental migraine pathophysiology and may open future avenues for treatment targets specific to children and adolescents.

Development of human visual cortical function: A scoping review of task- and naturalistic-fMRI studies through the interactive specialization and maturational frameworks.

Overarching theories such as the interactive specialization and maturational frameworks have been proposed to describe human functional brain development. However, these frameworks have not yet been systematically examined across the fMRI literature. Visual processing is one of the most well-studied fields in neuroimaging, and research in this area has recently expanded to include naturalistic paradigms that facilitate study in younger age ranges, allowing for an in-depth critical appraisal of these frameworks across childhood. To this end, we conducted a scoping review of 94 developmental visual fMRI studies, including both traditional experimental task and naturalistic studies, across multiple sub-domains (early visual processing, category-specific higher order processing, naturalistic visual processing). We found that across domains, many studies reported progressive development, but few studies describe regressive or emergent changes necessary to fit the maturational or interactive specialization frameworks. Our findings suggest a need for the expansion of developmental frameworks and clearer reporting of both progressive and regressive changes, along with well-powered, longitudinal studies.

Atypical Tactile Perception in Early Childhood Autism.

We assessed different aspects of tactile perception in young children (3-6 years) with autism. Autistic and neurotypical children completed vibrotactile tasks assessing reaction time, amplitude discrimination (sequential and simultaneous) and temporal discrimination (temporal order judgment and duration discrimination). Autistic children had elevated and more variable reaction times, suggesting slower perceptual-motor processing speed and/or greater distractibility. Children with autism also showed higher amplitude discrimination and temporal order judgement thresholds compared to neurotypical children. Tactile perceptual metrics did not associate with social or tactile sensitivities measured by parent-reports. Altered tactile behavioral responses appear in early childhood, can be quantified but appear dissociated from sensitivity. This implies these measures are complementary, but not necessarily related, phenomena of atypical tactile perception in autism.

Development and validation of the Social Reward Questionnaire-Early Childhood.

Social interactions like group inclusion, receiving praise, or treating others kindly can be motivating and enjoyable. Social reward sensitivity, including motivation and enjoyment, varies between individuals. In early childhood, this variation may relate to differences in social experience and development. Social reward questionnaires have been developed to measure individual differences in social enjoyment for adolescents and adults, but no early childhood measure currently exists. Here, we describe the development and validation of the parent/caregiver report Social Reward Questionnaire-Early Childhood (SRQ-EC) for children aged 3-7 years. The SRQ-EC was developed to quantify both wanting (motivation) and liking (enjoyment) of social rewards, which were considered in separate factor models. For wanting and liking models, exploratory (N = 126) and confirmatory (N = 344) factor analyses identified that three subscales best represented early childhood social reward sensitivity, which were: Sociability (large groups), Admiration (praise and positive attention), and Prosocial Interactions and Compliance (kindness and rule following). SRQ-EC subscales were internally consistent (ω = 0.76-0.91, α = 0.75-0.88, mean interitem correlations = 0.38-0.60) with high test-retest reliability over 2-weeks (r = 0.66-0.85, all p < .001). Subscales differentially associated with other social behavior and personality measures, suggesting construct validity. SRQ-EC subscale scores further showed differential and significant associations with autistic-like traits in nonautistic children. These results suggest that SRQ-EC subscale scores are reliable for assessing social reward sensitivity during early childhood, which could offer key developmental insight regarding interindividual variation in early social behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nonlinear age effects in tactile processing from early childhood to adulthood.

BACKGROUND: Tactile processing plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. An understanding of how tactile processing changes with age from early childhood to adulthood is fundamental in understanding altered tactile experiences in neurodevelopmental disorders, such as autism spectrum disorder. METHODS: In this cross-sectional study, 142 children and adults aged 3-23 years completed a vibrotactile testing battery consisting of 5 tasks, which rely on different cortical and cognitive mechanisms. The battery was designed to be suitable for testing in young children to investigate how tactile processing changes from early childhood to adulthood. RESULTS: Our results suggest a pattern of rapid, age-related changes in tactile processing toward lower discrimination thresholds (lower discrimination thresholds = greater sensitivity) across early childhood, though we acknowledge limitations with cross-sectional data. Differences in the rate of change across tasks were observed, with tactile performance reaching adult-like levels at a younger age on some tasks compared to others. CONCLUSIONS: While it is known that early childhood is a period of profound development including tactile processing, our data provides evidence for subtle differences in the developmental rate of the various underlying cortical, physical, and cognitive processes. Further, we are the first to show the feasibility of vibrotactile testing in early childhood (<6 years). The results of this work provide estimates of age-related differences in performance, which could have important implications as a reference for investigating altered tactile processing in developmental disorders.

Harmonization of multi-site MRS data with ComBat.

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to measure brain chemistry in vivo and has been used to study the healthy brain as well as neuropathology in numerous neurological disorders. The number of multi-site studies using MRS are increasing; however, non-biological variability introduced during data collection across multiple sites, such as differences in scanner vendors and site-specific acquisition implementations for MRS, can obscure detection of biological effects of interest. ComBat is a data harmonization technique that can remove non-biological sources of variance in multisite studies. It has been validated for use with structural and functional MRI metrics but not for MRS measured metabolites. This study investigated the validity of using ComBat to harmonize MRS metabolites for vendor and site differences. Analyses were performed using data acquired across 20 sites and included edited MRS for GABA+ (N = 218) and macromolecule-suppressed GABA data (N = 209), as well as standard PRESS data to quantify NAA, creatine, choline, and glutamate (N = 190). ComBat harmonization successfully mitigated vendor and site differences for all metabolites of interest. Moreover, significant associations were detected between sex and choline levels and between age and glutamate and GABA+ levels that were not detectable prior to harmonization, confirming the importance of removing site and vendor effects in multi-site data. In conclusion, ComBat harmonization can be successfully applied to MRS data in multi-site MRS studies.

Autism interest intensity in early childhood associates with executive functioning but not reward sensitivity or anxiety symptoms.

LAY ABSTRACT: Personal interests in autism are a source of joy, pride, and assist with the formation of social relationships. However, highly intense engagement can also interfere with other activities including activities of daily living. Theories have suggested that intense interests relate to executive functioning, reward sensitivity, and anxiety symptoms; but none of these theories have been tested in early childhood. Understanding which behavioral traits relate to intense interests in early childhood could help understand how intense interests may emerge, while also providing clues for how to manage interest intensity and best promote the many benefits of personal interests. We recruited families with autistic and non-autistic children aged 3-6 years. Parents completed questionnaires to assess children's interest diversity and intensity, executive functioning, reward sensitivity, and anxiety symptoms. We found that for autistic and non-autistic children, greater difficulty shifting attention between activities related to more intense interests. In autistic children only, difficulty with inhibitory control of attention also related to more intense interests. However, reward sensitivity and anxiety symptoms did not relate to interest intensity. Based on these observations, assisting young children with developing executive functioning skills could help with mediating the interference of interests in daily life to ultimately promote the many benefits of personal interests.

Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum.

BACKGROUND: Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features (< age 3) and their potential impact on development and quality of life, little is known about the neural mechanisms underlying sensory reactivity in early childhood autism. METHODS: Here, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3-6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to "real-world" parent-reported tactile reactivity. RESULTS: As expected, we found elevated tactile reactivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) was shorter in young children with autism compared to NT children, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile reactivity as a grouping variable found that enhanced early neural responses were associated with greater tactile reactivity in autism. LIMITATIONS: The relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results. CONCLUSIONS: Our findings suggest that electrophysiological somatosensory cortex processing measures may be indices of "real-world" tactile reactivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile reactivity in early childhood autism and, in the clinical context, may have therapeutic implications.