Although motor deficits are common in autism, the neural correlates underlying the disruption of even basic motor execution are unknown. Motor deficits may be some of the earliest identifiable signs of abnormal development and increased understanding of their neural underpinnings may provide insight into autism-associated differences in parallel systems critical for control of more complex behaviour necessary for social and communicative development. Functional magnetic resonance imaging was used to examine neural activation and connectivity during sequential, appositional finger tapping in 13 children, ages 8-12 years, with high-functioning autism (HFA) and 13 typically developing (TD), age- and sex-matched peers. Both groups showed expected primary activations in cortical and subcortical regions associated with motor execution [contralateral primary sensorimotor cortex, contralateral thalamus, ipsilateral cerebellum, supplementary motor area (SMA)]; however, the TD group showed greater activation in the ipsilateral anterior cerebellum, while the HFA group showed greater activation in the SMA. Although activation differences were limited to a subset of regions, children with HFA demonstrated diffusely decreased connectivity across the motor execution network relative to control children. The between-group dissociation of cerebral and cerebellar motor activation represents the first neuroimaging data of motor dysfunction in children with autism, providing insight into potentially abnormal circuits impacting development. Decreased cerebellar activation in the HFA group may reflect difficulty shifting motor execution from cortical regions associated with effortful control to regions associated with habitual execution. Additionally, diffusely decreased connectivity may reflect poor coordination within the circuit necessary for automating patterned motor behaviour. The findings might explain impairments in motor development in autism, as well as abnormal and delayed acquisition of gestures important for socialization and communication.
The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated problems with learning and socioemotional development negatively impact PBT survivors’ overall health-related quality of life, educational attainment and employment rates. Multiple factors including tumor features and associated complications, treatment methods, individual protective and vulnerability factors and accessibility of environmental supports contribute to the neurocognitive and psychosocial outcomes in PBT survivors. Declines in overall measured intelligence are common and may persist years after treatment. Core deficits in attention, processing speed and working memory are postulated to underlie problems with overall intellectual development, academic achievement and career attainment. Additionally, psychological problems after PBT can include depression, anxiety and psychosocial adjustment issues. Several intervention paradigms are briefly described, though to date research on innovative, specific and effective interventions for neurocognitive late effects is still in its early stages. This article reviews the existing research for understanding PBT late effects and highlights the need for innovative research to enhance neurocognitive and psychosocial outcomes in PBT survivors.
BackgroundSurvivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).MethodsPediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation—including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning—were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time.ResultsBetween 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P < 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (β = 10.6, P = 0.048) and processing speed (β = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (β = 9.9, P = 0.06) and general adaptive functioning (β = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09).ConclusionsPRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.
Background and Purpose White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were to: (1) apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus; (2) quantify early neuropsychological deficits; and (3) explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. Methods A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, RD were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical and motor skills. The correlation between the Motor scale and DTI indices in the PLIC was analyzed. Results DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD driven by the increased RD with statistical significance (p<0.05) or trend level significance (p=0.06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (p<0.05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills and motor skills were significantly lower in children with hydrocephalus (all at p level <0.05). The MD and RD value in the PLIC were found to have trend level or significant correlation with the Motor scale (p=0.057, 0.041, respectively). Conclusions DTI reveals alterations in white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.
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