Journal of Neurodevelopmental Disorders最新文献

Background: The interhemispheric transfer deficit theory proposes that individuals with dyslexia have impaired interhemispheric transfer, particularly affecting the integration of visual information from the left and right visual fields. This study aimed to evaluate this hypothesis by examining interhemispheric transfer in dyslexia using visual half-field tasks targeting both linguistic and visuospatial processing.

Methods: We examined interhemispheric transfer in dyslexia using two visual half-field tasks: a lexical decision task to assess written word processing, and a symmetry decision task to examine visuospatial processing. We compared reaction times and accuracy in 90 Dutch-speaking participants (45 with dyslexia, 45 controls) across left, right, and bilateral stimulus presentations.

Results: While both tasks successfully captured expected visual half-field differences in the control group, favoring the right visual field in the lexical decision task and the left visual field in the symmetry detection task, we did not observe that the dyslexia group showed increased differences between the two fields, as predicted by the interhemispheric transfer deficit theory. Furthermore, the dyslexia group benefited just as much as controls from stimuli presented simultaneously to both visual fields. Thus, no evidence of interhemispheric transfer deficits related to dyslexia was found in either task.

Conclusions: These findings challenge the broad applicability of the interhemispheric transfer deficit theory in dyslexia, suggesting that such impairments may be task-dependent rather than domain-general. Future studies should further explore the conditions under which interhemispheric transfer deficits might occur in dyslexia.

Background: Movement differences in autism have attracted growing attention in recent years. Anecdotally, autistic movement has been likened to that of Parkinson's Disease (PD). Given that PD assessments are primarily movement-based, it is important to ensure that autistic individuals are not scoring highly on PD diagnostic criteria due to autism-related movement differences. Quantifying overlap in movement profiles and identifying distinguishing features is essential, particularly given increased PD diagnosis rates in the autistic population.

Methods: We conducted the first direct comparison study of autistic and parkinsonian movement. Autistic individuals (N = 31), individuals with PD (N = 32) and control participants (N = 31) completed a Shapes Tracing Task and a Reaction Time Task. Kinematic features were compared between groups and classification algorithms were run to distinguish between groups.

Results: Groups were distinguishable based on kinematic features. The autistic group differed from both PD and control groups in speed modulation and sub-movements, and from the PD group in reaction time. Classification algorithms for clinical (autism and PD) versus non-clinical groups, and for autism versus PD, were most accurate when combining kinematic and questionnaire data. There were no kinematic similarities between autism and PD that were also distinct from controls.

Conclusions: Whilst kinematic features did not appear similar between autism and PD, they were informative for group classification. This proof-of-concept study highlights that movement-based metrics may aid in identifying whether someone belongs to a clinical group, and which one - suggesting potential for refining diagnostic approaches for both autism and PD.

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of paternally expressed genes on chromosome 15q11-13, including NDN, which encodes necdin. Necdin deficiency has been linked to impaired visuospatial memory, social recognition, and stress regulation-features also seen in PWS. Previous work showed that necdin-deficient (Ndn + m/-p) mice exhibit reduced activity of noradrenergic neurons in the locus coeruleus (LC), a nucleus essential for arousal and stress responses. However, the mechanisms underlying LC hypoactivity remain unclear. Because GABAergic signaling is critical for LC excitability, this study examined the role of GABA_A ​and GABA_B ​receptor-mediated inhibition in Ndn + m/-p mice.

Methods: Electrophysiological recordings from brainstem slices of wild-type (WT) and Ndn + m/-p mice were used to measure spontaneous firing rates (SFRs) of LC noradrenergic neurons. The effects of bicuculline (GABA_A​ antagonist) and CGP54626 (GABA_B​ antagonist) were tested. Whole-cell patch-clamp recordings assessed receptor-mediated currents. Western blotting quantified receptor subunit expression in peri-LC tissue. Immunocytochemistry and ELISA examined GABA_B​ receptor expression and GABA release in cultured astrocytes.

Results: LC-NE neurons in Ndn + m/-p mice exhibited significantly reduced baseline SFR compared with WT. Bicuculline did not alter firing in either genotype, whereas CGP54626 significantly increased SFR in WT but not in Ndn + m/-p neurons, indicating impaired GABA_B receptor-mediated tonic inhibition. Whole-cell patch-clamp experiments confirmed intact GABA_A receptor-mediated inward currents in both genotypes, while no GABA_B receptor-mediated phasic currents were detected. Western blot analysis revealed comparable expression of GABA_A receptor α2 subunit and GABA_BR1 in peri-LC tissue between WT and Ndn + m/-p mice, suggesting functional rather than expression-level deficits. GFAP-positive cell density in the LC region was unchanged in vivo; however, in astrocyte cultures, Ndn + m/-p astrocytes exhibited greater proliferation by DIV 19 and consistently secreted higher levels of GABA, with significant elevations at later culture stages.

Conclusion: Necdin deficiency selectively disrupts GABA_B receptor-mediated tonic inhibition of LC-NE neurons while preserving GABA_A receptor function. Elevated astrocytic proliferation and GABA release may further enhance ambient inhibition, contributing to LC hypoactivity and the neurobehavioral phenotypes of PWS. These findings identify GABA_B receptor dysfunction and astrocytic dysregulation as potential mechanistic targets for therapeutic intervention in PWS.

Background: To classify MRI patterns in children with cerebral palsy (CP) using the MRI Classification System (MRICS) and examine their associations with perinatal risk factors and clinical outcomes.

Methods: This retrospective cohort study included 1,403 children with CP who underwent post-neonatal cranial MRI between 2011 and 2020. MRI patterns were categorized using MRICS. We analyzed the associations between MRI findings and perinatal risk factors (e.g., gestational age, birth weight, sex, perinatal adversity, plurality) using univariate and multivariable multinomial logistic regression. Clinical outcomes-including CP subtype, gross motor function, intellectual disability, epilepsy, and composite impairment index-were assessed using chi-square, Kruskal-Wallis tests, and correspondence analysis.

Results: MRI abnormalities were observed in 86.5% of children, with predominant white matter injury (PWMI) being most common (46.5%). Preterm birth and perinatal adversity significantly increased the risk of PWMI and PGMI. PWMI was linked with spastic CP, better motor outcomes, and lower rates of intellectual disability. In contrast, PGMI and maldevelopments were associated with epilepsy, hearing loss, and severe impairment. Importantly, a subset of children with normal MRI findings still exhibited substantial functional impairments, emphasizing the limitations of structural imaging alone.

Conclusions: MRI patterns, as classified by MRICS, provide critical insight into the neurodevelopmental heterogeneity of CP. Normal MRI findings do not preclude significant clinical impairment, underscoring the need for integrated neuroimaging and clinical-genetic assessment in CP management.

Fragile X Syndrome (FXS), the leading known inherited cause of atypical behaviors associated with autism spectrum disorders (ASD), arises due to the reduced expression or absence of the Fragile X Messenger Ribonucleoprotein 1 (FMRP). Individuals with ASD and FXS often experience atypical sensory processing across modalities such as touch, hearing, and/or vision. The consequences of altered sensory processing can be debilitating, leading to impairments in sensory discrimination and an inability to filter out irrelevant sensory stimuli such as innocuous sounds, smells, sights, or touches. Currently, there is a significant knowledge gap in the field of FXS regarding the circuit mechanisms that drive atypical sensory processing and how these contribute to hypersensitivity and secondary effects, such as learning impairments and increased anxiety. Animal models of FXS mirror many of the sensory hypersensitivity issues observed in humans, exhibiting heightened anxiety, as well as learning and social impairments. Here, we discuss the dysfunctional neural dynamics underlying atypical sensory processing across modalities in FXS, potential therapeutic interventions targeting specific ion channels, receptors, and circuits, and propose future research directions that could pave the way for circuit-targeted therapies.