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BioRxiv : the Preprint Server For... Jun 2024The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here,...
UNLABELLED
The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here, we explored the expression dynamics of cortical and neuropsychiatric disorder-associated genes in datasets generated from human NSCs across telencephalic fate transitions in vitro and in vivo. We identified risk genes expressed in brain organizers and sequential gene regulatory networks across corticogenesis revealing disease-specific critical phases, when NSCs are more vulnerable to gene dysfunctions, and converging signaling across multiple diseases. Moreover, we simulated the impact of risk transcription factor (TF) depletions on different neural cell types spanning the developing human neocortex and observed a spatiotemporal-dependent effect for each perturbation. Finally, single-cell transcriptomics of newly generated autism-affected patient-derived NSCs in vitro revealed recurrent alterations of TFs orchestrating brain patterning and NSC lineage commitment. This work opens new perspectives to explore human brain dysfunctions at the early phases of development.
ONE-SENTENCE SUMMARY
The temporal analysis of gene regulatory networks in human neural stem cells reveals multiple early critical phases associated with cortical disorders and neuropsychiatric traits.
PubMed: 38915580
DOI: 10.1101/2024.06.14.598925 -
Pharmacological Reviews Jun 2024Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to...
Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases such as epilepsy, neuropathic pain, psychosis, autism and cardiac arrhythmia. Many venom peptides selectively act on Na channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense, but which are also valuable pharmacological tools for the identification and/or treatment of human diseases. Typically, conotoxins contain two or three disulfide bonds and these internal cross-braces contribute to conotoxins having compact, well-defined structures and high stability. Of the conotoxins containing three disulfide bonds some selectively target mammalian Na channels and can block, stimulate, or modulate these channels. Such conotoxins have great potential to serve as pharmacological tools for studying the functions and characteristics of Na channels or as drug leads for neurological diseases related to Na channels. Accordingly, discovering or designing conotoxins targeting Na channels with high potency and selectivity is important. The amino acid sequences, disulfide bond connectivity, and three-dimensional structures are key factors that affect the biological activity of conotoxins, and targeted synthetic modifications of conotoxins can greatly improve their activity and selectivity. This review examines Na channel-targeted conotoxins, focusing on their structures, activities and designed modifications, with a view towards expanding their applications. Na channels are crucial in various neurological diseases. Some conotoxins selectively target Na channels, causing either blockade or activation, thus enabling their use as pharmacological tools for studying the channels' characteristics and functions. Conotoxins also have promising potential to be developed as drug leads. The disulfide bonds in these peptides are important for stabilizing their structures, thus leading to enhanced specificity and potency. Together, conotoxins targeting Na channels have both immediate research value and promising future application prospects.
PubMed: 38914468
DOI: 10.1124/pharmrev.123.000923 -
PloS One 2024Motor issues are frequently observed accompanying core deficits in autism spectrum disorder (ASD). Impaired motor behavior has also been linked to cognitive and social...
Motor issues are frequently observed accompanying core deficits in autism spectrum disorder (ASD). Impaired motor behavior has also been linked to cognitive and social abnormalities, and problems with predictive ability have been suggested to play an important, possibly shared, part across all these domains. Brain imaging of sensory-motor behavior is a promising method for characterizing the neurobiological foundation for this proposed key trait. The present functional magnetic resonance imaging (fMRI) developmental study, involving children/youth with ASD, typically developing (TD) children/youth, and neurotypical adults, will investigate brain activations during execution and observation of a visually guided, goal-directed sequential (two-step) manual task. Neural processing related to both execution and observation of the task, as well as activation patterns during the preparation stage before execution/observation will be investigated. Main regions of interest include frontoparietal and occipitotemporal cortical areas, the human mirror neuron system (MNS), and the cerebellum.
Topics: Humans; Magnetic Resonance Imaging; Child; Brain; Male; Adolescent; Female; Adult; Brain Mapping; Autism Spectrum Disorder; Movement; Autistic Disorder; Young Adult; Psychomotor Performance; Mirror Neurons
PubMed: 38913636
DOI: 10.1371/journal.pone.0296225 -
ELife Jun 2024Autism spectrum disorder (ASD) presents a range of challenges, including heightened sensory sensitivities. Here, we examine the idea that sensory overload in ASD may be...
Autism spectrum disorder (ASD) presents a range of challenges, including heightened sensory sensitivities. Here, we examine the idea that sensory overload in ASD may be linked to issues with efference copy mechanisms, which predict the sensory outcomes of self-generated actions, such as eye movements. Efference copies play a vital role in maintaining visual and motor stability. Disrupted efference copies hinder precise predictions, leading to increased reliance on actual feedback and potential distortions in perceptions across eye movements. In our first experiment, we tested how well healthy individuals with varying levels of autistic traits updated their mental map after making eye movements. We found that those with more autistic traits had difficulty using information from their eye movements to update the spatial representation of their mental map, resulting in significant errors in object localization. In the second experiment, we looked at how participants perceived an object displacement after making eye movements. Using a trans-saccadic spatial updating task, we found that those with higher autism scores exhibited a greater bias, indicating under-compensation of eye movements and a failure to maintain spatial stability during saccades. Overall, our study underscores efference copy's vital role in visuo-motor stability, aligning with Bayesian theories of autism, potentially informing interventions for improved action-perception integration in autism.
Topics: Humans; Male; Female; Autism Spectrum Disorder; Adult; Young Adult; Eye Movements; Psychomotor Performance; Visual Perception; Adolescent; Saccades; Autistic Disorder
PubMed: 38913073
DOI: 10.7554/eLife.94946 -
Ochsner Journal 2024Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and...
Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and current research into attachment-based interventions are centered on early childhood. Minimal research has been conducted in school-aged children with autism spectrum disorder (ASD), and even less research has focused on attachment-based interventions for children with significant comorbidities such as catatonia. We present the case of a 12-year-old female that involved dyadic work in conjunction with biologic interventions for the treatment of ASD and catatonia. Psychosocial interventions were centered on an attachment-based framework and behavioral skills training that incorporated elements of parent management training. We observed and tracked the patient's uncooperativeness, underproductive speech, emotional withdrawal, and anxiety via the Brief Psychiatric Rating Scale for Children. Attachment- and behavioral-based interventions in conjunction with psychotropic medications and electroconvulsive therapy resulted in improvements. This case illustrates the potential advantages that attachment- and behavioral-based psychotherapeutic interventions can confer in complex cases involving neurodivergent patients. The case also highlights the lack of current research into and understanding of attachment theory in children and adolescents with ASD. Research is needed into the role of attachment-based interventions in patients with ASD and other psychiatric comorbidities, particularly in patient populations beyond preschool age. Initiating nonbiologic interventions in conjunction with biologic interventions may also enhance outcomes and warrants further investigation.
PubMed: 38912185
DOI: 10.31486/toj.23.0095 -
Frontiers in Psychology 2024Affective decision-making is a prominent topic in consumer psychology research, with its core assumption being that consumers tend to purchase brands and commodities...
INTRODUCTION
Affective decision-making is a prominent topic in consumer psychology research, with its core assumption being that consumers tend to purchase brands and commodities they like. However, the reasons behind why we develop emotional responses of liking or disliking toward certain commodities, as well as what the underlying neural mechanisms are, remain largely unknown.
METHODS
This study utilized the S1-S2 paradigm in an experiment wherein S1 presented 12 types of commodities and S2 displayed 48 distinct colored squares. Participants were instructed to assess whether they "Like" or "Dislike" the commodity in S1, which was colored with the S2 color. Electroencephalogram (EEG) recordings were obtained during the reaction process and subsequently analyzed to examine the components of S2-induced event-related potentials (ERPs).
RESULTS
The analysis revealed that S2 elicited a significant N270 in the prefrontal scalp area under both the "Like" and "Dislike" conditions. Interestingly, the amplitude of the N270 was significantly higher during the "Dislike" condition compared to the "Like" condition.
DISCUSSION
The N270 component was shown to reflect the conflict in physical attributes between S1 and S2, as well as the conflict between commodity and color. This highlights the potential utility of this component as an objective EEG indicator of consumer commodity color preferences in future marketing research.
PubMed: 38911956
DOI: 10.3389/fpsyg.2024.1350358 -
Frontiers in Psychology 2024To examine the scope of existing literature on the conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities.
INTRODUCTION
To examine the scope of existing literature on the conceptualization, use, and outcomes associated with compassion in the care of youth with childhood-onset disabilities.
METHODS
A protocol was developed based on the Joanna Briggs Institute (JBI) scoping review method. MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and EBSCOhost CINAHL, were searched.
RESULTS
Eight studies were selected for inclusion; four used quantitative methodology, and four used qualitative methods. Compassion was not defined or in any of the included studies. The concept of self-compassion was explicitly defined only for parents of youth with childhood-onset disabilities in three studies . The most reported outcome measure was self-compassion in parents of youth with childhood-onset disabilities. Self-compassion among parents was associated with greater quality of life and resiliency and lower stress, depression, shame and guilt.
DISCUSSION
There is limited evidence on the conceptualization, use, and outcomes associated with compassion among youth with childhood-onset disabilities. Self-compassion may be an effective internal coping process among parents of youth with childhood-onset disabilities. Further research is required to understand the meaning of compassion to youth with childhood-onset disabilities, their parents and caregivers.
SYSTEMATIC REVIEW REGISTRATION
https://doi.org/10.17605/OSF.IO/2GRB4.
PubMed: 38911955
DOI: 10.3389/fpsyg.2024.1365205 -
Frontiers in Psychiatry 2024Although some adults with autism spectrum disorder (ASD) require intensive and specialized ASD treatment, there is little research on how these adults experience the...
INTRODUCTION
Although some adults with autism spectrum disorder (ASD) require intensive and specialized ASD treatment, there is little research on how these adults experience the recovery process. Recovery is defined as the significant improvement in general functioning compared to the situation prior to treatment.
METHODS
This qualitative study describes the recovery process from the perspective of adults on the autism spectrum during intensive inpatient treatment. Semi-structured interviews (n = 15) were carried out and analyzed according to the principles of grounded theory.
RESULTS
Our results indicate that, given the specific characteristics of autism, therapeutic interventions and goal-oriented work cannot be carried out successfully, and the recovery process cannot begin, if no good working relationship has been established, and if care is not organized in ways that a person on the autism spectrum finds clear and predictable.
PubMed: 38911701
DOI: 10.3389/fpsyt.2024.1383138 -
International Journal of Nanomedicine 2024Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a...
BACKGROUND
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR TItpr3/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.
METHODS
Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.
RESULTS
Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX and SOX2/GFAP cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.
CONCLUSION
In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.
Topics: Animals; Mice, Inbred C57BL; Mice; Fullerenes; Autism Spectrum Disorder; Cognitive Dysfunction; Disease Models, Animal; Male; Doublecortin Protein; Social Behavior; Behavior, Animal; Hippocampus; Vascular Endothelial Growth Factor A; Neuroprotective Agents; Neurogenesis; Autistic Disorder
PubMed: 38911505
DOI: 10.2147/IJN.S459511 -
Cureus May 2024YouTube serves as a good source of information on autism; however, the reliability and quality of such content remain uncertain. This study aimed to evaluate the...
YouTube serves as a good source of information on autism; however, the reliability and quality of such content remain uncertain. This study aimed to evaluate the reliability and quality of autism-related information presented in YouTube videos using the Global Quality Score (GQS) and Reliability Score. Methods: A cross-sectional observational study was conducted in November 2023. A total of 48 autism-related videos on YouTube were sourced using keywords such as 'autism', 'autism cause', 'autism treatment', and 'autism kids'. The authors then viewed the videos and collected data regarding the number of views, likes and comments, uploader type, and type of information disseminated. The authors also used The GQS and modified DISCERN score to assess the quality and reliability of information in the videos. The data was then subjected to statistical analysis using the Kruskal-Wallis test and IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). Results: Out of 48 videos, seven videos were excluded, leaving 41 for analysis. The included videos amassed 25,540,635 views, 304,557 likes, and 37,039 comments. The majority of videos were uploaded by hospitals (n=15; 36.59%), followed by news channels (n=12; 29.27%). Most videos described autism symptoms (n=26; 63.41%), with fewer addressing potential etiology (n=16; 39.02%). The median GQS was highest for videos uploaded by healthcare professionals (n=5), contrasting with news channels. The Kruskal-Wallis test revealed significant differences (p=0.02). Conclusion: These videos collectively garnered substantial viewership, likes, and comments. Most videos described autism symptoms, although fewer addressed potential causes. Notably, videos uploaded by healthcare professionals achieved the highest GQSs, highlighting their significance in disseminating reliable autism information. Healthcare professionals therefore play a crucial role in disseminating reliable autism information via YouTube. Encouraging their involvement in creating informative videos can enhance public understanding of autism.
PubMed: 38910775
DOI: 10.7759/cureus.60904