关键词: 孤独症, 小脑, 结构功能, 模式动物

Abstract:

Despite occupying only 10% of the total volume of the human brain, the cerebellum contains over half of its neurons. Traditionally viewed as primarily responsible for coordinating motor movements, recent research has shown that the cerebellum is also closely associated with higher cognitive functions such as learning, attention, memory, and language, and participates in regulating various non-motor functions. Concurrently, abnormal cerebellar development has been closely linked to several neurodevelopmental disorders, including Autism Spectrum Disorder (ASD), characterized by social impairments, repetitive behaviors, and language deficits, often accompanied by sensory abnormalities. Clinical studies have found structural and functional alterations in the cerebellum of individuals with autism. For example, studies show that individuals with autism have reduced cerebellar volume, particularly in certain regions of the cerebellar hemispheres. Additionally, functional magnetic resonance imaging (fMRI) studies have found abnormal activity patterns in the cerebellum of autism patients when processing social information and performing executive function tasks. Interestingly, similar cerebellar phenotypes, such as cerebellar neuron dysplasia and dysfunction, have been observed in animal models of autism spectrum disorders. Importantly, specific knockout of autism susceptibility genes in cerebellar neurons can induce typical autism-like behaviors in model animals, suggesting that abnormal cerebellar development is a key pathological mechanism underlying autism spectrum disorders. This article will briefly summarize the relationship between the cerebellum and Autism Spectrum Disorder from both clinical and basic research perspectives, providing new insights for the diagnosis and treatment of autism.

Currently, research and clinical trials targeting the cerebellum as a treatment focus for ASD are gradually progressing. Early studies suggest that improving cerebellar function and structure can significantly enhance social and cognitive functions in ASD patients. For example, some studies have improved cerebellar structure and function through behavioral interventions and physical training, thereby enhancing social skills and cognitive abilities in ASD patients. Neuroregulation and pharmacological interventions are believed to potentially improve ASD symptoms by modulating the activity of cerebellar neural circuits. Techniques such as neurofeedback, deep brain stimulation, and neural circuit modulation have shown some effectiveness in certain ASD patients. These techniques intervene in cerebellar regions through electrical stimulation or neuroregulatory devices to improve the functionality and integration of neural circuits, thus alleviating core symptoms of ASD.

In the future, personalized treatment strategies based on the cerebellum will be at the forefront of ASD treatment. As our understanding of cerebellar neural circuits and functions deepens, future research will focus on developing more personalized and precise treatment approaches. By integrating genomics and brain imaging technologies, specific subtypes of cerebellar abnormalities in ASD patients can be accurately identified, allowing for the selection of the most effective treatment methods. For example, analyzing genetic variations in autism patients through genomics can provide a basis for individualized treatment. Collaborative interdisciplinary research teams will drive a comprehensive analysis of the relationship between the cerebellum and ASD, combining neuroscience, genetics, psychology, and clinical medicine to offer new perspectives and treatment pathways for understanding the complex neurodevelopmental mechanisms of ASD.

However, targeting the cerebellum for ASD treatment has certain limitations. Firstly, ASD-related neurodevelopmental abnormalities involve complex interactions between multiple brain regions, so relying solely on cerebellar treatment may not fully address the etiology and symptoms. For example, autism may involve abnormalities in both the cerebral cortex and the cerebellum, suggesting that a comprehensive treatment approach might be more effective. Secondly, individual differences and heterogeneity among ASD patients mean that treatment effects targeting the cerebellum may vary, and the long-term efficacy and safety of current treatment strategies still need to be validated. Future research should continue to explore multi-faceted treatment strategies, including personalized and comprehensive interventions considering multiple brain regions, to enhance treatment outcomes and quality of life. These studies will help develop more comprehensive and effective treatment plans, providing better prognosis and quality of life for ASD patients.

Key words: Autism spectrum disorder, cerebellum, structural and functional, model animals