Schiefelbusch Institute for Life Span Studies and Clinical Child Psychology Program, University of Kansas, Lawrence, Kansas.
Kansas Center for Autism Research and Training, University of Kansas Medical School, Kansas City, Kansas.
J Neurophysiol. 2019 Oct 1;122(4):1330-1341. doi: 10.1152/jn.00286.2019. Epub 2019 Jul 17.
In addition to core deficits in social-communication abilities and repetitive behaviors and interests, many patients with autism spectrum disorder (ASD) experience developmental comorbidities, including sensorimotor issues. Sensorimotor issues are common in ASD and associated with more severe clinical symptoms. Importantly, sensorimotor behaviors are precisely quantifiable and highly translational, offering promising targets for neurophysiological studies of ASD. We used functional MRI to identify brain regions associated with sensorimotor behavior using a visually guided precision gripping task in individuals with ASD ( = 20) and age-, IQ-, and handedness-matched controls ( = 18). During visuomotor behavior, individuals with ASD showed greater force variability than controls. The blood oxygen level-dependent signal for multiple cortical and subcortical regions was associated with force variability, including motor and premotor cortex, posterior parietal cortex, extrastriate cortex, putamen, and cerebellum. Activation in the right premotor cortex scaled with sensorimotor variability in controls but not in ASD. Individuals with ASD showed greater activation than controls in left putamen and left cerebellar lobule VIIb, and activation in these regions was associated with more severe clinically rated symptoms of ASD. Together, these results suggest that greater sensorimotor variability in ASD is associated with altered cortical-striatal processes supporting action selection and cortical-cerebellar circuits involved in feedback-guided reactive adjustments of motor output. Our findings also indicate that atypical organization of visuomotor cortical circuits may result in heightened reliance on subcortical circuits typically dedicated to motor skill acquisition. Overall, these results provide new evidence that sensorimotor alterations in ASD involve aberrant cortical and subcortical organization that may contribute to key clinical issues in patients. This is the first known study to examine functional brain activation during precision visuomotor behavior in autism spectrum disorder (ASD). We replicate previous findings of elevated force variability in ASD and find these deficits are associated with atypical function of ventral premotor cortex, putamen, and posterolateral cerebellum, indicating cortical-striatal processes supporting action selection and cortical-cerebellar circuits involved in feedback-guided reactive adjustments of motor output may be key targets for understanding the neurobiology of ASD.
除了社交沟通能力和重复行为和兴趣的核心缺陷外,许多自闭症谱系障碍(ASD)患者还存在发育共病,包括感觉运动问题。感觉运动问题在 ASD 中很常见,并与更严重的临床症状相关。重要的是,感觉运动行为可以精确量化,并且具有高度的可转换性,为 ASD 的神经生理学研究提供了有前途的目标。我们使用功能磁共振成像(fMRI),通过对 ASD 患者(n=20)和年龄、智商和惯用手匹配的对照组(n=18)进行视觉引导的精确抓握任务,来识别与感觉运动行为相关的大脑区域。在视觉运动行为中,ASD 患者的力变异性大于对照组。多个皮质和皮质下区域的血氧水平依赖信号与力变异性相关,包括运动和前运动皮质、后顶叶皮质、外纹状体、壳核和小脑。右侧前运动皮质的激活与对照组的感觉运动变异性成正比,但与 ASD 患者不成正比。与对照组相比,ASD 患者的左壳核和左小脑小叶 VIIb 区的激活程度更高,这些区域的激活与 ASD 的临床症状更严重有关。总的来说,这些结果表明,ASD 患者的感觉运动变异性较大与支持动作选择的皮质-纹状体过程以及涉及运动输出反馈引导反应性调整的皮质-小脑回路的改变有关。我们的研究结果还表明,视觉运动皮质回路的异常组织可能导致对通常专门用于运动技能获得的皮质下回路的过度依赖。总体而言,这些结果提供了新的证据,表明 ASD 中的感觉运动改变涉及异常的皮质和皮质下组织,这可能是患者关键临床问题的原因。这是第一项研究自闭症谱系障碍(ASD)患者在精确视觉运动行为中的功能大脑激活。我们复制了 ASD 中力变异性升高的先前发现,并发现这些缺陷与腹侧前运动皮质、壳核和后外侧小脑的异常功能有关,表明支持动作选择的皮质-纹状体过程和涉及运动输出反馈引导反应性调整的皮质-小脑回路可能是理解 ASD 神经生物学的关键目标。