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一个新的脑部影像研究显示，自闭症系列障碍(autism spectrum disorder，ASD)的小孩在听觉传导上会有数秒的延迟，但这可能是影响此类病患语言发展的核心。
前述研究发表于北美放射医学会第94届科学研讨会暨年会中，使用脑磁图仪(MEG)的影像研究结果显示，ASD小孩处理母音声调比健康小孩慢了几秒。
主要研究者、宾州儿童医院的Timothy Roberts博士向Medscape Psychiatry表示，藉由MEG，我们观察发现，相较于年龄相仿的同侪，自闭症小孩对于一些简单声音的处理会有些微明显的延迟；不过，这只是几秒之差，但是对于语言会有严重的影响。
【与言谈理解有关】
他表示，这个延迟反应大约是1/50秒、或称20毫秒，表面上看来只是个小小的延迟，不过，Roberts博士指出，说话时的音节只持续约四分之一秒、或者250毫秒；他解释，20毫秒的延迟对于了解多音节字汇时会引起相当大的延迟与负担，所以，自闭症患者比较难跟得上。
MEG一般用来手术前辨识癫痫等病患等的脑部神经活性功能区域；不过，Roberts博士表示，研究者指出，此技术具有提供脑部功能之即时讯息的潜力。
他表示，此观察以及少数理论派文献认为，自闭症可能不会有明显的架构支持，但事实上可能是脑部功能区域的异常连结，因而促成本研究。
他表示，这引起我检测连接性的一个方法，或者说至少是一种可能的连结失能，将着眼于有关听觉刺激之神经细胞反应的异常时机。
根据Roberts博士表示，MEG可以撷取脑中的磁性区域，使得可以侦测时间上微妙的延迟，这是其他主要撷取构造性脑部异常的技术，如电脑断层、核磁共振造影(MRI)或者功能性MRI所无法做到的。
【处理延迟越长 语言缺损越严重】
本研究包括64名年纪在6至15岁的研究对象，其中30名有ASD诊断，合并或未合并语言缺损，其他34名小孩是年龄相仿的健康对照组；所有的小孩都接受MEG研究，在一连串的单一音节声调中检视他们的听觉刺激。
Roberts博士表示，我们发现自闭症小孩的听觉处理有相当程度的延迟，我们无法预期在听觉处理上这么早发现问题，实际上是延迟约十分之一秒听到那个声音，但是这一旦发生，就是问题。
他指出，这表示有某种的感觉处理问题，和自闭症所见的行为及传言的观点不一样，但这令我惊讶的是，我们可以用相对简单的听觉皮质与听觉处理报告解释这许多的语言缺损。
此外，研究者发现，延迟的程度与语言缺损程度有关，所以处理延迟越久的小孩，语言缺损越严重。
【阐明ASD异质性】
Roberts博士表示，这些发现的价值在于有潜力促进早期诊断与更精确的治疗，有助于解开ASD的一些异质性特征。
我们寻找的或许是个生物标记，可以用来建立自闭症的次类别；每个小孩的延迟程度多少不太一样，这表示可能需要不同的行为介入。
他表示，举例来说，ASD特定次类别中，严重听觉处理延迟的小孩，其治疗介入可能要更注重在语言治疗，而不同于其他延迟较不严重的ASD次类别。
目前的自闭症诊断有赖行为与临床评估，Roberts博士形容为旷时且往往是不确定结果的一些过程，特别是在幼童，语言发展和社会互动技巧上有相当大的变数。
他指出，虽然MEG不太可能取代临床评估，它最后可能是个可以帮助医师确认或驳斥ASD诊断的工具。
Roberts博士表示，在历史上，进行自闭症小孩的研究是困难的，主要是因为他们通常抗拒进行行为测试。
这类病患使用MEG的一个主要好处是，实际上并不需要病童的合作。他表示，这些是脑部对于特定刺激的自动反应，所以我们不用问小孩的反应，我们问的是他们的脑部。
虽然这些结果需要由其他研究者确认，但Roberts博士对于MEG最后将成为ASD或者其他疾病如注意力缺损过动异常之可行的诊断工具感到乐观。
作者报告没有相关利益冲突。本研究由国家健康研究中心、Nancy Lurie Marks Family基金会、与Jeffrey and Christina Lurie Family基金会等支持。
RSNA 2008: 北美放射医学会第94届科学研讨会暨年会：摘要VP11-03。发表于2008年12月1日。
Imaging Study Reveals Explanation for Language Delays in Autism
By Caroline Cassels
Medscape Medical News
A new brain imaging study shows children with autism spectrum disorder (ASD) have a very small delay in auditory processing that amounts to fractions of a second but that may be at the heart of the hampered language development that is a common characteristic in this patient population.
Presented here at the 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America, results of an imaging study using magnetoencephalography (MEG) show that children with ASD process vowel sounds and tones a fraction of a second more slowly than healthy controls.
"Using MEG, we observed that there is a small but robust delay in the evoked response to simple sound processing in children with autism, compared with their age-matched peers. Although we are only talking about fractions of a second, these can have a catastrophic impact on spoken language," principal investigator Timothy Roberts, PhD, from Children's Hospital of Philadelphia, in Pennsylvania, told Medscape Psychiatry.
Playing Catch-Up
This delayed response, he said, is approximately 1/50th of a second, or 20 ms. On the surface this small delay may seem of little consequence. However, Dr. Roberts noted that a spoken syllable only lasts a quarter of a second, or 250 ms. A 20-ms delay in detecting a syllable in a multisyllable word, he explained, leads to a "cascade of delay" and overload so that, in effect, an individual with autism is never able to catch up.
MEG is routinely used for presurgical mapping to identify areas of functional brain activity in patients with neurological conditions such as epilepsy. However, said Dr. Roberts, the investigators noticed the technology had the potential to offer insights into the timing of brain function.
This observation, he said, coupled with an awareness of a small body of theoretical literature indicating that autism may not have obvious structural underpinnings but may in fact be consequent to abnormal connectivity of brain functional areas led to the current study.
"It occurred to me that 1 way of testing connectivity, or at least a possible dysfunction of connectivity, would to look at the abnormal timing of neuro–nerve cell activity in response to stimuli," he said.
According to Dr. Roberts, the ability of MEG to pick up magnetic fields in the brain makes it ideally suited to detect subtle delays in timing that would not be visible with other technologies, including computed tomography, magnetic resonance imaging (MRI), or functional MRI, which primarily pick up structural brain abnormalities.
Longer Processing Delays, More Severe Language Impairment
The study included 64 subjects aged 6 to 15 years. Of these, 30 had a diagnosis of ASD, with or without concomitant language impairment. The remaining 34 children were healthy, age-matched controls.
All children underwent MEG studies in which they were presented with auditory stimuli in the form of single vowel sounds or tones in rapid succession.
"We found a very robust delay in auditory processing right across the board in children with autism. We didn't expect to see a problem so early in the auditory process, literally a tenth of a second after hearing a sound, and yet that is when it showed up," said Dr. Roberts.
"This suggests there is some sort of sensory processing problem, which is not inconsistent with behavioral and anecdotal views on autism, but I think it is surprising we can account for such a lot of the language impairment with relatively straightforward auditory cortex and auditory processing observations," he added.
In addition, the researchers found the degree of delay was well correlated with the degree of language impairment, so that children with longer processing delays had more severe language impairment.
Unraveling ASD Heterogeneity
The value of these findings, said Dr. Roberts, lies in their potential to facilitate earlier diagnosis and more targeted treatment and to help unravel some of the heterogeneity that characterizes ASD.
"What we are seeing here perhaps is a biomarker that might be used to create subpopulations of autism. Some children may display more or less of these delays, which might warrant different behavioral interventions."
For instance, he said, a child in a particular subpopulation of ASD with severe auditory processing delays may have a treatment intervention that has a greater focus on speech therapy vs a child in another ASD subpopulation with less severe auditory processing difficulties.
Current diagnosis of autism relies on behavioral and clinical assessment, which Dr. Roberts described as a time-consuming and frequently uncertain process, particularly in very young children, where there can be significant variability in the development of language and social skills.
While MEG is unlikely to replace clinical evaluation, it could turn out to be a valuable tool that would help clinicians confirm or refute a diagnosis of ASD, he added.
Historically, said Dr. Roberts, conducting outcomes research in children with autism has been difficult, mainly because they are often resistant to performing behavioral tests.
One of the major advantages of using MEG in this patient group is the fact that it does not require the cooperation of the child. "These are automatic responses of the brain to particular stimuli, so we don't ask the child to respond, we ask the child's brain," he said.
While these results need to be confirmed by other investigators, Dr. Roberts is optimistic MEG will eventually turn out to be a viable diagnostic tool for ASD and possibly other conditions, including attention deficit hyperactivity disorder.
The authors report no relevant conflicts of interest. The study was supported by the National Institutes of Health, the Nancy Lurie Marks Family Foundation, and the Jeffrey and Christina Lurie Family Foundation.
RSNA 2008: 94th Scientific Assembly and Annual Meeting of the Radiological Society of North America: Abstract VP11-03. Presented December 1, 2008.