MEG Detects Abnormal Cerebro-Cerebellar Functional Connectivity During Processing of Spoken Sentences in Autism Spectrum Disorder
Key findings
- This study investigated how cerebellar activity and cerebro–cerebellar functional connectivity during the processing of spoken sentences are affected by the presence versus absence of lexical–semantic information in autism spectrum disorder (ASD)
- MEG data were collected from 25 children and adolescents diagnosed with ASD, 7 to 17 years old, and 26 age-matched typically developing children during passive processing of meaningful versus meaningless spoken sentences
- For cortical areas considered lower in the cortical hierarchy and where connectivity from the cerebellum peaked earlier, differences between the two groups were driven by directional connectivity from the cerebellum to cortex
- Later connectivity between right lobule VI and left frontal and temporal regions was more reciprocal in nature
- Importantly, the functional connectivity measures showing significant group differences correlated with behavioral measures of ASD severity and the ability to inhibit involuntary attention
Many children with autism spectrum disorder (ASD) have impairments in speech and language, and Massachusetts General Hospital researchers have been investigating the neural mechanisms underlying these problems.
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In 2021, a Mass General team reported in Progress in Neurobiology that children with ASD had weaker responses to meaningful sentences compared with meaningless sentences in the same left temporal and parietal language regions where typically developing children had stronger responses to meaningful sentences. Moreover, the amplitude of the responses was associated with ASD severity.
That study used magnetoencephalography (MEG), which indirectly measures brain waves by measuring magnetic fields produced by electrical activity. With much higher temporal resolution than functional MRI, this technology can detect changes over tens of milliseconds. Due to the limitations of MEG at the time, though, the Mass General study was restricted to cortical language regions.
Thanks to advances in MEG, the team now has been able to investigate the interactions between the cerebellum and the cortex using the same protocol as in the earlier research. In addition to its well-established role in motor control, the cerebellum has been demonstrated to be central to cognitive function, including language processing.
Jussi Alho, PhD, and Tal Kenet, PhD, researchers in the Department of Neurology and the Martinos Center for Biomedical Imaging, and colleagues detected significant differences in cerebro–cerebellar functional connectivity during speech processing in children with ASD compared with typically developing children. They detail the findings and their implications in Human Brain Mapping.
Methods
The researchers obtained MEG data from 25 children with ASD and 26 typically developing children, 7 to 17 years old. The stimuli were spoken meaningful sentences ("Two blue fish swam in a tank" and "The tiny girl took off her hat"), and matched meaningless "Jabberwocky" sentences where words were replaced by pseudowords.
The participants watched a movie with the sound off while the sentences were presented randomly via earphones. Amplitude-modulated noise was used as a control stimulus.
Principal Results
The key findings were:
- Evoked responses of typically developing children showed selectivity to meaningful versus meaningless sentences in right cerebellar lobule VI, but there was no such differentiation in children with ASD.
- In the time window of 600–1400 ms, there was atypically weak functional connectivity in children with ASD for meaningful versus meaningless sentences between right lobule VI and extensive left-hemisphere sensorimotor and language regions.
- Between 600 and 1150 ms the differences between groups were driven primarily by directional connectivity from right lobule VI to left supramarginal gyrus and primary motor cortex, while later connectivity with left frontal and temporal regions aligned with a bidirectional pattern of reduced connectivity.
- For left primary auditory cortex in an earlier time window (50–300 ms), group differences were reversed in direction: there was increased functional connectivity in children with ASD in response to meaningful versus meaningless sentences, and these differences were driven by directional connectivity from right lobule VI to left primary auditory cortex.
- As in the earlier work, the functional connectivity measures showing significant group differences correlated with behavioral measures of ASD severity and the ability to inhibit involuntary attention.
Conclusions
Corroborating the earlier work, these findings imply aberrant attentional orienting in ASD. In addition, considering that all the implicated regions are associated with motor (or sensorimotor) processing, a link can be drawn between the attention and motor systems in auditory speech perception.
The directionality of the atypical cerebro–cerebellar connectivity, from the cerebellum to cortex, suggests the dysfunction in language processing in ASD has a cerebellar origin. That insight may aid in the development of ASD therapies.
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