Using MEG to Measure Rhythm Specific Functional Connectivity in ASD

Background:

Since about 2004, findings of functional connectivity (FC) abnormalities have motivated an important line of research on the neurophysiological etiology of autism spectrum disorder (ASD). These findings led to the framing of ASD as a disorder of brain connectivity, with the most common hypothesis being that long-range FC is abnormally reduced in the brain in ASD, and local FC is abnormally increased. While appealing in its simplicity, this idea has been repeatedly challenged over the past few years by inconsistent and conflicting findings. In parallel, the importance of the cortical rhythms has become central in the study of both normal and abnormal brain function. However, despite many studies in Autism Spectrum Disorders (ASD), there remains a gap in our understanding of how the 5 intrinsic neuronal rhythms delta, theta, alpha, beta and gamma contribute to cortical function abnormalities in ASD in general, and across different spatial scales of functional connectivity more specifically.

Objectives:

To test rhythm specific functional connectivity abnormalities in ASD, both locally, and across distant cortical regions (long-range), from childhood through adolescence.

Methods:

We used source localized magnetoencephalography, which has millisecond temporal resolution and good spatial resolution, to probe frequency-band specific functional connectivity differences in ASD across a range of paradigms, spatial scales, and measures. We examined the results in a wide age range (7-18); sample sizes varied by paradigm, and ranged from about 15 to 40 per group.

Results:

Results from multiple paradigms converged towards normal or reduced local functional connectivity in ASD, alongside increased functional connectivity in the bottom-up direction and reduced functional connectivity in the top-down direction. More specifically, results from a somatosensory based paradigm indicated increased long-range functional connectivity in ASD in the bottom-up direction alongside reduced local functional connectivity. Results from visual somatosensory paradigms indicated reduced local and top-down long-range functional connectivity. Results from resting state were consistent with reduced long-range functional connectivity in the top-down direction, manifesting in the beta (13-30Hz) frequency band, and increased long-range functional connectivity in the bottom-up direction, manifesting in the gamma (30-80Hz) frequency band. In parallel, we also found that the results were dependent on the age of the participants, which shifts occurring over adolescence.

Conclusions:

The pattern of functional connectivity abnormalities in ASD is extremely complex, and cannot be reduced to general hypotheses. Spatial scale (local versus long-range) is a critical variable when considering these abnormalities, but even when narrowing down spatial scale, factors such as the specific frequency band, age of the participants, directionality, and the paradigms used, need to be considered carefully.