Local Functional Connectivity in ASD Is Reduced, Not Increased

Background: The hypothesis that long-range functional connectivity (FC) is reduced in ASD while local FC is increased is widely accepted. While a large body of evidence supports the hypothesis of reduced long-range FC in ASD, there is no neurophysiological evidence in support of increased local FC in ASD. The nature of local neurophysiological interactions in ASD thus remains an important open question.

Objectives: A relatively new finding about neuronal oscillations is that different frequencies in the brain are often coupled locally, where “local” refers to a functionally defined brain region. This cross-frequency coupling (CFC) reflects local FC as mediated by neural entrainment across different frequency bands, and has been shown to play an important functional role in cognitive cortical processes. Our objective was to measure CFC in the cortex in order to determine whether local FC as mediated by CFC is normal, reduced, or increased in ASD. We hypothesized that CFC would be decreased in ASD individuals relative to typically developing (TD) individuals. 

Methods: We tested our hypothesis using magnetoencephalography (MEG), a non-invasive method that combines millisecond time resolution with good spatial resolution. We focused on face processing, a paradigm that taps into the core social deficits of ASD, and in which abnormalities in long-range FC in ASD are well documented. We recorded MEG data from 17 male participants ages 14-20 with ASD, and 20 TD participants matched by age, IQ, gender, and handedness, while they viewed houses and neutral, fearful, and angry faces. We mapped the MEG data onto the cortex, identified the fusiform face area (FFA) for each participant, and computed the individual levels of CFC inside the FFA for each condition. 

Results: During viewing of houses, both groups showed similar levels of CFC between alpha phase and low-gamma amplitude. During viewing of faces, alpha phase to low-gamma CFC increased in the TD group, and strong CFC between alpha phase and high gamma amplitude also emerged. In the ASD group, CFC during viewing of faces was identical to CFC during viewing of houses; i.e., no increase in CFC was observed. Furthermore, we found that local CFC measures were correlated with long-range FC measures of coherence between the FFA and three contralateral cortical regions. Finally, we found that these neurophysiological measures were predictive of whether a participant belonged to the ASD group and of ASD severity.  

Conclusions: This is the first direct neurophysiological study of local FC in ASD. Failure to increase CFC in the ASD group during a task that elicited a large increase in CFC in the TD group meant that local FC in the ASD group was reduced relative to the TD group. This is also the first study to find a link between local and long-range FC measures. This means that the two processes are dependent on one another, and studying them in unison is crucial in order to understand the neural substrates of ASD. Finally, the correlation of these neurophysiological measures with ASD diagnosis and severity makes them potential biomarkers for ASD.