Local and long-range functional connectivity is reduced in concert in autism spectrum disorders

Abstract

Long-range cortical functional connectivity is often reduced in autism spectrum disorders (ASD), but the nature of local cortical functional connectivity in ASD has remained elusive. We used magnetoencephalography to measure task-related local functional connectivity, as manifested by coupling between the phase of alpha oscillations and the amplitude of gamma oscillations, in the fusiform face area (FFA) of individuals diagnosed with ASD and typically developing individuals while they viewed neutral faces, emotional faces, and houses. We also measured task-related long-range functional connectivity between the FFA and the rest of the cortex during the same paradigm. In agreement with earlier studies, long-range functional connectivity between the FFA and three distant cortical regions was reduced in the ASD group. However, contrary to the prevailing hypothesis in the field, we found that local functional connectivity within the FFA was also reduced in individuals with ASD when viewing faces. Furthermore, the strength of long-range functional connectivity was directly correlated to the strength of local functional connectivity in both groups; thus, long-range and local connectivity were reduced proportionally in the ASD group. Finally, the magnitude of local functional connectivity correlated with ASD severity, and statistical classification using local and long-range functional connectivity data identified ASD diagnosis with 90% accuracy. These results suggest that failure to entrain neuronal assemblies fully both within and across cortical regions may be characteristic of ASD.

Fig. 1.

Evoked responses in the FFA. (A) Functionally determined seed FFA (yellow) in an individual subject. The FreeSurfer fusiform gyrus anatomical label is shaded in purple. (B) Evoked responses to neutral faces and to houses in the FFA. (C) Evoked responses to fearful and angry faces in the FFA. Shaded areas in B and C delineate the standard error (SE).

Fig. 2.

Coherence for emotional faces normalized by coherence for houses (Z-Coherence), between the FFA and the rest of the cortex for the TD group (Upper) and ASD group (Lower). The Z-Coherence values shown are masked by the three clusters that showed statistically significant differences (P < 0.05 corrected) between the groups (i.e., all values not within these clusters were set to 0). The significant clusters overlap with precuneus (A), ACC (B), and IFG (C) anatomical labels from FreeSurfer (purple shading). For each cluster, the maps are shown at the time of maximal group difference.

Fig. 3.

PAC in the FFA. (A) PAC in each condition for each group. (B) PAC for emotional faces normalized by PAC for houses (Z-PAC) for the TD group (Upper) and ASD group (Lower). Dotted lines indicate significant group differences in Z-PAC. (C) Z-PAC as in B but between alpha and high gamma only, computed over the entire cortex, for each group. The functionally determined FFA is outlined in bold.

Fig. 4.

Mean Z-Coherence value (Fig. 2) between the FFA and the precuneus (A), the ACC (B), and the IFG (C) plotted against the Z-PAC value in the FFA (Fig. 3B; alpha phase to high gamma amplitude). The shaded area delineates the SE, and the dashed lines encompass 99% of the confidence interval for correlation. Boxes mark the two participants shown in Fig. S1A.

Fig. 5.

Correlations between behavioral and neurophysiological data. (A) Individual Z-PAC scores are correlated with the social component of the ADOS score. The black box indicates the participant with ASD shown in Fig. S1A. The shaded area delineates the SE, and the dashed lines encompass 99% of the confidence interval of correlation. (B) Five-dimensional visualization of QDA analysis using the full dataset: the three Z-Coherence values for the precuneus, ACC, and IFG (the three axes); the Z-PAC (size of marker); and the probability of a participant having a diagnosis of ASD (color of the marker). Plain circles represent the participants with ASD, and crossed circles represent the TD participants.