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.coherence | parvalbumin O scillations in the brain underlie many key cortical functions and coordinate activity between distant brain areas. These rhythmic oscillations are typically studied in distinct frequency bands, often segregated as delta (1-2 Hz), theta (3-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), low gamma (30-60 Hz), and high gamma (>60 Hz). Each frequency band has been associated with specific cognitive and synaptic processes, with some overlaps among bands (1). Substantial evidence indicates that abnormalities in long-range interregional functional connectivity, usually mediated by theta and alpha oscillations, are common in neurodevelopmental disorders (2), including autism spectrum disorders (ASD) (3).The nature of functional connectivity in ASD has been under intense investigation since the publication of a 2004 report showing reduced long-range functional connectivity in ASD (4). The prevailing hypothesis in the field is that ASD is characterized by reduced long-range functional connectivity and increased local functional connectivity (5-7). The hypothesis that local functional connectivity is increased in ASD is motivated primarily by genetic and histological evidence of reduced neuronal inhibition in ASD (8-10). Although a large body of functional evidence supports the hypothesis of generally reduced long-range functional connectivity in ASD (11), neurophysiological signatures of local functional connectivity in ASD have r...

Perceptual Integration Deficits in Autism Spectrum Disorders Are Associated with Reduced Interhemispheric Gamma-Band Coherence

“…Brock et al (2002) suggested that WCC-associated perceptual integration deficits reflect reduced synchronization of gammaband activity between local networks. Our results strongly support this hypothesis (also see evidence on reduced interhemispheric M/EEG coherence in frequencies Ͻ13 Hz) (Isler et al, 2010;Catarino et al, 2013;Khan et al, 2013;Carson et al, 2014). Yet, in relation to WCC, it has also been suggested that local synchronization within networks is intact or even enhanced (Brock et al, 2002;Belmonte et al, 2004); this could be reflected in higher or no power differences in ASD.…”

“…The pSTS has been considered as an integrative multimodal brain area (Beauchamp et al, 2004;Beauchamp, 2005), bridging across various functions, such as perceptual integration of visual shape and visual motion (Jellema et al, 2004), biological motion (Grossman and Blake, 2002), and social cognition (Yang et al, 2015). Indeed, people with ASD show deficits related to these functions (Koldewyn et al, 2011;Pelphrey et al, 2011;Scheel et al, 2011;Shih et al, 2011), clearly implicating pSTS as a critical area in disturbed brain networks in ASD.…”

“…Indeed, reduced gamma-band activity has been previously associated with perceptual binding deficits in ASD; these studies focused on local synchronization processes and static, illusory stimuli, such as the Kanizsa square and Mooney faces (Sun et al, 2012;e.g., Stroganova et al, 2012). Structural results from diffusion tensor imaging (Travers et al, 2012), as well as functional data from MRI (e.g., Anderson et al, 2011;Dinstein et al, 2011) and M/EEG coherence (e.g., Isler et al, 2010;Khan et al, 2013) also suggest generally compromised anatomical and functional connectivity between distant cortical areas in ASD.…”

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia

“…We determined whether these parameters --SW phase at spindle peak and consistency --differed by group and, to test our main hypothesis, we correlated them with sleep dependent memory consolidation. (C) As a secondary analysis to confirm timing results we used the standard technique, phase amplitude coupling (PAC) [40][41][42] , which uses all spindle time points to identify the SW phase at which sigma amplitude is maximal and tests the significance of this coupling.…”

Inhibition-Based Biomarkers for Autism Spectrum Disorder

“…In another category of network-level inhibition-related findings in ASD, phase amplitude coupling (PAC; in which the phase of a slow oscillation modulates the amplitude of a fast oscillation) measured by MEG in response to faces has been found to be reduced in people with ASD compared with controls; additionally, the degree of reduction in PAC correlated with the social score on the Autism Diagnostic Observation Schedule, offering potential as a stratification or prognostic biomarker [62]. Interestingly, similar reductions in PAC were found in mice in which GABAergic inhibition onto parvalbumin-positive interneurons was removed, suggesting altered inhibition as a potential underlying mechanism for this finding [63].…”