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...

Response inhibition, or the suppression of prepotent but contextually inappropriate behaviors, is essential to adaptive, flexible responding. Individuals with autism spectrum disorders (ASD) consistently show deficient response inhibition during antisaccades. In our prior functional MRI study, impaired antisaccade performance was accompanied by reduced functional connectivity between the frontal eye field (FEF) and dorsal anterior cingulate cortex (dACC), regions critical to volitional ocular motor control. Here we employed magnetoencephalography (MEG) to examine the spectral characteristics of this reduced connectivity. We focused on coherence between FEF and dACC during the preparatory period of antisaccade and prosaccade trials, which occurs after the presentation of the task cue and before the imperative stimulus. We found significant group differences in alpha band mediated coherence. Specifically, neurotypical participants showed significant alpha band coherence between the right inferior FEF and right dACC and between the left superior FEF and bilateral dACC across antisaccade, prosaccade, and fixation conditions. Relative to the neurotypical group, ASD participants showed reduced coherence between these regions in all three conditions. Moreover, while neurotypical participants showed increased coherence between the right inferior FEF and the right dACC in preparation for an antisaccade compared to a prosaccade or fixation, ASD participants failed to show a similar increase in preparation for the more demanding antisaccade. These findings demonstrate reduced long-range functional connectivity in ASD, specifically in the alpha band. The failure in the ASD group to increase alpha band coherence with increasing task demand may reflect deficient top-down recruitment of additional neural resources in preparation to perform a difficult task.

BackgroundThe neurometabolic profile of associated with autism spectrum disorder (ASD) has been reported to be abnormal by some studies showing region specific metabolite levels in ASD, while others report no group differences. The neurometabolic profile of the left dorsolateral prefrontal cortex (DLPFC) is of particular interest due to the DLPFC relevance to cognitive and executive function, and to ASD.MethodWe used 1H-MRS to investigate neurometabolic profiles in the DLPFC of ASD and sex/IQ-matched typically developing (TD) children (ages 9-13). We focused on levels of Glutamate and Glutamine (Glx) due to many reported Glx abnormalities ASD, and of Choline (Cho) because of its relationship to intelligence quotient (IQ) and to attentional re-orienting difficulties.ResultsWhile no significant group differences were observed in absolute concentrations, metabolite levels were correlated with the behavioral phenotype of ASD children. In the ASD group but not the TD group, nonverbal IQ (NVIQ) was negatively associated with Cho (r=-0.59, p=0.026) and positively associated with Glx/Cr (r=0.66, p=0.011). Furthermore, attentional-switching scores in the ASD group correlated negatively with Cho (r=-0.69, p=0.009), and positively with Glx/Cr for both the ASD (r=0.73, p=0.004) and TD (r=0.54, p=0.040) groups.ConclusionsCho and Glx/Cr have different neurometabolic roles in modulating NVIQ in ASD compared to TD children, while their role in attentional switching seems preserved in ASD. Elucidating the apparently divergent role of neurometabolites in ASD in the absence of significant group differences in absolute levels is an important step towards understanding and mapping the neural correlates of ASD. These results are also relevant in the context of the significant cognitive function heterogeneity associated with the ASD phenotype, as they suggest possible underlying neural mechanisms that do not overlap which those expected from typical development.