Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder.

Sheraz Khan,Konstantinos P Michmizos,Hari M Bharadwaj,Manfred G Kitzbichler,Keri-Lee A Garel,Manuel Zetino,Matti S Hämäläinen,Fahimeh Mamashli,Tal Kenet,Santosh Ganesan,Javeria A Hashmi

doi:10.3389/fnins.2016.00255

Abstract

Abnormalities in cortical connectivity and evoked responses have been extensively documented in autism spectrum disorder (ASD). However, specific signatures of these cortical abnormalities remain elusive, with data pointing toward abnormal patterns of both increased and reduced response amplitudes and functional connectivity. We have previously proposed, using magnetoencephalography (MEG) data, that apparent inconsistencies in prior studies could be reconciled if functional connectivity in ASD was reduced in the feedback (top-down) direction, but increased in the feedforward (bottom-up) direction. Here, we continue this line of investigation by assessing abnormalities restricted to the onset, feedforward inputs driven, component of the response to vibrotactile stimuli in somatosensory cortex in ASD. Using a novel method that measures the spatio-temporal divergence of cortical activation, we found that relative to typically developing participants, the ASD group was characterized by an increase in the initial onset component of the cortical response, and a faster spread of local activity. Given the early time window, the results could be interpreted as increased thalamocortical feedforward connectivity in ASD, and offer a plausible mechanism for the previously observed increased response variability in ASD, as well as for the commonly observed behaviorally measured tactile processing abnormalities associated with the disorder.

Highlights

Autism spectrum disorder (ASD) is diagnosed by hallmark abnormalities in social behavior, and has a complex genetic basis (Berg and Geschwind, 2012; Skafidas et al, 2014; Pramparo et al, 2015) with no clear disease etiology
When the cortical response was examined over the onset time window in the time-frequency domain, i.e., with spectral specificity rather than averaging over the frequency domain as for the standard evoked response shown in Figure 2A, significant group differences emerged (Figure 2B, p = 0.0470, corrected)
In our prior study using the same paradigm (Khan et al, 2015), we showed that the observed increases in steady state responses in the autism spectrum disorder (ASD) group at 25 Hz in S2, were due to increased feedforward connectivity from S1

Summary

INTRODUCTION

Autism spectrum disorder (ASD) is diagnosed by hallmark abnormalities in social behavior, and has a complex genetic basis (Berg and Geschwind, 2012; Skafidas et al, 2014; Pramparo et al, 2015) with no clear disease etiology. While the response in S1 was significantly increased at onset in the ASD group, it was not possible to determine, based on our prior analysis, whether this increase was generated locally, or via abnormal long-range connectivity, such as reduced feedforward functional connectivity from the thalamus for instance. To test our hypothesis, that the increase in the transient evoked response observed in ASD is due to feedforward inputs from subcortical regions, we applied a novel measure that indicates how activation of a small neural population spreads in adjoining areas to become locally synchronized (Khan et al, 2009) This method, which is referred to as Spatio-Temporal Divergence (S-T Div), uses techniques based on the concept of optical flow, and was recently adapted to map the time-course of spatiotemporal propagation of brain activity across different cortical region (Khan et al, 2011)

RESULTS

DISCUSSION

Participants