Neuromagnetic Responses to Tactile Stimulation of the Fingers: Evidence for Reduced Cortical Inhibition for Children with Autism and Children with Epilepsy

Background:  Magnetoencephalographic (MEG) measurements of somatosensory evoked responses to tactile stimulation of the digits result in an early cortical response labelled the ‘_TP30m’ and a ‘_TP50m’ which occurs at approximately 50ms following the presentation of a transient mechanical stimulus (e.g., a finger tap). Several lines of evidence support the position that the _TP50m response is associated with GABA dependent post-excitatory inhibition. Moreover, GABA signaling is thought to be downregulated in both children with autism (ASD) and children with epilepsy (EPI).

Objectives:  Our objective was to compare _TP50m responses from a group of 15 children with ASD (mean age 9.95 ±1.23 SD years; 3 female), and a separate group of 17 children with EPI (mean age 10.57 ±1.72 SD years; 4 female) with _TP50m responses recorded from a group of 15 age matched typically developing (TD) controls (mean age 10.21±1.61 SD years; 2 female). We hypothesized that separately, for children with EPI and children with ASD, we would observe decreased SEF_TP50m response amplitudes to tactile stimulation of the digits.

Methods:  MEG recordings were performed at the Lurie Family Foundations’ MEG Imaging Center of the Department of Radiology at the Children’s Hospital of Philadelphia in a magnetically shielded room using a whole-cortex 275-channel MEG system. Somatosensory stimuli were presented to the left and right index fingers sequentially using pneumatic pulses of compressed air (30 p.s.i.) delivered via clip-on balloon diaphragms. Stimulation duration was 40ms and jittered between 0.5 and 0.7s random ISI. Data were collected in epochs of -0.1 to 0.3s for a total of 500 trials. Source localization of the _TP50m response yielded a _TP50m response strength parameter (i.e. equivalent current dipole (ECD) moment) as well as a peak latency which we considered in our linear mixed model using subject as a random effect, group and hemisphere as fixed effects, and age as a covariate.

Results:  We observed a significant overall group effect of reduced _TP50m dipole moment F(2,41)=3.99, P<0.05. Independent post-hoc pair wise comparisons for dipole moment showed marginal means were significantly different comparing TD (21.3±1.8nAm) vs. ASD (15.4±1.9nAm), P=0.027 as well as TD vs. EPI (14.9±1.7nAm), P=0.014. In addition, we observed a significant overall group effect for _TP50m peak latency F(2,41)=4.66, P<0.05. Post-hoc pair wise comparisons for dipole latency showed this to be driven by a latency delay of ~8ms in the EPI group: marginal means were significantly different comparing TD (50±2ms) and EPI (58ms±2ms), P=0.014, and not significant for TD vs. ASD (50±2ms), P=0.9.

Conclusions:  We observed significant decreases in _TP50m dipole moment values from the ECD source localized _TP50m response, for children with EPI and children with ASD. In addition, the latency of the _TP50m peak was observed to be equivalent between TD and ASD groups but was significantly delayed in children with EPI by approximately 8 ms. The failure to observe a latency difference in TD vs ASD is interesting in relation to the well-established finding of delayed auditory responses known to occur in children with ASD and will be the subject of future investigation.