A Visual Perceptual Task Provides Evidence
for an Excitatory:Inhibitory Imbalance in
Adults with Autism
Jamie Horder, Mendez MA, Spain D, Faulkner J, De La Harpe Golden D,
Murphy DGM
Department of Forensic and Neurodevelopmental Sciences
Institute of Psychiatry, King’s College London
United Kingdom
Background - general
Converging evidence implicates
excitatory neurotransmitter
glutamate and inhibitory GABA in
ASD.
 Altered excitatory:inhibitory (“E:I”)
balance may be key

Background: elusive GABA?
We
have observed alterations in glutamate using [1H]MRS (Horder
et al 2013; Horder et al in prep), and have preliminary evidence of
GABA receptors abnormalities (Mendez et al 2013),
But
we found no differences in GABA itself in adults with ASD
(Horder et al in prep). For more on these results…
“Abnormalities in Subcortical Glutamate/Glutamine, but Not GABA,
in Adults with an ASD: A [1H]MRS Study”
Saturday 10:42 AM
Marquis A Room
Background: a selective deficit?

However it’s possible that GABA deficits in ASD are limited
to a subset of inhibitory interneurons:

If so, changes might be hard to detect with MRS, yet of
functional importance.

A hypothesis:
Background - probing GABA

GABAergic inhibition has numerous well-defined
roles in sensory pathways.

Perceptual tasks could probe cortical GABA.

We chose the paradoxical motion perception
(PMP) visual task.
Paradoxical Motion Perception
In the visual cortex, contrast-coding
neurons inhibit motion-coding cells via
lateral GABA firing.
With large stimuli, it is harder to see motion
in higher-contrast images compared to low
contrast ones. GABA drives this.
‘Paradoxical’: large, high-contrast stimuli
are usually easier to see!
If there is a GABA deficit, the paradoxical
effect should be lower in ASD i.e. high
contrast performance should be better.
It has been used as a probe of GABA in
healthy volunteers (Glasser et al 2010) and
in depression (Golomb et al 2009) etc.
Participants

Adult males with a diagnosis of ASD, IQ>70 and control males matched on
age and full-scale IQ (t-test, all p>0.4). N = 30 (12 + 18).

Ages: 18-56 years (mean 30.6). Full scale IQ: 95-139 (mean 119).

ASD diagnosis by expert clinical judgement using ICD-10-R criteria based
on ADOS Module IV and, except where caregivers were unavailable, ADIR.

No history of epilepsy, genetic disorder, psychosis, drug and alcohol
abuse. Depression and anxiety were not exclusion criteria.

Participants were not on any psychoactive medication at the time of
scanning, and for at least six weeks previously.
Results
In the ASD group, the degree of the
paradoxical effect was reduced (p=0.022)
implying reduced GABA signalling within
the visual cortex.
As expected, a paradoxical effect was
observed over all participants taken as a
whole (higher sensory threshold for large,
bright stimuli, compared to small bright)
Discussion

This is the first study to use the paradoxical
motion perception task in adults with ASD.

In children, Foss-Feig et al (2013) showed a
slightly different pattern of results - no difference
in paradoxical spatial suppression, but, improved
performance at high contrast overall.

Further work should extend these results to
larger samples including more diverse patients
Conclusions

We found perceptual performance consistent with reduced
GABAergic inhibition in visual cortex in unmedicated adult
males with an ASD

Data are consistent with an excitatory-inhibitory balance
theory of autism and we hypothesise that GABA abnormalities
may be better measured at a functional rather than a
molecular level.

Some questions:
Do ‘objectively’ measured perceptual abnormalities relate to the
subjective sensory symptoms common in ASD?
 Could electrophysiology (EEG/MEG) probe perceptual
hyperexcitability?
 Useful as an outcome measure for pharmacology?

Acknowledgements



Laura Ajram
Ellie Wilson
Eileen Daly  EU-AIMS Consortium
 MRC
 NIHR
 Wellcome Trust