Stereological Study of the Superior Temporal Gyrus in ASD

Background:

The superior temporal gyrus (STG) is a polysensory region that processes and integrates complex information from the auditory, somatosensory and visual cortices and is thus implicated in complex and social and linguistic functions. Since social communication deficiencies lie at the core of autism spectrum disorder (ASD), the STG is a prominent region of interest to investigate the etiology of this disorder. Magnetic resonance imaging (MRI) studies have demonstrated that cortical growth of the temporal lobe deviates substantially in children with ASD compared to TD controls (Schumann et al. 2010) and at the genetic level, microRNAs are differentially expressed in ASD and TD cases (Ander et al., 2015).

Objectives:

This study builds upon prior MRI findings, and moves towards elucidating the cellular underpinnings responsible for aberrant brain development in this region. Here we estimate neuron number and size in the supra- and infra-granular cell layers of the STG in TD and ASD cases using comprehensive stereological parameters.

Methods:

Sixteen postmortem histological samples were assembled from the Autism Celloidin Library (ACL), comprising of 8 typically developing and 8 ASD cases (age, sex and hemisphere matched, ASD cases diagnosed using the Autism Diagnostic Interview–revised ADI-R). Celloidin-embedded hemispheres were cut at 200μm, 300 μm or 600 μm and stained with gallocyanin (Wegiel et al., 2014). STG boundaries were traced in accordance with Barger et al, (2015) using StereoInvestigator software (MBF Biosciences), and delineated into supra- (layers II-III) and infra-granular (layer V-VI) regions. The optical fractionator and nucleator modules of StereoInvestigator were used to estimate neuron number and cell volumes, respectively. Neurons were marked as pyramidal or non-pyramidal and the somal volume of every fifth neuron was recorded.

Results:

In an preliminary analysis of a small subset (6 TD and 6 ASD cases, aged 7-48 years old) of the full case list, we have found a comparable number of pyramidal and non-pyramidal neurons in the supra and infra-granular regions of the STG in TD and ASD cases, however pyramidal neurons across both regions were found to be 20% larger in ASD than in TD cases.

Conclusions:

Greater somal volume of neurons in the ASD cases could explain the enlargement of the STG observed with MRI studies. However, prior postmortem studies of a similar nature, some with an overlapping sample population used here, have reported smaller somal volumes in subcortical brain regions in ASD cases versus TD controls. Together these data highlight that ASD pathology varies by region, age and cell type and warrants further detailed cellular studies to truly understand the etiology of ASD.