Structural-Morphometric Examination of the Thalamus in Individuals with Autism Spectrum Disorder

Background: The thalamus has been implicated as a potential location of neural disruption in autism spectrum disorder (ASD). This subcortical nuclear complex plays a critical role in sensory processing, an aspect of functioning which is affected in many individuals with ASD. Whereas previous studies reported atypical thalamic volume in this population (Hardan et al., 2006, 2008; Perich-Alsina et al., 2002; Tsatsanis et al., 2003), the pattern of results across studies remains inconsistent. Differences in methodologies (e.g., image resolution, analysis software, segmentation approach, anatomical boundary definitions) as well as sample characteristics (e.g., age, symptom severity) may have contributed to past disparate findings. Given these discrepancies and methodological constraints, the exact nature of thalamic abnormalities in ASD remains unclear.

Objectives: Potential ASD-related abnormalities in thalamic morphometry (e.g. shape and size) were examined via semi-automated MRI-based segmentation. The relationship between thalamic morphometry and autism symptomatology was also evaluated.

Methods: A sample of 57 individuals with ASD (mean age = 15.1 years) and a demographically-matched comparison group of 62 typically developing individuals without ASD (mean age = 15.6 years) participated. A 3T Siemens Trio MRI scanner with a standard 8-channel head coil was used to obtain high-resolution T1-weighted structural images of the brain. Following acquisition, the structural MRI data for each participant was rotated into AC-PC coordinates. Volumetric and vertex data were obtained via semi-automated MRI-based segmentation (FSL-FIRST) for the left and right thalamus. FSL-FIRST is a model-based vertex analysis software that provides localized estimates of subcortical shape and size. It provides parameterized volumetric data as surface meshes and then estimates the most probable shape based on a library of subcortical models constructed from manually segmented images (Dean et al., 2016; Opel et al., 2014).

Results: As anticipated, we found autism-related abnormalities in thalamic morphometry. The vertex analysis showed significant group differences in left thalamic shape. Compared to the non-ASD group, the ASD group was associated with significant surface depression in dorsal and anterior-ventral aspects of the left thalamus (p < .05 in aforementioned areas). Vertex results were supported by volumetric data, which showed a trend towards a group-difference in left thalamic volume [F(1, 115) = 3.07, p = .08, η_p² = .03]. In addition, we found that, within the ASD group, bilateral thalamic volume was significantly smaller in individuals with ASD who experienced sensory abnormalities (per parent report) as compared to those with ASD whom did not [F(1, 31) = 4.50, p = .04, η_p² = .13]. Lastly, we found a significant negative correlation between bilateral thalamic volume and ASD symptom severity as measured by the Social Responsiveness Scale (SRS; r = -.37, p = .006).

Conclusions: The current results are consistent with previous findings of thalamic abnormalities in autism and suggest a link between thalamic size and sensory symptoms as well as more general social communication difficulties. Also, the present vertex-based approach provides an additional metric for thalamic investigation and allows for the identification of specific thalamic regions that may be particularly relevant to ASD and its manifestation.