Contribution of Thalamic Developmental Changes to the Autistic Phenotype

Background: Some clinical signs of autism, such as verbal and nonverbal communication deficits, sensory abnormalities, skeletal muscle hypotonia, and cognition could be a result of developmental abnormalities in the thalamus. The lateral thalamus is closely related to language function including mechanical processes for articulation and respiration (Ojemann, 1971, 1977; Oke et al., 1978). The thalamus is involved in sensory (pain) and motor function and cognition, including memory. Pallidal input to the thalamus serves to control muscle tone. These data indicate that the thalamus may contribute to the clinical signs of autism.

Objectives: We assume that the thalamus, interacting with the neocortex and entorhinal cortex, and very closely with the amygdala and the striatal system, may have its own developmental changes contributing to motor, sensory and language deficits observed in autism. The goal of this study is to determine whether the thalamus is affected by a similar neuronal developmental delay as are the basal ganglia and cortex.

Methods: In the human thalamus, more than 50 subnuclei with specific connectivities have been identified. To detect a global pattern of neuronal development and maturation in the thalamus, rather than thalamic subregion - specific characteristics, the mean volume of neurons and neuronal nuclei was determined in the entire thalamus in 7 autistic and 7 control subjects 4 to 23 years of age. Unbiased morphometric methods of estimation of thalamic volume, number of neurons, and volume of neurons and neuronal nuclei were applied.

Results: The volume of the thalamus in autistic and control subjects is the same. However, the mean volume of neuronal soma in 4- to 8- year old children was 27% less in autistic subjects than in controls, but the difference was undetectable in older children and young adults (11-23 years old). The volume of neuronal nuclei in the youngest autistic children was reduced by 37%, whereas in older subjects, it was insignificantly higher than in controls.

Conclusions: A smaller volume of the cell body and cell nucleus in thalamic neurons in the youngest autistic children and an almost normal size in late childhood and adulthood suggests a significant delay of neuronal growth in the early stages of brain development and acceleration of growth in late childhood compensating for developmental deficits. The presence of a similar developmental delay of neuronal growth in the thalamus and the neuronal networks interacting with the thalamus suggests that each component of these complex neuronal networks may make its own contribution to the clinical phenotype of autism.