Developmental Heterochronicity of Neuron Growth in the Memory System of Autistic Subjects

Background: Reduced volume of both the hippocampal formation and the amygdala were noted in subjects examined by Aylward et al. (1999), but not in populations examined by other researchers (Piven et al., 1998). Smaller and more densely packed neurons were found in various portions of the hippocampal formation, entorhinal cortex and medial nuclei of the amygdala (Bauman and Kemper, 1985; Kemper and Bauman, 1993).

Objectives: We hypothesize that postmortem morphometric studies will help to identify the type, distribution and severity of developmental abnormalities in major components of the memory system. These may contribute to memory system abnormalities in a structure-specific way. The entorhinal cortex is a developmental hybrid providing major input from association cortices and the amygdala to the hippocampus. The hippocampus is involved in processing and storage of information. The amygdala is the component of the memory system that processes social and emotional signals. 

Methods: To test this hypothesis, we examined neurons in entorhinal cortex layers II, III, V and VI; in cornu Ammonis sectors 1, 2, 3 and 4; and in four nuclei of the amygdala of 10 autistic and 10 control subjects 4 to 56 years of age. Unbiased morphometric methods of estimation of brain structure volume, number of neurons and volume of neurons and neuronal nuclei were applied.

Results: Finding a reduced size of neurons in 4 to 8 years old children in layer II (islands) by 20%, in layer III by 33%, and layers V and VI by 33% and 26%, respectively, and a similar range of reduction of size of neurons in the amygdala (from 22% in accessory basal to 34% in basal nucleus), but the lack of a significant difference in the volume of neurons in all four sectors of the cornu Ammonis suggests that the memory system is affected in an early stage of brain development but in a structure-specific way.

Conclusions: The cornu Ammonis does not show a pattern of cortical and basal ganglia developmental delay. Selective preservation of the developmental pattern of neurons in the cornu Ammonis involved in storage of information from affected structures including the entorhinal cortex and amygdala may help explain memory abnormalities mixed with restricted interests and abilities.