Congenital hypothyroidism (CH) is a pediatric endocrine disorder caused by an insufficiency of thyroid hormone. Despite treatment following newborn screening, CH is associated with persisting memory weaknesses. Given animal research has shown thyroid hormone plays a crucial role in the development of the hippocampus, a brain structure required for normal declarative memory, it is possible that altered hippocampally-dependent processes underlie the memory weakness associated with CH. Previous studies of individuals with CH have found reduced memory abilities and left hippocampal volumes but no study has thoroughly assessed memory abilities or how the hippocampus functions to support memory. Thus, the present study compared individuals with CH and typically developing adolescents using clinical memory tests and two associative memory tasks shown in adults to activate the hippocampus during functional magnetic resonance imaging (fMRI). Results indicated groups did not differ in memory accuracy on clinical measures or either fMRI task. However, fMRI revealed hippocampal activation differed between the groups when performing the associative memory tasks. The first task utilized a visuospatial paired associates novelty detection paradigm to show the CH group increased activation relative to controls in left hippocampus and recruited right hippocampus when controls did not. Since previous research suggested the left hippocampus and verbal memory were more vulnerable to the effects of CH, the second task utilized a verbal paired associates paradigm to demonstrate that when making old and new judgments about associations versus items, the CH group increased activation relative to controls in left hippocampus. Further investigation revealed that when recognizing old associations versus items, the CH group had increased bilateral posterior hippocampal activation whereas controls showed increased activation in right anterior hippocampus, a distinction noted in previous research with this paradigm which suggests individuals with CH may retrieve associations in a less flexible manner than controls. In addition, worse memory performance and increased hippocampal activation, particularly on the left, was predicted by severity of hypothyroidism experienced early in life. In conclusion, these studies demonstrate that early thyroid hormone insufficiency associated with CH alters the functioning of the hippocampus and engenders use of compensatory mechanisms to support associative memory functions.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31971 |
| Date | 12 January 2012 |
| Creators | Wheeler, Sarah |
| Contributors | Rovet, Joanne |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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