A series of empirical studies is presented that examine the contribution of Fragile X Mental Retardation 1 (FMR1) gene expression to the structure and function of the visual system. This contribution is documented using a histological approach in human and nonhuman primate tissue in conjunction with psychophysical testing of Fragile X Syndrome affected patients who are lacking FMR1 expression. / In the first set of experiments, immunohistological studies of unaffected human and primate brain tissue were carried out to reveal the staining pattern for Fragile X Mental Retardation Protein (FMRP), the protein product of the FMR1 gene, within the two main subcortical pathways at the level of the lateral geniculate nucleus (LGN). FMRP is expressed in significantly greater quantity within the magnocellular (M) neurons of the LGN when compared to levels obtained from the parvocellular (P) neurons. This finding suggests that M neurons depend on FMRP to greater extent than P neurons for determining their normal structure and function. A subsequent histological analysis of the LGN from a FXS affected individual revealed atypical LGN composed of small-sized neurons that were more P- than M-like. This result supports the notion that with the lack of FMR1 expression as occurs in FXS, the impact is greatest to M neuron morphology. / A second set of experiments explored the idea that the M neuron pathology in FXS results in a functional deficit for processing of visual information carried by this pathway. Detection thresholds for stimuli known to probe either M or P-pathway integrity were obtained from individuals affected by FXS as well as age- and developmental-matched control participants. In support of this hypothesis, FXS affected individuals displayed significantly elevated thresholds for M-but not P-specific achromatic visual stimuli. The selectivity of this deficit was verified in a consequent experiment that evaluated colour vision, a visual attribute known to be exclusively processed by the P-pathway. Affected individuals did not differ significantly from developmental-matched control participants in their ability to detect chromatic stimuli. Finally, the effect of the M pathway deficit on cortical visual function was assessed. Results of these experiments reveal that the thresholds for detection of coherent motion, but not form, are significantly elevated in the FXS group. This finding suggests that the parietal (dorsal) visual stream, the major cortical recipient of input from the M pathway, is detrimentally affected in FXS. / A third experiment examines the extent to which the M pathway deficit impacts on cortical visual functioning by employing stimuli of varying complexity that probe the parietal (dorsal) and temporal (ventral) visual streams separately. Results suggest that FXS affected individuals have a pervasive deficit in their ability to detect both simple and more complex forms of motion. In contrast, these same individuals have normal detection thresholds for simple form stimuli. However, with more complex form stimuli affected individuals have significant elevations in threshold. Taken together these results support the notion that the M pathway deficit is amplified at higher levels of visual processing and further, that FXS affected individuals have difficulties integrating all early visual information.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85927 |
| Date | January 2005 |
| Creators | Kogan, Cary Samuel |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Psychology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002268640, proquestno: AAINR21664, Theses scanned by UMI/ProQuest. |
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