Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 283-289).

Indiana University-Purdue University Indianapolis (IUPUI) / The mongoloid face and craniofacial skeleton has been characterized by many investigators using clinical impressions and soft tissue measurements on living and autopsy material. Few studies have included data derived from cephalometric radiographs. The present study was designed to describe the mongoloid face and cranial base and to analyze the data. Twenty mongoloid children ranging in age from three years to 12 years, and their siblings were selected for study. A control group of children were selected on the basis of their essentially normal occlusion and facial skeleton. The data obtained from the cephalometric radiographs were analyzed in three ways. Each of the three groups of children, normal, mongoloid and their siblings were divided into four age groups, approximately three, five, seven and 11 years of age and means for the individual measurements were calculated. The sibling measurements were "corrected” to the age of the mongoloid child using the growth progression data from the normal children. The mean measurements of the “corrected” siblings and mongoloids were then compared using “t” tests for statistical significance. All children were then divided into three comparison pairs, normal-sibling, normal-mongoloid, and mongoloid-sibling, and the cephalometric measurements subjected to a multivariate, step-wise regression analysis. The growth of the maxillae and mandible were retarded in the Mongoloid children. The maxilla and mandible were positioned anteriorly under the cranial base.

Indiana University-Purdue University Indianapolis (IUPUI) / The relationship between gene copy number and protein expression levels has not thoroughly been examined in humans or mouse models of Down syndrome (DS) in relationship to developmental changes in the trisomic brain. Found on human chromosome 21 (Hsa21) and triplicated in DS, Dual-specificity tyrosine-phosphorylated regulated kinase 1A (DYRK1A) has been linked in DS to neurological deficits by restricting cell growth and proliferation. Little information exists regarding DYRK1A during perinatal development and how its expression may lead to cognitive deficits, and none exists that explores the gene-to-protein relationship during these critical time periods. This study aims to 1) Quantify variable DYRK1A expression across development as a function of age, sex, and brain region in trisomic Ts65Dn mice compared to euploid counterparts and 2) establish that the spatiotemporal pattern of developmental DYRK1A in the brain is not influenced solely by gene copy number, and that reduction of Dyrk1a in euploid and trisomic mice does not result in a corresponding global reduction of DYRK1A expression. DYRK1A was quantified in three areas of the postnatal brain at seven ages using the Ts65Dn mouse, the most studied model of DS, and found that trisomic expression is significantly increased on postnatal day ([P]6), declining by the third week to near euploid levels. We also uncovered a sexual dimorphic expression of DYRK1A when comparing animals of different sexes within the same genotype. Data from Dyrk1a knockdown mice indicated that reducing only Dyrk1a in euploid and in otherwise trisomic animals yields highly variable levels of DYRK1A, dependent on sex and tissue type, supporting the non-intuitive relationship between gene dosage and protein expression. These data emphasize the need to understand the age-dependent regulation of antecedent conditions that are causing changes in Dyrk1a expression in the brain.

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Previous research has indicated found that individuals with Down syndrome (DS) have difficulties in processing auditory information for the planning of movements relative to their peers with undifferentiated developmental handicaps. This modality-specific information-processing difficulty has been found for the preprogramming of goal-directed aiming movements (Le Clair & Elliott, 1995) and in simple reaction times (Davis, Sparrow, & Ward, 1991; Hermelin, 1964). The purpose of the present study was to assess whether or not a model of atypical cerebral specialization for the perception of speech sounds, proposed by Elliott and colleagues, could explain these findings. Thus, participants performed a choice reaction aiming task under three conditions. Colour-coded targets were cued by a visual cue at the target location, a visual cue remote from the target location, or a verbal cue identifying the target. Results revealed that while the reaction times did nCit differ between the two groups with handicaps, the participants with DS, unlike the two control groups, had significantly longer movement times in the verbal than in two visual conditions. These results support the model of biological dissociation. / Thesis / Master of Science (MS)

BACKGROUND: The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. METHODS: We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. RESULTS: We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. CONCLUSIONS: These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated with Down syndrome can modulate the brain's response to violence and other complex emotive ideas.

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Trisomies 18 and 13 are rare genetic conditions (occurring around 1 in 6,000 and 10,000 newborns respectively) which are caused by an extra copy of either chromosome 18 or 13, similar to trisomy 21 (Down syndrome). The only known risk factor for these syndromes is maternal age, however previous cluster analyses have linked trisomy risk to a number of alternate factors, including radiation exposure and infection. Cases of trisomies 18 and 13 from the National Down Syndrome Cytogenetic Register (NDSCR) were scanned for temporal and spatial clusters throughout England and Wales between 2004 and 2010. No temporal clusters were detected, however there were multiple significant spatial clusters detected for both trisomies in London. These clusters were likely caused by advanced maternal age in the region, and it is also possible that regional differences in gestational age at the time of prenatal screening could have contributed to these clusters. In order to account for maternal age and gestational age at diagnosis, a novel method was developed in R to directly weight cases based on these factors. Applying weights to cases directly allowed both factors to be simultaneously accounted for by multiplying weights together. This method was evaluated using synthetic data and compared with an alternate method in the widely used program SaTScan. Both programs returned similar results when the weighting method was mild, but when extreme weights were applied at random significant clusters were observed in SaTScan but not in R. The NDSCR data was weighted and then rescanned for spatial clusters in both programs. No evidence of clustering was detected using the novel method, while SaTScan returned multiple highly significant clusters. These findings, combined with those obtained using the synthetic data, indicate that the novel method produces more reliable results than SaTScan when extreme adjustment is applied.