The corpus callosum (CC) is the largest fiber¹ tract in the brain and connects homological regions of the two cerebral hemispheres. Research with split-brain patients, whose CC has been surgically severed, and neurologically intact groups has shown that the CC is important for sustained and divided attention. Due to its role in attention, the CC is of interest to clinical conditions in which attention is affected, such as attention deficit hyperactivity disorder (ADHD). Although the size of the CC has been examined in children and adolescents with ADHD, the results have been inconsistent. Therefore, the first of three studies in this thesis synthesized the current research in a metaanalysis, which analyzed the data from 13 studies that examined CC area in children and adolescents with ADHD, when compared to healthy controls. This study found that the splenium, the most posterior region of the CC, was smaller in ADHD and the rostral body, an anterior region, was smaller in boys with ADHD compared with controls. Thus, there is evidence for differences in area in both the anterior and posterior regions of the CC in ADHD. It was not known whether these differences persist into adulthood, however, because CC size had not been examined in adults with ADHD. Therefore, the second study examined CC area and structural integrity in young adults with ADHD compared with healthy controls using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), respectively. The difference in the size of the splenium was not present in this adult sample, although the genu (an anterior region of the CC) was smaller and two midposterior regions were larger in adults with ADHD when compared with controls. In addition, a reduction in the integrity of the genu and greater integrity in the splenium was found in ADHD. The relationship between CC morphology and measures of attention and IQ was also examined in young adults with ADHD and controls in order to assess the functional significance of differences in the CC. The integrity of the splenium was correlated with performance on the Stroop task, which requires attentional control. Hence, this study indicated that the morphology of the CC is atypical in young adults with ADHD and that these differences in the CC may impact on cognitive functioning. Interestingly, an estimate of performance IQ was negatively correlated with CC area in controls. This result conflicts with previous research on the relationship between IQ and the CC in healthy adults although the literature has yielded inconsistent findings. The third study, therefore, examined the relationship between IQ and both CC area and integrity in more detail in a larger sample of young adults. A negative correlation was found between the area of posterior regions of the CC and an estimate of performance IQ, while an estimate of verbal IQ was associated with decreased structural integrity in the genu. This study supports the hypothesis that differences in CC size and or integrity may have cognitive consequences. In summary, this thesis confirms the view that the development of the CC is atypical in children and young adults with ADHD. In addition, differences in CC integrity were associated with cognitive functioning in young adults with ADHD. Finally, the morphology of the CC is related to cognitive performance in healthy adults. ¹ American spelling is used throughout the thesis in order to be consistent with the published papers which have been published or prepared using American spelling. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1367349 / Thesis (Ph.D.) -- University of Adelaide, School of Psychology, 2009

The corpus callosum (CC) is the largest fiber¹ tract in the brain and connects homological regions of the two cerebral hemispheres. Research with split-brain patients, whose CC has been surgically severed, and neurologically intact groups has shown that the CC is important for sustained and divided attention. Due to its role in attention, the CC is of interest to clinical conditions in which attention is affected, such as attention deficit hyperactivity disorder (ADHD). Although the size of the CC has been examined in children and adolescents with ADHD, the results have been inconsistent. Therefore, the first of three studies in this thesis synthesized the current research in a metaanalysis, which analyzed the data from 13 studies that examined CC area in children and adolescents with ADHD, when compared to healthy controls. This study found that the splenium, the most posterior region of the CC, was smaller in ADHD and the rostral body, an anterior region, was smaller in boys with ADHD compared with controls. Thus, there is evidence for differences in area in both the anterior and posterior regions of the CC in ADHD. It was not known whether these differences persist into adulthood, however, because CC size had not been examined in adults with ADHD. Therefore, the second study examined CC area and structural integrity in young adults with ADHD compared with healthy controls using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), respectively. The difference in the size of the splenium was not present in this adult sample, although the genu (an anterior region of the CC) was smaller and two midposterior regions were larger in adults with ADHD when compared with controls. In addition, a reduction in the integrity of the genu and greater integrity in the splenium was found in ADHD. The relationship between CC morphology and measures of attention and IQ was also examined in young adults with ADHD and controls in order to assess the functional significance of differences in the CC. The integrity of the splenium was correlated with performance on the Stroop task, which requires attentional control. Hence, this study indicated that the morphology of the CC is atypical in young adults with ADHD and that these differences in the CC may impact on cognitive functioning. Interestingly, an estimate of performance IQ was negatively correlated with CC area in controls. This result conflicts with previous research on the relationship between IQ and the CC in healthy adults although the literature has yielded inconsistent findings. The third study, therefore, examined the relationship between IQ and both CC area and integrity in more detail in a larger sample of young adults. A negative correlation was found between the area of posterior regions of the CC and an estimate of performance IQ, while an estimate of verbal IQ was associated with decreased structural integrity in the genu. This study supports the hypothesis that differences in CC size and or integrity may have cognitive consequences. In summary, this thesis confirms the view that the development of the CC is atypical in children and young adults with ADHD. In addition, differences in CC integrity were associated with cognitive functioning in young adults with ADHD. Finally, the morphology of the CC is related to cognitive performance in healthy adults. ¹ American spelling is used throughout the thesis in order to be consistent with the published papers which have been published or prepared using American spelling. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1367349 / Thesis (Ph.D.) -- University of Adelaide, School of Psychology, 2009

The cerebral cortex is the largest subdivision of the human brain and is associated with higher cognitive functions. These functions are based on the interconnections between the neurons that form pre- and postnatally in the different telencephalic regions. The processes of neurons with similar functions and connectivity follow the same course and form axon tracts. There are three main axons tracts analysed in this thesis the corpus callosum, the corticothalamic/thalamocortical tracts and the lateral olfactory tract that transfers olfactory information to the telencephalon. In the mouse, these tracts are generated during embryogenesis as axons project to their target area. The mechanisms by which axons navigate still need to be elucidated. Studies of a number of mutant mice have shown that axon pathfinding is under the control of genes. Gli3 is a zinc finger transcription factor with known roles in axon pathfinding. Gli3 is widely expressed in progenitor cells of the dorsal and ventral telencephalon complicating the elucidation of the molecular mechanisms by which Gli3 controls axon tract formation. My aim here is to investigate the spatial and temporal requirements for Gli3 in axon pathfinding in the forebrain using Gli3 conditional mutants as a tool. Regarding the corpus callosum, my findings demonstrated a crucial role for Gli3 in the dorsal telencephalon, but not in the septum or medial ganglionic eminence, to control corpus callosum formation and indicated that defects in the formation of the corticoseptal boundary affect the positioning of callosal guidepost cells. Moreover, conditional inactivation of Gli3 in dorsal telencephalic progenitors led to few corticothalamic axons leaving the cortex in a restricted lateral neocortical domain. This restricted entry is at least partially caused by an expansion of the piriform cortex, which forms from an enlarged progenitor domain of the ventral pallium. Transplantation experiments showed that the expanded piriform cortex repels corticofugal axons. Moreover, expression of Sema5B, a chemorepellent for corticofugal axons produced by the piriform cortex, is similarly expanded. Hence, control of lateral cortical development by Gli3 at the progenitor level is crucial for corticothalamic pathfinding. Finally, by using Emx1Cre;Gli3fl/fl mutants I analysed the consequences of the expansion of the piriform cortex on the formation of the lateral olfactory tract (LOT). This analysis showed that LOT axons also appear to be medially shifted with LOT collaterals aberrantly colonising the expanded piriform cortex. Time course analysis confirmed an expansion of the paleocortical primordium from E13.5 onwards, coinciding with the arrival of the LOT axons. Hence, it is possible that the expanded piriform cortex contributed to the medial shift of the LOT. In conclusion, these findings support a strong link between Gli3 controlled early patterning defects and axon pathfinding defects and form the basis for future analysis of the molecular mechanisms by which Gli3 controls axon pathfinding in the forebrain. My findings also reveal how alterations in GLI3 function may contribute to connectivity defects in human patients with mutations in GLI3.

Disorders of the corpus callosum (ADCC) present developmental challenges to children and adults. These disorders are characterized by symptoms of abnormal behaviors and/or thinking patterns. Because ADCC may exist in combination with other disabilities, individual IQs and the severity and problems vary from individual to individual. Using the double ABCx model of family adaptation to stress related to a family member with a disability, the purpose of this cross-sectional study was to provide the first evaluation of parental adaptation among parents of children with ADCC. The final sample, 265 mothers of children with ADCC, was recruited through online support groups for ADCC parents. Parent adaptation was operationally defined as quality of life and operationalized by scores on the World Health Organization (WHO) Quality of Life Questionnaire (QOL). The predictors were measured by the Questionnaire on Resources and Stress (QRS), Family Empowerment Scale (FES), Sense of Coherence Scale (SOC), and Coping Health Inventory for Parents (CHIP). Linear regressions were used to evaluate the predictors in the 4-factor double ABCx prediction model of parent adaptation. Except for parent stress level, family empowerment, sense of coherence, and coping styles were statistically significant predictors of parental quality of life. That is, mothers who reported experiences of empowerment, coherence, and positive coping also have high self-reported quality of life. The findings, the first for experiences of parents of children with ADCC, provide valuable information for further research, but also for other parents and those who may be instrumental in the development of supportive services for this population.

Researchers have long been interested in the role of the corpus callosum in reading disorder, but existing studies have yielded inconsistent results. Some have found larger corpus callosa in those with reading disorder, others have found smaller corpus callosa, and some have found no differences in the corpus callosa of persons with and without reading disability. Some possible problems with past studies include failure to control for whole brain size, intelligence, gender, lateral dominance, and the presence of other syndromes such as Attention Deficit Hyperactivity Disorder. The current study is an examination of the corpus callosum in 68 readers nested in 24 families. Data were centered around the family mean so that the variance within families could be determined. Corpus callosum volumes were measured and controlled for whole brain volume, intelligence, and gender. A series of regressions were used to determine whether the volume of the corpus callosum significantly contributed to the variance in oral reading, phonological processing, and rapid naming. The midsagittal slice was segmented into fifths, and similar regressions were performed. A logistic regression was used to determine whether variation in corpus callosum volume could predict RD and no RD group membership. Finally, left and right volumes were compared and a correlation between corpus callosum volume and area at the midsagittal slice were conducted. Results suggest that better readers within families have larger corpus callosum areas in the midsagittal slice at the midbody. Better phonological processors within families had smaller corpus callosum volumes, but a problem with restricted range for phonological processing scores renders this finding unreliable. Rapid naming scores appear to be unrelated to the corpus callosum in this sample. Differences in the corpus callosum are not robust enough to predict diagnostic group and there appears to be no differences between left and right hemisphere volumes of the corpus callosum. Measurements of area at the midsagittal slice are highly correlated with the volumetric measurements suggesting that for subsequent studies, area at the midsagittal slice may be sufficient. / text

Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN or HMSN/ACC) is a severe polyneuropathy affecting both the peripheral nervous system and the central nervous system. It is transmitted as an autosomal recessive trait and is particularly frequent in the French Canadian population of Quebec (Canada). The disease was linked to chromosome 15 in 1996 by Dr. Rouleau's team. / We genotyped polymorphic markers in the ACCPN candidate region on chromosome 15 in over 67 patients and 200 control individuals. Observation of affected haplotypes confirmed the presence of a founder effect in the French Canadian population. Recombination analysis reduced the candidate interval to approximately 2 cM between markers D15S1040 and ACTC on chromosome 15. Linkage disequilibrium analysis suggested the gene resides nearest marker D15S1232. A physical map of the newly refined candidate region was constructed using YAC, BAC and PAC clones. These clones were used to confirm the position of candidate ESTs and genes as being either within or outside the ACCPN candidate region. / The connexin 36 gene, which was confirmed to reside within the region, was excluded as the gene responsible for ACCPN using SSCP analysis. The SLC12A6 gene was also confirmed to reside within the candidate interval and was tested for mutations using SSCP, dHPLC and sequence analyses. We found a total of four disease-specific mutations in SLC12A6, all of which are expected to truncate the KCC3 protein (the protein produced by the SLC12A6 gene). Two of the four mutations were identified in the French Canadian population; 80 French Canadian ACCPN patients are homozygous for the c.2436delG in exon 18 and one French Canadian patient is a compound heterozygote, having the c.2436delG mutation as well as the 1584_1585delCTinsG mutation in exon 11. Two additional mutations were identified in one Turkish and one Italian family in exons 22 and 15 respectively. The effects of the c.2436delG mutation on KCC3 function was studied in X. laevis oocytes and the truncated protein is not functional. Finally, collaborators at Vanderbilt University disrupted the slc12a6 gene in the mouse and found a phenotype similar to the human disease. / Identification of SLC12A6 as the gene mutated in ACCPN will allow for accurate molecular diagnosis as well as carrier testing in the French Canadian population. It is also the first step in understanding the molecular mechanism leading to the disease.

Thesis (Ph. D.)--University of California, San Diego, 1999. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Chicago, Department of Psychology, June 2000. / Includes bibliographical references. Also available of the Internet.

Thesis (Ph. D.)--University of California, San Diego, 2008. / Title from first page of PDF file (viewed November 10, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

This study served as a pilot study of cingulate gyrus surface areas and their relation to intelligence in individuals with hydrocephalus. Surface areas of the corpus callosum and cingulate gyrus regions were compared between individuals with early hydrocephalus (n = 9) and controls (n = 7). Subsequently, the surface areas were correlated with full-scale intelligence scores and the verbal and nonverbal discrepancy scores. Corpus collosum surface areas were significantly smaller in participants with hydrocephalus. These areas also robustly correlated with full-scale intelligence scores. Although the cingulate gyrus did not differ significantly between the groups, the cingulate gyrus regions were increasingly divergent the more posterior the region. Additionally, the caudal anterior and the posterior cingulate gyrus regions had only moderate positive correlations with full-scale intelligence scores. Although the participants with hydrocephalus had a significantly lower mean performance IQ compared to verbal IQ, the discrepancy scores did not correlate significantly with any of the regions of interest.