Cerebellar vermis lobules VIII-X in autism.

1. The aim was to investigate cerebellar vermis cross-sectional area in a group of high-functioning autistic children and normal control children. 2. Cerebellar vermis area measurements were completed on MRI scans from 8 autistic children (mean age 12.5 +/- 2.2, mean IQ 83.3 +/- 11.9) and 21 normal children (mean age 12.0 +/- 2.8, mean IQ 115 +/- 11). 3. The area of cerebellar vermis lobules VIII-X was significantly smaller in the autistic children than in the normal control subjects. ANCOVA demonstrated a confounding effect of IQ on these results. 4. Larger studies of autistic and normal subjects will be needed to assess the relationship between cerebellar abnormalities, autistic symptoms and IQ.

Medial temporal lobe in childhood-onset schizophrenia.

The majority of anatomic and neuroimaging studies in adult-onset schizophrenia demonstrate decreased volumes of the medial temporal lobe when compared with findings in normal individuals. The goal of this study was to investigate the hypothesis that subjects with childhood-onset schizophrenia would show decreased volumes of the medial temporal lobe when compared to normal children. Thirteen children meeting DSM-III-R criteria for schizophrenia (mean age 14.2+/-3.8 years) and 20 normal children (mean age 12.0+/-2.8 years) were investigated. MRI scans were performed on a 1.5-T GE Signa MR scanner using a coronal plane SPGR at 1.4-mm slice thickness. Volumes were assessed by manually tracing bilateral hippocampus, amygdala and temporal lobes. After adjustment for age and total brain volume, the amygdala was significantly larger in the schizophrenics than in the control subjects, and this volume increase was more pronounced on the left side. Hippocampus volumes did not differ significantly across groups. There was a nearly significant left-greater-than-right asymmetry of the amygdala in the schizophrenic group but not in the normal group. A nearly significant right-greater-than-left asymmetry was found in the anterior hippocampus for both schizophrenic and control groups. These findings are consistent with previous reports of at least initial sparing of temporal lobe regions in childhood-onset schizophrenia.

Mapping cortical asymmetry and complexity patterns in normal children.

This study reports the first comprehensive three-dimensional (3D) maps of cortical patterns in children. Using a novel parametric mesh-based analytic technique applied to high-resolution T1-weighted MRI scans, we examined age (6-16 years) and gender differences in cortical complexity (the fractal dimension or complexity of sulcal/gyral convolutions) and asymmetry of 24 primary cortical sulci in normally developing children (N=24). Three-dimensional models of the cerebral cortex were extracted and major sulci mapped in stereotaxic space. Given the documented age-related changes in frontal lobe functions and several neuroimaging studies that have reported accompanying volumetric changes in these regions, we hypothesized that, with age, we would find continued modifications of the cerebrum in frontal cortex. We also predicted that phylogenetically older regions of the cerebrum, such as olfactory cortex, would be less variable in anatomic location across subjects and with age. Age-related increases in cortical complexity were found in both left and right inferior frontal and left superior frontal regions, possibly indicating an increase in secondary branching with age in these regions. Moreover, a significant increase in the length of the left inferior frontal sulcus and a posterior shifting of the left pre-central sulcus was associated with age. Three-dimensional asymmetry and anatomic variability maps revealed a significant left-greater-than-right asymmetry of the Sylvian fissures and superior temporal sulci, and increased variance in dorsolateral frontal and perisylvian areas relative to ventral regions of the cortex. These results suggest increases in cortical complexity and subtle modifications of sulcal topography of frontal lobe regions, likely reflecting ongoing processes such as myelination and synaptic remodeling that continue into the second decade of life. More studies in a larger sample set and/or longitudinal design are needed to address the issues of normal individual variation and sulcal development.

Individual differences in the hemispheric specialization of dual route variables.

The dual route model suggests that reading of letter strings can occur through both a lexical and a nonlexical route. Hemispheric specialization of these routes has also been posited, suggesting that the left hemisphere has both lexical and nonlexical routes while the right hemisphere has only a lexical route. However, some recent data conflict with this hemispheric dual route model, suggesting that both hemispheres may have access to both routes. The purpose of the present study was to investigate individual differences in the hemispheric specialization of these routes and to determine whether these group differences in their specialization might explain conflicts in the literature. The effect of four individual difference factors was explored: handedness, biological sex, menstrual stage (i.e., fluctuations in estrogen), and self-rated degree of masculinity (i.e., sexual attribution). We looked at the interaction of these individual differences with the following dual route variables: (i) string length, (ii) word frequency, (iii) regularity of grapheme-phoneme correspondences of words, and (iv) the interaction of frequency and regularity using a bilateral lexical decision task. We observed that sex, menstrual stage, and masculinity each affected hemispheric specialization of the dual route variables, but did so in different ways. We posit that both hemispheres have orthographical (lexical) access as well as phonological (nonlexical) access to words. Further, we suggest that the presence of phonological processing in the right hemisphere depends on available resources and the strategies used, which are subject to individual differences.

The impact of dementia on the sufferer and available treatment interventions: an overview.

An overview of the psychological and behavioral consequences of dementia on sufferers is provided. Psychological interventions for improving the quality of life of patients, difficulties of diagnosis, the role of general practitioners, and th contribution of psychologists in the management of dementia are discussed.

DSC1-MCB regulation of meiotic transcription in Schizosaccharomyces pombe.

Meiosis is initiated from the G1 phase of the mitotic cell cycle, and consists of pre-meiotic S-phase followed by two successive nuclear divisions. Here we show that control of gene expression during pre-meiotic S-phase in the fission yeast Schizosaccharomyces pombe is mediated by a DNA synthesis control-like transcription factor complex (DSC1), which acts upon M lu1 cell cycle box (MCB) promoter motifs. Several genes, including rec8+, rec11+, cdc18+, and cdc22+, which contain MCB motifs in their promoter regions, are found to be co-ordinately regulated during pre-meiotic S-phase. Both synthetic and native MCB motifs are shown to confer meiotic-specific transcription on a heterologous reporter gene. A DSC1-like transcription factor complex that binds to MCB motifs was also identified in meiotic cells. The effect of mutating and over-expressing individual components of DSC1 (cdc10+, res1+, res2+, rep1+ and rep2+) on the transcription of cdc22+, rec8+ and rec11+ during meiosis was examined. We found that cdc10+, res2+, rep1+ and rep2+ are required for correct meiotic transcription, while res1+ is not required for this process. This work demonstrates a role for MCB motifs and a DSC1-like transcription factor complex in controlling transcription during meiosis in fission yeast, and suggests a mechanism for how this specific expression occurs.

Repression at a distance by the global regulator KorB of promiscuous IncP plasmids.

KorB protein (358 amino acids) binds to 12 highly conserved sequences on the RK2 genome and co-ordinates the expression of at least five operons encoding genes for stable inheritance and plasmid transfer. KorB represses the trfA, korA and klaA promoters where it binds 4 bp upstream of the -35 region (class I KorB operators, OB). We show here that KorB on its own can also repress the trbA, trbB, kfrA and kleA promoters where OB is between 80 and 189 bp away from the transcription start point (class II operator). A C-terminal deletion of 17 amino acids resulted in the loss of KorB's ability to repress through class II operator but not through class I operator. This deletion reduced multimerization of His6-tailed KorB protein in vitro and greatly reduced binding specificity for fragments containing OB sequences. At the trbBp region, where OB9 lies 189 bp upstream of the transcription start point, mutagenesis of a proposed secondary binding site overlapping the trbBp -35 region had no effect on the ability of KorB to repress trbBp. Nevertheless, gel retardation analysis showed that KorB binding is promoted by sequences upstream and downstream of OB9 and that KorB can form higher order complexes on DNA. However, DNase I footprinting suggested that RNA polymerase may interact directly with KorB bound at OB9 and implied that contacts between these proteins could be responsible for the action of KorB at a distance.