Consequences of large interindividual variability for human brain atlases: converging macroscopical imaging and microscopical neuroanatomy

In human brain imaging studies, it is common practice to use the Talairach stereotaxic reference system for signifying the convergence of brain function and structure. In nearly all neuroimaging reports, the studied cortical areas are specified further with a Brodmann Area (BA) number. This specification is based upon macroscopic extrapolation from Brodmann’s projection maps into the Talairach atlas rather than upon a real microscopic cytoarchitectonic study. In this review we argue that such a specification of Brodmann area(s) via the Talairach atlas is not appropriate. Cytoarchitectonic studies reviewed in this paper show large interindividual differences in 3-D location of primary sensory cortical areas (visual cortex) as well as heteromodal associational areas (prefrontal cortical areas), even after correction for differences in brain size and shape. Thus, the simple use of Brodmann cortical areas derived from the Talairach atlas can lead to erroneous results in the specification of pertinent BA. This in turn can further lead to wrong hypotheses on brain system(s) involved in normal functions or in specific brain disorders. In addition, we will briefly discuss the different ‘Brodmann’ nomenclatures which are in use for the cerebral cortex.     

Refined mapping of eight cosmid markers on human chromosome 22

Summary Eight cosmid clones were regionally assigned to small subregions of chromosome 22 by hybridization with a total of 22 somatic cell hybrids. One cosmid was localized to the proximal part of 22q which contained the region commonly deleted in the DiGeorge syndrome. Seven cosmids showing restriction fragment length polymorphisms were localized to the telomeric region distal to the MB locus, which was reported to be frequently deleted in sporadic meningioma. These cosmids, when finely mapped and ordered, are considered useful for the identification of genetic alterations on this chromosome arm.     

Chromosome mapping ofSoa,a gene influencing gustatory sensitivity to sucrose octaacetate in mice

Strain distribution patterns among recombinant inbred strains suggested that a locus influencing taste sensitivity to sucrose octaacetate was on chromosome 6. A location forSoa was established by linkage analysis of behavioral and electrophoretic data from outbred and congenic strains and from test-cross progeny. Haplotyping of 41 outbred CFW-Cr animals with a cDNA probe showed perfect cosegregation ofSoa andPrp, a gene for salivary proline-rich proteins. Five of twelve B6. SW-Soa ^a strains were found to retainLdr-1, lactate dehydrogenase regulator-1, on chromosome 6 as an allelic passenger from the SWR/J donor strain (source of theSoa ^a Taster allele). Centimorgan distance was estimated using the ABP/Le linkage-testing strain (non-Taster,Soa ^b) and the SWR/J strain (Taster,Soa ^a) in a testcross breeding system. The data are consistent with a position for theSoa locus on mouse chromosome 6, 62 cM from the centromere.This research was supported in part by Grants DC00150 (G. W.) and DE003658 (E.A.A.). This paper is based on a thesis submitted to the Florida State University by the first author in partial fulfillment of the requirements for the Master of Sciences degree.     

Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene

Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family.     

Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation

Prepubertal periodontitis (PPP) is a rare and rapidly progressive disease of young children that results in destruction of the periodontal support of the primary dentition. The condition may occur as part of a recognised syndrome or may occur as an isolated finding. Both autosomal dominant and recessive forms of Mendelian transmission have been reported for PPP. We report a consanguineous Jordanian family with four members affected by PPP in two nuclear sibships. The parents of the affected subjects are first cousins. We have localised a gene of major effect for PPP in this kindred (Zmax=3.55 for D11S901 at θ=0.00) to a 14 cM genetic interval on chromosome 11q14 flanked by D11S916 and D11S1367. This PPP candidate interval overlaps the region of chromosome 11q14 that contains the cathepsin C gene responsible for Papillon-Lefèvre and Haim-Munk syndromes. Sequence analysis of the cathepsin C gene from PPP affected subjects from this Jordanian family indicated that all were homozygous for a missense mutation (1040A→G) that changes a tyrosine to a cysteine. All four parents were heterozygous carriers of this Tyr347Cys cathepsin C mutation. None of the family members who were heterozygous carriers for this mutation showed any clinical findings of PPP. None of the 50 controls tested were found to have this Tyr347Cys mutation. This is the first reported gene mutation for non-syndromic periodontitis and shows that non-syndromic PPP is an allelic variant of the type IV palmoplantar ectodermal dysplasias.


Keywords: prepubertal periodontitis; periodontal disease; cathepsin C; linkage     

Multimodal architectonic mapping of human superior temporal gyrus

Although it is generally accepted that human superior temporal gyrus is activated by a huge variety of auditory and linguistic tasks, little is known about the exact positions and extents of cortical areas that are located on the lateral convexity of the gyrus (e.g., Brodmann’s area 22). Such information, however, is relevant for a rigorous testing of structural-functional relationships in both normal volunteers and patients suffering from disorders of auditory and language perception. The present combined cytoarchitectonic and receptorarchitectonic study identifies a distinct area (Te3) in the lateral bulge of the superior temporal gyrus by using an algorithm-based approach for the detection of cortical borders. Our mapping data show that, in contrast to Brodmann’s area (BA) 22, only small portions of Te3 reach the dorsal and ventral banks of the gyrus. Therefore, we labelled the newly defined area as “Te3” and not as “BA 22”. The cytoarchitectonically defined borders of Te3 coincide with abrupt changes in the receptorarchitecture of several classical neurotransmitters, suggesting that Te3 represents a functionally relevant area of the human superior temporal gyrus. Since position and extent of area Te3 varied considerably between subjects, probability maps were created that show for each voxel of the standard references space, the frequency with which Te3 was present in it. These maps, in combination with previously published maps of the primary auditory cortex, can directly be compared with functional imaging data, and may open new perspectives for the analysis of structural-functional correlations in the human auditory and language systems.     

基于fMRI加权约束的FOCUSS迭代脑电源定位方法及其初步应用

脑电(Electroencephalography, EEG)和功能磁共振(Functional magnetic resonance imaging, fMRI)技术的结合,可以实现两者优势的互补,获得更加合理的源定位结果.本文报道的是一种将fMRI先验信息结合到脑电源定位中的新方法.在该方法中,先利用SPM方法计算获得fMRI的统计映射参数,然后将基于计算获得的统计参数构造的权矩阵结合到FOCUSS的迭代过程中,对脑电的反演提供具有fMRI先验空间位置信息的约束,提高脑电的源空间定位精度,从而获得更加合理的定位结果.通过对一形状知觉实验fMRI和脑电数据的结合定位分析,结果初步证实了改进方法能获得和生理更加一致的结果.     

Restriction fragment differences between the genomes of the Oka varicella vaccine virus and American wild-type varicella-zoster virus

The Oka vaccine strains of varicella-zoster virus (VZV) have a significantly different BgII DNA restriction pattern from that of American wild-type isolates of VZV. This difference consists primarily of an additional BgII site, which lies within the BamHI "D" fragment. In conjunction with a study of the efficacy of an experimental Merck/Oka VZV vaccine, the area of the genome from which the most marked restriction pattern alteration arises was studied more closely to determine if there are other significant differences between the Oka strains and American wild-type strains. BamHI "D" fragments from the DNA of the Oka parent strain (the progenitor of the vaccine strain), the RIT/Oka vaccine strain (a derivative of the Oka parent strain), the Merck/Oka vaccine strain, and the EF strain (an American wild type), were submitted to extensive endonuclease digestion studies to ascertain if additional unique restriction sites are present in the Oka parent or vaccine strains. The extra BgII restriction site characteristic of the Merck/Oka vaccine strain is also present in the DNA of the parent virus as well as its derivatives and was therefore not produced by the "attenuation" process. No other novel sites were found in the Oka parent or Oka-derived strains in this section of the genome. The Merck/Oka vaccine strain of VZV, despite its Japanese origin, is therefore quite similar to circulating American varicella-zoster virus strains. Varicella-zoster virus DNA, at least in the area of the BamHI D fragment, also appears to be remarkably stable from strain to strain.     

非接触标测和频谱分析迷走神经介导的心房颤动

目的： 对在体犬迷走神经介导的心房颤动（房颤）进行非接触标测和频谱分析，以探讨其发生和维持机制。方法: 测定8只犬基础情况及双侧迷走神经刺激时心房有效不应期及其离散度，非接触标测和频谱分析房颤时左、右房的电活动。结果: 迷走神经刺激与基础情况相比，左、右心房有效不应期缩短，但有效不应期离散度增大仅见于左房。迷走神经刺激时房颤易诱发和维持，房颤显示反复有序的激动经优先传导路径传播仅见于左房；频谱分析显示左房的主导频谱高于右房［（12.5±1.5)Hz vs (9.3 ±1.2) Hz，P<0.05］。停止迷走神经刺激，左、右房房颤频谱降低［（9.2±0.5)Hz vs (8.5±0.6)Hz， P>0.05］，房颤自发终止。结论: 左、右房电生理特性改变、激动模式差异以及频谱梯度提示迷走神经介导的房颤发生和维持依赖于左房。     

Construction of radiation-reduced hybrids and their use in mapping of microclones from chromosome 10p11.2-q11.2

Summary Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus betweenFNRB (10p-11.2) andRBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescencein situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10.