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Dimensions of affective semantic meaning--behavioral and evoked potential correlates in Chinese subjects.

The affective meaning of words can be quantified statistically by the 'semantic differential technique'. We studied a total of 55 Chinese adults in two experiments: first, 210 nouns were rated by 32 subjects. Factor analysis on these data yielded three independent semantic dimensions. Semantically unique words were used in electrophysiological experiments in another group of 23 healthy right-handed adults. Words of similar physical appearance belonging to different semantic classes were presented visually in random order. The electroencephalogram [corrected] was recorded in 32 channels. Evoked activity was computed for each semantic class. Significant differences in electrical brain activation between semantic word classes were seen as early as 80 ms after stimulus onset confirming related findings in German subjects. These results illustrate similar early neural activation in subject groups of different language and culture.

Adult↗

Quantitative multi-modal functional MRI with blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR).

A magnetic resonance imaging (MRI) method is described that allows interleaved measurements of transverse (R(2)(*) and R(2)) and longitudinal (R(1)) relaxation rates of tissue water in conjunction with spin labeling. The image-contrasts are intrinsically blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) weighted, but each contrast is made quantitative by two echo time (TE) and inversion recovery time (TIR) acquisitions with gradient echo (GE) and spin echo (SE) weighted echo-planar imaging (EPI). The EPI data were acquired at 7 Tesla with nominal spatial resolution of 430 x 430 x 1000 microm(3) in rat brain in vivo. The method is termed as blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR) and allows acquisition of R(2)(*), R(2), and CBF maps in an interleaved manner within approximately 12 minute. The basic theory of the method, associated experimental/systematic errors, and temporal restrictions are discussed. The method is validated by comparison of multi-modal maps obtained by BOLDED AFFAIR (i.e., two TE and TIR values with GE and SE sequences) and conventional approach (i.e., multiple TE and TIR values with GE and SE sequences) during varied levels of whole brain activity. Preliminary functional data from a rat forepaw stimulation model demonstrate the feasibility of this method for functional MRI (fMRI) studies. It is expected that with appropriate precautions this method in conjunction with contrast agent-based MRI has great potential for quantitative fMRI studies of mammalian cortex.

Animals↗

Brain symmetry and topographic analysis of lateralized event-related potentials.

OBJECTIVE: We investigated the influence of symmetry assumptions implicit in the derivation and the use of event-related lateralized potentials (ERLs), such as the lateralized readiness potential (LRP). We describe these assumptions and demonstrate several alternative computational methods. METHODS: Using analytical methods and forward simulations, we computed the error in the ERL topography that results from deviations in symmetry between homologous brain areas. Based on analytical considerations we show that, for source analysis, the ERL derivation provides no benefits compared to a single subtraction of the two (left-lateralized and right-lateralized) conditions underlying the ERL. RESULTS: Relative errors of 10% in the ERL topography are found if the location of an active region in one hemisphere differs by 10 mm from the symmetric location as compared to the other hemisphere A difference of 30 degrees in orientation results in a relative error of the ERL of 40%. Differences in source strength between hemispheres result in an ERL error that is half the size of the relative strength difference. CONCLUSIONS: We estimate that, due to violations of the symmetry assumption underlying the ERL, errors in the ERL topography of 10-40% can be expected. Source analysis does not benefit from the ERL. In topographic mapping and source analysis, the double subtraction of the ERL should be approached with caution and the single subtraction of the ERPs of two lateralized conditions should be first analyzed whenever possible. We suggest that analyses based on the topography of the ERL should only be performed after the assumption of symmetry has been validated.

Brain↗

Awake craniotomy: controversies, indications and techniques in the surgical treatment of temporal lobe epilepsy.

In 1886, Victor Horsley excised an epileptogenic posttraumatic cortical scar in a 23-year-old man under general anaesthesia and discussed his choice of anaesthesia: "I have not employed ether in operations on man, fearing that it would tend to cause cerebral excitement; chloroform, of course, producing on the contrary, well-marked depression." His concerns regarding anaesthesia are reiterated 100 years later as evidenced by the ongoing controversy over the choice of anaesthetic in surgical procedures for epilepsy. The current controversies regarding the necessity for local anaesthesia in temporal lobe epilepsy operations concern the utility of electrocorticography in surgical decision making, its relationship to seizure outcome and the value of intraoperative language mapping in dominant temporal lobe resections. The increasing sophistication of pre-operative investigation and localization of both areas of epileptogenesis and normal brain function and the introduction of minimally invasive surgical techniques and smaller focal resections are changing the indications for local anaesthesia in temporal lobe epilepsy. Thus, indications which were previously absolute are now perhaps relative. This article reviews the current indications for craniotomy under local anaesthesia in the surgical treatment of temporal lobe epilepsy.

Anesthesia, Local↗

Genetics of autism: overview and new directions.

Genetic epidemiology is the study of inherited factors involved in the etiology of a disease or disorder and uses the methods of both medical genetics and clinical epidemiology. In general, genetic epidemiology tries to answer the following four questions: Is the disorder inherited; What phenotype is inherited; How is it inherited or what is the mode of transmission; and What is the nature of the genetic mutation, if any, that gives rise to the disorder? The hope is that by identifying the gene or genes involved in pathophysiology, a much better understanding of the steps from gene product to phenotype will be possible, leading to improvements in diagnosis, an opportunity for thoughtful family planning, and perhaps, most important, to the development of treatments based on an understanding of the biochemistry of the disorder. We review the current knowledge of the genetic epidemiology of autism and the other pervasive developmental disorders (PDDs) and highlight promising new directions. There seems to be widespread agreement that the PDDs are caused, at least in part, by genetic factors. There is also some agreement on the phenotypic boundaries associated with these same genetic factors. However, many points of uncertainty remain, and several methodologic issues need to be resolved before further progress in mapping susceptibility genes is possible. We do not specifically review molecular studies, medical conditions associated with autism, or the broader autism phenotype, as these topics are covered in other papers in this special issue.

Autistic Disorder↗

Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes.

May-Hegglin anomaly (MHA) and Fechtner (FTNS) and Sebastian (SBS) syndromes are autosomal dominant platelet disorders that share macrothrombocytopenia and characteristic leukocyte inclusions. FTNS has the additional clinical features of nephritis, deafness, and cataracts. Previously, mutations in the nonmuscle myosin heavy chain 9 gene (MYH9), which encodes nonmuscle myosin heavy chain IIA (MYHIIA), were identified in all three disorders. The spectrum of mutations and the genotype-phenotype and structure-function relationships in a large cohort of affected individuals (n=27) has now been examined. Moreover, it is demonstrated that MYH9 mutations also result in two other FTNS-like macrothrombocytopenia syndromes: Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia (APSM). In all five disorders, MYH9 mutations were identified in 20/27 (74%) affected individuals. Four mutations, R702C, D1424N, E1841K, and R1933X, were most frequent. R702C and R702H mutations were only associated with FTNS, EPS, or APSM, thus defining a region of MYHIIA critical in the combined pathogenesis of macrothrombocytopenia, nephritis, and deafness. The E1841K, D1424N, and R1933X coiled-coil domain mutations were common to both MHA and FTNS. Haplotype analysis using three novel microsatellite markers revealed that three E1841K carriers--one with MHA and two with FTNS--shared a common haplotype around the MYH9 gene, suggesting a common ancestor. The two new globular-head mutations, K371N and R702H, as well as the recently identified MYH9 mutation, R705H, which results in DFNA17, were modeled on the basis of X-ray crystallographic data. Altogether, our data suggest that MHA, SBS, FTNS, EPS, and APSM comprise a phenotypic spectrum of disorders, all caused by MYH9 mutations. On the basis of our genetic analyses, the name "MYHIIA syndrome" is proposed to encompass all of these disorders.

Amino Acid Sequence↗

Extraction of protein interaction information from unstructured text using a context-free grammar.

MOTIVATION: As research into disease pathology and cellular function continues to generate vast amounts of data pertaining to protein, gene and small molecule (PGSM) interactions, there exists a critical need to capture these results in structured formats allowing for computational analysis. Although many efforts have been made to create databases that store this information in computer readable form, populating these sources largely requires a manual process of interpreting and extracting interaction relationships from the biological research literature. Being able to efficiently and accurately automate the extraction of interactions from unstructured text, would greatly improve the content of these databases and provide a method for managing the continued growth of new literature being published. RESULTS: In this paper, we describe a system for extracting PGSM interactions from unstructured text. By utilizing a lexical analyzer and context free grammar (CFG), we demonstrate that efficient parsers can be constructed for extracting these relationships from natural language with high rates of recall and precision. Our results show that this technique achieved a recall rate of 83.5% and a precision rate of 93.1% for recognizing PGSM names and a recall rate of 63.9% and a precision rate of 70.2% for extracting interactions between these entities. In contrast to other published techniques, the use of a CFG significantly reduces the complexities of natural language processing by focusing on domain specific structure as opposed to analyzing the semantics of a given language. Additionally, our approach provides a level of abstraction for adding new rules for extracting other types of biological relationships beyond PGSM relationships. AVAILABILITY: The program and corpus are available by request from the authors.

Algorithms↗

Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications.

The striatum receives projections from the entire cerebral cortex. Different, but not mutually exclusive, models of corticostriatal connectivity have been proposed, including connectivity based on proximity, parallel loops, and a model of a tripartite division of the striatum into motor, associative, and limbic areas. All these models were largely based on studies of anatomic connectivity in nonhuman mammals and lesion studies in animals and humans. Functional neuroimaging has the potential to discern patterns of functional connectivity in humans in vivo. We analyzed the functional connectivity between the cortex and the striatum in a meta-analysis of 126 published functional neuroimaging studies. We mapped the peak activations listed in each publication into stereotaxic space and used standard functional imaging statistical methods to determine which cortical areas were most likely to coactivate with different parts of the striatum. The patterns of functional connectivity between the cortex and the different striatal nuclei are broadly consistent with the predictions of the parallel loop model. The rostrocaudal and dorsoventral patterns of corticostriatal functional connectivity are consistent with the tripartite division of the striatum into motor, associative, and limbic zones.

Basal Ganglia↗

Emotional perception: correlation of functional MRI and event-related potentials.

Dense-array electrocortical and functional hemodynamic measures of human brain activity were collected to assess the relationship between 2 established neural measures of emotional reactivity. Recorded in parallel sessions, the slow-wave late positive potential (LPP) and visual cortical blood oxygen level-dependent (BOLD) signals were both modulated by the rated intensity of picture arousal. The amplitude of the LPP correlated significantly with BOLD intensity in lateral occipital, inferotemporal, and parietal visual areas across picture contents. Estimated strength of modeled regional sources did not correlate significantly with regional BOLD intensity. These data suggest that the enhanced positive slow wave seen over posterior sites during emotional picture processing represents activity in a circuit of visual cortical structures, reflecting a perceptual sensitivity to the motivational relevance of visual scenes.

Adult↗

Age effects on the neural correlates of episodic retrieval: increased cortical recruitment with matched performance.

Functional neuroimaging investigations have revealed a range of age-related differences in the neural correlates of episodic memory retrieval. Typically, whereas activity is reduced in older compared with younger adults in some regions, other regions are engaged exclusively, or to a greater extent, in older adults. It is unclear whether such differences merely represent the neural correlates of the lower levels of memory performance and impaired recollection typical of older adults. This issue was addressed in the present event-related functional magnetic resonance imaging study. The level of recollection was matched between groups of healthy younger and older adults for a subset of picture items in a source memory task by manipulating the number of study presentations. Contrasts of the activity elicited by old items attracting correct source judgments and correctly identified new items revealed that the 2 groups recruited many of the same brain regions. However, a striking pattern of age-related differences was also observed. In older adults, retrieval-related increases in activity were more widespread and of greater magnitude than in the young. Moreover, regions demonstrating retrieval-related decreases in activity were almost absent in the older participants. These findings suggest an age-related decline in the efficiency with which neural populations support cognitive function.

Adolescent↗

A microsatellite-based multilocus screen for the identification of local selective sweeps.

With the availability of completely sequenced genomes, multilocus scans of natural variability have become a feasible approach for the identification of genomic regions subjected to natural and artificial selection. Here, I introduce a new multilocus test statistic, ln RV, which is based on the ratio of observed variances in repeat number at a set of microsatellite loci in two groups of populations. The distribution of ln RV values captures demographic history of the populations as well as variation in microsatellite mutation among loci. Given that microsatellite loci associated with a recent selective sweep differ from the remainder of the genome, they are expected to fall outside of the distribution of neutral ln RV values. The ln RV test statistic is applied to a data set of 94 loci typed in eight non-African and two African human populations.

Chromosome Mapping↗

Nomenclature for N-acetyltransferases.

A consolidated classification system is described for prokaryotic and eukaryotic N-acetyltransferases in accordance with the international rules for gene nomenclature. The root symbol (NAT) specifically identifies the genes that code for the N-acetyltransferases, and NAT* loci encoding proteins with similar function are distinguished by Arabic numerals. Allele characters, denoted by Arabic numbers or by a combination of Arabic numbers and uppercase Latin letters, are separated from gene loci by an asterisk, and the entire gene-allele symbols are italicized. Alleles at the different NAT* loci have been numbered chronologically irrespective of the species of origin. For designation of genotypes at a single NAT* locus, a slash serves to separate the alleles; in phenotype designations, which are not italicized, alleles are separated by a comma.

Alleles↗