FMRI activation in language areas correlates with verb generation performance in children.

Functional MRI mapping of language areas in children frequently employs a covert verb generation task. Because responses are not monitored, the relationship between fMRI activation and task performance is unknown. We compared fMRI activation during covert and overt verb generation to performance during the overt task. 15 children, ages 11-13 years, listened to concrete nouns and responded with related verbs covertly and overtly. A clustered fMRI acquisition allowed for recording of overt responses without motion artifacts. Region of interest analysis was also performed in areas that exhibited correlation between activation and performance during overt verb generation in left inferior frontal and left superior temporal gyri (along with their right hemisphere homologues). Regression analysis determined that during both covert and overt generation, left hemisphere regions showed positive correlations with average counts of verbs generated during the overt task. These results suggest that increased verb generation performance leads to increased activation. In addition, overt performance may be used as an estimator of covert performance.

Unwanted sexual contact on campus: a comparison of women's and men's experiences.

While sexual victimization continues to be a problem on college campuses, recent attention has been drawn to understanding gender differences in victimization rates and consequences. To date, these studies remain relatively few in number. The current study surveyed 651 male and female undergraduate students about unwanted sexual experiences during 1 academic year. Comparison of men and women revealed expected differences in incidence rates, with women reporting higher rates of unwanted contact. Within the subsample of reported victims, however, there was gender similarity in terms of the context of unwanted sexual experiences. Analyses also revealed the negative consequences of these experiences for both men and women and low rates of disclosure regardless of gender. Across the full sample of students surveyed, there were interesting gender differences in knowledge of campus support services, with women more likely to have attended a prevention program and to have indicated greater knowledge of rape crisis services.

Functional magnetic resonance imaging reveals atypical language organization in children following perinatal left middle cerebral artery stroke.

We used verb generation and story listening tasks during fMRI to study language organization in children (7, 9 and 12 years old) with perinatal left MCA infarctions. Healthy, age-matched comparison children (n = 39) showed activation in left Broca's area during the verb generation task; in contrast, stroke subjects showed activation either bilaterally or in the right hemisphere homologue during both tasks. In Wernicke's area, comparison subjects showed left lateralization (verb generation) and bilateral activation (L > R) (story listening). Stroke subjects instead showed bilateral or right lateralization (verb generation) and bilateral activation (R > L) (story listening). Language is distributed atypically in children with perinatal left hemisphere stroke.

Normal fMRI brain activation patterns in children performing a verb generation task.

Although much is known concerning brain-language relations in adults, little is known about how these functions might be represented during the developmental period. We report results from 17 normal children, ages 7-18 years, who have successfully completed a word fluency paradigm during functional magnetic resonance imaging at 3 Tesla. Regions of activation replicate those reported for adult subjects. However, a statistically significant association between hemispheric lateralization of activation and age was found in the children. Specifically, although most subjects at all ages showed left hemisphere dominance for this task, the degree of lateralization increased with age. This study demonstrates that fMRI can reveal developmental shifts in the pattern of brain activation associated with semantic language function.

Right hemisphere contribution to developmental language disorder: Neuroanatomical and behavioral evidence.

UNLABELLED: Developmental language disorder (DLD) is identified by virtue of the verbal deficits that define it. However, numerous studies have also documented nonverbal deficits in this population. This study attempts to explain the co-occurrence of both verbal and nonverbal deficits in this population from a brain-based perspective. Two samples of adults selected for DLD were compared with subjects without such a history on verbal and nonverbal skills in exploratory and confirmatory studies. Subjects also received MRI scans, which were used to determine the relation between left- and right-hemisphere regions hypothesized to relate to the behavioral skills tested. Results revealed replicable differences between groups on both verbal and nonverbal tasks. In addition, a significant association between performance on tests sensitive to facial affect and spatial rotation with the gray matter volume within the right supramarginal gyrus was found in both samples. These results support the hypothesis of a right hemisphere contribution to the profile of DLD. LEARNING OUTCOMES: As a result of this activity, the participant will be able to describe evidence in support of a role for the right hemisphere in DLD.

Electrophysiological dissociation between verbal and nonverbal semantic processing in learning disabled adults.

Event-related potentials (ERPs) were recorded as 16 adults with learning disabilities (LD) and 16 controls were presented with two sets of stimuli. The first set comprised pairs of line drawings and environmental sounds (nonverbal condition); the second consisted of printed and spoken words (verbal condition). In the controls, semantically related items elicited smaller N400s than unrelated items in both conditions, with opposing hemispheric asymmetries for spoken words and environmental sounds. The LD group did not show a significant difference between related and unrelated words, despite a robust context effect for nonspeech sounds. The results suggest anomalous processing limited to the verbal domain in a simple semantic association task in the LD group. Semantic deficits in this group may reflect a relatively specific deficit in forming verbal associations rather than a more general difficulty that spans both verbal and nonverbal domains.

Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy.

To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and of 12 age-matched normal controls. The numbers of unmyelinated axons, myelinated nerve fibers, denervated Schwann cell units and collagen pockets were quantified and related to the clinical and electrophysiological data of the patients with CIDP. In 4 patients with a rapid onset of the neuropathy and a highly elevated CSF protein, the numbers of both unmyelinated axons and myelinated nerve fibers were decreased equally. In 8 patients we found that the unmyelinated axons were relatively spared compared with the loss of myelinated nerve fibers. In these patients, however, the presence of denervated Schwann cell units and of collagen pockets was increased. We conclude that unmyelinated nerve fibers are affected in patients with CIDP.

The distinct HERG missense mutation L564P causes long QT syndrome in one French Canadian family.

BACKGROUND: Long QT syndrome is a congenital abnormality of cardiac repolarization causing syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. This hereditary cardiac disorder often shows an increase of the value of the QT interval corrected for heart rate over 0.45 s in a 12-lead electrocardiogram. OBJECTIVE: To find and identify pertinent mutations occurring in French Canadians by extracting genomic DNA from blood samples and performing a combination of polymerase chain reaction (PCR), single-strand conformational polymorphism and DNA sequencing. RESULTS: A novel mutation was identified in the S5 region of the HERG potassium channel. In codon 564 CTA, T was replaced by C, resulting in a leucine to proline substitution. Two family members had the mutation in two distinct generations. A new restriction site was created at this position and therefore enabled the development of a rapid diagnostic test using PCR. HERG wild type and mutant potassium channel mRNAs were then expressed in Xenopus laevis oocytes. CONCLUSION: This electrophysiological study suggests that coexpression of HERG wild type and mutant L564P results in a dominant negative effect of the mutation.

Time course of word identification and semantic integration in spoken language.

The minimum duration signal necessary to identify a set of spoken words was established by the gating technique; most words could be identified before their acoustic offset. Gated words were used as congruous and incongruous sentence completions, and isolation points established in the gating experiment were compared with the time course of semantic integration evident in event-related brain potentials. Differential N400 responses to contextually appropriate and inappropriate words were observed about 200 ms before the isolation point. Semantic processing was evident before the acoustic signal was sufficient to identify the words uniquely. Results indicate that semantic integration can begin to operate with only partial, incomplete information about word identity. Influences of semantic constraint, word frequency, and rate of presentation are described.

Criteria for SLI: the Stark and Tallal legacy and beyond.

Since it first appeared, the Stark and Tallal (1981 ) criteria for the selection of children with specific language impairment (SLI) has had a profound influence on research with this population. A review of the recent literature indicates that these criteria continue to be used, in part or in whole, in current research. However, the recent literature also provides illustrations of the use and interpretations of norm-referenced tests that can serve to update current best practices in subject selection. The original criteria for IQ and language test scores, along with their more recent adaptations, are reconsidered in light of current information on the use of tests with SLI.

Morphology of the inferior frontal gyrus in developmentally language-disordered adults.

The inferior frontal gyrus has traditionally been considered an important cortical region for language and may be important for understanding developmental language disorders. The morphology of the inferior frontal gyrus, as it appeared on T1-weighted sagittal magnetic resonance imaging (MRI) scans, was evaluated using a classification system that distinguished between seven basic morphological variants of the gyral and sulcal patterns in this region. This classification scheme was applied to the MRI scans of 41 neurologically normal adult subjects. To examine the relation between sulcal morphology and subject status, these subjects were sorted first by family history for developmental language disorders and then resorted by expression of behavioral signs consistent with a diagnosis of this disorder as determined by standardized testing. Morphological types that included an extra sulcus in the inferior frontal gyrus were statistically associated with the behaviorally based classification of subjects, but not with a positive family history for developmental language disorders. Because gyral patterns are prenatally determined, this finding is consistent with the theory that altered prenatal development contributes to the expression of a developmental language disorder.

Image manipulation and error estimation for MRI analysis.

Manipulation of MRI images prior to volumetric analysis is a common practice that may unwittingly lead to errors in measurement. In this study, we examine the effects of two types of image manipulation: changes in the total number of slices used to obtain volume estimates (slice sampling rate) and image rotation. A phantom containing two regularly-shaped and two irregularly-shaped regions of interest (ROIs) was scanned using an SPGR sequence and 1-mm slices. Changes in slice sampling rate produced marked effects on volume estimation of irregularly-shaped ROls. Comparatively little error was associated with changes in slice sampling rates for regularly-shaped ROIs. In addition, there was an interaction between image rotation in non-orthogonal planes and slice sampling rate. The data suggests that the ability to detect anatomical effects may be influenced by an investigator's choices concerning the number of slices included in a region of interest and image rotation when estimating volumes.

Short-term and working memory differences in language/learning disabled and normal adults.

Fifteen adults who reported a childhood history of speech-language and/or learning disability (L/LD) were tested on two verbal memory tasks. Their performance on sentence repetition and reading span measures was compared with that of a matched control group who reported no childhood history of L/LD. Results indicated statistically significant group performance differences on both short-term and working memory tasks. This suggests that verbal memory difficulties may be a longterm component of L/LD.

IQ variability in children with SLI: implications for use of cognitive referencing in determining SLI.

The practice of cognitive referencing assumes that IQ scores can be used as a measure of intellectual potential from which language scores may deviate. To test the validity of this assumption the WISC scores of children with specific language impairment were compared over time. The variability of WISC scores from children with SLI from their initial evaluation and from the federally-mandated three year re-evaluation was analyzed. Significant differences in the performance scale scores were found. This indicates that the IQ scores of these children are more properly interpreted as reflecting current abilities rather than potential for language learning. This further calls into question the practice of cognitive referencing as a method of determining the presence of a language impairment, eligibility for services, and the service delivery model for which a child qualifies.

Sea anemone toxin (ATX II) modulation of heart and skeletal muscle sodium channel alpha-subunits expressed in tsA201 cells.

We have expressed recombinant alpha-subunits of hH1 (human heart subtype 1), rSkM1 (rat skeletal muscle subtype 1) and hSkM1 (human skeletal muscle) sodium channels in human embryonic kidney cell line, namely the tsA201 cells and compared the effects of ATX II on these sodium channel subtypes. ATX II slows the inactivation phase of hH1 with little or no effect on activation. At intermediate concentrations of ATX II the time course of inactivation is biexponential due to the mixture of free (fast component, taufasth) and toxin-bound (slow component, tauslowh) channels. The relative amplitude of tauslowh allows an estimate of the IC50 values approximately 11 nM. The slowing of inactivation in the presence of ATX II is consistent with destabilization of the inactivated state by toxin binding. Further evidence for this conclusion is: (i) The voltage-dependence of the current decay time constants (tauh) is lost or possibly reversed (time constants plateau or increase at more positive voltages in contrast to these of untreated channels). (ii) The single channel mean open times are increased by a factor of two in the presence of ATX II. (iii) The recovery from inactivation is faster in the presence of ATX II. Similar effects of ATX II on rSkM1 channel behavior occur, but only at higher concentrations of toxin (IC50 = 51 nM). The slowing of inactivation on hSkM1 is comparable to the one seen with rSkM1. A residual or window current appears in the presence of ATX II that is similar to that observed in channels containing mutations associated with some of the familial periodic paralyses.

Classification of adults for family studies of developmental language disorders.

A variety of approaches has been used to classify the status of adult subjects in familial studies of developmental language disorders. In this report, we directly compare the results of four different methods that appear in the research literature. Two of the approaches rely on case history reports, and two are performance-based methods. Subjects included 24 parents (12 mothers, 12 fathers) of children with developmental language disorders and 24 unrelated adult control subjects (12 female, 12 male) who completed case history items and standardized language testing designed for classification purposes. All classification methods identified more parents than control subjects as "affected". However, classification by case history methods resulted in fewer affected adults than classification through standardized testing. This outcome suggests that the variability in classification rates in studies to date may be the result of method rather than subject sample differences.

Gyral morphology in the posterior Sylvian region in families affected by developmental language disorder.

This study describes the family aggregation of gyral morphology in the posterior perisylvian region in families that contain one or more children with a developmental language disorder. The probands in these families were 8 male and 2 female children referred through therapy programs and schools for children with language and reading problems. Family members included both biological parents (10 m, 10 f) and all available siblings (6 m, 4 f). Gyral morphology in the members of these families was compared with control subjects (10 m, 10 f) who were without a personal or family history of developmental language disorders. Gyral morphology was evaluated using T1-weighted sagittal scans from a GE Signa 1.5T magnet, 5 mm consecutive slices through the full brain volume. A less common type of Sylvian fissure morphology was more frequently found in the hemispheres of language-disordered subjects and their first-degree relatives than in control subjects. In addition, the pattern of Sylvian fissure morphology across generations within the families suggests that this feature might be inherited from either parent. The elevated rate of extra gyri in the posterior perisylvian region in families affected by language disorder links an anomaly within a language-related brain region with familial risk for this disorder.