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Biomedical subjects

B Dräger

Publications and source records attributed to B Dräger.

At least 19 recordsLinked to original sources

Language lateralization in young children assessed by functional transcranial Doppler sonography.

Compared to adults, children show superior recovery of language function after damage to the dominant brain hemisphere. Possible explanations are that children have different patterns of language representation or display different patterns of reorganization. Information about language lateralization in children could provide insights into the repair mechanisms of the young brain. While functional magnetic resonance imaging (fMRI) is usually difficult to perform in children younger than 5 years, functional transcranial Doppler sonography (fTCD) is nonfrightening and readily applicable in young and very young children. However, for serial examinations, sufficient validity and reliability are required. To this end, we designed a picture-description language task (PDLT) for fTCD examinations in children, compared the outcome to established protocols and determined the 1 month retest-reliability of the measurement in 16 children aged 2-9 years. The dependent variable was the task-related hemispheric perfusion difference based on averaged relative cerebral blood flow velocity (CBFV) increases in the middle cerebral arteries. This picture-description language lateralization index was compared to language lateralization by a phonetic word generation task (PWGT) in adults revealing good intermethod validity (r=0.70; P <or= 0.05). The 1 month retest-reliability of the PDLT in the children was r=0.87 (P <or= 0.05). With this degree of reliability, fTCD seems a promising tool for the assessment of changes in hemispheric involvement in language in young and very young children.

Algorithms↗

Familial aggregation of strong hemispheric language lateralization.

The most conspicuous aspect of the neural basis of language is the uneven involvement of the cerebral hemispheres. The familial distribution of variable degrees of left-hemispheric language lateralization was investigated. A significant familial aggregation of strong left-hemispheric language lateralization and a positive association of the degree of language lateralization between parents and their children were found. These data strongly suggest a genetic determination of the degree of language lateralization.

Adolescent↗

How does the brain accommodate to increased task difficulty in word finding? A functional MRI study.

In functional imaging of the brain, the difficulty of a task may be critical for the pattern of activation. Increased task difficulty could lead to increased activation in task-specific regions or to activation of additional, "compensatory" regions. A previous study with functional transcranial Doppler sonography (fTCD) showed no evidence that increased difficulty in word retrieval leads to a recruitment of areas homologous to language-related regions. The question remains how the brain accommodates increasing task difficulty. Because of limitations of fTCD method, we used functional magnetic resonance imaging (fMRI) in this study. We manipulated word retrieval difficulty in healthy subjects (n = 14) to determine whether the classical language-related brain regions are activated with increasing difficulty in word retrieval. fMRI demonstrated that with increased task difficulty (I) the lateralization of language-associated brain activation remained constant, (II) no additional activation of language-related regions of the dominant hemisphere, nor of homologous regions of the subdominant hemisphere, was evident, (III) additional activation was found in right posterior parietal cortex--typically associated with sustained attention and executive control. Thus, increased difficulty in word retrieval leads to coactivation of distinct brain areas, working together in a large cognitive network, rather than to increased activation of typically language-related areas.

Adult↗

When finding words becomes difficult: is there activation of the subdominant hemisphere?

Language-related activation has been observed in the right cerebral hemisphere by functional imaging in dysphasic patients who had partially recovered from a left hemispheric ischemic stroke with aphasia. It has been cautioned that, because dysphasic patients have difficulties in retrieving words, a right-hemisphere activation could be the result of an unspecific increase in global brain activation because of an increased effort. To test this hypothesis, we increased the difficulty of finding words in a word completion task in healthy subjects (n = 14) and measured hemispheric activation by functional transcranial Doppler sonography (fTCD). The sensitivity of fTCD for this approach was validated with an established motor paradigm by detecting a steady increase in bilateral cerebral perfusion in parallel to increasing the speed of finger tapping. Conversely, in the linguistic task, increasing the difficulty of word completion did not change task related perfusion of the dominant or subdominant hemisphere (repeated measurement ANOVA: P = 0.8). These results demonstrate that difficult to perform word searches do not lead to an additional involvement of the subdominant hemisphere. This suggests that after stroke, language-related activation of the subdominant hemisphere is not simply an effort-related effect.

Adult↗

Degree of language lateralization determines susceptibility to unilateral brain lesions.

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Adult↗

Language and spatial attention can lateralize to the same hemisphere in healthy humans.

BACKGROUND: Disorders of language classically occur after left brain lesions, and disorders of spatial attention after right brain lesions. It is unclear whether the hemispheric dissociation of functions is a fixed pattern of brain organization. OBJECTIVE: The authors determined whether lateralization of language and lateralization of spatial attention also dissociate in people with atypical (i.e., right hemispheric) language dominance. METHODS: The authors selected 10 subjects with typical, i.e., left hemispheric, and 10 with atypical, i.e., right hemispheric, language representation on a random basis from a sample of 326 healthy volunteers examined with functional transcranial Doppler sonography (fTCD) for language dominance. In these subjects, hemispheric lateralization of cerebral perfusion during a line bisection task was determined with fTCD. RESULTS: The authors found a dissociation between dominance for language and spatial attention in all but four subjects. In the latter subjects, there was a significant lateralization to the right hemisphere for both tasks. The four subjects showed normal intellectual, linguistic, and spatial performance, with normal EEG and MRI scans of the brain. CONCLUSION: Even in the absence of brain pathology, the same hemisphere can be dominant in control of both language and spatial attention.

Adult↗

Automated multiple development thin layer chromatography for calystegines and their biosynthetic precursors.

Automated multiple development thin layer chromatography (AMD-TLC) was used for separation of calystegines, a class of nortropane alkaloids, and of precursors of their biosynthesis. The calystegines differ in the number of hydroxyl groups at the nortropane ring system and in the substitution pattern. A combination of TLC methods allows the separation of the individual calystegines and separation of possible precursors of the biosynthesis. Solvent combination, development time, the number of development steps, the drying time between each run and the preconditioning parameters of the silica gel TLC plates were optimised. Limits of detection were evaluated for several detection reagents.

Alkaloids↗

Pulsed amperometric detection of calystegines separated by capillary electrophoresis.

Calystegines are polyhydroxyalkaloids with a nortropane skeleton. They are oxidized by pulsed amperometry at a gold electrode due to their vicinal hydroxyl groups similar to monosaccharides, but at a slightly higher potential. Compared to carbohydrates, calystegines exhibit lower acidity, thus the effective electrophoretic mobility as anions in 0.1 M NaOH is lower, independent of their molecular mass. The acidity and mobility of calystegines increase with the number of hydroxyl groups. The influence of temperature and power dissipation in the capillary and changes of the inner surface on the migration times was eliminated by cooling and subtraction of the electroosmotic flow velocity. The high resolving power of capillary zone electrophoresis allows the separation of calystegines with the same number of hydroxyl groups. Detection is linear from 2 to 200 mg L(-1) with a 1 nL injection volume. Calystegines were determined in crude plant sap after filtration without further sample purification.

Alkaloids↗

Dihydroxynortropane alkaloids from calystegine-producing plants.

Three dihydroxynortropanes, 2alpha,7beta-dihydroxynortropane, 2alpha,3beta-dihydroxynortropane, and 3alpha,7beta-dihydroxynortropane, were isolated from calystegine-producing plants in the families Convolvulaceae and Solanaceae. 2alpha,7beta-Dihydroxynortropane was isolated from six species in the Convolvulaceae whereas only Calystegia soldanella contained it and 2alpha,3beta-dihydroxynortropane. Although neither of these were detectable in three species tested in the Solanaceae, 3alpha,7beta-dihydroxynortropane was, however, isolated from Duboisia leichhardtii.

Alkaloids↗

Calystegines in Calystegia sepium derive from the tropane alkaloid pathway.

Calystegines were measured in roots and aerial parts of Calystegia sepium. The accumulation appears developmentally regulated. Calystegine accumulation in hairy root cultures follows growth and reaches maximal values of 1,5 mg/g dry mass. 15N-Labelled tropinone was fed to root cultures and the incorporation of label into calystegines and further metabolites of the tropane alkaloid pathway was measured after 2, 4 and 6 days. Pseudotropine was completely labelled after 2 days, and calystegine A(3) was labelled faster than the calystegines of the B-group. 2,7-Dihydroxynortropane also incorporated 15N from tropinone and is suggested to be a by-product of the tropane alkaloid pathway leading to calystegines.

Alkaloids↗

Calystegines in root cultures of Atropa belladonna respond to sucrose, not to elicitation.

Calystegines are norpseudotropine alkaloids accumulating in root cultures of Atropa belladonna, together with tropine derivatives, e.g. hyoscyamine. Both alkaloid groups are derived from the tropane alkaloid pathway. For the investigation of the regulation and individual steps of tropane biosynthesis, methods for the induction of the pathway were tested. Elicitation by chitosan, or defence responses to ABA and methyl jasmonate did not enhance calystegine accumulation, but led to a more or less pronounced decrease. By blocking one arm of the diverged tropane pathway, calystegine accumulation can be increased, but total tropane alkaloid formation does not increase considerably. By elevation of sucrose supply, both, total alkaloids and calystegines in particular were increased approximately threefold. The mechanism of the induction of the biosynthesis by sucrose is not known and needs further experiments.

Journal Article↗

Behavioural relevance of atypical language lateralization in healthy subjects.

In most humans, language is lateralized to the left side of the brain. It has been speculated that this hemispheric specialization is a prerequisite for the full realization of linguistic potential. Using standardized questionnaires and performance measures, we attempted to determine if there are behavioural correlates of atypical, i.e. right-hemispheric and bilateral, language lateralization. The side and degree of language lateralization were determined by measuring the hemispheric perfusion differences by functional transcranial Doppler ultrasonography during a word generation task in healthy volunteers. Subjects with left (n = 264), bilateral (n = 31) or right (n = 31) hemisphere language representation did not differ significantly with respect to mastery of foreign languages, academic achievement, artistic talents, verbal fluency or (as assessed in a representative subgroup) in intelligence or speed of linguistic processing. These findings suggest that atypical hemispheric specialization for language, i.e. right-hemisphere or bilateral specialization, is not associated with major impairments of linguistic faculties in otherwise healthy subjects.

Adolescent↗

Language lateralization in healthy right-handers.

Our knowledge about the variability of cerebral language lateralization is derived from studies of patients with brain lesions and thus possible secondary reorganization of cerebral functions. In healthy right-handed subjects 'atypical', i.e. right hemisphere language dominance, has generally been assumed to be exceedingly rare. To test this assumption we measured language lateralization in 188 healthy subjects with moderate and strong right-handedness (59% females) by a new non-invasive, quantitative technique previously validated by direct comparison with the intracarotid amobarbital procedure. During a word generation task the averaged hemispheric perfusion differences within the territories of the middle cerebral arteries were determined. (i) The natural distribution of language lateralization was found to occur along a bimodal continuum. (ii) Lateralization was equivalent in men and women. (iii) Right hemisphere dominance was found in 7.5% of subjects. These findings indicate that atypical language dominance in healthy right-handed subjects of either sex is considerably more common than previously suspected.

Adolescent↗

Handedness and hemispheric language dominance in healthy humans.

In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between handedness and dominance has long been suspected. To clarify the relationship between handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-handedness, from 4% in strong right-handers (handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (handedness = -100). The relationship could be approximated by the formula: f1.gif" BORDER="0">. These results clearly demonstrate that the relationship between handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.

Adolescent↗

Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura.

The enzymes N-methylputrescine oxidase (MPO), the tropine-forming tropinone reductase (TRI), the pseudotropine-forming tropinone reductase (TRII), the tropine:acyl-CoA transferase (TAT) and the pseudotropine:acyl-CoA transferase (PAT) extracted from transformed root cultures of Datura stramonium and a Brugmansia candida x aurea hybrid were tested for their ability to accept a range of alternative substrates. MPO activity was tested with N-alkylputrescines and N-alkylcadaverines as substrates. TRI and TRII reduction was tested against a series of N-alkylnortropinones, N-alkylnorpelletierines and structurally related ketones as substrates. TAT and PAT esterification tests used a series of N-substituted tropines, pseudotropines, pelletierinols and pseudopelletierinols as substrates to assess the formation of their respective acetyl and tigloyl esters. The results generally show that these enzymes will accept alien substrates to varying degrees. Such studies may shed some light on the overall topology of the active sites of the enzymes concerned.

Datura stramonium↗

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization.

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.

Adult↗