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Biomedical subjects

Bernd Weber

Publications and source records attributed to Bernd Weber.

10 recordsLinked to original sources

Neural evidence for Reference-dependence in real-market-transactions.

Human decision making has become one of the major research-foci in economics, marketing and in neuroscience. This study integrates perspectives from these disciplines by examining neurophysiological correlates to Reference-dependence of utility evaluations in real market contexts both before and after choice. First, by comparing buying and selling decisions, we observe an activation of the amygdala only in the latter. We interpret this as loss aversion with respect to prior possessions. This finding contributes to the settling of an ongoing fundamental dispute in economic theory by indicating the absence of loss aversion for money in routine transactions. Second, ex post satisfaction statements are accompanied by an activation of the reward processing orbitofrontal cortex, if the evaluation context is framed by a high external reference price instead of a lower internal reference price. This indicates a nonrational Reference-dependence--despite the neoclassical view of a rational Homo Economicus--of satisfaction measures and challenges a central marketing variable.

Adult↗

Interaction of the amyloid precursor like protein 1 with the alpha2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase.

Alpha2-adrenergic receptor agonists exert potent analgesic and sedative/hypnotic effects. In addition, they have been shown to be neuroprotective, but the mechanisms of these actions are still poorly defined. To isolate proteins that may control alpha2-adrenergic receptor function or trafficking, we performed a two-hybrid screen using the carboxy-terminal fourth intracellular tail of the alpha2A-adrenergic receptor as bait. This screen identified the amyloid precursor like protein 1 (APLP1), a homologue of the beta-amyloid precursor protein involved in Alzheimer's disease, as alpha2A-adrenergic receptor-binding protein. GST affinity chromatography revealed that APLP1 specifically interacts with all three human alpha2-adrenergic receptor subtypes and deletion mutant analysis confined the APLP1 domain involved in binding to alpha2-adrenergic receptors to the 13 amino acid residues Ser599-Ala611. Coimmunoprecipitations of transiently transfected cells with epitope-tagged APLP1 and alpha2-adrenergic receptors confirmed the interaction. Agonist treatment tended to increase the amount of alpha2A-adrenergic receptor associated with APLP1 while coimmunoprecipitations were not affected by the state of receptor phosphorylation or cotransfection of arrestin-3. Confocal laser microscopy showed that APLP1 causes a considerable shift of the alpha2A-adrenergic receptor localization from plasma membrane to intracellular compartments. Furthermore, cotransfection of alpha2A-adrenergic receptor and APLP1 into HEK293 cells significantly increased norepinephrine mediated inhibition of adenylate cyclase activity. These results suggest a possible role of APLP1 in regulation of alpha2A-adrenergic receptor trafficking. Moreover, we speculate that this interaction may present one mechanism by which alpha2-adrenergic receptor agonists exert their neuroprotective effects.

Adenylyl Cyclase Inhibitors↗

Highly functional ipsilateral motor control after extensive left hemispheric damage during gestation.

In large early cortical lesions, one of the most devastating consequences is the impaired motor dexterity of the contralateral limb. We present the case of an 8-year-old girl with a large left hemispherical porencephaly. Unlike previous reports, the girl exhibited high dexterity of the contralateral hand with preserved independent finger movements. We performed functional MRI of hand motor functions and diffusion tensor imaging, which revealed activation of the ipsilateral motor cortex and absence of a contralateral corticospinal tract. These observations suggest that by intensive training in early life, a complete transhemispheric shift of motor control with high skills can be achieved.

Brain Injuries↗

Presurgical language fMRI in patients with drug-resistant epilepsy: effects of task performance.

PURPOSE: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels. METHODS: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels. RESULTS: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation. CONCLUSIONS: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.

Adult↗

Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy.

It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the hippocampus has been challenged by recent studies. This study was undertaken to assess the effect of lesions in different parts of the left hemisphere, lesions present during language acquisition, on language lateralization. We investigated 84 adult patients with drug-resistant focal epilepsy with structural lesions and 45 healthy control subjects with an established functional MRI language paradigm. Out of the 84 patients 43 had left hippocampal sclerosis, 13 a left frontal lobe lesion and 28 a left temporal-lateral lesion. All these lesions were likely to have been present during the first years of life during language acquisition. To assess the lateralization of cerebral language representation globally as well as regionally, we calculated lateralization indices derived from activations in four regions of interest (i.e. global, inferior frontal, temporo-parietal and remaining prefrontal). Patients with left hippocampal sclerosis showed less left lateralized language representations than all other groups of subjects (P < 0.005). This effect was independent of the factor of region, indicating that language lateralization was generally affected by a left hippocampal sclerosis. Patients with left frontal lobe or temporal-lateral lesions displayed the same left lateralization of language-related activations as the control subjects. Thus, the hippocampus seems to play an important role in the establishment of language dominance. Possible underlying mechanisms are discussed.

Adolescent↗

Association between scalp hair-whorl direction and hemispheric language dominance.

Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Adult↗

Phase/amplitude reset and theta-gamma interaction in the human medial temporal lobe during a continuous word recognition memory task.

We analyzed intracranial electroencephalographic (EEG) recordings from the medial temporal lobes of 12 epilepsy patients during a continuous word recognition paradigm, contrasting trials of correctly recognized repeated words (hits) and correctly identified new words (correct rejections). Using a wavelet-based analysis, we investigated how power changes and phase clustering in different frequency bands contribute to the averaged event-related potentials (ERPs). In addition, we analyzed the actual mean phases of the different oscillations. Our analyses yielded the following results: (1) power changes contributed significantly only to the late components of the ERPs (>400 ms) (2) earlier ERP components were produced by a stimulus-related broad-band phase and amplitude reset of ongoing oscillatory activity about 190 ms after stimulus onset that involved not only the theta band, but also covered alpha and lower beta band frequencies (3) phase and amplitude reset occurred during an epoch of increased phase entrainment over time that lasted for about two oscillation periods for all involved frequencies and was more pronounced for correct rejections than for hits. The broad-band phase and amplitude reset was observed for both hits and correct rejections, and therefore, did not appear to support a specific cognitive function, but rather to act as a general facilitating factor for the processes involved in this memory task. Further analyses of synchronization between oscillations and power changes in different frequency bands revealed a task-dependent modulation of gamma activity by the entrained theta cycle, a mechanism potentially related to memory encoding and retrieval in the rhinal cortex and hippocampus, respectively.

Adult↗

Interaction between the human hippocampus and the caudate nucleus during route recognition.

Navigation through familiar environments can rely upon distinct neural representations that are related to different memory systems with either the hippocampus or the caudate nucleus at their core. However, it is a fundamental question whether and how these systems interact during route recognition. To address this issue, we combined a functional neuroimaging approach with a naturally occurring, well-controlled human model of caudate nucleus dysfunction (i.e., preclinical and early-stage Huntington's disease). Our results reveal a noncompetitive interaction so that the hippocampus compensates for gradual caudate nucleus dysfunction with a gradual activity increase, maintaining normal behavior. Furthermore, we revealed an interaction between medial temporal and caudate activity in healthy subjects, which was adaptively modified in Huntington patients to allow compensatory hippocampal processing. Thus, the two memory systems contribute in a noncompetitive, cooperative manner to route recognition, which enables the hippocampus to compensate seamlessly for the functional degradation of the caudate nucleus.

Adult↗

Age differences in neural correlates of route encoding and route recognition.

Spatial memory deficits are core features of aging-related changes in cognitive abilities. The neural correlates of these deficits are largely unknown. In the present study, we investigated the neural underpinnings of age-related differences in spatial memory by functional MRI using a navigational memory task with route encoding and route recognition conditions. We investigated 20 healthy young (18-29 years old) and 20 healthy old adults (53-78 years old) in a random effects analysis. Old subjects showed slightly poorer performance than young subjects. Compared to the control condition, route encoding and route recognition showed activation of the dorsal and ventral visual processing streams and the frontal eye fields in both groups of subjects. Compared to old adults, young subjects showed during route encoding stronger activations in the dorsal and the ventral visual processing stream (supramarginal gyrus and posterior fusiform/parahippocampal areas). In addition, young subjects showed weaker anterior parahippocampal activity during route recognition compared to the old group. In contrast, old compared to young subjects showed less suppressed activity in the left perisylvian region and the anterior cingulate cortex during route encoding. Our findings suggest that age-related navigational memory deficits might be caused by less effective route encoding based on reduced posterior fusiform/parahippocampal and parietal functionality combined with diminished inhibition of perisylvian and anterior cingulate cortices correlated with less effective suppression of task-irrelevant information. In contrast, age differences in neural correlates of route recognition seem to be rather subtle. Old subjects might show a diminished familiarity signal during route recognition in the anterior parahippocampal region.

Adolescent↗

Polymer rings and chains consisting of doubly silyl-bridged metallocenes.

With the formation of novel organometallic macromolecules in mind, the polycondensation of transition metal ions and bridged cyclopentadienyl ligands was studied. To this end solvated salts MX2 (M = Fe, Ni, and Cr) were treated with a ligand that consisted of two doubly silyl-bridged cyclopentadienyl anions. For M = Fe and diluted solutions a series of rings Oi was obtained that consisted of a minimum of six (O6) and up to 17 (O17) ferrocene moieties in the backbone. They were separated partly by medium pressure liquid chromatography. The macrocycles were established by high-resolution MALDI-TOF mass spectroscopy which also yielded the molecular weight, the polydispersion, and the mean ring size, chi n, of the mixture of reaction products. When the reaction temperature was decreased from 25 degrees C to -20 degrees C, chi n increased from 8.1 to 10.8. Ferrocene-containing chains, lambda j, with 2 < or = j < or = 12 were obtained in addition to rings in the presence of water; the terminal groups were cyclopentadiene moieties. The reaction of two ferrocene-fused cyclopentadienyl anions with [FeCl2(thf)1.5] gave chains consisting of exclusively uneven numbers of ferrocenes. For M = Ni and Cr the formation of doubly silyl-bridged nickelocenes and chromocenes was proven by NMR spectroscopy. MALDI-TOF mass spectroscopy showed nickelocene-containing chains accompanied by some rings. For M = Fe the H,H-DQF COSY spectra established the structure of O7, O8, and O9. The oxidation of the ferrocene-containing ring O7 with I2, NOPF6, and AgPF6 gave ionic species [O7]n+ which suffered from low stability. The ring-closing reaction is discussed, and the relative abundance of the various rings is related to MNDO calculations.

Journal Article↗