The modulation of the Ne-like wave on correct responses foreshadows errors

In reaction time (RT) tasks, event-related potentials (ERPs) reveal a response-locked negative wave when subjects commit errors. This wave, termed "error negativity" (Ne) or "error-related negativity" (ERN), is thought to index response-monitoring processes. With conventional monopolar recordings, this negativity is hardly seen on correct responses, likely overlapped by a large positive wave. Indeed, after Laplacian transformation (a spatial high-pass filter), a small Ne-like wave is unmasked. Recently, it has been shown that the positivity on monopolar recordings was larger for correct responses preceding an error than for correct responses preceding a correct trial. After Laplacian transformation, it appears that this effect is due, at least in part, to a decrease of the Ne-like wave on correct responses preceding an error. This result indicates that, as the Ne on errors, the Ne-like wave on correct responses is sensitive to performance and hence is likely related to response-monitoring processes.     

ERP components on reaction errors and their functional significance: a tutorial

Some years ago we described a negative (Ne) and a later positive (Pe) deflection in the event-related brain potentials (ERPs) of incorrect choice reactions [Falkenstein, M., Hohnsbein, J., Hoormann, J., Blanke, L., 1990. In: Brunia, C.H.M., Gaillard, A.W.K., Kok, A. (Eds.), Psychophysiological Brain Research. Tilburg Univesity Press, Tilburg, pp. 192-195. Falkenstein, M., Hohnsbein, J., Hoormann, J., 1991. Electroencephalography and Clinical Neurophysiology, 78, 447-455]. Originally we assumed the Ne to represent a correlate of error detection in the sense of a mismatch signal when representations of the actual response and the required response are compared. This hypothesis was supported by the results of a variety of experiments from our own laboratory and that of Coles [Gehring, W. J., Goss, B., Coles, M.G.H., Meyer, D.E., Donchin, E., 1993. Psychological Science 4, 385-390. Bernstein, P.S., Scheffers, M.K., Coles, M.G.H., 1995. Journal of Experimental Psychology: Human Perception and Performance 21, 1312-1322. Scheffers, M.K., Coles, M. G.H., Bernstein, P., Gehring, W.J., Donchin, E., 1996. Psychophysiology 33, 42-54]. However, new data from our laboratory and that of Vidal et al. [Vidal, F., Hasbroucq, T., Bonnet, M., 1999. Biological Psychology, 2000] revealed a small negativity similar to the Ne also after correct responses. Since the above mentioned comparison process is also required after correct responses it is conceivable that the Ne reflects this comparison process itself rather than its outcome. As to the Pe, our results suggest that this is a further error-specific component, which is independent of the Ne, and hence associated with a later aspect of error processing or post-error processing. Our new results with different age groups argue against the hypotheses that the Pe reflects conscious error processing or the post-error adjustment of response strategies. Further research is necessary to specify the functional significance of the Pe.     

Beeinflussung der Arzneimittelwirkung durch Erbfaktoren und Erkrankungen

Zum Thema Der genetische Polymorphismus zahlreicher Enzyme bewirkt deutliche interindividuelle und interethnische Unterschiede bei der Metabolisierung von Pharmaka, die durchaus von klinischer Relevanz sein k?nnen. Neben unerwünschten Arzneimittelwirkungen kann ein rascherer oder langsamerer Metabolismus zu ernsthaften Erkrankungen bis hin zur Entwicklung von Karzinomen führen. Die Auswirkungen dieser genetischen Variabilit?t, die sich mittels Genotypisierung darstellen l?sst, werden in diesem Beitrag am Beispiel eines Isoenzyms des Cytochrom P450-Systems und der N-Acetyltransferase eingehend dargestellt. Auch verschiedene Erkrankungen k?nnen sich auf die Pharmakokinetik und Pharmakodynamik von Medikamenten auswirken. Besonders bei ?lteren, multimorbiden Patienten werden diese Interaktionen h?ufig nicht ausreichend berücksichtigt. Die Auswirkungen von Leberfunktionsst?rungen und Niereninsuffizienz werden daher nachfolgend ausführlicher erl?utert.     

Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II—Report from the German/Swiss SIOP-LGG 2004 cohort

Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment.     

Mannheim classification of nongenomically initiated (rapid) steroid action(s)

There is increasing evidence for rapid effects of steroids that are incompatible with the classical model of genomic steroid action. To address the diversity of mechanisms for rapid steroid signaling described over the past years, a classification of rapid steroid effects has been proposed to promote the discussion and understanding of nongenomic steroid action.     

Therapy with ribozyme to the proliferating cell nuclear antigen-ribozyme and 5-fluorouracil of experimental choroidal neovascularization in rats.

PURPOSE: The aim of this study was to evaluate the efficacy of hammerhead ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU) in experimental choroidal neovascularization (CNV) model in rats. METHODS: Laser was used to induce CNV in each eye of 44 rats. For angiography studies, injections of either a mixture of PCNA-Rz 10 microg/microL and 5-FU 1.5 microg/microL, versus the same dose of either drug alone versus a control injection of Hanks' Balanced Salt Solution (HBSS) were performed. We also studied this regimen to evaluate scar size and volume. RESULTS: There was significantly less angiographic leakage for the treated eyes compared to the controls by 3.53 grading points (P = 0.0005); CNV leakage was reduced in the combination group compared to 5-FU alone by 1.75 grading units (P = 0.04) and compared to PCNARz by 2.22 grading units (P = 0.07). The scar size and volume were smaller (diameter 354.6 +/- 174.2 microm vs 477.3 +/- 157.0 microm), (thickness 52.7 +/- 43.0 microm versus 79.6 +/- 46.2 microm) with a reduction in scar volume of 44.8%. CONCLUSIONS: Subretinal injection of PCNA-Rz and 5-FU mixture is more effective as treatment of laser-induced CNV, than either drug alone. The majority of the antiangiogenic effect is a result of 5-FU activity with a contribution by the PCNA ribozyme.