P3-like signatures of temporal predictions: a computational EEG study.

Many cognitive processes, ranging from perception to action, depend on the ability to predict the timing of forthcoming events. Yet, how the brain uses predictive models in the temporal domain is still an unsolved question. In previous work, we began to explore the neural correlates of temporal predictions by using a computational approach in which an ideal Bayesian observer learned the temporal probabilities of target onsets in a simple reaction time task. Because the task was specifically designed to disambiguate updating of predictive models and surprise, changes in temporal probabilities were explicitly cued. However, in the real world, we are usually incidentally exposed to changes in the statistics of the environment. Here, we thus aimed to further investigate the electroencephalographic (EEG) correlates of Bayesian belief updating and surprise associated with incidental learning of temporal probabilities. In line with our previous EEG study, results showed distinct P3-like modulations for updating and surprise. While surprise was indexed by an early fronto-central P3-like modulation, updating was associated with a later and more posterior P3 modulation. Moreover, updating was associated with a P2-like potential at centro-parietal electrodes, likely capturing integration processes between prior beliefs and likelihood of the observed event. These findings support previous evidence of trial-by-trial variability of P3 amplitudes as an index of dissociable inferential processes. Coupled with our previous findings, the present study strongly bolsters the view of the P3 as a key brain signature of temporal Bayesian inference. Data and scripts are shared on OSF: osf.io/sdy8j/.

Caregiver burden and health-related quality of life in idiopathic dystonia patients under botulinum toxin treatment: a cross-sectional study.

Dystonia is a chronic movement disorder that is associated with a reduction in health-related quality of life (HR-QoL) and restriction of activities of daily living. Botulinum neurotoxin (BT) improves disease-specific HR-QoL by reducing abnormal movements, postures, and pain. We examined the burden of the corresponding primary caregiver as a potential important factor for disease management and HR-QoL of dystonia patients under treatment with BT. 114 patients with focal, segmental, or generalized dystonia were recruited, together with 93 corresponding caregivers, whose burden was investigated using the Caregiver Burden Inventory. In addition, all participants were assessed for cognitive impairment, depression, anxiety, alexithymia, and HR-QoL. Only a small proportion of caregivers suffered from caregiver burden. Despite BT therapy, patients' HR-QoL was decreased compared to the age-matched general German population. Psychological symptoms, notably anxiety, and depression correlated significantly with reduced HR-QoL. Our data imply that caregiver burden emerged to be an issue in subgroups of dystonia patients. Furthermore, HR-QoL of dystonia patients is reduced even under optimized BT treatment in a specialized center.

Validation of the γH2AX biomarker for genotoxicity assessment: a review.

The H2AX histone protein is rapidly phosphorylated at the serine-139 position (γH2AX) in response to a broad range of DNA lesions. γH2AX induction is one of the earliest events in the DNA damage response (DDR) and plays a central role in sensing and repairing DNA damage. Since its discovery, measuring γH2AX formation using numerous methods in in vitro and in vivo experiments has been an attractive endpoint for the detection of genotoxic agents. Our review focuses on validation studies performed using this biomarker to detect the genotoxicity of model chemicals using different methods. To date, nearly two hundred genotoxic and carcinogenic model chemicals have been shown to induce in vitro γH2AX in different cell lines by numerous laboratories. Based on 27 published reports comprising 329 tested chemicals, we compared the performance of the γH2AX assay with other genotoxic endpoints (Ames assay, micronucleus, HPRT and comet) regularly used for in vitro genotoxicity assessment. Notably, the γH2AX assay performs well (91% predictivity) and efficiently differentiates aneugenic and clastogenic compounds when coupled with the pH3 biomarker. Currently, no formal guidelines have been approved for the γH2AX assay for regular genotoxicity studies, but we suggest the γH2AX biomarker could be used as a new standard genotoxicity assay and discuss its future role in genotoxicity risk assessment.

Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report.

WHAT IS KNOWN AND OBJECTIVE: The interaction between valproic acid (VPA) and carbapenem antibiotics is well described with previous reports suggesting a reduction in VPA half-life between 47% and 90%. As described in this case, this interaction might be beneficial in the setting of toxic VPA ingestion. CASE DESCRIPTION: An intubated, unresponsive patient arrived via emergency medical services after toxic VPA ingestion. Meropenem was prescribed for a suspected pneumonia and to take advantage of the VPA interaction. We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for short-term carbapenem therapy for VPA overdose.

Liver-on-chip model and application in predictive genotoxicity and mutagenicity of drugs.

Currently, there is no test system, whether in vitro or in vivo, capable of examining all endpoints required for genotoxicity evaluation used in pre-clinical drug safety assessment. The objective of this study was to develop a model which could assess all the required endpoints and possesses robust human metabolic activity, that could be used in a streamlined, animal-free manner. Liver-on-chip (LOC) models have intrinsic human metabolic activity that mimics the in vivo environment, making it a preferred test system. For our assay, the LOC was assembled using primary human hepatocytes or HepaRG cells, in a MPS-T12 plate, maintained under microfluidic flow conditions using the PhysioMimix® Microphysiological System (MPS), and co-cultured with human lymphoblastoid (TK6) cells in transwells. This system allows for interaction between two compartments and for the analysis of three different genotoxic endpoints, i.e. DNA strand breaks (comet assay) in hepatocytes, chromosome loss or damage (micronucleus assay) and mutation (Duplex Sequencing) in TK6 cells. Both compartments were treated at 0, 24 and 45 h with two direct genotoxicants: methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), and two genotoxicants requiring metabolic activation: benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). Assessment of cytochrome activity, RNA expression, albumin, urea and lactate dehydrogenase production, demonstrated functional metabolic capacities. Genotoxicity responses were observed for all endpoints with MMS and EMS. Increases in the micronucleus and mutations (MF) frequencies were also observed with CP, and %Tail DNA with B[a]P, indicating the metabolic competency of the test system. CP did not exhibit an increase in the %Tail DNA, which is in line with in vivo data. However, B[a]P did not exhibit an increase in the % micronucleus and MF, which might require an optimization of the test system. In conclusion, this proof-of-principle experiment suggests that LOC-MPS technology is a promising tool for in vitro hazard identification genotoxicants.

Selected Extracts of Chinese Herbal Medicines: Their Effect on NF-κB, PPARα and PPARγ and the Respective Bioactive Compounds.

Chinese herbal medicinal (CHM) extracts from fourteen plants were investigated in cell-based in vitro assays for their effect on nuclear factor κB (NF-κB), a key regulator of inflammation, as well as on peroxisome proliferator-activated receptors (PPARs) being key regulators of genes involved in lipid and glucose metabolism. 43% of the investigated CHMs showed NF-κB inhibitory and 50% PPARα and PPARγ activating effects. Apolar extracts from cortex and flos of Albizia julibrissin Durazz. and processed rhizomes of Arisaema sp. and Pinellia ternata (Thunb.) Breit. that effectively inhibited TNF-α-induced NF-κB activation and dose-dependently activated PPARα and PPARγ were further investigated. Bioassay-guided fractionation and analysis by GC-MS led to the identification of fatty acids as PPAR agonists, including linoleic and palmitic acid.

[Reduced time-frame for ward rounds and patient satisfaction]. / Arbeitszeitkonformes Visitenmodell und Patientenzufriedenheit.

INTRODUCTION: The introduction in 2006 of the European legislation restricting physicians work-ing hours has had a dramatic impact on working conditions. This restriction called for a marked improvement in hospital workflow, leading to a reduction of time spent on ward rounds. We conducted an opinion survey assessing patient satisfaction in the area of markedly reduced ward rounds. MATERIALS AND METHODS: By January 2009, the time-frame allowed for morning ward rounds had been reduced by 33 % from 45 to 30 min. At the same time, the attendance of the senior staff surgeon was declared mandatory on each ward round. We conducted a prospective study, assessing patient satisfaction over a period of 3 months. RESULTS: 86 patients with an average age of 56.7 years were repeatedly questioned by a single investigator. Average length of hospital stay was 7.2 days. Patients expected ward rounds to average 5.3 min, which was significantly higher than actually observed. However, an overall patient satisfaction of above 80 % could be measured. CONCLUSION: In spite of the reduced time spent on ward rounds, a high level of overall patient satisfaction can be obtained due to the regular attendance of a senior staff surgeon. Process management is furthermore endorsed by the routine -application of clinical pathways in patient management.

Rapid effective dose calculation for raster-scanning 4He ion therapy with the modified microdosimetric kinetic model (mMKM).

PURPOSE: To develop and verify effective dose (DRBE) calculation in 4He ion beam therapy based on the modified microdosimetric kinetic model (mMKM) and evaluate the bio-sensitivity of mMKM-based plans to clinical parameters using a fast analytical dose engine. METHODS: Mixed radiation field particle spectra (MRFS) databases have been generated with Monte-Carlo (MC) simulations for 4He-ion beams. Relative biological effectiveness (RBE) and DRBE calculation using MRFS were established within a fast analytical engine. Spread-out Bragg-Peaks (SOBPs) in water were optimized for two dose levels and two tissue types with photon linear-quadratic model parameters αph, ßph, and (α/ß)ph to verify MRFS-derived database implementation against computations with MC-generated mixed-field α and ß databases. Bio-sensitivity of the SOBPs was investigated by varying absolute values of ßph, while keeping (α/ß)ph constant. Additionally, dose, dose-averaged linear energy transfer, and bio-sensitivity were investigated for two patient cases. RESULTS: Using MRFS-derived databases, dose differences ≲2% in the plateau and SOBP are observed compared to computations with MC-generated databases. Bio-sensitivity studies show larger deviations when altering the absolute ßph value, with maximum D50% changes of ~5%, with similar results for patient cases. Bio-sensitivity analysis indicates a greater impact on DRBE varying (α/ß)ph than ßph in mMKM. CONCLUSIONS: The MRSF approach yielded negligible differences in the target and small differences in the plateau compared to MC-generated databases. The presented analyses provide guidance for proper implementation of RBE-weighted 4He ion dose prescription and planning with mMKM. The MRFS-DRBE calculation approach using mMKM will be implemented in a clinical treatment planning system.

Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.

BACKGROUND: Biologic pathways and metabolic mechanisms underpinning early systemic disease in cystic fibrosis (CF) are poorly understood. The Baby Observational and Nutrition Study (BONUS) was a prospective multi-center study of infants with CF with a primary aim to examine the current state of nutrition in the first year of life. Its secondary aim was to prospectively explore concurrent nutritional, metabolic, respiratory, infectious, and inflammatory characteristics associated with early CF anthropometric measurements. We report here metabolomics differences within the urine of these infants as compared to infants without CF. METHODS: Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15). RESULTS: Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins. CONCLUSIONS: Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease. TRIAL REGISTRATION: United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).

Yarrow (Achillea millefolium L. s.l.): pharmaceutical quality of commercial samples.

Yarrow (Achillea millefolium L. s.l.) is traditionally used against inflammatory and spasmodic gastrointestinal complaints, hepato-biliary disorders, as an appetite enhancing drug, against skin inflammations and for wound healing due to its antiphlogistic, choleretic and spasmolytic properties. The main pharmacologically active principles were shown to be the essential oil (antimicrobial), proazulenes and other sesquiterpene lactones (antiphlogistic), dicaffeoylquinic acids (choleretic) and flavonoids (antispasmodic). In order to assess the pharmaceutical quality of the drug we evaluated the content of these bioactive compounds in 40 commercial drug samples. The essential oil and the proazulenes were analysed according to the European Pharmacopoeia, whereas the content of dicaffeoylquinic acids and flavonoids was determined by solid phase extraction (SPE)-HPLC. This comprehensive survey revealed that the quality of the drug material was very heterogenous, and only 50% of the samples met the standards of the European Pharmacopoeia. Moreover, this study gives information about the content of phenolic compounds in the drug and allowed to establish tentative reference values which may be used as additional parameters in the quality control of the drug.

Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines.

Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO2 > CdCl2 > PbCl2 (only in LS-174T cells) > As2 O5 > SbCl3 > K2 TeO3 > As2 O3 . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc.

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet.

Through diet, people are exposed simultaneously to a variety of contaminants (e.g. heavy metals, mycotoxins, pesticides) that could have combined adverse effects on human health. A previous study identified six main mixtures of food contaminants to which French adult consumers are exposed. These complex mixtures are comprised of 11 to 19 chemicals that have numerous toxic properties. In the present study, we investigated the genotoxic effects of these food contaminants, as single molecules and in mixtures that reflect their occurrence in the French diet, using the γH2AX assay in two human cell lines (HepG2, LS-174 T). Results of detailed analysis of the 49 individual contaminants (including 21 tested in this study) demonstrated a positive genotoxic response to 14 contaminants in HepG2 and 12 in LS-174 T cells. Next, our results indicated that two mixtures out of six triggered significant γH2AX induction after 24 hr of treatment, at concentrations for which individual compounds did not induce any DNA damage, suggesting more than additive interactions between chemicals. γH2AX positive mixtures were then tested for mutagenicity with the innovative in vitro PIG-A assay in HepG2 cells coupled with the soft agar colony formation assay. The two γH2AX positive mixtures led to a significant increase in the frequency of PIG-A GPI-deficient cells and in the number of colonies formed in soft agar. In conclusion, our study demonstrates that two mixtures of contaminants present in the French diet induce genotoxicity and mutagenicity, and that the combined effects of single molecules present in these mixtures are likely not additive, highlighting potential problems for hazard assessment of mixtures. Environ. Mol. Mutagen. 59:742-754, 2018. © 2018 Wiley Periodicals, Inc.

Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificity.

Valerian is a commonly used herbal medicinal product for the treatment of anxiety and insomnia. Here we report the stimulation of chloride currents through GABA(A) receptors (I(GABA)) by valerenic acid (VA), a constituent of Valerian. To analyse the molecular basis of VA action, we expressed GABA(A) receptors with 13 different subunit compositions in Xenopus oocytes and measured I(GABA) using the two-microelectrode voltage-clamp technique. We report a subtype-dependent stimulation of I(GABA) by VA. Only channels incorporating beta(2) or beta(3) subunits were stimulated by VA. Replacing beta(2/3) by beta(1) drastically reduced the sensitivity of the resulting GABA(A) channels. The stimulatory effect of VA on alpha(1)beta(2) receptors was substantially reduced by the point mutation beta(2N265S) (known to inhibit loreclezole action). Mutating the corresponding residue of beta(1) (beta(1S290N)) induced VA sensitivity in alpha(1)beta(1S290N) comparable to alpha(1)beta(2) receptors. Modulation of I(GABA) was not significantly dependent on incorporation of alpha(1), alpha(2), alpha(3) or alpha(5) subunits. VA displayed a significantly lower efficiency on channels incorporating alpha(4) subunits. I(GABA) modulation by VA was not gamma subunit dependent and not inhibited by flumazenil (1 microM). VA shifted the GABA concentration-effect curve towards lower GABA concentrations and elicited substantial currents through GABA(A) channels at > or = 30 microM. At higher concentrations (> or = 100 microM), VA and acetoxy-VA inhibit I(GABA). A possible open channel block mechanism is discussed. In summary, VA was identified as a subunit specific allosteric modulator of GABA(A) receptors that is likely to interact with the loreclezole binding pocket.

Sulfur-enhanced defence: effects of sulfur metabolism, nitrogen supply, and pathogen lifestyle.

Evidence from field experiments indicates differential roles of sulfur and nitrogen supply for plant resistance against pathogens. Dissection of these observations in defined pathosystems and controlled nutritional conditions indicates an activation of plant sulfur metabolism in several incompatible and compatible interactions. Contents of cysteine and glutathione as markers of primary sulfate assimilation and stress response show increases in ARABIDOPSIS THALIANA upon infection, coinciding with the synthesis of sulfur-containing defence compounds. Similar increases of thiols were observed with necrotrophic, biotrophic, and hemibiotrophic pathogens. Sulfate supply was found to be neutral or beneficial for tolerance against fungal but neutral for bacterial pathogens under IN VITRO conditions. According to various reports and own observations the effects of nitrogen supply appeared to be neutral or harmful, depending on the pathogen. The activation of sulfur metabolism was a consequence of activation of gene expression as revealed by macroarray analysis of an A. THALIANA/ALTERNARIA BRASSICICOLA pathosystem. This activation appeared to be largely independent from sufficient or optimal sulfate supply and from the established sulfate deficiency response. The data suggest that plant-pathogen interactions and sulfur metabolism are linked by jasmonic acid as signal.

Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro.

OBJECTIVES: Osteosarcoma is the most common type of malignant bone tumour in children and adolescents; it has poor prognosis, is highly metastatic and is resistant to current therapeutic approaches. In this study, different herbal extracts used in phytotherapy have been screened after searching innovative natural anti-cancer components. MATERIALS AND METHODS: Twenty steroid glycosides were examined for accordance to their potential of inhibiting cell proliferation and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was examined using a CASY counter. Effects of cardiac glycosides on induction of apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity assay and measurement of mitochondrial membrane potential. RESULTS: The study revealed that various steroid glycosides suppress cell proliferation in a concentration-dependent manner. Further investigations indicated apoptotic induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolide proscillaridin A, arenobufagin, and cardenolides evomonoside, convallatoxol and ouabain waged strongest apoptotic induction, associated with breakdown of mitochondrial membrane potential and activation of caspases -8 and -9. In contrast, the bufadienolide resibufogenin and cardenolide uzarin had no effect on proliferation inhibition, apoptotic induction or change in mitochondrial membrane potential. CONCLUSION: These results indicate that bufadienolides proscillaridin A and arenobufagin and cardenolide evomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.

Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the intestine that is characterized by mononuclear cell infiltration and a predominant Th1 lymphocyte response. We tested the hypothesis that CC chemokine receptors CCR2 and CCR5 might be important in the regulation of the intestinal immune response in this disease, and we speculated that carriers of a defective 32 base pair deletion mutant of CCR5, CCR5Delta32, which results in a non-functional receptor, might be protected from CD. Using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) gene frequencies of CCR5Delta32 and of CCR2-641 (replacement of valine-64 by isoleucine in the CCR2 gene) in healthy controls (n=346) and in CD patients (n=235) were determined. In CD patients, subgroup phenotypic analyses were performed according to the Vienna classification. The overall gene frequency of CCR5Delta32 (9.8%) and CCR2-641 (7.6%) in CD patients did not deviate significantly from healthy controls (9.2 and 8.2%, respectively), nor did we observe a significant deviation from the predicted Hardy-Weinberg distribution. No significant differences in the CD phenotype classification for the different CCR5 and CCR2 alleles were observed, except for a trend to disease sparing of the upper gastrointestinal tract (carrier frequency 0 versus 19.6%, Delta=1 9.6%, P=0.079) as well as a more stricturing disease behaviour (23.5 versus 16.2%, Delta=7.3%, P=0.136) in carriers of the mutant CCR5Delta32 allele. These results indicate that the different CCR5 but not CCR2 alleles may influence disease behaviour and thereby contribute to the observed heterogeneity of CD. However, the associations observed are limited and await replication in other datasets. CCR2 and CCR5 polymorphisms are unlikely to be important determinants of overall disease susceptibility.

Stimulation of nitric oxide synthesis by the aqueous extract of Panax ginseng root in RAW 264.7 cells.

1. In this study, we investigated the effect of Panax ginseng root aqueous extracts upon inducible nitric oxide synthesis in RAW 264.7 cells. Panax ginseng root extract has been used in the Asian world for centuries as a traditional herb to enhance physical strength and resistance and is becoming more and more popular in Europe and North America. 2. Incubation of murine macrophages (RAW 264.7 cells) with increasing amounts of aqueous extracts of Panax ginseng (0.05 - 0.8 microg microl(-1)) showed a dose dependent stimulation of inducible nitric oxide synthesis. 3. Polysaccharides isolated from Panax ginseng showed strong stimulation of inducible nitric oxide synthesis, whereas a triterpene-enriched fraction from an aqueous extract of Panax ginseng did not show any stimulation. 4. Inducible nitric oxide synthase protein expression was enhanced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of Panax ginseng extract. This was associated with an incline in inducible nitric oxide synthase mRNA-levels as determined by semiquantitative polymerase chain reaction and electromobility shift assay studies indicated enhanced nuclear factor-kappaB DNA binding activity. 5. As nitric oxide plays an important role in immune function, Panax ginseng treatment could modulate several aspects of host defense mechanisms due to stimulation of the inducible nitric oxide synthase.

Error-correcting behavior in schizophrenic patients.

According to Frith (1987) the positive symptoms of schizophrenic patients result from an impaired central monitoring of their own actions. For motor behavior, this impairment implies deficient corrections of erroneous movements. Several studies found that schizophrenic patients did correct erroneous movements less frequently than various control groups. In these studies, movement errors were induced by instructing subjects to alternate between moving a joystick towards a target or away from it. In our study, 27 chronic schizophrenic patients, 27 healthy and 18 alcoholic controls were subjected to a similar task. Spatial and symbolic compatibility between stimuli and responses were varied in order to induce errors. Schizophrenic patients responded more slowly and took more time to reverse wrong movements than both control groups. They did not show fewer error corrections or increased correction latencies. These results did not support the supposed deficit in central monitoring of action. Schizophrenic patients exhibited more short latency movements with multiple changes of movement direction than the control groups. This may indicate a failure to inhibit the initiation of competing responses.

Reaction time paradigms in subjects at risk for schizophrenia.

Deviant response patterns in experimental reaction time paradigms in schizophrenic probands are well documented. Although simple reaction times are strongly influenced by the current psychopathological status of the proband (e.g. florid psychotic patients versus remitted patients) these influences are less clear for measures obtained from more complex reaction time paradigms. These include the crossover paradigm (reaction time to stimuli presented after constant preparatory intervals in comparison to reaction time to stimuli presented after irregular preparatory intervals) and the modality shift paradigm (reaction time to a stimulus (light or tone) when the modality of the stimulus on the preceding trial was the same compared to when it was different). It is not clear if these peculiarities of response patterns occur as a consequence of the disease or if they represent vulnerability markers for schizophrenia. Both crossover reaction time and modality shift reaction time paradigms were applied to 56 drug free schizophrenics, 45 healthy siblings of these patients and 68 healthy controls. The results indicate that retarded reaction times and the occurrence of the crossover effect as well as of the modality shift effect distinguish schizophrenics and controls. Healthy siblings of schizophrenics differed from healthy controls with regard to the crossover effect but not with regard to the modality shift effect. Therefore only the crossover effect represents a vulnerability marker for schizophrenia. Correlations between the modality shift and the crossover effect revealed strong correlations in the schizophrenic group only.

Plasticity in the motor system related to therapy-induced improvement of movement after stroke.

Neuroplasticity might play a beneficial role in the recovery of function after stroke but empirical evidence for this is lacking thus far. Constraint-induced (CI) therapy was used to increase the use of a paretic upper extremity in four hemiparetic stroke patients. Dipole modeling of steady-state movement-related cortical potentials was applied before and after training and 3 months later. The source locations associated with affected hand movement were unusual at follow-up because activation of the ipsilateral hemisphere was found in the absence of mirror movements of the unaffected hand. This long-term change may be considered as an initial demonstration of large-scale neuroplasticity associated with increased use of the paretic limb after application of CI therapy.