Biophysical foundations underlying TMS: Setting the stage for an effective use of neurostimulation in the cognitive neurosciences

Transcranial Magnetic Stimulation (TMS) induces electrical currents in the brain to stimulate neural tissue. This article reviews our present understanding of TMS methodology, focusing on its biophysical foundations. We concentrate on how the laws of electromagnetic induction apply to TMS; addressing issues such as the location, area (i.e., focality), depth, and mechanism of TMS. We also present a review of the present limitations and future potential of the technique.     

Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

Effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on the dopaminergic and cholinergic receptors as evaluated by positron emission tomography in the Rhesus monkey

Summary The effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) on the central cholinergic and dopaminergic systems in the Rhesus monkey brain were investigated by positron emission tomography (PET) with the muscarinic cholinergic receptor ligands (N-[¹¹C]methyl-benztropine) and dopaminergic receptor ligands selective for D₁ D₂, and D₃ subtypes ([¹¹C]SCH23390, N-[¹¹C]methyl-spiperone, and (+)[¹¹C]UH232, respectively). None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP used significantly affected the regional cerebral blood flow (rCBF as determined by Raichle's H₂ ¹⁵O method), and 10 mg/kg of R-THBP had little effect on the regional cerebral metabolic rate of glucose (rCMRglc) in the Rhesus monkey brain, as assessed by the graphical [¹⁸F]fluoro-deoxyglucose method. The effect of R-THBP on the muscarinic cholinergic system was dose dependent; while 3 mg/kg of R-THBP did not significantly alter the uptake ratio of N-[¹¹C]methyl-benztropine in several brain regions to that in the cerebellum, 10 and 30 mg/kg of R-THBP significantly reduced the uptake ratio in the thalamus, as well as in the frontal and temporal cortices. None of the doses (3, 10, and 30 mg/kg i.v.) of R-THBP tested affected [¹¹C]SCH23390 (dopamine D₁ receptor) binding. However, the k3 value for N-[¹¹C]methyl-spiperone (dopamine D₂ receptor) binding, which represents the association rate × B_max value, was significantly decreased in the striatum. The uptake ratio of (+)[¹¹C]UH232 (dopamine D₃ receptor) in the striatum to that in the cerebellum was also decreased by administration of R-THBP (3 and 30 mg/kg i.v.). These findings suggest that R-THBP acts on dopamine D₂ and D₃ receptors selectively without markedly affecting dopamine D₁ receptor binding. Furthermore, the changes in cholinergic and dopamine D₂ and D₃ receptors in vivo can not be attributed to a change in rCBF but may depend on the action of R-THBP.Abbreviations R-THBP 6R-L-erythro-5,6,7,8-tetrahydrobiopterin - PET positron emission tomography - rCBF regional cerebral blood flow - rCMRglc regional cerebral metabolic rate of glucose     

XPS analysis of poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] film surfaces exposed to an allylamine low-pressure plasma

Homogeneous and stable layers were deposited through allylamine plasma polymerization (75 W, 100 Pa, 15 min) onto poly[(3-hydroxybutyric acid)-co-(3-hydroxyvaleric acid)] (91 : 9 wt.-%) (P(HB-co-9%HV)) film surfaces, XPS analysis using take-off angles of 20° and 70° and performed 10 days and 20 days after plasma treatment gives information on the composition (in atom%) of the modified surface: C, 62.74; N, 19.60; O, 17.65. The unexpected oxygen percentage is weaker if argon plasma pretreatment (25 W, 40 Pa, 5 min) is applied. Then, a succinct mechanism is proposed. The study of changes in element ratios and binding energy values shows that the majority of incorporated functional groups seem to be amide and imine groups.     

Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy.

The frequency-dependent block of cardiac sodium channels by class 1 antiarrhythmic drugs can be described by a periodical ligand binding process between drug molecules and channel binding sites. This predicts a linear relation between onset-rate constant of frequency-dependent block and diastolic interval as well as saturation of block with high stimulation rates. From both relationships, the binding kinetics (time constant, tau on) and saturation level of block (bdinf) can be estimated. This is exemplified for the frequency-dependent block (reduction of the maximal upstroke velocity of action potentials) induced by prajmaline (10(-6) M). In the same way, the frequency-dependent effects of 11 other class 1 drugs reported in the literature were analyzed and compared with each other. When the drugs are ranked with respect to their binding kinetics (tau on), there is a close relationship to the subclasses (1a, 1b, 1c), with 1b drugs exhibiting the fastest and 1c drugs the slowest kinetics. However, differences also exist in the saturation behavior of frequency-dependent block even within the same subclasses (1a and 1c). Thus, the class 1 drugs can also be subdivided in three other groups exhibiting clearly separated bands of block-frequency relations, with half-maximal saturation occurring at different stimulation rates. Our findings may have differential implications for the antiarrhythmic and proarrhythmic efficacy of class 1 drugs.     

Peripheral gangrene associated with Kawasaki disease.

Three American infants with Kawasaki disease (KD) complicated by peripheral extremity gangrene are reported. Eight such patients (only 1 from Japan) have been reported previously. These 11 patients, infants less than 7 months old at onset of KD, are predominantly non-Asian. At least nine had associated giant coronary aneurysms, and eight had associated peripheral arterial aneurysms. In eight infants the diagnosis of KD was not established and therapy was not instituted until greater than or equal to 14 days after onset. Peripheral ischemia initially was noted 15-31 days after onset. Although the pathogenesis of this complication is not well understood, it likely includes some combination of local peripheral arteritis, arteriospasm, thrombosis peripherally and/or more proximally (e.g., in an axillary artery aneurysm), and cardiogenic shock. Treatment may include use of antiinflammatory agents such as salicylates and intravenous gamma globulin, vasodilative agents and/or methods, and thrombolytic and/or anticoagulant agents in an attempt to prevent the potentially devastating consequences of progressive gangrene.     

Multivariable non-linear controller for a synchronous generator

The problem of multivariable controller synthesis for a turbogenerator is considered. Using the feedback linearization approach for multi-input non-linear systems, the existence of a linearizing state feedback for the improved reduced-order model of a turbogenerator is proved and the simplest form of this feedback is derived. Application of the obtained non-linear controller to the multivariable control of a turbogenerator provides very good results not only for the reduced-order model but also for the ‘exact’ (Park's) model of a turbogenerator. Simulations of fault and post-fault conditions in the obtained nonlinear control system confirm its superiority over a system with a voltage regulator and power system stabilizer.