Showing papers by "Walter Paulus published in 2001"

Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans

Abstract: The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations. As revealed by transcranial magnetic stimulation, motor cortical excitability increased approximately 150% above baseline for up to 90 minutes after the end of stimulation. The feasibility of inducing long-lasting excitability modulations in a noninvasive, painless, and reversible way makes this technique a potentially valuable tool in neuroplasticity modulation.

Regional modulation of BOLD MRI responses to human sensorimotor activation by transcranial direct current stimulation.

Abstract: Blood oxygenation level dependent (BOLD) MRI was used to monitor modulations of human sensorimotor activity by prior transcranial direct current stimulation (tDCS). Activation maps for a right hand sequential finger opposition task were obtained for six subjects before as well as 0-5 min and 15-20 min after a 5-min period of 1 mA cathodal and, in a separate session, anodal tDCS of the left-hemispheric motor cortex. Cathodal tDCS resulted in a global decrease of the mean number of activated pixels by 38% (P < 0.01) 0-5 min after stimulation, which reduced to 28% (P < 0.05) 15-20 min after stimulation. A region-of-interest analysis revealed a 57% decrease of activated pixels (P < 0.001) in the supplementary motor area, but no change in the hand area of the primary motor cortex. Anodal tDCS yielded a nonsignificant 5% increase of activated pixels with no regional differences. These findings support the view that reduced neuroaxonal excitability after cathodal tDCS causes reduced brain activity. However, rather than affecting the primary sensorimotor input of an active task, the process appears to dampen those responses that rely on cortico-cortical connections and related processing. Magn Reson Med 45:196-201, 2001.

External modulation of visual perception in humans.

Abstract: Static and dynamic contrast sensitivities (sCS and dCS) were evaluated before, during, immediately after and 10 min after anodal and cathodal transcranial direct current stimulation (tDCS) applied to the occipital cortex of 15 healthy subjects. Using 4 c/d spatial and 4 Hz temporal frequencies significant sCS and dCS loss was found during and immediately after 7 min cathodal stimulation while anodal stimulation had no effect. Ten minutes after the end of the stimulation the sCS and dCS values had reached the baseline levels. Our results show that primary visual functions, such as contrast detection can be transiently altered by transcranial weak direct current stimulation, most probably modulating neural excitability, as has been shown in the motor cortex previously. The present study also support the view that this method using weak current can be a non-invasive promising tool to induce reversible focal changes in the nervous system.

Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS).

Abstract: The effects of repetitive transcranial magnetic stimulation (rTMS) on human brain activity and associated hemodynamics were investigated by blood-oxygenation-level-dependent (BOLD) MRI using echo-planar imaging at 2.0 T. Apart from bilateral activation of the auditory cortex by the audible rTMS discharges (23 bursts, 1 s duration, 10 Hz, 10-20 s interstimulus intervals), BOLD responses were restricted to cortical representations of actual finger movements performed either voluntarily or evoked by suprathreshold rTMS of the motor cortex. Neither subthreshold rTMS of the motor cortex nor suprathreshold rTMS of the lateral premotor cortex induced a detectable BOLD response. These findings suggest that neuronal depolarization as induced by rTMS modulates the spiking output of a brain area but does not automatically alter cerebral blood flow and oxygenation. The observation of BOLD MRI activations probably reflects the afferent intracortical processing of real movements. (C) 2001 Lippincott Williams & Wilkins.

The Role of Nitric Oxide in the Failing Heart

Abstract: Most experimental studies looking at contractile effects of nitric oxide (NO) tried to label NO as a positive or a negative inotrope for myocardial contractile performance [1]. In contrast to the well-defined vasodilator action of NO in the vasculature, experimental studies on the myocardial contractile effects of NO yielded contradictory results reporting both positive and negative inotropic actions [2]. This variability of the myocardial contractile response to NO resulted from methodological differences such as the source of NO, the amount of NO to which the experimental preparation was exposed, the presence of simultaneous neurohormonal stimuli and the prevailing redox balance. Although the initialin vitroexperiments mainly suggested a negative inotropic effect of NO [3], studies looking at left ventricular (LV) contractile performance in humans never observed a change in a LV contractility index such as LVdP/dtmaxduring intracoronary infusion of NO-donors [4,5], of inhibitors of NO synthase (NOS) [6] or of substance P [7], which triggers endothelial NO release. Only following pretreatment with β-agonists but not under baseline conditions did intracoronary infusion of substance P [8] or of a NOS inhibitor [9,10] result in significant changes in LVdP/dtmaxconsistent with a negative inotropic effect of NO.

Nitric Oxide and Cardiac Contractility in Human Heart Failure Time for Reappraisal

Abstract: The free radical gas nitric oxide (NO) is produced by 3 isoforms of nitric oxide synthase (NOS). All of them are present in the heart: NOS1 (nNOS, “neuronal” NOS) has been detected in cardiac conduction tissue and intracardiac neurons; NOS2 (iNOS, “cytokine-inducible” NOS) can be expressed by virtually all cells in the heart, often in conjunction with the expression of inflammatory cytokines; and finally, NOS3 (eNOS, “endothelial-constitutive” NOS) is expressed in coronary endothelium, endocardium, and cardiac myocytes. NOS3 regulates the tone of vascular smooth muscle cells; the permeability and platelet adhesion of endothelial cells; and the receptor-effector coupling, energetics, contractility, and apoptosis of cardiomyocytes.1,2 Since the original demonstration of myocardial NOS2 activity in idiopathic dilated cardiomyopathy,3 a negative inotropic effect of NO frequently was hypothesized to contribute to the depressed contractile function of failing myocardium. This hypothesis was inspired by the simultaneous publication of experimental results that showed a depressed contractile response of isolated cardiomyocytes to β-adrenergic agonists after NOS2 induction by lipopolysaccharides.4 See p 2318 To further explore this depressant action of NO on myocardial contractility, numerous experimental and clinical studies were performed, but they yielded apparently conflicting results on the inotropic effect of NO from either endogenous or pharmacological sources.2 As reported in this issue of Circulation , Cotton et al5 tackled the question of the inotropic action of NO by measuring left ventricular (LV) performance in normal control subjects and in patients with dilated cardiomyopathy during intracoronary infusion of the NOS inhibitor NG-monomethyl-l-arginine (L-NMMA). During L-NMMA infusion, Cotton et al5 observed a modest drop (14%) in LV dP/dtmax in the control group and no change in LV dP/dtmax in the cardiomyopathy group, despite myocardial expression of NOS2 in their patients. They concluded that the small …

Paired-pulse repetitive transcranial magnetic stimulation of the human motor cortex.

Abstract: In nine healthy humans we modulated corticospinal excitability by using conditioning-test paired-pulse transcranial magnetic stimulation in a repetitive mode (rTMS), and we compared its effect to conventional single-pulse rTMS. We applied 80 single pulses or 80 paired pulses to the motor cortex at frequencies ranging from 0.17 to 5 Hz. The conditioning-test intervals were 2, 5, or 10 ms. Motor evoked potential (MEP) amplitudes from the abductor digiti minimi (ADM) as target muscle and extensor carpi radialis (ECR) indicated the excitability changes during and after rTMS. During paired-pulse rTMS at a facilitatory conditioning-test interval of 10 ms, we observed a facilitation of MEPs at 1, 2, and 5 Hz. A similar facilitation was found during single-pulse rTMS, when stimulus intensity was adjusted to evoke MEPs of comparable size. Using an inhibitory conditioning-test interval of 2 ms, paired-pulse rTMS at frequencies of 1 and 2 Hz caused no change in MEP size during the train. However, paired-pulse rTMS at 5 Hz caused a strong enhancement of MEP size, indicating a loss of paired-pulse inhibition during the rTMS train. Since no facilitatory effect was observed during single-pulse rTMS with an adjusted stimulus intensity, the MEP enhancement during 5 Hz rTMS was specific for "inhibitory" paired-pulse rTMS. After 5 Hz rTMS MEPs were facilitated for 1 min, and this effect was not substantially different between paired-pulse rTMS and single-pulse rTMS. The correlation between ADM and ECR was most pronounced at 5 Hz rTMS. We conclude that paired-pulse rTMS is a suitable tool to study changes in corticospinal excitability during the course of rTMS. In addition, our data suggest that short trains of paired-pulse rTMS are not superior to single-pulse rTMS in inducing lasting inhibition or facilitation.

Treatment of restless legs syndrome with the dopamine agonist alpha-dihydroergocryptine.

Abstract: An open pilot study with the dopamine agonist α-dihydroergocryptine (DHEC) was conducted in 16 patients with idiopathic restless legs syndrome (RLS) over a period of 5 weeks. Following a drug-free interval of 1 week, the patients were treated with daily doses of 10 to 40 mg DHEC. As compared to baseline values, treatment led to a statistically significant reduction of subjective RLS symptoms. Overall complaints at night decreased significantly by 63.9 ± 38.1% as measured by a visual analogue scale. Detailed evaluation of sensory discomfort, motor restlessness, involuntary movements, as well as sleep quality also showed significant improvement. Side effects were mostly mild and affected mainly the gastrointestinal tract. Five patients needed domperidone for treatment of concomitant nausea. One patient stopped the study due to nausea. In conclusion, the results of this open study suggest a role for DHEC in the treatment of RLS. © 2001 Movement Disorder Society.

Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.

Abstract: Recently, it has been suggested that alcohol-induced hyperhomocysteinaemia in patients suffering from chronic alcoholism might be a risk factor for alcohol withdrawal seizures. In the present follow-up study 12 patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine (Hcy) on admission (71.43 +/- 25.84 mol/l) than patients (n = 37) who did not develop seizures (32.60 +/- 24.87 mol/l; U = 37.50, p = 0.0003). Using a logistic regression analysis, withdrawal seizures were best predicted by a high Hcy level on admission (p < 0.01; odds ratio 2.07). Based on these findings we developed an artificial neural network system (Kohonen feature map, KFM) for an improved prediction of the risk of alcohol withdrawal seizures. Forty-nine patients with chronic alcoholism (12 with alcohol withdrawal seizures and 37 without seizures) were randomized into a training set and a test set. Best results for sensitivity of the KFM was 83.3% (five of six seizure patients were predicted correctly) with a specificity of 94.4% (one false positive prediction of 19 patients). We conclude that in patients with alcohol-induced hyperhomocysteinaemia the KFM is a useful tool to predict alcohol withdrawal seizures.

Method, device and system for inducing changes in the excitability of the brain of a living organism

Abstract: The invention relates to a method, a device and a system for inducing changes in the excitability of the brain of a living organism. The brain is stimulated with direct current and a sufficient current strength and/or current conduction duration is/are selected to a produce a neuroplasticity effect.

Quantitative volumetry in patients with carotid disease--effects of acetazolamide.

Abstract: The intracranial effects of acetazolamide on flow velocities can be monitored noninvasively by transcranial Doppler (TCD) sonography. Extracranial volume flow changes can now reliably be measured with color duplex M-mode systems. The authors tested the volumetric effects of acetazolamide in patients with high-grade unilateral carotid disease to quantify the amount of flow changes. Patients in group 1 had a high-grade > 70% internal carotid artery (ICA) stenosis, without collateral flow through the ophthalmic artery (OA). Patients with occluded ICA were included in group 2 (patent OA collateralization) or group 3 (no OA collateralization) (n = 6 per group). In group 1, common carotid artery (CCA) volume flow in the stenotic (normal contralateral) side increased from 271 (388) ml/min by 52 (54%) with 1 g aceta-zolamide intravenously. Simultaneously, middle cerebral artery (MCA) flow velocities increased from 54 (56) cm/s by 47 (53%). In group 2, extracranial volume flow increased from 166 (444) ml/min by 19 (52)%. MCA flow velocities increased from 43 (65) cm/s by 13 (30)%. In group 3, volume flow increased from 159 (467) ml/min by 2 (46)%. Intracranial flow velocities rose from 49 (54) cm/s by 27 (41)%. Volume flow data showed the expected decline in patients with high-grade ICA stenosis and even more pronounced in patients with occlusion of the vessel. Cerebral reserve capacity was less sufficient in patients with a patent OA, despite an additional supply of 30 ml/min, indicating a hemodynamically critical situation.