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Biomedical subjects

Walter Paulus

Publications and source records attributed to Walter Paulus.

At least 19 recordsLinked to original sources
PubMed2006

Sex differences in cortical neuroplasticity in humans.

In the present study, we explore sex differences of neuroplasticity in humans, as revealed by transcranial direct current stimulation, which induces motor cortical excitability changes both during and after stimulation. We retrospectively re-analyzed data collected from previous transcranial direct current stimulation studies. In women, the excitability-diminishing after-effects of cathodal transcranial direct current stimulation were relevantly prolonged compared with the male group. Similarly, during a short direct current stimulation that elicits no after-effects, the female group showed more inhibition. In contrast, no significant differences between male and female study participants were found for excitability-enhancing anodal transcranial direct current stimulation. These results suggest sex differences, possibly due to the effects of sex hormones, in the modulation of human cortical plasticity.

Adult↗
PubMed2006

Transcranial direct current stimulation applied over the somatosensory cortex - differential effect on low and high frequency SEPs.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has an influence on the excitability of the human motor cortex measured by motor evoked potentials (MEPs) after transcranial magnetic stimulation. Low and high frequency (HFOs) components of somatosensory evoked potentials (SEPs) were studied questioning whether a comparable effect can be observed after applying tDCS to the human somatosensory cortex. METHODS: Multichannel median nerve SEPs were recorded before and after applying tDCS of 1mA over a period of 9min with the cathode placed over the somatosensory cortex and the anode over the contralateral forehead and vice versa in a second session. The source activity of the N20, N30 and HFOs was evaluated before and after application of tDCS. RESULTS: After cathodal tDCS to the somatosensory cortex we found a significant reduction of the N20 source amplitude while there was no effect after anodal stimulation. For the N30 component and HFOs no change in source activity was observed. CONCLUSIONS: Corresponding to the results for the motor cortex a sustained reduction of the excitability of the somatosensory cortex after cathodal tDCS was shown. SIGNIFICANCE: We demonstrated differential effects of tDCS on the high and low frequency components of SEPs confirming the hypothesis of locally and functionally distinct generators of these two components.

Adult↗
PubMed2006

Task-related temporal and topographical changes of cortical activity during ultra-rapid visual categorization.

The aim of our study was to provide electrophysiological evidence about the modulation of the categorization process by task requirements in the human brain. Event-related potentials (ERP) were recorded during three different categorization tasks using matched stimulus sets. In all cases, the subjects were required to differentiate between "animal" and "non-animal" stimuli. In the first task (two-choice task), they were asked to press corresponding buttons to each stimulus types. The second task was a go/no-go paradigm, only animal stimuli required motor response. The third task was a counting task; participants had to count the animal stimuli without any motor response. The reaction times in the go/no-go paradigm were significantly shorter. ERP differences between animal and non-animal pictures in the go/no-go task also appeared earlier and were localized at more posterior scalp positions compared to the two-choice task. Comparing animal responses in the two-choice task and in the go/no-go paradigm, we found a significant difference in the 130- to 170-ms time window over the fronto-central, centro-parietal regions. Similar differences were found between the responses to animal pictures in the two-choice task and in the counting paradigm. We used brain electric source analysis (BESA) algorithm on difference waves to localize the best fitting dipoles and determine the localization of brain areas contributing to scalp potential differences. The results show that different task requirements evoke different activity in the medial part of the temporal pole. The data we provided here draw attention to the careful handling of results obtained from categorization experiments, because different task requirements can affect the early categorization process itself.

Adult↗
PubMed2006

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.

Adaptation, Physiological↗
PubMed2006

ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia.

Spastin, the most commonly mutated protein in the autosomal dominant form of hereditary spastic paraplegia (AD-HSP) has been suggested to be involved in vesicular cargo trafficking; however, a comprehensive function of spastin has not yet been elucidated. To characterize the molecular function of spastin, we used the yeast two-hybrid approach to identify new interacting partners of spastin. Here, we report ZFYVE27, a novel member of the FYVE-finger family of proteins, as a specific spastin-binding protein, and we validate the interaction by both in vivo coimmunoprecipitation and colocalization experiments in mammalian cells. More importantly, we report a German family with AD-HSP in which ZFYVE27 (SPG33) is mutated; furthermore, we demonstrate that the mutated ZFYVE27 protein shows an aberrant intracellular pattern in its tubular structure and that its interaction with spastin is severely affected. We postulate that this specific mutation in ZFYVE27 affects neuronal intracellular trafficking in the corticospinal tract, which is consistent with the pathology of HSP.

Adenosine Triphosphatases↗
PubMed2006

Temporal pattern of source activities evoked by different types of motion onset stimuli.

The aim of this study was to compare the time course of motion-related source activities evoked by the onset of different kinds of visual motion stimuli in human subjects. Event-related potentials (ERP) were recorded from 64 scalp electrodes in ten healthy subjects while they were viewing four different types of motion stimuli (translation, rotation, expansion and contraction). Following a new approach combining a current density reconstruction with clustering algorithms, source maxima in the time range from 50 to 400 ms after the onset of the visual stimulus were localized and the time courses of activation were elaborated. Six regions contributed significantly to source activity, half originating in the occipital lobe and half in the right parietal and right temporal cortex. The comparison of their time courses led to the following conclusions: (i) the different kinds of motion stimuli activated about the same areas of the brain but with different temporal patterns. (ii) Mainly parietal and extrastriate areas, but not V1/V2, were significantly involved in the differentiation of different kinds of motion. (iii) Contrasting the different kinds of motion onsets, responses from parietal areas were found mainly before those from lateral occipital areas. (iv) The classically defined N2 and P2 components were significantly different among the four motion conditions, but not P1. The N2 motion-related component was elicited not only by lateral occipital areas and middle temporal areas but also by right parietal areas. (v) The rotation condition evoked a novel component P180, concomitant with an increased activity in the left middle temporal gyrus.

Adult↗
PubMed2006

Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex.

OBJECTIVE: To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. METHODS: We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. RESULTS: The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. CONCLUSIONS: The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. SIGNIFICANCE: This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.

Adult↗
PubMed2006

Circadian distribution of motor-activity in unilaterally 6-hydroxy-dopamine lesioned rats.

Sleep abnormalities in idiopathic Parkinson's disease (PD) frequently consist in a reduction of total sleep time and efficacy and subsequent excessive daytime sleepiness. As it remains unclear whether these phenomena are part of the disease itself or result from pharmacological treatment, animal models for investigating the pathophysiology of sleep alterations in PD may add knowledge to this research area. In the present study, we investigate whether changes in circadian motor activity occur in 6-OHDA-lesioning model for PD, and allow a screening for disturbed sleep-waking behaviour. Activity measurements of six male Wistar rats with 6-OHDA-lesions in the medial forebrain bundle and six controls were carried out in two consecutive 12:12 h light-dark (LD) cycles. A computer-based video-analysis system, recording the animals' movement tracks was used. Distance travelled and number of transitions between movement periods and resting periods were determined. Although 6-OHDA-lesioned animals show a reduced locomotor activity compared to non-lesioned rats, the circadian distribution basically remained intact. However, some lesioning effects were more pronounced in the resting phase than in the activity phase, possibly paralleling nocturnal akinesia in PD. In order to further elucidate the described phenomena, it will be necessary to perform studies combining sleep recordings with locomotor activity measurements.

Analysis of Variance↗
PubMed2006

Restless legs syndrome: diagnostic assessment and the advantages and risks of dopaminergic treatment.

In the past few years, major advances have been made in the field of restless legs syndrome (RLS). New tools have been developed to assess the presence and severity of RLS and its complications. Furthermore new concepts of the phenotype are emerging.With a high likelihood a slight dopaminergic hypofunction contributes essentially to the pathophysiology of most phenotypes of RLS. Dopaminergic substitution either with L-DOPA or with dopamine agonists ameliorates symptoms in the large majority of patients. Too high of doses of either type of drug may be involved in the development of augmentation caused by treatment-induced alterations in dopaminergic neurotransmission. Dopaminergic agents are currently the agents of first choice to treat RLS, and large multicenter trials support the evidence of efficacy. Very careful tailoring of the dose is required to avoid the development of treatment complications, specifically augmentation.

Dopamine Agonists↗
PubMed2006

Dopamine and the spinal cord in restless legs syndrome: does spinal cord physiology reveal a basis for augmentation?

The pathophysiology of restless legs syndrome (RLS) is incompletely understood. L-DOPA, as the precursor of dopamine, as well as dopamine agonists, plays an essential role in the treatment of RLS leading to the assumption of a key role of dopamine function in the pathophysiology of RLS. Periodic limb movements in sleep are a key feature of RLS. They are generated in the spinal cord. Here we review RLS phenomenology on the basis of known dopaminergic influence on spinal control, which has been studied a great deal in recent decades in animals. In particular, we propose that the differential effects of l-DOPA and opioids on early and late flexor reflexes may be linked to the phenomenon of augmentation.

Afferent Pathways↗
PubMed2006

Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome.

Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and generate periodic limb movements; iron deficiency may be a main predisposing factor of augmentation, probably caused by a reduced function of the dopamine transporter; therapy with levodopa or dopamine agonists should remain at low doses and; iron supplementation and opiates are the therapy of choice to counter augmentation.

Circadian Rhythm↗
PubMed2006

Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex.

Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical excitability, e.g. migraine and epilepsy.

Adult↗
PubMed2006

Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the rat cortical ramp model of focal epilepsy.

PURPOSE: Weak direct currents induce lasting alterations of cortical excitability in animals and humans, which are controlled by polarity, duration of stimulation, and current strength applied. To evaluate its anticonvulsant potential, transcranial direct current stimulation (tDCS) was tested in a modified cortical ramp-stimulation model of focal epilepsy. METHODS: The threshold for localized seizure activity (TLS) was determined in freely moving rats by applying a single train of rising bipolar pulses through a unilateral epicranial electrode. After tDCS, TLS was determined repeatedly for 120 min at intervals of 15 min. The first group of animals received two sessions of cathodal tDCS at 100 microA, one for 30 and one for 60 min. A third session consisted of 60 min of anodal tDCS. A second group received cathodal tDCS at 200 microA for 15 and for 30 min, as well as anodal tDCS for 30 min. RESULTS: Sixty minutes of cathodal tDCS at 100 microA resulted in a TLS increase lasting for >or=2 h. When the intensity was increased to 200 microA, a similar lasting TLS elevation occurred after a stimulation of just 30-min duration. In contrast, anodal tDCS at identical stimulation durations and current strengths had no significant effect on TLS. CONCLUSIONS: The anticonvulsive effect induced by cathodal tDCS depends on stimulation duration and current strength and may be associated with the induction of alterations of cortical excitability that outlast the actual stimulation. The results lead to the reasonable assumption that cathodal tDCS could evolve as a therapeutic tool in drug-refractory partial epilepsy.

Animals↗
PubMed2006

Pregabalin exerts oppositional effects on different inhibitory circuits in human motor cortex: a double-blind, placebo-controlled transcranial magnetic stimulation study.

PURPOSE: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). METHODS: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. RESULTS: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 +/- 7% of unconditioned response) compared with placebo (60 +/- 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 +/- 4% of unconditioned response) compared with placebo (45 +/- 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 +/- 8 ms or 145 +/- 8 ms after placebo to 162 +/- 7 ms or 161 +/- 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. CONCLUSIONS: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest gamma-aminobutyric acid (GABA)B-receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the alpha2-delta subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine.

Adult↗
PubMed2005

Transcranial direct current stimulation and the visual cortex.

Neuroplastic changes are defined as enduring changes in the organization of the central nervous system, such as the strength of connections, representational patterns, or neuronal properties, either morphological or functional. In recent years, new tools have emerged to induce and manipulate ongoing neuroplastic changes by external stimulation, either by modification of synchronized neuronal activity or modulation of the spontaneous firing rate. The first is performed by transcranial magnetic stimulation (TMS), the latter by direct current stimulation (tDCS). tDCS as a tool aims to induce prolonged neuronal excitability and activity alterations in the human brain via alterations of the neuronal membrane potential and results in prolonged synaptic efficacy changes. Apart from its impressive persistent excitability effects, it is a non-invasive method and can be applied painlessly. Most likely that up- or downregulation of different cortical areas by tDCS will open a new branch in the area of visual psychophysics.

Animals↗
PubMed2005

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex.

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input-output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input-output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.

Adult↗