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Frithjof Tergau

Publications and source records attributed to Frithjof Tergau.

At least 19 recordsLinked to original sources
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

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↗
PubMed2005

Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation.

Specific stimulation of neuronal circuits may promote selective inhibition or facilitation of corticospinal tract excitability. Monophasic stimulation is more likely to achieve direction-specific neuronal excitation. In 10 healthy subjects, we compared four types of repetitive transcranial magnetic stimulation (rTMS), monophasic and biphasic stimuli with the initial current in the brain flowing antero-posteriorly ("posteriorly directed") or postero-anteriorly ("anteriorly directed"). We applied rTMS over the primary motor cortex contralateral to the dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation was always more efficient than biphasic. Facilitation was induced by intracerebral anteriorly directed current flow and inhibition by posteriorly oriented current flow, although only initially for approximately 30 pulses. The early inhibition was absent when studied during a tonic muscle contraction. Several mechanisms could account for these findings. They include a more efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a back-propagating D-wave inhibiting early I-waves and thus inducing early inhibition of MEP amplitude. In any case biphasic rTMS results can be explained by a mixture of monophasic opposite stimulations. We propose the use of monophasic pulses for maximizing effects during rTMS.

Adult↗
PubMed2004

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Adult↗
PubMed2004

Levetiracetam influences human motor cortex excitability mainly by modulation of ion channel function--a TMS study.

PURPOSE: Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a selective N-type-calcium-channel blocker. METHODS: We used transcranial magnetic stimulation (TMS) in order to investigate if ion-channel blockade is relevant to the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a valid TMS parameter to detect this mode of action. In a double blind, placebo-controlled, crossover study, the effects of single oral doses of 500 and 2000 mg LEV on motor thresholds, recruitment curves (REC), cortical induced silent period (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied in 10 healthy subjects. RESULTS: A significant increase of motor thresholds was noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had no significant effect on CSP or on intracortical excitability as measured by inhibition and facilitation. CONCLUSIONS: We conclude that the modulation of ion-channel function, reflected by motor threshold elevation and a trend towards recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV. GABAergic or glutamatergic mechanisms seem to be less important in vivo as measured by TMS.

Adult↗
PubMed2004

Consolidation of human motor cortical neuroplasticity by D-cycloserine.

D-Cycloserine (CYC), a partial N-methyl-D-aspartate (NMDA) agonist, has been shown to improve cognitive functions in humans. However, the neurophysiological basis of this effect is unclear so far. We studied the impact of this drug on long-lasting after-effects of transcranial direct current (tDCS)-generated motor cortical excitability shifts, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials. While anodal tDCS enhances motor cortical excitability, cathodal tDCS diminishes it. Both effects seem to be NMDA receptor dependent. D-CYC selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-CYC alone did not modulate excitability. The potency of this drug to consolidate neuronal excitability enhancements, most probably by stabilizing the strengthening of NMDA receptors, which is a probable neurophysiological derivate of learning processes, makes it an interesting substance to improve cognitive functions.

Adult↗
PubMed2004

Human cortical motor representation of the larynx as assessed by transcranial magnetic stimulation (TMS).

OBJECTIVES: To analyze characteristic features and details on motor-evoked potentials (MEPs) of the cricothyroid and vocalis muscles from single-pulse cortical transcranial magnetic stimulation (TMS) in normal subjects to characterize cortical motor representation of laryngeal muscles. STUDY DESIGN: Prospective, experimental investigation on healthy volunteers. METHOD: MEPs of the cricothyroid and vocalis muscles elicited by cortical TMS with a figure-8-shaped coil were investigated in two groups of six healthy subjects each, with special regard to MEP amplitude as a function of the coil position on the head surface along the interaural line. RESULTS: Bilateral reproducible responses of the cricothyroid and the vocalis muscles could be observed in all subjects. For the cricothyroid muscle, maximal responses were obtained at mean stimulus positions of 7.5 +/- 1.4 cm (contralateral) and of 7.3 +/- 1.3 cm (ipsilateral), respectively. For the vocalis muscle, we found maximal responses at mean stimulus positions of 10.3 +/- 1.9 cm (contralateral) and of 9.6 +/- 1.6 cm (ipsilateral), respectively. Despite a considerable overlap of these coil positions, from which reproducible MEPs could be elicited in both groups of the laryngeal muscles, statistically significant separation of the cricothyroid-and vocalis-associated cortical representation areas was possible. CONCLUSIONS: Our observations point to two different cortical motor representation areas, with the cricothyroid muscle-related area being located more medially.

Adult↗
PubMed2004

GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.

Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.

Adult↗
PubMed2004

Bilateral changes in cortical motor representation of the tongue after unilateral peripheral facial paralysis: evidence from transcranial magnetic stimulation.

Motor evoked potentials of the lingual muscles due to focal cortical transcranial magnetic stimulation were investigated in 5 patients with unilateral total facial paralysis with regard to amplitude as a function of the coil position on the interaural line. Maximum bilateral responses could be obtained at mean stimulus positions of about 6 to 8 cm lateral to the vertex. In comparison with healthy subjects, the patient group had significantly smaller mediolateral calculated centers for ipsilateral and contralateral responses. At the optimum stimulus positions, the patients' mean motor evoked potential amplitudes were significantly lower than those in healthy subjects. These alterations could be observed on both cortical hemispheres, but were more pronounced for the hemisphere contralateral to the side of facial paralysis. Thus, we provide strong evidence of bilateral changes in lingual cortical motor representation following facial paralysis with an invasion of the facial motor area by the tongue motor representation.

Adult↗
PubMed2003

Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human.

Transcranially applied weak direct currents are capable of modulating motor cortical excitability in the human. Anodal stimulation enhances excitability, cathodal stimulation diminishes it. Cortical excitability changes accompany motor learning. Here we show that weak direct currents are capable of improving implicit motor learning in the human. During performance of a serial reaction time task, the primary motor cortex, premotor, or prefrontal cortices were stimulated contralaterally to the performing hand. Anodal stimulation of the primary motor cortex resulted in increased performance, whereas stimulation of the remaining cortices had no effect. We conclude that the primary motor cortex is involved in the acquisition and early consolidation phase of implicit motor learning.

Analysis of Variance↗
PubMed2003

Focal reduction of intracortical inhibition in the motor cortex by selective proprioceptive stimulation.

The influence of proprioception on motorcortical excitability was assessed by muscle vibration (MV; 80 Hz, 0.5 mm amplitude) of the flexor carpi radialis muscle (FCR) and compared to voluntary contraction and relaxation conditions. Motor thresholds, motor-evoked potentials (MEPs) in response to single pulses of transcranial magnetic stimulation (TMS) and the intracortical inhibition (ICI) and facilitation (ICF) after paired magnetic stimuli were studied. A control experiment using TMS inducing posteriorly directed current was performed. MEPs were recorded simultaneously from the FCR, the extensor carpi radialis, the abductor pollicis brevis and the first dorsal interosseus. In the FCR, MV led to an increase of excitability shown by a decrease of motor threshold, a facilitation of MEPs in response to single-pulse TMS, a reduction of ICI and an increase of ICF. Since especially the ICI and ICF remain unchanged in other recorded muscles, this increase of excitability is specific for the vibrated muscle. With posteriorly directed current the ICI in the FCR was reduced as well, showing an involvement of later I-waves. We suggest that MV induces a focused motorcortical activation which relies on a reduced activity of intracortical inhibitory interneuronal circuits targeting selectively the motorcortical representation of the vibrated muscle.

Adult↗
PubMed2003

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.

Adult↗
PubMed2003

Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation.

The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2-8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant (P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose-response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.

Administration, Oral↗
PubMed2003

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

OBJECTIVE: To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. METHODS: Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. RESULTS: Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. CONCLUSIONS: Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Adult↗