Satisfaction with and reliability of in-hospital video-EEG monitoring systems in epilepsy diagnosis - A German multicenter experience.

OBJECTIVE: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics. METHODS: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics. RESULTS: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service. CONCLUSION: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management. SIGNIFICANCE: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement.

Quality of life, anxiety and depression in adult patients after add-on of levetiracetam and conversion to levetiracetam monotherapy.

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (≥50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction.

Circadian modulation of GABA-mediated cortical inhibition.

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.

H-coil: Induced electric field properties and input/output curves on healthy volunteers, comparison with a standard figure-of-eight coil.

OBJECTIVE: To acquire information about the physical properties and physiological effects of the H-coil. METHODS: We used a robotized system to measure the electric field (E-field) generated by a H-coil prototype and compared it with a standard figure-of-eight coil. To explore the physiological properties of the coils, input/output curves were recorded for the right abductor digiti minimi muscle (ADM) as target muscle. To explore focality of stimulation, simultaneous recordings were performed for the left ADM, right abductor pollicis brevis (APB), extensor digitorum communis (EDC) and biceps brachii (BB) muscles. RESULTS: Physical measurements of the H-coil showed four potentially stimulating foci, generating different electric field intensities along two different spatial orientations. RMT was significantly lower for H-coil- as compared to figure-of-eight coil stimulation. When stimulation intensity for the input-output curve was determined by percent of maximum stimulator output, the H-coil produced larger MEPs in the right ADM, as compared to the figure-of-eight coil, due to the larger relative enhancement of stimulation intensity of the H-coil. When stimulation intensity was adjusted to RMT, MEPs elicited at the right ADM were larger for figure-of-eight coil than for H-coil stimulation, while this relation was reversed for distant non-target muscles, with low stimulation intensities. With high stimulation intensities, the H-coil elicited larger MEPs for all tested muscles. Onset latency of the MEPs was never shorter for H-coil than for figure-of-eight coil stimulation of the target muscles. CONCLUSIONS: These results are in favor for a non-focal, but not deeper effect of the H-coil, as compared to a figure-of-eight coil. SIGNIFICANCE: This is the first neurophysiological study exploring the focality and depth of stimulation delivered by the H-coil systematically in humans. We found no advantage of this coil with regard to depth of stimulation in comparison to the figure-of-eight coil. Future studies have to show if the non-focality of this coil differs relevantly from that of other non-focal coils, e.g. the round coil.

Limited impact of homeostatic plasticity on motor learning in humans.

Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a de-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agonist d-cycloserine, which selectively enhances efficacy of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential motor learning.

Timing-dependent modulation of associative plasticity by general network excitability in the human motor cortex.

Associative neuroplasticity, which encompasses the modification of synaptic strength by coactivation of two synaptic inputs, has been linked to learning processes. Because unlimited plasticity destabilizes neuronal networks, homeostatic rules were proposed and experimentally proven that control for the amount and direction of plasticity dependent on background network activity. Accordingly, low background activity would enhance facilitatory plasticity, whereas high background activity would inhibit it. However, the impact of background excitability on associative plasticity has not been studied so far in humans. Facilitatory associative plasticity was induced by paired associative stimulation (PAS) in the human motor cortex, whereas background activity was enhanced or diminished by transcranial direct current stimulation (tDCS). When applied before PAS, excitability-enhancing tDCS also boosted the efficacy of PAS, whereas excitability-diminishing tDCS turned it into inhibition. Thus, previous background activity does not influence associative plasticity homeostatically. When tDCS and PAS were applied simultaneously, now in accordance with homeostatic rules of neuroplasticity, reduced background activity resulted in a prolonged excitability enhancement by PAS, whereas enhanced background activity turned it into inhibition. We conclude that background network activity can influence associative plasticity homeostatically. However, only simultaneous modulation of both parameters is in accordance with homeostatic concepts. These findings might be of importance for the development of plasticity-inducing stimulation protocols supporting information processing in humans.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.