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Objectives: Persistent developmental stuttering is a speech fluency disorder defined by its symptoms, where the underlying neurophysiological causes remain uncertain. This study examined the underlying neurophysiological mechanisms of the speech planning process, using facilitation in the motor cortex during speech preparation as an analogue. Methods: transcranial magnetic stimulation (TMS) pulses induced motor evoked potentials (MEPs), which were recorded from the tongue. Eighteen adults who stutter (AWS) and 17 adults who do not stutter (ANS) completed three experiments, which involved reading a German prefix+verb utterance from a screen. Each experiment involved 120 trials with three distinct levels of speech production: immediate speech, delayed speech without pacing and delayed speech with predefined pacing. TMS was applied shortly before speech onset. Trial MEPs were normalised to average non-speech MEPs. MEP amplitude, MEP facilitation ratio (amplitude: pre-speech offset) and group difference were the outcomes of interest analysed by multiple regression, as well as speech reaction time analysed by correlation. Results: MEP values were 11·1%-23·4% lower in AWS than ANS (by standardised Beta), across all three experiments. MEP facilitation ratio slopes were also 4·9%-18·3% flatter in AWS than ANS across all three experiments. Reaction times for AWS were only significantly slower than for ANS in immediate speech and predefined pacing experiments. No stuttering was detected during the trials. The group difference in immediate speech was 100% and 101% greater than the other two experiments respectively. Discussion: While performance of both ANS and AWS worsens under disturbed speech conditions, greater disturbance conditions affected controls worse than AWS. Future research and therapy in stuttering should focus on non-disturbed speech. [ABSTRACT FROM AUTHOR]

The ability to simultaneously process and maintain multiple pieces of information is limited. Over the past 50 years, observational methods have provided a large amount of insight regarding the neural mechanisms that underpin the mental capacity that we refer to as “working memory.” More than 20 years ago, a neural coding scheme was proposed for working memory. As a result of technological developments, we can now not only observe but can also influence brain rhythms in humans. Building on these novel developments, we have begun to externally control brain oscillations in order to extend the limits of working memory. [ABSTRACT FROM AUTHOR]

This dataset contains three repeated measures of a standard reward-based reinforcement-learning task from 29 healthy male individuals who participated in three experimental sessions exploring cognitive placebo effects on reward learning. The dataset includes behavioural data (accuracy, reaction times) during learning and transfer, estimates of model-free computational analysis, self-reported arousal values, and expectations about the interventions' efficacy. The data were collected in 2014 at the Department of Clinical Neurophysiology, University Medical Center Goettingen, Germany. The data collection and formal analysis used a triple-blind study design as participants, operator and analyst were unaware of conditions. A github repository contains data and analyses for the paper "Placebo Intervention Enhances Reward Learning in Healthy Individuals". The dataset can be used for further analysis, reference, validation studies, teaching purposes, and collaborative research. [ABSTRACT FROM AUTHOR]

Key points Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings., However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects., We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation., For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability., Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations., Abstract Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI1mV (stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS. [ABSTRACT FROM AUTHOR]

Purpose: Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. Methods: These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. Results: Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS. To induce these long-lasting effects, a sufficient duration of stimulation (20 minutes or more) was found to may be required rather than high stimulation intensity. Conclusion: We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity. [ABSTRACT FROM AUTHOR]

Background: Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. Methods: We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. Results: The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. Conclusion: rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Activation of neurons not only changes their membrane potential and firing rate but as a secondary action reduces membrane resistance. This loss of resistance, or increase of conductance, may be of central importance in non-invasive magnetic or electric stimulation of the human brain since electrical fields cause larger changes in transmembrane voltage in resting neurons with low membrane conductances than in active neurons with high conductance. This may explain why both the immediate effects and after-effects of brain stimulation are smaller or even reversed during voluntary activity compared with rest. Membrane conductance is also increased during shunting inhibition, which accompanies the classic GABAA IPSP. This short-circuits nearby EPSPs and is suggested here to contribute to the magnitude and time course of short-interval intracortical inhibition and intracortical facilitation. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI). We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1–100 Hz; hf-tRNS 101–640 Hz, respectively) and sham stimulation over the primary motor cortex (M1) during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation with weak direct currents (transcranial direct current stimulation (tDCS)) has emerged as one of the major tools to induce neuroplastic cortical excitability alterations in humans since its (re-) introduction to the arsenal of plasticity-inducing brain stimulation tools. In this review, we gather newly emerged knowledge about the effect of tDCS on brain function in both, basic and applied research. This overview will deliver an update of the last two years of research, because especially during this time numerous important studies were published covering the above-mentioned fields. [ABSTRACT FROM AUTHOR]

The visual system has the most complex circuitry of all the sensory systems and it also possesses the ability to undergo induced and spontaneous neuroplastic changes. Most of what we know about the functional organization of the visual system is derived from animal experiments or by correlating circumscribed anatomical lesions in patients and their visual perceptual deficits or dysfunctions. However, in the past years, significant achievements have been made in characterizing visual information processing in the human using non-invasive neurophysiological techniques, such as electrical stimulation of the brain. Transcranial direct (tDCS) and alternating current stimulation (tACS) applied through the skull was shown to directly modulate the excitability of the motor and visual cortices in human subjects. This review article focuses on these stimulation methods and summarizes the latest results with regard to the application of these method over the visual areas in healthy subjects and clinical populations. [ABSTRACT FROM AUTHOR]

Background and Purpose: Neuroplastic alterations of cortical excitability and activity represent the likely neurophysiological foundation of learning and memory formation. Beyond their induction, alterations of these processes by subsequent modification of cortical activity, termed metaplasticity, came into the focus of interest recently. Animal slice experiments demonstrated that neuroplastic excitability enhancements, or diminutions, can be abolished by consecutive subthreshold stimulation. These processes, termed de-potentiation, and de-depression, have so far not been explored in humans. Methods: We combined neuroplasticity induction by transcranial direct current stimulation (tDCS) applied to the hand area of primary motor cortex (M1), which can be used to induce long-lasting excitability enhancements or reductions, dependent on the polarity of stimulation, with short-lasting voluntary muscle contraction (VMC), which itself does not induce plastic cortical excitability changes. Corticospinal and intra-cortical M1 excitability were monitored by different transcranial magnetic stimulation (TMS) protocols. Results: VMC reduced or tended to reverse the anodal tDCS-driven motor cortical excitability enhancement and the cathodal tDCS-induced excitability diminution. Our findings thus demonstrate de-potentiation- and de-depression-like phenomena at the system level in the human motor cortex. Conclusion: This neurophysiological study may contribute to a better understanding of the balance between induction and reversal of plasticity associated with motor learning and rehabilitation processes. [ABSTRACT FROM AUTHOR]

From all rTMS protocols at present, the theta burst stimulation (TBS) is considered the most efficient in terms of number of impulses and intensity required during a given stimulation. The aim of this study was to investigate the effects of inhibitory and excitatory TBS protocols on motor cortex excitability when the duration of stimulation was doubled. Fourteen healthy volunteers were tested under four conditions: intermittent theta bust stimulation (iTBS), continuous theta burst stimulation (cTBS), prolonged intermittent theta bust stimulation (ProiTBS) and prolonged continuous theta burst stimulation (ProcTBS). The prolonged paradigms were twice as long as the conventional TBS protocols. Conventional facilitatory iTBS converted into inhibitory when it was applied for twice as long, while the normally inhibitory cTBS became facilitatory when the stimulation duration was doubled. Our results show that TBS-induced plasticity cannot be deliberately enhanced simply by prolonging TBS protocols. Instead, when stimulating too long, after-effects will be reversed. This finding supplements findings at the short end of the stimulation duration range, where it was shown that conventional cTBS is excitatory in the first half and switches to inhibition only after the full length protocol. It is relevant for clinical applications for which an ongoing need for further protocol improvement is imminent. [ABSTRACT FROM AUTHOR]

Dopamine improves learning and memory formation. The neurophysiological basis for these effects might be a focusing effect of dopamine on neuroplasticity: Accordingly, in humans L-dopa prolongs focal facilitatory plasticity, but turns nonfocal facilitatory plasticity into inhibition. Here we explore the impact of D1 receptors on plasticity. Nonfocal plasticity was induced by transcranial direct current stimulation (tDCS), and focal plasticity by paired associative stimulation (PAS). Subjects received sulpiride, a D2 antagonist, to increase the relative contribution of D1 receptors to dopaminergic activity, combined sulpiride and L-dopa, to increase the relation of D1/D2 activity further, or placebo medication. Under placebo, anodal tDCS and excitatoryPAS(ePAS) increased motor cortex excitability. Cathodal tDCS and inhibitory PAS (iPAS) reduced it. Sulpiride abolished iPAS-induced inhibition, but not ePAS-generated facilitation, underlining the importance of D1-receptor activity for focal facilitatory neuroplasticity. Combining sulpiride with L-dopa reestablished iPAS-induced inhibition, but did not affect ePAS-induced plasticity. tDCS-induced plasticity, which was abolished by sulpiride in a former study, also recovered. Thus enhancing D1 activity further relative to D2 activity is relevant for facilitatory and inhibitory plasticity. However, comparison with former results show that an appropriate balance of D1 and D2 activity seems necessary to (1) consolidate the respective excitability modifications and (2) to elicit a focusing effect. [ABSTRACT FROM AUTHOR]

We briefly summarized several new stimulation techniques. There are many new methods of human brain stimulation, including modification of already known methods and brand-new methods. In this article, we focused on theta burst stimulation (TBS), repetitive monophasic pulse stimulation, paired- and quadri-pulse stimulation, transcranial alternating current stimulation (tACS), paired associative stimulation, controllable pulse shape TMS (cTMS), and deep-brain TMS. For every method, we summarized the state of the art and discussed issues that remain to be addressed. [Copyright &y& Elsevier]

Studies in animal models and humans indicate that chronic nicotine intake influences neuronal excitability, resulting in functional and structural CNS changes. The aim of the present study was to explore human primary motor cortex (M1) excitability with transcranial magnetic stimulation (TMS) in chronic smokers. A total of 44 right-handed volunteers, aged 20–30 years, participated in the study. Chronic smokers were compared with age- and sex-matched healthy nonsmokers. We tested cortical excitability with single- and paired-pulse TMS to the left M1 and short-latency afferent inhibition (SAI) by combining median nerve stimulation and motor cortex TMS. Compared with nonsmoking controls, chronic smokers showed a significantly larger amount of SAI, which is thought to depend upon the activity of cholinergic inhibitory circuits produced by somatosensory inputs. Moreover, TMS-evoked inhibitory cortical silent periods were prolonged, whereas paired-pulse intracortical facilitation and motor-evoked potentials during moderate contraction were reduced. The results suggest that chronic nicotine intake may not only strengthen cholinergic inhibitory circuits, but could also be associated with enhanced inhibitory and reduced facilitatory mechanism of specific neuronal circuits in motor cortex. These changes may form a physiological basis for neurobiological and behavioral variations associated with chronic smoking.Neuropsychopharmacology (2008) 33, 2517–2523; doi:10.1038/sj.npp.1301645; published online 5 December 2007 [ABSTRACT FROM AUTHOR]

D-Cycloserine (CYC), a partial N-methyI-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. [ABSTRACT FROM AUTHOR]

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10–20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research. [ABSTRACT FROM AUTHOR]

• Neuromodulation techniques have a therapeutic potential in movement disorders. • Techniques of invasive and non-invasive brain stimulation, spinal cord stimulation, and focused ultrasound are reviewed. • Botulinum toxin injections can benefit from electromyography to accurately identify the muscles to treat. In this review, different aspects of the use of clinical neurophysiology techniques for the treatment of movement disorders are addressed. First of all, these techniques can be used to guide neuromodulation techniques or to perform therapeutic neuromodulation as such. Neuromodulation includes invasive techniques based on the surgical implantation of electrodes and a pulse generator, such as deep brain stimulation (DBS) or spinal cord stimulation (SCS) on the one hand, and non-invasive techniques aimed at modulating or even lesioning neural structures by transcranial application. Movement disorders are one of the main areas of indication for the various neuromodulation techniques. This review focuses on the following techniques: DBS, repetitive transcranial magnetic stimulation (rTMS), low-intensity transcranial electrical stimulation, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), and focused ultrasound (FUS), including high-intensity magnetic resonance-guided FUS (MRgFUS), and pulsed mode low-intensity transcranial FUS stimulation (TUS). The main clinical conditions in which neuromodulation has proven its efficacy are Parkinson's disease, dystonia, and essential tremor, mainly using DBS or MRgFUS. There is also some evidence for Tourette syndrome (DBS), Huntington's disease (DBS), cerebellar ataxia (tDCS), and axial signs (SCS) and depression (rTMS) in PD. The development of non-invasive transcranial neuromodulation techniques is limited by the short-term clinical impact of these techniques, especially rTMS, in the context of very chronic diseases. However, at-home use (tDCS) or current advances in the design of closed-loop stimulation (tACS) may open new perspectives for the application of these techniques in patients, favored by their easier use and lower rate of adverse effects compared to invasive or lesioning methods. Finally, this review summarizes the evidence for keeping the use of electromyography to optimize the identification of muscles to be treated with botulinum toxin injection, which is indicated and widely performed for the treatment of various movement disorders. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the importance of the distance between stimulation electrodes, in various montages, on the ability to induce sustained cortical excitability changes using transcranial direct and random noise stimulation. Methods: Twelve healthy subjects participated in four different experimental conditions. The stimulation electrode was always placed over the primary motor cortex; the reference electrode was placed at the contralateral orbit or at the ipsilateral/contralateral arm. MEPs were recorded in order to measure changes in cortical excitability over time. Results: The distance between the two electrodes correlates negatively with the duration and magnitude of induced after-effects. Conclusions: In particular when using extracephalic reference electrodes with transcranial electric stimulation techniques, the stimulation intensity has to be adapted to account for interelectrode distance. Significance: Electrode distance plays a critical role in the induction for stimulation after-effects in tDCS and tRNS studies, and must be taken into account in future studies and also when making comparisons with the published literature. [ABSTRACT FROM AUTHOR]

Neurophysiological techniques have been applied in restless legs syndrome (RLS) to obtain direct and indirect measures of central and peripheral nervous system excitability, as well as to probe different neurotransmission pathways. Data converge on the hypothesis that, from a pure electrophysiological perspective, RLS should be regarded as a complex sensorimotor disorder in which cortical, subcortical, spinal cord, and peripheral nerve generators are all involved in a network disorder, resulting in an enhanced excitability and/or decreased inhibition. Although the spinal component may have dominated in neurophysiological assessment, possibly because of better accessibility compared to the brainstem or cerebral components of a hypothetical dysfunction of the diencephalic A11 area, multiple mechanisms, such as reduced central inhibition and abnormal peripheral nerve function, contribute to the pathogenesis of RLS similarly to some chronic pain conditions. Dopamine transmission dysfunction, either primary or triggered by low iron and ferritin concentrations, may also bridge the gap between RLS and chronic pain entities. Further support of disturbed central and peripheral excitability in RLS is provided by the effectiveness of nonpharmacological tools, such as repetitive transcranial magnetic stimulation and transcutaneous spinal direct current stimulation, in transiently modulating neural excitability, thereby extending the therapeutic repertoire. Understanding the complex interaction of central and peripheral neuronal circuits in generating the symptoms of RLS is mandatory for a better refinement of its therapeutic support. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST). Methods: QST was performed upon the radial part of both hands of eight healthy subjects (3 female, 5 male, 25–41years of age). These subjects were examined before and after cathodal, anodal or sham tDCS, applied in a random order. TDCS was administered for 15min at a 1mA current intensity, with the active electrode placed over the left primary motor cortex and the reference electrode above the right orbit. Results: After cathodal tDCS, cold detection thresholds (CDT), mechanical detection thresholds (MDT), and mechanical pain thresholds (MPT) significantly increased in the contralateral hand, when compared to the baseline condition. Conclusions: Cathodal tDCS temporarily reduced the sensitivity to A-fiber mediated somatosensory inputs. Significance: Impairment of these somatosensory percepts suggests a short-term suppression of lemniscal or suprathalamic sensory pathways following motor cortex stimulation by cathodal tDCS. [ABSTRACT FROM AUTHOR]

Background: Modulation of the serotonergic system affects long-term potentiation (LTP) and long-term depression (LTD), the likely neurophysiologic derivates of learning and memory formation, in animals and slice preparations. Serotonin-dependent modulation of plasticity has been proposed as an underlying mechanism for depression. However, direct knowledge about the impact of serotonin on neuroplasticity in humans is missing. Here we explore the impact of the serotonin reuptake blocker citalopram on plasticity induced by transcranial direct current stimulation (tDCS) in humans in a single-blinded, placebo-controlled, randomized crossover study. Methods: In 12 healthy subjects, anodal excitability-enhancing or cathodal excitability-diminishing tDCS was applied to the motor cortex under a single dose of 20-mg citalopram or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation (TMS). Results: Under placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for about 60–120 min. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS, whereas it turned cathodal tDCS-induced inhibition into facilitation. Conclusions: Serotonin has a prominent impact on neuroplasticity in humans, which is in favor for facilitatory plasticity. Taking into account serotonergic hypoactivity in depression, this might explain deficits of learning and memory formation. Moreover, the results suggest that for therapeutic brain stimulation in depression and other neuropsychiatric diseases (e.g., in neurorehabilitation), serotonergic reinforcement may enhance facilitatory aftereffects and thereby increase the efficacy of these tools. [Copyright &y& Elsevier]

Objectives This study examined underlying neurophysiological mechanisms of developmental stuttering – facilitation in the motor cortex during speech preparation served as analogue to the speech planning process. Methods Transcranial Magnetic Stimulation pulses induced Motor Evoked Potentials (MEPs), recorded from the tongue. 18 Adults Who Stutter (AWS) and 17 Adults who do Not Stutter (ANS) completed three experiments: spontaneous speech, planned speech and speech with predefined pacing. Each experiment involved 120 trials. In each trial, participants read a German prefix + verb utterance from a screen; the pulse was applied shortly before speech onset. Trial MEPs were normalised to average non-speech MEPs. MEP amplitude, MEP facilitation ratio (amplitude:pre-speech offset) and group difference were analysed by multiple regression, and speech reaction time analysed by correlation. Results MEP base values were 11.1–23.4% lower in AWS than ANS (by standardised Beta), across all three experiments. MEP facilitation ratio slopes were also 4.9–18.3% smaller in AWS than ANS across all three experiments. Reaction times for AWS were only significantly slower than ANS in the spontaneous speech and predefined pacing experiments. No stuttering was detected during the trials. The group difference in spontaneous speech was 100% and 101% greater than the other two experiments respectively. Discussion While both performance of ANS and AWS worsens under disturbed speech conditions, AWS responded better than controls to greater disturbance. Conclusions Research and therapy in stuttering should focus on non-disturbed speech. Significance These findings give insight into both fluent and dysfluent speech planning, especially in the context of fluency therapies. [ABSTRACT FROM AUTHOR]

Introduction Repetitive transcranial magnetic stimulation (rTMS) has been found to be a promising noninvasive therapeutic tool for a variety of neuropsychiatric conditions. Variable pulse shapes can now be generated with a controllable pulse stimulator TMS (cTMS). We looked into two main characteristics of the pulse: the pulse width and the pulse direction. The pulse direction was expressed by the M ratio which refers to the ratio between the amplitude of the main phase and the second phase i.e.: the lowest is monophasic while the highest is biphasic with two equal amplitude phases. Objectives To investigate the effect of different pulse widths and phase directions in rTMS on plastic aftereffects. Methodology MEP latencies were compared among TMS pulses with different pulse durations (40 μ s, 80 μ s and 120 μ s) using 0.2 M ratio pulses, and with different pulse directions (0.2, 0.6 and 1.0 M ratios) 80 μ s wide pulses. We also examined effects of AP 1 Hz rTMS with 900 pulses on the motor evoked potential (MEP) amplitude. Results During AP stimulation, results from 12 subjects showed that the narrower pulse shapes had longer onset and peak latencies while wider pulse shapes showed shorter latencies. Preliminary rTMS results from3 subjects showed that the shortest pulse width of 40 μ s was inhibitory and the longest width of 120 μ s was excitatory in terms of the MEP amplitude. We expect the 0.2 M ratio TMS pulses to exhibit inhibitory after-effects similar to mono-phasic pulses and the 1.0 ratio to be similar to biphasic pulses in its excitatory outcomes in line with (Sommer 2012). Discussion The shorter pulse width stimuli probably caused preferentially inhibition as they stimulated a smaller number of neurons as a portion from the local circuit causing the stimulated neurons to desynchronize the firing of the local neuronal network. In comparison the wider pulse stimuli likely stimulated a wider area setting the pace for the neuronal networking firing rate. In line with similar own unpublished data phase also affected the outcome especially in the AP direction rTMS. Significance Figuring out the optimal pulse shape for either excitation or inhibition of the brain would help understand how its effect is actually propagating through local cortical networks and eventually being able to fine-tune its therapeutic efficacy. [ABSTRACT FROM AUTHOR]