Delayed auditory feedback and transcranial direct current stimulation treatment for the enhancement of speech fluency in adults who stutter: Protocol for a randomized controlled trial

Background: Stuttering is a complex speech disorder that affects speech fluency. Recently, it has been shown that noninvasive brain stimulation may be useful to enhance the results of fluency interventions in adults who stutter. Delayed auditory feedback (DAF) is a method to enhance speech fluency in individuals who stutter. Adjunctive interventions are warranted to enhance the efficacy of this intervention. Objective: Individuals who stutter have pathological activation patterns in the primary and secondary auditory areas. Consequently, in this study, we hypothesize that stimulation of these areas might be promising as an adjunctive method to fluency training via DAF to enhance speech therapy success in individuals with a stutter. We will systematically test this hypothesis in this study. Methods: This study is designed as a randomized, double-blind, sham-controlled clinical trial. All participants will receive DAF. The intervention group will additionally receive real transcranial direct current stimulation, while the control group will be exposed to sham stimulation. The assignment of the participants to one of these groups will be randomized. Before starting the treatment program, 2 preintervention assessments will be conducted to determine the severity of stuttering. Once these assessments are completed, each subject will participate in 6 intervention sessions. Postintervention assessments will be carried out immediately and 1 week after the last intervention session. Subsequently, to explore the long-term stability of the treatment results, the outcome parameters will be obtained in follow-up assessments 6 weeks after the treatment. The primary outcome measurement�the percentage of stuttered syllables�will be calculated in pre-, post-, and follow-up assessments; the secondary outcomes will be the scores of the following questionnaires: the Stuttering Severity Instrument�Fourth Edition and the Overall Assessment of the Speaker�s Experience of Stuttering. Results: This protocol was funded in 2019 and approved by the Research Ethics Committee of the Iran University of Medical Sciences in June 2019. Data collection started in October 2019. As of February 2020, we have enrolled 30 participants. We expect data analysis to be completed in April 2020, and results will be published in summer 2020. Conclusions: We anticipate that this study will show an adjunctive effect of transcranial direct current stimulation, when combined with DAF, on stuttering. This should include not only a reduction in the percentage of stuttered syllables but also improved physical behavior and quality of life in adults who stutter. © 2020 Journal of Medical Internet Research. All rights reserved

Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. RESULTS: There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. CONCLUSION: These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement

Reorganizing the Intrinsic Functional Architecture of the Human Primary Motor Cortex during Rest with Non-Invasive Cortical Stimulation

The primary motor cortex (M1) is the main effector structure implicated in the generation of voluntary movements and is directly involved in motor learning. The intrinsic horizontal neuronal connections of M1 exhibit short-term and long-term plasticity, which is a strong substrate for learning-related map reorganization. Transcranial direct current stimulation (tDCS) applied for few minutes over M1 has been shown to induce relatively long-lasting plastic alterations and to modulate motor performance. Here we test the hypothesis that the relatively long-lasting synaptic modification induced by tDCS over M1 results in the alteration of associations among populations of M1 neurons which may be reflected in changes of its functional architecture. fMRI resting-state datasets were acquired immediately before and after 10 minutes of tDCS during rest, with the anode/cathode placed over the left M1. For each functional dataset, grey-matter voxels belonging to Brodmann area 4 (BA4) were labelled and afterwards BA4 voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal network parameters which characterize the architecture of functional networks (connectivity degree, clustering coefficient and characteristic path-length) were computed, transformed to volume maps and compared before and after stimulation. At the dorsolateral-BA4 region cathodal tDCS boosted local connectedness, while anodal-tDCS enhanced long distance functional communication within M1. Additionally, the more efficient the functional architecture of M1 was at baseline, the more efficient the tDCS-induced functional modulations were. In summary, we show here that it is possible to non-invasively reorganize the intrinsic functional architecture of M1, and to image such alterations

Task-Specific Effects of tDCS-Induced Cortical Excitability Changes on Cognitive and Motor Sequence Set Shifting Performance

In this study, we tested the effects of transcranial Direct Current Stimulation (tDCS) on two set shifting tasks. Set shifting ability is defined as the capacity to switch between mental sets or actions and requires the activation of a distributed neural network. Thirty healthy subjects (fifteen per site) received anodal, cathodal and sham stimulation of the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1). We measured set shifting in both cognitive and motor tasks. The results show that both anodal and cathodal single session tDCS can modulate cognitive and motor tasks. However, an interaction was found between task and type of stimulation as anodal tDCS of DLPFC and M1 was found to increase performance in the cognitive task, while cathodal tDCS of DLPFC and M1 had the opposite effect on the motor task. Additionally, tDCS effects seem to be most evident on the speed of changing sets, rather than on reducing the number of errors or increasing the efficacy of irrelevant set filtering

Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG

Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity

Cross Section Limits for the 208^{208}Pb(86^{86}Kr,n)293^{293}118 Reaction

In April-May, 2001, the previously reported experiment to synthesize element 118 using the $^{208}$Pb($^{86}$Kr,n)$^{293}$118 reaction was repeated. No events corresponding to the synthesis of element 118 were observed with a total beam dose of 2.6 x 10$^{18}$ ions. The simple upper limit cross sections (1 event) were 0.9 and 0.6 pb for evaporation residue magnetic rigidities of 2.00 $T m$ and 2.12 $T m$, respectively. A more detailed cross section calculation, accounting for an assumed narrow excitation function, the energy loss of the beam in traversing the target and the uncertainty in the magnetic rigidity of the Z=118 recoils is also presented. Re-analysis of the primary data files from the 1999 experiment showed the reported element 118 events are not in the original data. The current results put constraints on the production cross section for synthesis of very heavy nuclei in cold fusion reactions.Comment: 7 pages, 2 figures. Submitted to EPJ

Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence

The present study demonstrates that tDCS can alter WM performance by modulating the underlying neural oscillations. This result can be considered an important step towards a better understanding of the mechanisms involved in tDCS-induced modulations of WM performance, which is of particular importance, given the proposal to use electrical brain stimulation for the therapeutic treatment of memory deficits in clinical settings

Genomic Expression Libraries for the Identification of Cross-Reactive Orthopoxvirus Antigens

Increasing numbers of human cowpox virus infections that are being observed and that particularly affect young non-vaccinated persons have renewed interest in this zoonotic disease. Usually causing a self-limiting local infection, human cowpox can in fact be fatal for immunocompromised individuals. Conventional smallpox vaccination presumably protects an individual from infections with other Orthopoxviruses, including cowpox virus. However, available live vaccines are causing severe adverse reactions especially in individuals with impaired immunity. Because of a decrease in protective immunity against Orthopoxviruses and a coincident increase in the proportion of immunodeficient individuals in today's population, safer vaccines need to be developed. Recombinant subunit vaccines containing cross-reactive antigens are promising candidates, which avoid the application of infectious virus. However, subunit vaccines should contain carefully selected antigens to confer a solid cross-protection against different Orthopoxvirus species. Little is known about the cross-reactivity of antibodies elicited to cowpox virus proteins. Here, we first identified 21 immunogenic proteins of cowpox and vaccinia virus by serological screenings of genomic Orthopoxvirus expression libraries. Screenings were performed using sera from vaccinated humans and animals as well as clinical sera from patients and animals with a naturally acquired cowpox virus infection. We further analyzed the cross-reactivity of the identified immunogenic proteins. Out of 21 identified proteins 16 were found to be cross-reactive between cowpox and vaccinia virus. The presented findings provide important indications for the design of new-generation recombinant subunit vaccines