Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.</p> <p>Methods</p> <p>48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.</p> <p>Trial registration</p> <p>The trial was registered with the clinical trials register of <url>http://www.clinicaltrials.gov</url> (NCT00518024).</p

Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation

A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes

Radio detection of cosmic ray air showers with LOPES

In the last few years, radio detection of cosmic ray air showers has experienced a true renaissance, becoming manifest in a number of new experiments and simulation efforts. In particular, the LOPES project has successfully implemented modern interferometric methods to measure the radio emission from extensive air showers. LOPES has confirmed that the emission is coherent and of geomagnetic origin, as expected by the geosynchrotron mechanism, and has demonstrated that a large scale application of the radio technique has great potential to complement current measurements of ultra-high energy cosmic rays. We describe the current status, most recent results and open questions regarding radio detection of cosmic rays and give an overview of ongoing research and development for an application of the radio technique in the framework of the Pierre Auger Observatory.Comment: 8 pages; Proceedings of the CRIS2006 conference, Catania, Italy; to be published in Nuclear Physics B, Proceedings Supplement

Radio emission of highly inclined cosmic ray air showers measured with LOPES

LOPES-10 (the first phase of LOPES, consisting of 10 antennas) detected a significant number of cosmic ray air showers with a zenith angle larger than 50$^{\circ}$, and many of these have very high radio field strengths. The most inclined event that has been detected with LOPES-10 has a zenith angle of almost 80$^{\circ}$. This is proof that the new technique is also applicable for cosmic ray air showers with high inclinations, which in the case that they are initiated close to the ground, can be a signature of neutrino events.Our results indicate that arrays of simple radio antennas can be used for the detection of highly inclined air showers, which might be triggered by neutrinos. In addition, we found that the radio pulse height (normalized with the muon number) for highly inclined events increases with the geomagnetic angle, which confirms the geomagnetic origin of radio emission in cosmic ray air showers.Comment: A&A accepte

A Randomized Double-Blind Crossover Study of Phase-Shift Sound Therapy for Tinnitus

Objective. The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. Study Design. A double-blind crossover randomized controlled trial. Setting. This study was conducted at the University Medical Center Groningen. Subjects and Methods. Twenty-two patients with predominantly tonal tinnitus underwent both intervention and control treatments. Each treatment consisted of three 30-minute sessions in 1 week. The control treatment was identical to the intervention treatment, except that the stimulus was a pure tone without phase shifting. Questionnaires, tinnitus loudness match, and annoyance and loudness ratings were used to measure treatment effects. Results. Pure-tone treatment and phase-shift treatment had no significant effect on tinnitus according to questionnaires (Tinnitus Handicap Index, Tinnitus Reaction Questionnaire, Hospital Anxiety and Depression Scale, and Maastricht Questionnaire), audiological matching procedures, and loudness and annoyance ratings of tinnitus. Furthermore, phase-shift treatment showed no additional significant improvement in comparison with pure-tone treatment. Changes in questionnaire scores due to pure-tone and the phase-shift treatment were correlated. Conclusion. On average across the group, both treatments failed to demonstrate a significant effect. Both treatments were beneficial for some patients. However, a positive effect was not demonstrated that could be attributed to the periodic shifting of the phase of the stimulus tone

Radio Emission in Atmospheric Air Showers: First Measurements with LOPES-30

When Ultra High Energy Cosmic Rays interact with particles in the Earth's atmosphere, they produce a shower of secondary particles propagating toward the ground. LOPES-30 is an absolutely calibrated array of 30 dipole antennas investigating the radio emission from these showers in detail and clarifying if the technique is useful for largescale applications. LOPES-30 is co-located and measures in coincidence with the air shower experiment KASCADE-Grande. Status of LOPES-30 and first measurements are presented.Comment: Proceedings of ARENA 06, June 2006, University of Northumbria, U

Investigation of the Properties of Galactic Cosmic Rays with the KASCADE-Grande Experiment

The properties of galactic cosmic rays are investigated with the KASCADE-Grande experiment in the energy range between $10^{14}$ and $10^{18}$ eV. Recent results are discussed. They concern mainly the all-particle energy spectrum and the elemental composition of cosmic rays.Comment: Proc. RICAP 09, Nucl. Instr. and Meth. in pres

Radio emission of highly inclined cosmic ray air showers measured with LOPES

LOPES (LOFAR Prototype Station) is an array of dipole antennas used for detection of radio emission from air showers. It is co-located and triggered by the KASCADE (Karlsruhe Shower Core and Array Detector) experiment, which also provides informations about air shower properties. Even though neither LOPES nor KASCADE are completely optimized for the detection of highly inclined events, a significant number of showers with zenith angle larger than 50$^o$ have been detected in the radio domain, and many with very high field strengths. Investigation of inclined showers can give deeper insight into the nature of primary particles that initiate showers and also into the possibility that some of detected showers are triggered by neutrinos. In this paper, we show the example of such an event and present some of the characteristics of highly inclined showers detected by LOPES

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson\u27s disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson\u27s disease