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Author: admin | 25.12.2015 | Category: Ginkgo Biloba Tinnitus

AbstractIntroduction: Some forms of tinnitus are considered to be auditory phantom phenomena related to reorganization and hyperactivity of the auditory central nervous system. Forty-six patients with narrow band noise or white noise tinnitus, which is unilateral or predominantly perceived as coming from one side, are included in the study. De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, Verlooy J, Van de Heyning P, Moller A. Correspondence to: Dirk De Ridder, Dept of Neurosurgery, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. TMS involves the use of very short pulses of magnetic energy to stimulate nerve cells in the brain. The procedure has the following advantages: There is no need for anesthesia, the procedure is painless, there are no adverse effects, very quick results, clinical improvement between the fourth and the seventh day of treatment. Brazil attractions There is a very special attraction that you only discover when you come here: the Brazilian people. Negev Travel Logistics Company Sao Paulo is the largest metropolis in Latin America and has all features of development to provide excellent stay. We will be provided with an authorization token (please note: passwords are not shared with us) and will sync your accounts for you. The editor and reviewers' affiliations are the latest provided on their Loop research profiles and may not reflect their situation at time of review. Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. Tinnitus is the perception of sound in the absence of a corresponding external auditory stimulus. But although increasing knowledge about tinnitus generation has been revealed by neuroscientific research during the last decades, the pathophysiology of tinnitus is still incompletely understood and there exists no well established causally oriented treatment (Langguth et al., 2013). Due to these limitations, it is important to collect and combine information from different methods in order to obtain an elaborate knowledge about the neuronal correlates of chronic tinnitus. Here, we investigated the effects of single sessions of low-frequency rTMS over the left and right temporal and prefrontal cortices on oscillatory brain activity. Patients with chronic bilateral tinnitus, who had consulted the multidisciplinary Tinnitus Clinic of the University of Regensburg, were included in the study. Twenty four patients with chronic tinnitus were included in the study, but only the data of 20 patients could be analyzed. Pulses were delivered with a Medtronic system (Medtronic, USA) and a passive-cooled figure of eight coil (MCF B-65). After recording, EEG data were filtered with a high-pass filter of 1 Hz and a low-pass filter of 45 Hz and segmented into epochs of 2 s skipping the first and last two segments of the recording. After preprocessing which was done with EEGLAB (Delorme and Makeig, 2004), data were converted into Fieldtrip format (Oostenveld et al., 2011) for power spectrum analysis.
Researchers from the Oregon Health & Science University (OHSU) and the Veterans Affairs (VA) Portland Medical Center have devised a novel cure for tinnitus, a hearing impairment that involves sounds that are heard by an individual, even when there are no external sound sources present. For the present study, the researchers conducted trials on 64 subjects who were diagnosed with tinnitus. The participants chosen needed to have had symptoms of tinnitus for at least one full year. This pioneering research sure would have an estimated 45 million people, mostly veteran soldiers living in the US (who are usually diagnosed with having this condition), heave a sigh of relief. El Segundo, Manhattan Beach, Hermosa Beach, West Hollywood, Mar Vista, Venice CA, Rancho Palos Verdes and the surrounding area. Tinnitus is usually manifested by hearing unrelenting sound which could vary from ringing or buzzing to a simple hiss or hum without any sound source. No proven treatment is available until now, but patients could develop their own coping mechanisms to manage tinnitus, such as taking medications, noise suppression and now, rTMS. Folmer and his team conducted the study by designing a TMS system that releases a conical magnetic field that go through the scalp and skull, which in turn connects with the brain tissue.
The Food and Drug Administration has approved the use of transcranial magnetic stimulation but for depression only. The result of the study, published in JAMA Otolaryngology-Head & Neck Surgery, revealed positively with regards to the treatment but researchers cautioned replacement for current treatment protocols.
Using low-frequency rTMS was found to have a good effect in minimizing the activity occurring in this part of the brain.
Theta, alpha and beta burst transcranial magnetic stimulation: brain modulation in tinnitus. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool capable of modulating human brain activity, using single pulse or burst stimuli. Some forms of tinnitus are considered to be auditory phantom phenomena [1] similar to central neuropathic pain [2] related to reorganization [3, 4] and hyperactivity [5, 6] of the auditory central nervous system. All participants undergo both burst and tonic rTMS of the auditory cortex at two separate dates.
Our data demonstrate that it is not possible to suppress this kind of tinnitus by tonic rTMS. First used in 1985, TMS has been used by researchers to help understand the function of different parts of the brain.
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This page doesn't support Internet Explorer 6, 7 and 8.Please upgrade your browser or activate Google Chrome Frame to improve your experience. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus.
Here, we suggest the use of another method which might overcome some of the above mentioned limitations: combined measurements of transcranial magnetic stimulation (TMS) and EEG to investigate differences between people with and without tinnitus in the reaction to magnetic stimulation.
We concentrated on effects of 1 Hz rTMS as there is most clinical evidence for 1 Hz stimulation in chronic tinnitus. Subjects with history or presence of severe and relevant somatic, neurologic, or mental disorders were not included. In addition participants answered questions with respect to demographic and tinnitus-related characteristics, usage of psychoactive substances, and handedness (Oldfield, 1971). Measurements were done on the same weekday and at the same time except in two cases in the patient and in two cases in the control group. Study procedures with single sessions of repetitive transcranial magnetic stimulation (rTMS) and measurement with resting state electroencephalography (EEG). Randomization was guided by the rationale to stimulate one frontal, one temporal, and one parietal (=sham) cortical site per session (Figure 1), resulting in 24 possible combinations for the first session. Three patients did not complete both sessions and data of one patient could not be analyzed because of a high amount of artifacts in the EEG recordings.
Demographic, tinnitus-related, and measurement-related data of the patient and control group. Each stimulation protocol consisted of 200 pulses applied with 1 Hz at 60% stimulator output lasting about 3 min and 20 s.
Sixty two equidistant electrodes that were mounted in an elastic cap (EasyCap, Germany) were referenced to FCz during recording. Thereafter segments were visually inspected for distinct and visible aberrations from the overall recording to identify muscle artifacts (short high frequency oscillations), single channels with low signal-to-noise ratio (zero line in the EEG, main hums, or not smooth trajectories), or other large amplitude physiological artifacts (movement artifacts). For power analyses we used the minimal number of available epochs of each measurement (all subjects and all conditions) and therefore chose the first 79 epochs of each measurement. The transcranial magnetic stimulation (TMS) involves a system that produces a magnetic field shaped like a cone, which can penetrate the scalp and skull of an individual in order to interact with tissues in the brain. Out of the 32 individuals who were given an active TMS treatment, it was seen that in 18 individuals, the tinnitus symptoms were considerably lessened for six months. Folmer, the study's lead researcher who works for the National Center for Rehabilitative Auditory Research at the VA Portland Health Care System, reported. This could prove inconvenient to an individual, which could either lead to lack of sleep or distracted concentration. Higher stimulation intensity causes the magnetic field to go deeper, affecting neural activity even further. Instead, rTMS could augment existing tinnitus therapies and provide a viable option for patients who do not respond favorably to other treatments," Folmer continued.


Recently it has been shown that stimulation of specific regions of the human brain can alter (suppress) tinnitus in some patients [7, 8]. All patients who experience a tinnitus suppression during either tonic or burst rTMS or both sessions also undergo a sham stimulation: the presence of a placebo effect is tested by placing the coil perpendicular to the auditory cortex at the frequencies that yield maximal tinnitus suppression rates both for tonic and burst rTMS. Tinnitus suppression was better in all patients with burst rTMS than tonic rTMS, therefore further analyses are done on burst data only.
This could be due the simple fact that burst neuromodulation is more powerful than tonic neuromodulation or to a differential effect of burst and tonic stimulation on the lemniscal and extralemniscal auditory system.
TMS Therapy has been used around the world as a treatment for major depression and other psychiatric and neurologic diseases (anxiety, insomnia, PTSD, OCD, tinnitus, Postpartum depression, Parkinson's disease, pain management, auditory hallucinations schizophrenia, and fibromyalgia).
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The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). The rationale of this approach is that the way how the brain reacts to a specific stimulation protocol differs between people with and without tinnitus. However, treatment effects are only small and individually highly variable (Langguth et al., 2012).
Intake of psychotropic medication, participating in rTMS interventions within 1 year before the present study and wearing metal implants were further exclusion criteria.
Furthermore, hearing level was measured with a standard audiogram using frequencies ranging from 125 Hz to 8 kHz (Madsen Midimate 622D; GN Otometrics, Denmark). At each session three rTMS protocols were tested and four EEG recordings (before and after each rTMS intervention) were done. In the second session the contralateral stimulation (sham stimulation was unchanged for both measurements) sites were stimulated in the same order as in the first session. Stimulation intensity was set to a fixed value of 60% stimulator output and not adjusted to the individual motor threshold as stimulation was done through the EEG cap hampering exact motor threshold measurements.
After the fast fourier transformation using a hanning window (Fieldtrip parameters mtmfft and hanning) the power spectrum of each channel, condition, and subject was normalized by dividing the power of each frequency bin by the mean power of the whole power spectrum. In a second step, we substracted the baseline-corrected data of the sham condition from the baseline-corrected data for the different active conditions (stimulation site specific changes minus sham-induced change). Until date, the use of this system has only been allowed for treating depression, by the USFDA. However, the researchers felt that a larger trial was needed to establish the suitability of TMS for clinical applications.
Auditory cortex stimulation can be performed with a strong impulse of magnetic field that induces an electrical current in the brain (transcranial magnetic stimulation (TMS)) or with implanted electrodes [7, 8]. Of the participants, 14 (30,4 %) demonstrated no placebo effect on both tonic and burst rTMS, 9 (19,6%) did have a placebo suppression, and 23 (50%) showed no suppressive response to either burst nor tonic rTMS. To assess differences in tinnitus suppression between genders, an independent sampled t-test was performed with burst rTMS stimulation as dependent variable and gender as grouping variable. The difference in the effect of single pulses and bursts on tinnitus may be explained by the fact that burst stimulation is more powerful in activating the cerebral cortex than tonic stimulation [11-14]. Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity.
Decreased output from the cochlea leads to neuroplastic changes along the auditory pathway including changes of the spontaneous firing rate, evoked activity and tonotopic reorganization. Nevertheless we have to be aware that each of these methods has both strengths and weaknesses. We aimed at testing if this procedure can be used (1) as marker for altered neuroplasticity in chronic tinnitus (pre- to post-rTMS effects); and (2) as indicator for rTMS induced tinnitus loudness reduction. The control group was recruited by advertisements and matched for age, sex, handedness, education, and hearing level. The TMS motor threshold was assessed with the EEG cap on the head at the beginning of each session. The 24 possible combinations were randomized before study begin for the patient and control group separately.
We measured 20 healthy controls which were comparable to the patients for age, sex, handedness, education, and hearing level. Nevertheless, motor threshold was determined in each participant by beginning the search for the hot spot in the area of C3 followed by stepwise adjustment of the stimulation intensity. The data excluding electrodes with low signal-to-noise ratio (maximum of five per measurement) was then subjected to an infomax independent component analysis in order to identify artifact components. These baseline- and sham-controlled data of patients and controls were compared in an unpaired t-test using a non-parametric permutation test (Fieldtrip parameter montecarlo) with 1000 iterations and a cluster correction to control for alpha inflation due to multiple testing of 63 electrodes.
For the 10 days the trial lasted, each participant received 2,000 TMS pulses in each session. Methods: rTMS is performed both in tonic and burst mode in 46 patients contralateral to the tinnitus side, at 5, 10 and 20 Hz. Repetitive TMS (rTMS) is a non-invasive tool that makes it possible to selectively and safely stimulate specific regions of the human brain. To assess differences in distress caused by tinnitus depending on the side (left or right) an independent sampled t­-test was performed with Tinnitus Questionnaire (TQ) score as dependent variable and tinnitus side as grouping variable.
This may be related to the fact that burst activation requires less temporal integration to reach the threshold of a neuron and bursts may activate neurons that are not activated by tonic stimulations (unmasking dormant synapses) [2].A second hypothetical explanation could be that only burst stimulation is capable of modifying the function of the extralemniscal (nonspecific or non-classical) system, the neurons of which are known to fire in bursts [20, 21]. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system.
As tinnitus is continuously perceived in most cases, resting state measurements were assumed to be best suited to identify the neuronal correlates of tinnitus.
TMS-EEG studies enable the measurement of neural reactivity (TMS evoked activity after single pulses) and of neuroplasticity (resting state measurements before and after short repetitive transcranial magnetic stimulation (rTMS) interventions) free of cognitive confounders.
The rational of this approach is to reduce putative over-activation and hyper-connectivity in chronic tinnitus (Eichhammer et al., 2003). Concerning the first question we hypothesized that neuroplastic effects of rTMS over temporal and frontal brain areas will differ between tinnitus patients and controls.
The study was approved by the Ethics Committee of the University of Regensburg (12-101-0216). Motor threshold was defined as the minimal stimulation intensity at which visible muscle twitches of the fingers of the right hand were obtained in at least five out of ten pulses. The signals were digitized at a rate of 500 Hz (BrainAmp DC, Vision Recorder, Brain Products, Germany).
Horizontal and vertical eye movement artifact components were removed and the remaining components were back-projected to the EEG signal space. For the baseline and sham conditions the two available measurements (one from session 1, one from session 2) were averaged.
In other words we calculated the following t-test for each stimulation site: patients [(verum-baseline)-(sham-baseline)] vs. The electrical current induced in brain tissue by a strong single pulse magnetic field can temporarily excite or inhibit neuronal activity depending on the stimulation parameters [9].
Since the rTMS machine generates a clicking sound on each magnetic pulse delivery, using only results from placebo negative patients prevents the possible influence of sound from the rTMS masking the tinnitus. Pearson's correlations were performed to assess significant correlations between variables. Tonic or single spike firing is the main firing mode of neurons in the tonotopically organized lemniscal auditory system [20-22].
Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. However, in most of the EEG-, MEG-, PET- and fMRI-resting state studies perceptual, attentional and cognitive processes during the measurement were not specified.
All participants gave written informed consent after a comprehensive explanation of the procedures. In all participants, educational years, hyperacusis, depressivity and intelligence were recorded and considered in the statistical analysis. In most cases the motor threshold was ≤60% stimulator output with the exception of one patient in session one and another patient in session two.
For the sham condition (single blinded; patients were not informed about a placebo stimulation) the back-side of the passive cooled coil was put over the electrode position CPz with the handle pointing backwards.
Finally, the data was carefully visually inspected a second time for any remaining artifacts.


Results: In 5 patients, maximal tinnitus suppression is obtained with theta, in 2 with alpha and in 7 with beta burst stimulation.
So far it has only been possible to suppress pure tone tinnitus whereas narrow band or white noise tinnitus remains unaffected by such stimulation [7, 10].As burst firing is a more powerful activator of the cortex than tonic firing [11-14] it may be expected that burst rTMS is more powerful in suppressing abnormal activity perceived as tinnitus than tonic rTMS. The rTMS is performed as a part of a continuing clinical protocol for selection of candidates for implantation of permanent electrodes for electrical stimulation of the auditory cortex for treatment for tinnitus [7, 8] the multidisciplinary tinnitus clinic of the University Hospital of Antwerp, Belgium. Burst firing has been found to occur normally in neurons in the non-tonotopically organized extralemniscal auditory system [20-22].
Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Repetitive TMS (rTMS; rhythmic repetition of single pulses at specific frequencies or with specific protocols) induces prolonged changes for up to 2 h which can be measured by resting state EEG before and after the intervention (Thut and Pascual-Leone, 2010). Thereafter the data was re-referenced to an average reference, the online-reference FCz was reconstructed, and electrodes with signal loss were interpolated. Recently it has become possible to deliver stimulations that consist of bursts of magnetic impulses (burst rTMS) [15]. All prospective participants undergo a complete audiological, ENT and neurological investigation to rule out possible treatable causes for their tinnitus.
Some cells in the ventral medial geniculate body (MGBv) of the thalamus can fire in both modes depending on their membrane potential [23, 24]. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Resting state studies assume that the tinnitus percept and the related neural changes are constant over time.
Non-clinical studies have shown that short bursts of high-frequency (50 Hz) magnetic impulses repeated at 5 Hz (the frequency of the theta rhythm in the EEG) produce a controllable, consistent, long-lasting and powerful effect on motor [15, 16] and visual cortex [17] by suppressing excitatory circuits [16].In this paper we describe that burst rTMS at frequencies of the EEG theta (5 Hz), alpha (10 Hz) and beta (20 Hz) rhythms applied to the auditory cortex can temporarily suppress narrow band noise or white noise tinnitus.
Tinnitus matching is performed by presenting sounds to the ear in which the tinnitus is not perceived, and both tinnitus pitch and tinnitus intensity (above hearing threshold) are matched to the perceived tinnitus.
In a depolarized state they fire in a tonic mode, in a hyperpolarized state they fire in burst mode. In a recent analysis a substantial variability of oscillatory brain activity during the measurements was reported (Schlee et al., 2014). To sum up, combined TMS-EEG studies enable the measurement of TMS evoked activity after single pulses (neural reactivity) and of changes in resting state activity from before to after a single sessions of rTMS (neuroplasticity). After each stimulation protocol tinnitus patients were asked to rate the loudness change of their tinnitus on a percentage scale.
Technical investigations include MRI of the brain and posterior fossa, pure tone and speech audiometry, Auditory Brainstem Response (ABR) and tympanometry.
During alertness, neurons in the MGBv encode sound signals by firing action potentials in a tonic mode. The order of rTMS protocols was randomized over two sessions with 1 week interval in between.
An alternative approach to resting state is to measure, whether the brain’s reaction to an external stimulus differs in tinnitus patients as compared to healthy controls. For the present study we used TMS-EEG to investigate alterations of neuroplasticity in tinnitus. Based on these findings together with numerous findings of increased temporal and prefrontal activity and connectivity in chronic tinnitus (for review, see De Ridder et al., 2011, 2014), we deduced the hypothesis that tinnitus loudness reductions are associated with reductions in gamma power. Assessment of tinnitus loudness is analysed by Visual Analogue Scale (VAS) while tinnitus severity is analysed by the Tinnitus Questionnaire[18] (TQ).
When these neurons fire in burst, connections to other parts of the central nervous system may be opened through unmasking dormant synapses [2]. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. Moreover, we expected that the increased connectivity of frontal and auditory areas in tinnitus will result in remote rTMS effects in the tinnitus group. Discussion: Burst rTMS can be used clinically, not only theta burst, but also alpha and beta burst.
Externally applied burst stimuli may have the same effect.There are indications that the extralemniscal auditory system is abnormally involved in tinnitus [25]. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. Furthermore, animal studies demonstrate that both tonic [26, 27] and burst [28, 29] firing are increased in the lemniscal and extralemniscal system respectively under conditions that are assumed to mimic tinnitus in humans. If a tinnitus-like sound is used for stimulation it is a challenge to exactly measure the pitch and volume of the tinnitus (Hoare et al., 2014).
Therefore, increased activation of the burst-firing non-tonotopic extralemniscal pathways may lead to perception of tinnitus of noise character, whereas increased activation of the tonic firing tonotopic lemniscal system may produce pure tone tinnitus.
In some patients only alpha or beta burst rTMS is capable of suppressing tinnitus, and theta burst not. The intensity of the magnetic stimulation is slowly increased until a clear contraction is observed in the contralateral thenar muscle.
The fact that bursts may activate neurons that are not activated by tonic stimulations [2] may explain why neural activity in the extralemniscal pathways cannot be suppressed by tonic stimulation but only by burst stimulation.The second hypothesis is supported by the finding that patients who perceive their tinnitus having a low centered pitch respond better to burst stimulation than higher pitches.
This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. Other studies contrasted conditions where patients were instructed to distract or to focus on their tinnitus by using cognitive tasks (Andersson et al., 2006). The coil is then moved to a location over the auditory cortex contralateral to the side to where the patients refer their tinnitus (5-6 cm in above the entrance of auditory meatus on straight line to the vertex).
Neurons in the nuclei of the ascending auditory pathways that are tuned to low frequency sounds generally have wider tuning curves than neurons tuned to high frequency sounds. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Results obtained with such techniques are confounded by activation related to the cognitive effort. With the intensity of the stimulation set at 90% of the motor threshold, the site of maximal tinnitus suppression is determined using 1 Hz stimulation. This means that auditory cortex cells processing low pitch sounds are less frequency specific than those processing high pitch sounds, and thus respond more like a non-tonotopic system in general. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. When tinnitus suppression is noted that patient is asked to estimate the decrease in tinnitus in percentage using the VAS. The tonotopic organization of Heschl's gyrus (primary auditory cortex) in humans demonstrates [4, 30-32] neural generators for low frequency sounds more laterally, and higher pitch sounds more medially. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity. Moreover these techniques are limited by invasiveness or low prevalence of such kind of patients, respectively (Lanting et al., 2009). The procedure is repeated with stimulations at 5 Hz (= theta frequency), followed by 10 Hz (= alpha frequency) and 20 Hz (= beta frequency), each stimulation session consisting of 200 pulses.
This could lead to the suggestions that low frequency tinnitus, generated more superficially, might be reached easier with rTMS than higher pitched tinnitus, which is presumably generated deeper in the Silvian valley.
When tinnitus suppression is induced by rTMS the patient is asked to notify when the tinnitus has returned back to baseline, i.e. Finally we found that in this study left sided tinnitus is perceived as more distressing than right sided tinnitus. For each patient the tonic and burst rTMS frequency that yield maximal tinnitus suppression was compared.
This is in accordance with published epidemiological data that show that people suffering left sided tinnitus complain more from tinnitus than people with right sided tinnitus [36].



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