Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil

The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil

Identifying Tinnitus-Related Genes Based on a Side-Effect Network Analysis

Tinnitus, phantom sound perception, is a worldwide highly prevalent disorder for which no clear underlying pathology has been established and for which no approved drug is on the market. Thus, there is an urgent need for new approaches to understand this condition. We used a network pharmacology side-effect analysis to search for genes that are involved in tinnitus generation. We analyzed a network of 1,313 drug–target pairs, based on 275 compounds that elicit tinnitus as side effect and their targets reported in databases, and used a quantitative score to identify emergent significant targets that were more common than expected at random. Cyclooxigenase 1 and 2 were significant, which validates our approach, since salicylate is a known tinnitus generator. More importantly, we predict previously unknown tinnitus-related targets. The present results have important implications toward understanding tinnitus pathophysiology and might pave the way toward the design of novel pharmacotherapies.Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Langguth, B.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: Nowak, Wanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Schecklmann, M.. University of Regensburg. Interdisciplinary Tinnitus Clinic. Department of Psychiatry and Psychotherapy; AlemaniaFil: de Ridder, D.. University of Otago. Dunedin School of Medicine. Unit of Neurosurgery. Department of Surgical Sciences; Nueva ZelandaFil: Vanneste, S.. University of Texas at Dallas. School of Behavioral and Brain Sciences. Laboratory for Auditory & Integrative Neuroscience; Estados Unido

Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample

Background: Suicide is a major public health problem. About 90% of suicide victims have one or more major psychiatric disorder, with a reported 20-fold increased risk for suicide in patients with affective disorders in comparison with healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective alternative or adjunctive treatment option for patients with depressive disorders, but little is known about its effects on suicide risk. Objective: For the assessment of the effectiveness of rTMS on suicidal ideation and behaviors, we performed a retrospective analysis of a large sample of patients with depressive disorders, who were treated with rTMS. Methods: We analyzed the records of 711 TMS in- and out-patients with depressive affective disorders in a tertiary referral hospital between 2002 and 2017. Out of these patients we were able to collect Hamilton depression rating scale (HAMD) data of 332 patients (180 females, 152 males; age range 20 to 79 years; mean age 47.3 ± 12.3) for which we analyzed the change of suicidal ideation by using item 3 (suicidality) of HAMD. Results: Out of all 711 patients treated with rTMS for their depression, one patient (0.1%) committed suicide during the TMS treatment. In the statistical analysis of the subsample with 332 patients there was an overall amelioration of depressive symptoms accompanied by a significant decrease in the suicidality item with a medium effect size. Decrease in suicidality was not inferior to changes in other items as indicated by effect sizes. Forty-seven percent of patients showed an amelioration in suicidality, 41.3% of patients did not show a change in their suicidality’s scores, and 11.7% of patients showed an increase in suicidality’s scores from baseline to final rating. Correlation of item 3 (suicidality) and item 7 (drive) demonstrated a significant positive association, revealing improved drive with a parallel decreased suicidality. Conclusion: Based on the proposed data, there is no evidence that rTMS increases the risk for suicide during the course of the treatment. Conversely, rTMS tends to reduce suicidal ideation. Our findings call for further rTMS controlled studies using large sample sizes and specific suicidality assessment measures to obtain more conclusive results

Predictors for rTMS response in chronic tinnitus

Background: Repetitive transcranial magnetic stimulation (rTMS) has been studied as a treatment option for chronic tinnitus for almost 10 years now. Although most of these studies have demonstrated beneficial effects, treatment results show high interindividual variability and yet, little is known about predictors for treatment response. Methods: Data from 538 patients with chronic tinnitus were analyzed. Patients received either low-frequency rTMS over the left temporal cortex (n = 345, 1 Hz, 110% motor threshold, 2000 stimuli/day) or combined temporal and frontal stimulation (n = 193, 110% motor threshold, 2000 stimuli at 20 Hz over left dorsolateral prefrontal cortex plus 2000 stimuli at 1 Hz over temporal cortex). Numerous demographic, clinical, and audiological variables as well as different tinnitus characteristics were analyzed as potential predictors for treatment outcome, which was defined as change in the tinnitus questionnaire (TQ) score. Results: Both stimulation protocols resulted in a significant decrease of TQ scores. Effect sizes were small, however. In the group receiving combined treatment, patients with comorbid temporomandibular complaints benefited more from rTMS than patients without those complaints. In addition, patients with higher TQ scores at baseline had more pronounced TQ reductions than patients with low TQ baseline scores. Also, patients who had already improved from screening to baseline benefited less than patients without initial improvement. Conclusions: The results from this large sample demonstrate that rTMS shows only small but clinically significant effects in the treatment of chronic tinnitus. There are no good demographic or clinical predictors for treatment outcome

Trauma-Associated Tinnitus: Audiological, Demographic and Clinical Characteristics

Background: Tinnitus can result from different etiologies. Frequently, patients report the development of tinnitus after traumatic injuries. However, to which extent this specific etiologic factor plays a role for the phenomenology of tinnitus is still incompletely understood. Additionally, it remains a matter of debate whether the etiology of tinnitus constitutes a relevant criterion for defining tinnitus subtypes. Objective: By investigating a worldwide sample of tinnitus patients derived from the Tinnitus Research Initiative (TRI) Database, we aimed to identify differences in demographic, clinical and audiological characteristics between tinnitus patients with and without preceding trauma. Materials: A total of 1,604 patients were investigated. Assessment included demographic data, tinnitus related clinical data, audiological data, the Tinnitus Handicap Inventory, the Tinnitus Questionnaire, the Beck Depression Inventory, various numeric tinnitus rating scales, and the World Health Organisation Quality of Life Scale (WHOQoL). Results: Our data clearly indicate differences between tinnitus patients with and without trauma at tinnitus onset. Patients suffering from trauma-associated tinnitus suffer from a higher mental burden than tinnitus patients presenting with phantom perceptions based on other or unknown etiologic factors. This is especially the case for patients with whiplash and head trauma. Patients with posttraumatic noise-related tinnitus experience more frequently hyperacousis, were younger, had longer tinnitus duration, and were more frequently of male gender. Conclusions: Trauma before tinnitus onset seems to represent a relevant criterion for subtypization of tinnitus. Patients with posttraumatic tinnitus may require specific diagnostic and therapeutic management. A more systematic and - at best - standardized assessment for hearing related sequelae of trauma is needed for a better understanding of the underlying pathophysiology and for developing more tailored treatment approaches as well.Fil: Kreuzer, Peter M.. Universitat Regensburg; AlemaniaFil: Landgrebe, Michael. Universitat Regensburg; AlemaniaFil: Schecklmann, Martin. Universitat Regensburg; AlemaniaFil: Staudinger, Susanne. Universitat Regensburg; AlemaniaFil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Vielsmeier, Veronika. The TRI Database Study Group; AlemaniaFil: Kleinjung, Tobias. The TRI Database Study Group; AlemaniaFil: Lehner, Astrid. The TRI Database Study Group; AlemaniaFil: Poeppl, Timm B.. The TRI Database Study Group; AlemaniaFil: Figueiredo, Ricardo. The TRI Database Study Group; AlemaniaFil: Azevedo, Andréia. The TRI Database Study Group; AlemaniaFil: Binetti, Ana Carolina. The TRI Database Study Group; AlemaniaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. The TRI Database Study Group; AlemaniaFil: Rates, Marcelo. The TRI Database Study Group; AlemaniaFil: Coelho, Claudia. The TRI Database Study Group; AlemaniaFil: Vanneste, Sven. The TRI Database Study Group; AlemaniaFil: de Ridder, Dirk. The TRI Database Study Group; AlemaniaFil: van de Heyning, Paul. The TRI Database Study Group; AlemaniaFil: Zeman, Florian. The TRI Database Study Group; AlemaniaFil: Mohr, Markus. The TRI Database Study Group; AlemaniaFil: Koller, Michael. The TRI Database Study Group; Alemani

Working Memory and Response Inhibition as One Integral Phenotype of Adult ADHD? A Behavioral and Imaging Correlational Investigation

Objective: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). Method: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. Results: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop-signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. Conclusion: The authors' findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex

Working Memory and Response Inhibition as One Integral Phenotype of Adult ADHD? A Behavioral and Imaging Correlational Investigation

Objective: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). Method: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. Results: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop-signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. Conclusion: The authors’ findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex

Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus

Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8-10 Hz) but not for the upper alpha band (10-12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus

Daily high-frequency transcranial random noise stimulation of bilateral temporal cortex in chronic tinnitus – a pilot study

Several studies emphasized the potential of single and multiple transcranial random noise stimulation (tRNS) sessions to interfere with auditory cortical activity and to reduce tinnitus loudness. It was the objective of the present study to evaluate the use of high-frequency (hf) tRNS in a one-arm pilot study in patients with chronic tinnitus. Therefore, 30 patients received 10 sessions of high frequency tRNS (100-640 Hz; 2 mA; 20 minutes) over the bilateral temporal cortex. All patients had received rTMS treatment for their tinnitus at least 3 months before tRNS. Primary outcome was treatment response (tinnitus questionnaire reduction of >= 5 points). The trial was registered at clinicaltrials.gov (NCT01965028). Eight patients (27%) responded to tRNS. Exactly the same number of patients had responded before to rTMS, but there were only two "double responders" for both treatments. None of the secondary outcomes (tinnitus numeric rating scales, depressivity, and quality of life) was significant when results were corrected for multiple comparisons. tRNS treatment was accompanied by tolerable side effects but resulted in temporal increases in tinnitus loudness in 20% of the cases (2 drop-outs). Our trial showed that hf-tRNS is feasible for daily treatment in chronic tinnitus. However, summarizing low treatment response, increase of tinnitus loudness in 20% of patients and missing of any significant secondary outcome, the use of hf-tRNS as a general treatment for chronic tinnitus cannot be recommended at this stage. Differences in treatment responders between tRNS and rTMS highlight the need for individualized treatment procedures

Individualized rTMS treatment in chronic tinnitus?

Background: Prefrontal and temporo-parietal repetitive transcranial magnetic stimulation (rTMS) in patients suffering from chronic tinnitus have shown significant but only moderate effectiveness with high interindividual variability in treatment response. This open-label pilot study was designed to examine the general feasibility of an individualized fronto-temporal rTMS protocol and to explore what criteria are needed for a more detailed evaluation in randomized clinical studies. Methods: During the first session of a 2-week rTMS protocol, we applied different rTMS protocols to the left and right temporo-parietal and dorsolateral prefrontal cortex (DLPFC) in 25 tinnitus patients. Short trains of 1, 5, 10, and 20 Hz and continuous theta burst stimulation were applied, and patients were asked for immediate tinnitus reductions after each train. If a patient reported such improvements, rTMS treatment was applied over nine sessions with a combined protocol consisting of the most effective frontal and the most effective temporo-parietal stimulation protocol. Those patients who did not improve after the test session were treated with a standard prefrontal plus temporo-parietal protocol (20 Hz over left DLPFC + 1 Hz over temporo-parietal cortex). results: Almost half of the patients (12 of 25) reported immediate tinnitus reductions during the test session. In this group, the mean pre- to post-treatment amelioration in the tinnitus questionnaire was higher (medium to high effect sizes) in contrast to the patients who did not respond to the test session. Treatment outcome remained stable over a follow-up period of 10 weeks. Discussion: Individualized rTMS was shown to be feasible and effective in chronic tinnitus. The results obtained from this study provide tentative evidence in support of an individualized rTMS treatment approach and might provide a basis for a "tailored" application of rTMS in tinnitus and other neuropsychiatric disorders