Increased Alexithymia But No Profound Emotion Processing Disorder in Burnout Syndrome.

Our objectives were to investigate alexithymia in burnout patients while controlling for depression and anxiety, as well as to evaluate whether alexithymia may be part of a profound emotional processing disorder or of a mentalization deficit. Alexithymia, depressive, and anxious feelings were compared in patients with burnout, depression, and healthy controls using an age-, sex-, and education-matched cross-sectional design (n = 60). A facial emotion recognition task and an emotional mentalizing performance test as well as physical and emotional violation experiences were conducted. Alexithymia was significantly increased in burnout patients, mediated by negative affect in this group. No impairment of facial emotion recognition or mental attribution could be shown. Burnout patients demonstrated slightly increased emotional abuse experiences in early childhood. The present results corroborate the supposition that alexithymia in burnout primarily depends on affect and may rise due to current strain and overload experience, rather than based on a profound developmental disorder in emotion processing.

Effects of intranasal oxytocin on thermal pain in healthy men: a randomized functional magnetic resonance imaging study.

OBJECTIVE: Intranasal oxytocin has been shown to affect human social and emotional processing, but its potential to affect pain remains elusive. This randomized, placebo-controlled, double-blind, crossover trial investigated the effect of intranasal oxytocin on the perception and processing of noxious experimental heat in 36 healthy male volunteers. METHODS: Thermal thresholds were determined according to the Quantitative Sensory Testing protocol. A functional magnetic resonance imaging experiment including intensity and unpleasantness ratings of tonic heat was used to investigate the effects of oxytocin within the brain. RESULTS: Thirty men (aged 18-50 years) were included in the study. Intranasal oxytocin had no significant effect on thermal thresholds, but significantly (t = -2.06, p = .046) reduced heat intensity ratings during functional magnetic resonance imaging. The effect on intensity ratings was small (-3.46 points on a 100-point visual analog scale [95% confidence interval {CI} = -6.86 to -0.07] and independent of temperature. No effects of oxytocin on stimulus- or temperature-related processing were found at the whole-brain level at a robust statistical threshold. A region of interest analysis indicated that oxytocin caused small but significant decreases in left (-0.045%, 95% CI = -0.087 to -0.003, t = -2.19, p = .037) and right (-0.051%, 95% CI = -0.088 to -0.014], t = -2.82, p = .008) amygdala activity across all temperatures. CONCLUSIONS: The present study provides evidence for a significant but subtle inhibitory effect of oxytocin on thermal stimulus ratings and concurrent amygdala activity. Neither of the two effects significantly depended of temperature; therefore, the hypothesis of a pain-specific effect of oxytocin could not be confirmed. TRIAL REGISTRATION: EUDRA-CT 2009-015115-40.

Changes in motor cortex excitability associated with temporal repetitive transcranial magnetic stimulation in tinnitus: hints for cross-modal plasticity?

BACKGROUND: Motor cortex excitability was found to be changed after repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we investigated the effects of temporal low-frequency rTMS on motor cortex plasticity in a large sample of tinnitus patients. In 116 patients with chronic tinnitus different parameters of cortical excitability were assessed before and after ten rTMS treatment sessions. Patients received one of three different protocols all including 1 Hz rTMS over the left temporal cortex. Treatment response was defined as improvement by at least five points in the tinnitus questionnaire (TQ). Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). RESULTS: After rTMS treatment RMT was decreased by about 1% of stimulator output near-significantly in the whole group of patients. SICI was associated with significant changes with respect to treatment response. The group of treatment responders showed a decrease of SICI over the course of treatment, the group of non-responders the reverse pattern. CONCLUSIONS: Minor RMT changes during rTMS treatment do not necessarily suggest the need for systematic re-examination of the RMT for safety and efficacy issues. Treatment response to rTMS was shown to be related to changes in SICI that might reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS treatment effects.

Assessing the impact of sex on high-frequency repetitive transcranial magnetic stimulation´s clinical response in schizophrenia - results from a secondary analysis.

BACKGROUND: The evidence for repetitive transcranial magnetic stimulation (rTMS) to treat negative symptoms in schizophrenia (SCZ) is increasing, although variable response rates remain a challenge. Subject´s sex critically influences rTMS´ treatment outcomes. Females with major depressive disorder are more likely to respond to rTMS, while SCZ data is scarce. METHODS: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we assessed the impact of sex on rTMS´ clinical response rate from screening up to 105 days after intervention among SCZ patients. The impact of resting motor threshold (RMT) on response rates was also assessed. RESULTS: 157 patients received either active or sham rTMS treatment. No significant group differences were observed. Linear mixed model showed no effects on response rates (all p > 0.519). Apart from a significant sex*time interaction for the positive subscale of the positive and negative syndrome scale (PANSS) scores (p = 0.032), no other significant effects of sex on continuous PANSS scores were observed. RMT had no effect on response rate. CONCLUSION: In the largest rTMS trial on the treatment of SCZ negative symptoms we did not observe any significant effect of sex on treatment outcomes. Better assessments of sex-related differences could improve treatment individualisation.

Do cardiorespiratory variables predict the antinociceptive effects of deep and slow breathing?

UNLABELLED: Deep and slow breathing (DSB) is a central part of behavioral exercises used for acute and chronic pain management. Its mechanisms of action are incompletely understood. OBJECTIVES: 1) To test the effects of breathing frequency on experimental pain perception in a dose dependent fashion. 2) To test the effects of breathing frequency on cardiorespiratory variables hypothesized to mediate DSB analgesia. 3) To determine the potential of the cardiorespiratory variables to mediate antinociceptive DSB effects by regression analysis. DESIGN: Single-blind, randomized, crossover trial. SUBJECTS: Twenty healthy participants. INTERVENTIONS: Visually paced breathing at 0.14 Hz, 0.10 Hz, 0.06 Hz, and resting frequency. OUTCOME MEASURES: Cardiorespiratory variables: RR-interval (= 60 seconds/heart rate), standard deviation of the RR-interval (SDRR), and respiratory CO2 . Experimental pain measures: heat pain thresholds, cold pain thresholds, pain intensity ratings, and pain unpleasantness ratings. RESULTS: 1) There was no effect of DSB frequency on experimental pain perception. 2) SDRR and respiratory CO2 were significantly modulated by DSB frequency, while RR-interval was not. 3) Baseline-to-DSB and session-to-session differences in RR-interval significantly predicted pain perception within participants: Prolonged RR-intervals predicted lower pain ratings, while shortened RR-intervals predicted higher pain ratings. SDRR and respiratory CO2 were not found to predict pain perception. CONCLUSIONS: The present study could not confirm hypotheses that the antinociceptive effects of DSB are related to changes in breathing frequency, heart rate variability, or hypoventilation/hyperventilation when applied as a short-term intervention. It could confirm the notion that increased cardiac parasympathetic activity is associated with reduced pain perception.

Sleep deprivation in chronic somatoform pain-effects on mood and pain regulation.

Sleep deprivation was found to exert complex effects on affective dimensions and modalities of pain perception both in healthy volunteers and patients with major depression. Considering multifaceted links between mood and pain regulation in patients with chronic somatoform pain, it is intriguing to study sleep deprivation effects for the first time in this group of patients. Twenty patients with a somatoform pain disorder according to ICD-10 diagnostic criteria were sleep-deprived for one night, followed by one recovery night. Clinical pain complaints (visual analog scale), detection- and pain thresholds (temperature and pressure) as well as mood states (Profile of Mood States) were assessed on the day prior to the experiment, on the day after sleep deprivation and on the day after recovery sleep. We found a discrepancy between significantly increased clinical pain complaints and unaltered experimental pain perception after sleep deprivation. Only the clinical pain complaints, but not the experimental pain thresholds were correlated with tiredness-associated symptoms. Total mood disturbances decreased and feelings of depression and anger improved significantly after sleep deprivation. However, these changes were not correlated with a change in clinical pain perception. We conclude that sleep deprivation may generally change the reagibility of the limbic system, but mood processing and pain processing may be affected in an opposite way reflecting neurobiological differences between emotional regulation and interoceptive pain processing.

The effect of deep and slow breathing on pain perception, autonomic activity, and mood processing--an experimental study.

OBJECTIVE: Deep and slow breathing (DSB) techniques, as a component of various relaxation techniques, have been reported as complementary approaches in the treatment of chronic pain syndromes, but the relevance of relaxation for alleviating pain during a breathing intervention was not evaluated so far. METHODS: In order to disentangle the effects of relaxation and respiration, we investigated two different DSB techniques at the same respiration rates and depths on pain perception, autonomic activity, and mood in 16 healthy subjects. In the attentive DSB intervention, subjects were asked to breathe guided by a respiratory feedback task requiring a high degree of concentration and constant attention. In the relaxing DSB intervention, the subjects relaxed during the breathing training. The skin conductance levels, indicating sympathetic tone, were measured during the breathing maneuvers. Thermal detection and pain thresholds for cold and hot stimuli and profile of mood states were examined before and after the breathing sessions. RESULTS: The mean detection and pain thresholds showed a significant increase resulting from the relaxing DSB, whereas no significant changes of these thresholds were found associated with the attentive DSB. The mean skin conductance levels indicating sympathetic activity decreased significantly during the relaxing DSB intervention but not during the attentive DSB. Both breathing interventions showed similar reductions in negative feelings (tension, anger, and depression). CONCLUSION: Our results suggest that the way of breathing decisively influences autonomic and pain processing, thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception.

Polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia.

OBJECTIVE: It is a matter of debate whether patients with primary insomnia require a polysomnographic examination in order to exclude specific sleep disorders such as sleep apnea syndrome (SAS) or periodic limb movements (PLM). Using a prospective design, we investigated the prevalence of organic sleep disorders by means of polysomnography (PSG) in a series of patients who were previously diagnosed with primary insomnia. This diagnosis was based on a clinical exam and an ambulatory monitoring device or previous PSG. METHODS: Seventy-seven women and 16 men (mean age 55.12 ± 13.21 years) who were admitted for cognitive behavioral therapy for insomnia were evaluated by PSG including cardiorespiratory parameters and tibialis EMG. Among them, 50 patients had undergone a clinical exam by a sleep specialist; in 18 patients, actigraphy or portable monitoring had been performed to exclude SAS or PLM; 25 patients had undergone PSG in another sleep lab previously. RESULTS: In 32 patients (34% of the sample), a PSG revealed a specific sleep disorder (SAS 16; PLMD 11; both 5), resulting in therapeutic consequences for 21 patients (SAS 10; PLMD 9; both 2). SAS and PLM patients were older and SAS patients had a higher body mass index than insomnia patients without additional findings. CONCLUSION: Indications for a PSG should be handled less restrictively in the diagnostic workup of older insomnia patients since they have a higher risk of comorbid sleep disorders even in the absence of the clinical signs of SAS or PLM.

The psychological impact of prosthodontic treatment--a discrete response modelling approach.

Investigating the psychological impact of dental treatment is of high relevance to clinical decision makers and a promising approach for furthering patient satisfaction. This paper aims at detecting factors which influence the psychological impact of prosthodontic treatment and its relevance for the dentist. We apply microeconometric techniques and, specifically, control for sample selection bias in order to derive evidence from a panel database which measures oral health-related quality of life (OHIP-G) before and after treatment. The survey rests upon an initial evaluation of 381 patients between 2004 and 2005 and a follow-up in January 2006 (response rate 47%, corresponding to 180 patients) at the University Medical Centre Regensburg, Germany. Our findings indicate that persons of different age have unlike mindsets towards prosthodontic interventions and that there are gender differences with respect to the psychological sensitivity towards prosthodontic interventions. Moreover, the psychological impact attributable to treatment is influenced by the type of limitation in oral well-being before treatment. We could identify distinct factors including age, gender and the type of limitation in oral well-being as causing differentiation in the psychological impact of prosthodontic treatment. Specific patient characteristics may modulate the psychological impact of prosthodontic treatment.

Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression.

INTRODUCTION: Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS: The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS: Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis.

An increasing number of controlled studies strongly support an antidepressant effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex. However, these data come from highly selected study populations. Whether rTMS is a feasible therapeutic tool for the treatment of depression under naturalistic condition has not yet been addressed. Here, we report results from 232 depressive patients [aged 20-76 years, baseline Hamilton Depression Rating Score (HDRS-21) 24.0 ± 7.3] treated with rTMS add-on to continued psychopharmacological treatment in a naturalistic clinical setting. Two thousand stimuli of 20-Hz rTMS were applied daily over the left dorsolateral prefrontal cortex with an intensity of 110% of motor threshold. Treatment duration was individually planned and varied between 10 and 20 sessions. In average, patients received 13 ± 6.1 rTMS sessions. In 90% of the cases, treatment was terminated regularly. No severe side effects were observed. Only four patients stopped rTMS treatment because of side effects. Ratings with the HDRS-21 before and after treatment were available in 130 patients. The average improvement of the HDRS-21 in this subsample was 9.0 ± 9.2 points. Fifty-three patients had an improvement of 50% or more. These results document that rTMS is feasible, safe and well tolerated under naturalistic conditions.

Effects of high-frequency prefrontal rTMS on heart frequency rates and blood pressure in schizophrenia.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a safe non-invasive neuromodulation technique used for the treatment of various neuropsychiatric disorders. The effect of rTMS applied to the cortex on autonomic functions has not been studied in detail in patient cohorts, yet patients who receive rTMS may have disease-associated impairments in the autonomic system and may receive medication that may pronounce autonomic dysfunctions. METHODS: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we evaluated the effect of rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) on autonomic nervous system-related parameters such as blood pressure (BP) and heart rate (HR) in both reclining and standing postures from screening up to 105 days after intervention among patients with schizophrenia. RESULTS: 157 patients received either active (n = 76) or sham (n = 81) rTMS treatment. Apart from gender no significant group differences were observed. During intervention, Linear Mixed Model (LMM) analyses showed no significant time × group interactions nor time effects for any of the variables (all p > 0.055). During the whole trial beside a significant time × group interaction for diastolic BP (p = 0.017) in the standing posture, no significant time × group interactions for other variables (all p > 0.140) were found. CONCLUSION: These secondary analyses of the largest available rTMS trial on the treatment of negative symptoms in schizophrenia did not show a significant effect of active rTMS compared to sham rTMS on heart rate or blood pressure, neither during the intervention period nor during the follow-up period.

The effect of alexithymia and depressive feelings on pain perception in somatoform pain disorder.

OBJECTIVE: To investigate the relationship between alexithymia and depression and their influence on the subjective versus experimental pain perception in somatoform pain disorder. METHODS: Three groups consisting of 40 patients with somatoform pain disorder, 40 patients with depression, and 40 healthy controls were matched. They completed questionnaires regarding alexithymia (TAS26) and depressive feelings (BDI-II). In addition, pain patients rated their subjective pain intensity (NRS). Quantitative sensory testings were conducted in all participants examining temperature (CPT, HPT) and mechanical (MPT, PPT) thresholds. RESULTS: Analysis of variance showed that alexithymia was significantly increased in both patient groups compared to healthy controls, but with the highest amount in somatoform pain. Regression analyses confirmed that this finding was in part due to a high comorbidity of depressive feelings in both patient groups. We found a discrepancy between increased clinical pain ratings and elevated pressure pain thresholds, indicating a less intense mechanical pain perception in somatoform pain. Correlation analyses demonstrated a significant connection of subjective pain ratings and pressure pain thresholds with depressive feelings. CONCLUSION: Contrary to the results of other experimental pain studies on chronic muskuloskeletal pain syndromes, we could not confirm central sensitization in somatoform pain disorder. Our findings place the somatoform pain disorder more in the direction of affective disorder such as depression. These findings may improve a better understanding of the disease and also have direct therapeutic implications. The high occurrence of alexithymia and depressive feelings in somatoform pain should be considered in diagnostic and therapeutic regimens of these patients.

Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder.

Heterogeneity within Major Depressive Disorder (MDD) has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT1A [(11C)WAY-100635], as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT1A binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT1A BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets.

Efficacy of high-frequency repetitive transcranial magnetic stimulation in schizophrenia patients with treatment-resistant negative symptoms treated with clozapine.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation treatment for schizophrenia, however there are few controlled studies of rTMS augmentation of clozapine. METHODS: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we examined the impact of rTMS on PANSS total, general, positive and negative symptoms among participants on clozapine. rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) for five treatment sessions/week for 3-weeks as augmentation for patients with a predominant negative syndrome of schizophrenia, as rated on PANSS. RESULTS: 26 participants from the RESIS trial were on clozapine, receiving active (N=12) or sham (N=14) rTMS treatment. In our Linear Mixed Model (LMM) analysis, time×group interactions were significant in the PANSS positive subscale (p=0.003) (not being the corresponding behavioral output for DLPFC stimulation), the PANSS general subscale (p<0.001), the PANSS total scale (p=0.015), but not the PANSS negative subscale (p=0.301) (primary endpoint of the RESIS trial), when all PANSS measurements from screening to day 105 were included. Descriptive data suggests that in the active group the improvement was more pronounced compared to the sham rTMS group. CONCLUSIONS: In this largest available clozapine cohort, active rTMS may be more effective than sham rTMS when added to clozapine for positive and total psychotic symptoms. These findings should be interpreted with caution given this is a secondary analysis with a limited number of participants.

Modulation of human motor cortex excitability by quetiapine.

RATIONALE: Quetiapine is increasingly used for the treatment of patients with psychosis and bipolar disorder. However, the neurobiological mechanisms, which may account for the favourable risk/benefit profile of this drug, are not entirely understood. OBJECTIVES: Transcranial magnetic stimulation was used to investigate the effects of acute and repeated administration of quetiapine on cortical excitability in healthy volunteers. MATERIALS AND METHODS: Within a double-blind, placebo-controlled, randomized cross-over design motor threshold, intracortical inhibition, intracortical facilitation and cortical silent period were studied in 15 healthy volunteers before and after a single dose of placebo and 100 mg quetiapine. Additional measurements were performed after 5 days of daily intake of 100 mg quetiapine. RESULTS: We observed a significant prolongation of the cortical silent period after a single dose of quetiapine, whereas the placebo had no effects. After repeated administration, there was a trend towards CSP prolongation, which did not reach significance. However, plasma concentrations at this time point were relatively low, as measurements were performed 15 h after the last drug intake. Other parameters of cortical excitability remained unaffected. CONCLUSIONS: By lengthening CSP without affecting MT, ICI and ICF, quetiapine demonstrates a unique neurophysiological profile which differs distinctively from brain excitability profiles of typical antipsychotics such as haloperidol. Provided that the CSP prolongation reflects the antipsychotic potential of quetiapine, TMS may be developed as a tool to monitor neurobiological effects of quetiapine treatment in schizophrenic patients and to explore the efficacy of other antipsychotic drugs with a similar mode of action.

High-frequency priming stimulation does not enhance the effect of low-frequency rTMS in the treatment of tinnitus.

Based on its ability to reduce the excitability of the cortex locally, low-frequency repetitive transcranial magnetic stimulation (rTMS) has been investigated for the treatment of hyperexcitability disorders such as auditory hallucinations and tinnitus. Results are promising, but characterized by only moderate improvement and a high inter-individual variability. Experimental data from motor cortex stimulation in healthy subjects indicates that the depressant effect of low-frequency rTMS can be enhanced by high-frequency priming stimulation. Here we will investigate whether high-frequency priming also improves the therapeutic efficacy of low-frequency rTMS in a clinical application. 32 patients with chronic tinnitus were randomly assigned to either a standard protocol of low-frequency rTMS (110% motor threshold, 1 Hz, 2000 stimuli/day) or a stimulation protocol in which priming stimulation with 6 Hz (90% motor threshold, 960 stimuli) preceded low-frequency rTMS (110% motor threshold, 1 Hz, 1040 stimuli/day). Stimulation was applied over the left auditory cortex by using MRI-guided coil positioning. The treatment outcome was assessed with a standardized tinnitus questionnaire. There was no significant difference between the standard protocol and the protocol involving priming stimulation. Both stimulation protocols resulted in significant clinical improvement after 10 days of stimulation, as compared to baseline. Our data does not support an enhancing effect of higher frequency priming on low-frequency rTMS in the treatment of tinnitus.

Design of a placebo-controlled, randomized study of the efficacy of repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus.

BACKGROUND: Chronic tinnitus is a frequent condition, which can have enormous impact on patient's life and which is very difficult to treat. Accumulating data indicate that chronic tinnitus is related to dysfunctional neuronal activity in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method which allows to focally modulate neuronal activity. An increasing amount of studies demonstrate reduction of tinnitus after repeated sessions of low-frequency rTMS and indicate that rTMS might represent a new promising approach for the treatment of tinnitus. However available studies have been mono-centric and are characterized by small sample sizes. Therefore, this multi-center trial will test the efficacy of rTMS treatment in a large sample of chronic tinnitus patients. METHODS/DESIGN: This is a randomized, placebo-controlled, double-blind multi-center trial of two weeks 1 Hz rTMS-treatment in chronic tinnitus patients. Eligible patients will be randomized to either 2 weeks real or sham rTMS treatment. Main eligibility criteria: male or female individuals aged 18-70 years with chronic tinnitus (duration > 6 months), tinnitus-handicap-inventory-score > or = 38, age-adjusted normal sensorineural hearing (i.e. not more than 5 dB below the 10% percentile of the appropriate age and gender group (DIN EN ISO 7029), conductive hearing loss < or = 15dB. The primary endpoint is a change of tinnitus severity according to the tinnitus questionnaire of Goebel and Hiller (baseline vs. end of treatment period). A total of 138 patients are needed to detect a clinical relevant change of tinnitus severity (i.e. 5 points on the questionnaire of Goebel and Hiller; alpha = 0.05; 1-beta = 0.80). Assuming a drop-out rate of less than 5% until the primary endpoint, 150 patients have to be randomized to guarantee the target number of 138 evaluable patients. The study will be conducted by otorhinolaryngologists and psychiatrists of 7 university hospitals and 1 municipal hospital in Germany. DISCUSSION: This study will provide important information about the efficacy of rTMS in the treatment of chronic tinnitus. TRIAL REGISTRATION: Current Controlled Trials ISRCTN89848288.

Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study.

OBJECTIVES: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a new treatment strategy for patients with chronic tinnitus. However, functional abnormalities in tinnitus patients also involve brain structures used for attentional and emotional processing, such as the dorsolateral prefrontal cortex. Therefore, we have developed a new rTMS treatment strategy for tinnitus patients that consists of a combination of high-frequency prefrontal and low-frequency temporal rTMS. STUDY DESIGN: A total of 32 patients received either low-frequency temporal rTMS or a combination of high-frequency prefrontal and low-frequency temporal rTMS. Treatment effects were assessed with a standardized tinnitus questionnaire (TQ). RESULTS: Directly after therapy there was an improvement of the TQ-score for both groups, but no differences between groups. An evaluation after 3 months revealed a remarkable benefit from the use of combined prefrontal and temporal rTMS treatment. CONCLUSION: These results support recent data that suggest that auditory and nonauditory brain areas are involved in tinnitus pathophysiology.