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.

Factors associated with dropout in the longitudinal Vogel study of cognitive decline.

Dementia, including Alzheimer's disease, is a growing problem worldwide. Prevention or early detection of the disease or a prodromal cognitive decline is necessary. By means of our long-term follow-up 'Vogel study', we aim to predict the pathological cognitive decline of a German cohort (mean age was 73.9 ± 1.55 years at first visit) with three measurement time points within 6 years per participant. Especially in samples of the elderly and subjects with chronic or co-morbid diseases, dropouts are one of the biggest problems of long-term studies. In contrast to the large number of research articles conducted on the course of dementia, little research has been done on the completion of treatment. To ensure unbiased and reliable predictors of cognitive decline from study completers, our objective was to determine predictors of dropout. We conducted multivariate analyses of covariance and multinomial logistic regression analyses to compare and predict the subject's dropout behaviour at the second visit 3 years after baseline (full participation, partial participation and no participation/dropout) with neuropsychiatric, cognitive, blood and lifestyle variables. Lower performance in declarative memory, attention and visual-spatial processing predicted dropout rather than full participation. Lower performance in visual-spatial processing predicted partial participation as opposed to full participation. Furthermore, lower performance in mini-mental status examination predicted whether subjects dropped out or participated partially instead of full participation. Baseline cognitive parameters are associated with dropouts at follow-up with a loss of impaired participants. We expect a bias into a healthier sample over time.

Measurement invariance testing of longitudinal neuropsychiatric test scores distinguishes pathological from normative cognitive decline and highlights its potential in early detection research.

OBJECTIVE: Alzheimer's disease (AD) is a growing challenge worldwide, which is why the search for early-onset predictors must be focused as soon as possible. Longitudinal studies that investigate courses of neuropsychological and other variables screen for such predictors correlated to mild cognitive impairment (MCI). However, one often neglected issue in analyses of such studies is measurement invariance (MI), which is often assumed but not tested for. This study uses the absence of MI (non-MI) and latent factor scores instead of composite variables to assess properties of cognitive domains, compensation mechanisms, and their predictability to establish a method for a more comprehensive understanding of pathological cognitive decline. METHODS: An exploratory factor analysis (EFA) and a set of increasingly restricted confirmatory factor analyses (CFAs) were conducted to find latent factors, compared them with the composite approach, and to test for longitudinal (partial-)MI in a neuropsychiatric test battery, consisting of 14 test variables. A total of 330 elderly (mean age: 73.78 ± 1.52 years at baseline) were analyzed two times (3 years apart). RESULTS: EFA revealed a four-factor model representing declarative memory, attention, working memory, and visual-spatial processing. Based on CFA, an accurate model was estimated across both measurement timepoints. Partial non-MI was found for parameters such as loadings, test- and latent factor intercepts as well as latent factor variances. The latent factor approach was preferable to the composite approach. CONCLUSION: The overall assessment of non-MI latent factors may pose a possible target for this field of research. Hence, the non-MI of variances indicated variables that are especially suited for the prediction of pathological cognitive decline, while non-MI of intercepts indicated general aging-related decline. As a result, the sole assessment of MI may help distinguish pathological from normative aging processes and additionally may reveal compensatory neuropsychological mechanisms.

Reduced parietal activation in participants with mild cognitive impairments during visual-spatial processing measured with functional near-infrared spectroscopy.

Functional Near Infrared Spectroscopy (fNIRS) may be a suitable, simple, and cost-effective brain imaging technique for detecting divergent neuronal patterns at an early stage of neurodegeneration. In course of Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD), a deficit in visual-spatial processing, located in the parietal cortex, is a reliable risk factor. Earlier, we established the application of the clock-hand-angle-discrimination task (ADT) during fNIRS to identify neuronal correlates of the visual-spatial processing in a healthy elderly sample. In this analysis, we aimed to measure and find out differences in the hemodynamic response in MCI participants compared to matched healthy controls. As expected, MCI participants showed more errors over all conditions of pointer length and a higher reaction time in the long and middle pointer length condition. Moreover, results revealed a significant reduction of cortical activation in MCI patients. There was a generally increased activity in both the right as compared to the left hemisphere and the superior parietal brain region as compared to the inferior parietal brain region in both groups. In summary, fNIRS can be implemented in the measurement of visual-spatial processing in MCI patients and healthy elderly based on ADT. MCI participants had difficulties to cope with the ADT. Since neuronal hypoactivity occurs with concomitant behavioral deficits, an additional analysis was performed on a subgroup of MCI patients who performed as well as the control group in behavior. This subgroup analysis also showed a hypoactivation of the parietal cortex, without evidence of a compensatory activation. Therefore, we assume that MCI patients are characterized by a deficit in the parietal cortex. Overall, these findings confirm our hypothesis that hemodynamic deficits in visual-spatial processing, localized in the parietal cortex, are reliable and early diagnostic markers for cognitive decline in risk groups for the development of AD.

Can smoking cessation be taught online? A prospective study comparing e-learning and role-playing in medical education.

OBJECTIVES: We compared the effect of different didactic formats - e - learning and role-playing - on medical students' knowledge and counselling skills in smoking cessation training. METHODS: At a German medical school, 145 third-year students were randomly allocated to attend an online course with video examples or an attendance course with role-playing. Students were trained in smoking cessation counselling according to the 5A's (ask, advise, assess, assist, arrange) for approximately 90 minutes. Practical skills were measured in an objective structured clinical examination (OSCE) and represent the primary endpoint of this prospective comparative study. Additionally, changes in theoretic knowledge were assessed by pre - and post - interventional questionnaires and a final written exam. RESULTS: In the OSCE, overall scores were higher in the attendance group (Mdn=70.8 % vs. 62.8 %; U=119; p=.087, n=36), but a statistical advantage was only found in one single counselling sequence ("Assist": Mdn=66.7 % vs. 51.4 %; p = .049) and the rating of the standardised patients (M=4.7 vs. 4.2 out of 5 points, t(27.836)=2.0, p=.028). Students' results (n=130) from self-assessment and written exams suggest that both approaches are equally well suited to increase theoretical knowledge. The online course was more time efficient (90 vs. 73 minutes). CONCLUSIONS: Seminar and web-based training seem equally well suited for transferring knowledge and skills on tobacco cessation counselling. Considering their particular strengths, these two teaching approaches could be combined.

Micronucleus frequency in buccal mucosa cells of patients with neurodegenerative diseases.

Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome.

Neuronal correlates of the visual-spatial processing measured with functional near-infrared spectroscopy in healthy elderly individuals.

Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) are a globally rising issue. It is necessary to detect such diseases early to find strategies for prevention. Typically, patients with MCI or AD show deviant neuronal patterns, which could be detected early through brain imaging techniques enabling assumptions about pre-existing diseases. Functional Near-Infrared Spectroscopy (fNIRS) is an appropriate imaging method because of its easy and economical nature with hardly any drawbacks. An early measurable risk factor indicating neurodegenerative processes could be a deficit in visual-spatial processing, which is localized in the parietal cortex. In this study, we aimed to measure the hemodynamic response of the visual-spatial processing in the healthy elderly participants of our long-term Vogel Study with fNIRS during the clock-hand-angle-discrimination task (ADT) to deepen our understanding of healthy brain mechanisms. Our results revealed for our healthy sample a significantly increased neuronal brain activity with increasing task difficulties, namely from the long to the middle to the short clock hand during ADT and significantly higher activation in the right hemisphere compared to the left hemisphere as well as in the superior parietal cortex compared to the inferior parietal cortex. Additionally, our behavioral data demonstrated longer reaction times and more errors with an increasing task requirement. We, therefore, assume that visual-spatial processing can successfully be operationalized with fNIRS for healthy elderly people based on ADT. Further fNIRS analyses are planned to investigate pathological neuronal correlates of visual-spatial function in MCI or AD study participants.

Reduced spontaneous low frequency oscillations as measured with functional near-infrared spectroscopy in mild cognitive impairment.

Spontaneous low frequency oscillations (LFO) in functional imaging data have gained increased interest in the study of cognitive decline. Persons diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display alterations in their amount of LFO in various brain regions. This is commonly interpreted as disruptions in the autoregulation of the cerebral microvascular system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54 MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during rest over the frontal and the parietal cortex. Both MCI and healthy elderly controls showed less LFO in the frontal cortex as compared to young subjects. For the parietal cortex a decrease in LFO could be observed for the MCI group in comparison to healthy elderly subjects. Correlations of more LFO with worse performance in neuropsychological tests point to compensatory processes. LFO measured with NIRS might be especially suited for longitudinal studies aiming at predicting cognitive decline.

Modulation of sustained fear by transcranial direct current stimulation (tDCS) of the right inferior frontal cortex (rIFC).

Downregulation of emotional responses to threat is strongly associated with frontal cortex functions. Additionally pathological anxiety has been proposed to be associated with the altered frontal control. Understanding the frontal regulation of both initial and sustained fear responses seems to be crucial for further research on the treatment of anxiety disorders. Therefore, this study aims to examine the effects of transcranial direct current stimulation (tDCS) over the right inferior frontal cortex (rIFC) on the subjects' psychophysiological responses as measured by skin conductance reaction (SCR) during a sustained threat paradigm. 80 participants were randomly assigned to an anodal and sham stimulation group in a double-blinded manner. Indicated by visual cues, participants anticipated the temporally unpredictable occurrence of aversive or neutral auditory stimuli. We found a significant interaction effect of condition x tDCS for SCR during the sustained threat. Post-hoc tests revealed a significant reduction in SCR during sustained fear in verum stimulated group. The results confirm that tDCS of the rIFC attenuates sustained fear. This supports the suggested role of the rIFC in psychophysiological emotional regulation and the potential use of tDCS to enhance these effects.

Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS).

Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS- discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS- in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS-. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies.

Decreased hemodynamic response in inferior frontotemporal regions in elderly with mild cognitive impairment.

The verbal fluency task (VFT) is a well-established cognitive marker for mild cognitive impairment (MCI) in the prodromal stage of Alzheimer´s dementia (AD). The behavioral VFT performance of patients allows the prediction of dementia two years later. But effective compensatory mechanism might cover or reduce the predictive value of the VFT. Therefore the aim of this study is to measure the hemodynamic response during VFT in patients with mild cognitive impairment (MCI) to establish the hemodynamic response during the VFT as a screening instrument for the prediction of dementia. One method which allows measuring the hemodynamic response during speech production without severe problems with moving artifacts like in functional magnetic resonance imaging (fMRI) is the functional near-infrared spectroscopy (fNIRS). It is optimal as a screening instrument, as it is easy to apply and without any contraindications. In this study we assessed the hemodynamic response in prefrontal and temporal regions in patients with MCI as well as matched healthy controls with fNIRS. We found a decreased hemodynamic response in the inferior frontotemporal cortex for the MCI group. Our results indicate that a frontotemporal decreased hemodynamic response could serve as a diagnostic biomarker for dementia.

Relevance of Dorsolateral and Frontotemporal Cortex on the Phonemic Verbal Fluency - A fNIRS-Study.

Non-invasive brain stimulation is widely used to investigate and manipulate specific brain functions to broaden knowledge about healthy people, and also to provide for a potential treatment option for people with various psychopathological disorders that do not adequately benefit from traditional treatments. Nevertheless, the underlying mechanisms have not been fully investigated yet. The aim of the present study was to investigate whether we could alter the brain activity during a test for executive functioning. Therefore, we measured the activity in the prefrontal cortex (PFC) using near-infrared spectroscopy (NIRS) while applying bilateral anodal and cathodal transcranial direct current stimulation (tDCS, 1 mA) to the left and right dorsolateral PFC (dlPFC) during the phonemic part of the verbal fluency test (VFT). A total of 61 young and healthy participants were divided into three groups: left anodal/right cathodal, left cathodal/right anodal stimulation or sham. All participants performed the letter-cued part of the VFT and a control task. Brain activation was simultaneously measured using NIRS. We found only the frontotemporal cortex (FTC) but not the dorsolateral prefrontal cortex (DLPFC) to be activated. Furthermore, stimulating the DLPFC bilaterally by tDCS showed no significant differences between the three different groups when performing the VFT, neither in performance nor in cortical activation. Instead, we found a significant increase in deoxygenated hemoglobin [HHb] while performing the control task in the left anodal/right cathodal stimulation group compared to sham. Interestingly, also an influence on the mood of our participants was observed. These results are of importance especially regarding a better understanding of the influence of the dlPFC on the VFT.

Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.

Functional near-infrared spectroscopy (fNIRS) and vagus somatosensory evoked potentials (VSEP) show deviant patterns in subjects with Alzheimer's disease (AD) compared to healthy controls. We now aimed at testing the predictive value of these methods in the early diagnosis of AD. The Vogel study is a prospective, observational, long-term follow-up study with three time points of investigation within 6 years. Residents of the city of Würzburg born between 1936 and 1941 were recruited. Every participant underwent physical, psychiatric, and laboratory examinations, and performed an intense neuropsychological testing as well as VSEP and NIRS according to the published procedures. 604 subjects were included. Mean age of the participants was 73.9 ± 1.55 years. The most frequent pathological physical and laboratory examination results were observed for blood pressure (62%), body weight (54%), HbA1c (16%), cholesterol (42%), and homocysteine (69%). Comprehensive analysis of cognitive testing showed mild cognitive impairment (MCI) in 12.3% of the patients. Concurrent major depression was found in 6.6% of the patients. We observed a high rate of MCI and somatic comorbidity in our cohort. The high rate of vascular risk factors and depressive symptoms, all of which are known risk factors of AD, is consistent with the notion that there are multiple options to prevent or postpone the onset of AD in a geriatric population like the one of the Vogel studies.

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

BACKGROUND: Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. OBJECTIVE: This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. METHODS: Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. RESULTS: A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. CONCLUSION: Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. TRIAL REGISTRATION: Controlled Trials: http://www.isrctn.com/ISRCTN89848288.

Reduced Activity in the Right Inferior Frontal Gyrus in Elderly APOE-E4 Carriers during a Verbal Fluency Task.

Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70-77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT.

Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia.

BACKGROUND: Animal as well as human research indicated that the ventral medial prefrontal cortex (vmPFC) is highly relevant for fear extinction learning. Recently, we showed that targeting the vmPFC with high-frequency repetitive transcranial magnetic stimulation (rTMS) in a placebo-controlled study with 45 healthy controls induced higher prefrontal activity during extinction of conditioned stimuli (CS+) in the active compared to the sham stimulated group and better extinction learning as indicated by ratings, fear potentiated startles and skin conductance responses. OBJECTIVE: In this study, we aimed to proof our concept of accelerating extinction learning using rTMS of the mPFC in a group of anxiety disorder patients. METHODS: To specifically evaluate the impact of rTMS on exposure-based therapy, we applied a sham-controlled protocol over the vmPFC (FPz) succeeded by a virtual reality exposure therapy (VRET) in n = 20 participants with acrophobia and n = 19 controls. RESULTS: We found a significantly higher reduction in active compared to sham stimulated group for anxiety (t[37] = 2.33, p < 0.05) as well as avoidance ratings t[37] = 2.34, p < 0.05) from pre to post therapy. CONCLUSION: This study provides first clinical evidence that high-frequency rTMS over the vmPFC improves exposure therapy response of acrophobia symptoms.

Transcranial Direct Current Stimulation (tDCS) of the Right Inferior Frontal Gyrus Attenuates Skin Conductance Responses to Unpredictable Threat Conditions.

Patients with panic and post-traumatic stress disorders seem to show increased psychophysiological reactions to conditions of unpredictable (U) threat, which has been discussed as a neurobiological marker of elevated levels of sustained fear in these disorders. Interestingly, a recent study found that the right inferior frontal gyrus (rIFG) is correlated to the successful regulation of sustained fear during U threat. Therefore this study aimed to examine the potential use of non-invasive brain stimulation to foster the rIFG by means of anodal transcranial direct current stimulation (tDCS) in order to reduce psychophysiological reactions to U threat. Twenty six participants were randomly assigned into an anodal and sham stimulation group in a double-blinded manner. Anodal and cathodal electrodes (7 * 5 cm) were positioned right frontal to target the rIFG. Stimulation intensity was I = 2 mA applied for 20 min during a task including U threat conditions (NPU-task). The effects of the NPU paradigm were measured by assessing the emotional startle modulation and the skin conductance response (SCR) at the outset of the different conditions. We found a significant interaction effect of condition × tDCS for the SCR (F (2,48) = 6.3, p < 0.01) without main effects of condition and tDCS. Post hoc tests revealed that the increase in SCR from neutral (N) to U condition was significantly reduced in verum compared to the sham tDCS group (t (24) = 3.84, p < 0.001). Our results emphasize the causal role of rIFG for emotional regulation and the potential use of tDCS to reduce apprehension during U threat conditions and therefore as a treatment for anxiety disorders.

Transcranial direct current stimulation of the prefrontal cortex increases attention to visual target stimuli.

Both functional imaging or EEG studies and studies including neurological patients found the dorsolateral prefrontal cortex (dLPFC) to be an important brain area for the processing of emotion and attention. The aim of the present study was to investigate whether emotion and attention can be modulated through bilateral transcranial direct current stimulation (tDCS) of the dLPFC. Therefore, we measured electroencephalographic occipital (early posterior negativity, EPN) and parietal ERPs (late positive potential, LPP) during an emotional picture viewing paradigm with an additional attentional instruction while applying bilateral anodal and cathodal tDC-stimulation to the left and right dLPFC. Beyond the well-known emotion and attention effects for both EPN and LPP, we found that left cathodal/right anodal tDCS leads to increased LPP amplitudes to target stimuli. In contrast to our hypothesis bilateral tDCS over the dLPFC did not influence emotional processing.

Transcranial direct current stimulation of the prefrontal cortex reduces cue-reactivity in alcohol-dependent patients.

Alcohol craving has been shown to be an important factor for relapses in alcohol-dependent patients. Furthermore, brain activity in reward-related areas in response to alcohol-related cues is positively related to the amount of post-relapse alcohol consumption. On the other hand, it has been shown that cue-exposure based extinction training (CET) leads to larger decrease of striatal and left dorsolateral prefrontal cortex (dLPFC) cue-induced activation compared to standard clinical day-care treatment, but the effect sizes are relatively small. The question of this study was, whether it is possible to change cue-reactivity and subjective craving by applying bilateral prefrontal transcranial direct current stimulation (tDCS). We stimulated 30 detoxified alcohol-dependent patients (50 % with a sham and 50 % with left cathodal/right anodal stimulation) and presented emotional as well as alcohol-related pictures. We measured the emotional startle modulation and found significantly increased startle amplitudes in the verum stimulation condition for alcohol-related cues, indicating a more negative processing of this cues in alcohol-dependent patients after verum tDCS stimulation. Additionally we found tendencies for stronger reduction in subjective craving in verum-stimulated patients. Therefore our study underscores the positive value of DCS in reducing craving and might help to improve the understanding and therapy of alcohol dependence.

Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus.

PURPOSE: Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS). METHODS: Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response. RESULTS: Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group. CONCLUSIONS: In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials.