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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.

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.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.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.

Dementia, including Alzheimer's Disease (AD), 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 comorbid 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 (co-)variance (MANCOVAs) and multinomial logistic regression analyses to compare and predict the subject's dropout behavior at the second visit 3 years after baseline (full participation, partial participation, 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 (MMSE) 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.

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.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).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.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.

ZUSAMMENFASSUNGGegenstand und Ziel: Obwohl stress- und angstbedingte Störungen weit verbreitet sind, ist die Wirksamkeit entsprechender therapeutischer Maßnahmen nicht optimal. In jüngster Zeit wurde in einer Reihe von Studien der zusätzliche Nutzen einer nicht invasiven Hirnstimulation (NIBS) bei der Psychotherapie von Angsterkrankungen untersucht. Um die Effektivität der Hirnstimulation in Kombination mit einer Psychotherapieweiter zu verbessern, ist es notwendig, die Modulation von therapierelevanten Lernprozessen besser zu verstehen.Material und Methode: In diesem systematischen Review werden die Studien dargestellt, die eine Modulation der Furchtextinktion beim Menschen mittels NIBS untersuchen.Ergebnisse: Insgesamt konnten 7 Studien identifiziert und analysiert werden, die entweder die repetitive transkranielle Magnetstimulation (rTMS) oder die transkranielle Gleichstromstimulation (tDCS) bei der Furchtextinktion verwenden.Schlussfolgerungen: Das Review zeigt, dass mittels NIBS das Extinktionslernen verbessert werden kann. Die Übertragung dieser Ergebnisse in klinische Studien wurde bereits begonnen, sodass damit zu rechnen ist, dass in den nächsten Jahren genauere Informationen zu den optimalen Stimulationsparametern vorliegen.

Obgleich Angsterkrankungen sehr gut mithilfe der kognitiven Verhaltenstherapie (KVT) behandelt werden konnen, profitiert ein Teil der Patienten nicht optimal von der Therapie. In den letzten Jahren wurden nichtinvasive Hirnstimulationsverfahren („noninvasive brain stimulation“, NIBS) als „add-on“ zur Psychotherapie untersucht. Gibt es ausreichende Evidenz fur den Einsatz von NIBS als Erganzung zur Psychotherapie bei Patienten mit Angsterkrankungen? Systematisches Review zu bisherigen Therapiestudien, die NIBS-Verfahren begleitend zur KVT bei Angsterkrankungen uberprufen. Insgesamt konnten 4 randomisierte kontrollierte Therapiestudien gefunden und analysiert werden. Diese Arbeiten verwenden die repetitive transkranielle Magnetstimulation (rTMS) kurz vor oder wahrend einer expositionsbasierten Verhaltenstherapie. Der Einsatz einer aktiven Stimulation im Vergleich zu einer Placebostimulation geht mit einem positiven zusatzlichen Effekt im mittleren Bereich und einer durchschnittlichen Effektstarke von f = 0,3 einher. Erste Arbeiten zeigen einen zusatzlichen Nutzen der rTMS in Kombination mit KVT bei der Behandlung von Angsterkrankungen. In weiteren Studien muss aber gepruft werden, welche genauen Stimulationsparameter am besten geeignet sind, um eine Empfehlung fur die Behandlungspraxis abgeben zu konnen.

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.

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.

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.

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.

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 .

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.

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.

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.

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.

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 Wurzburg 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.

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.

Background Conventional vagus nerve stimulation (cVNS) is approved to treat major depression. Within this context, auricular VNS (aVNS) is of increasing interest due to its non-invasiveness. Still, the question of optimum stimulation parameters has to be solved. Method 50 subjects with major depressive disorder were stimulated over 20 min. in the area of the auricular branch of the vagus nerve. Control stimulation (CS) was done at the ear lobe. Before and after each stimulation the participants were asked to rate their actual affective state. 30 participants were stimulated continuously, while in 20 subjects, stimulation was interrupted every 5 min. for 30 s. (pulsatile stimulation). Results Only using pulsatile stimulation, participants significantly more often rated to feel better ( F 1 , 18 = 12.35 ; p = 0.002) and to be more optimistic ( F 1 , 18 = 12.24 ; p = 0.003) after aVNS than after CS. Using pulsatile as well as using continuous stimulation, subjects indicated to be more happy ( F 1 , 18 = 24.61 ; p F 1 , 28 = 8.03 ; p = 0.008, resp.). Rating of pictures of the Internatonal Affective Picture System (IAPS) showed no statistical significant difference between the stimulation methods. Conclusion Stimulating in a pulsatile way showed more difference between aVNS and CS than stimulating in a continuous way. Self rating of the emotional state by means of a visual analogue scale seems to be a reliable tool for the examination of non-invasive stimulation techniques.

In Alzheimer's disease (AD), the degeneration of brainstem nuclei is different from major depression (MD). Thus, vagus somatosensory evoked potentials (VSEP) proposed for the functional assessment of brainstem nuclei should show prolonged latencies in AD but not in MD. In 55 AD patients, 57 MD patients and two age-matched control groups evoked potentials were recorded upon stimulation of the auricular branch of the vagus nerve. In the AD, not in the MD group, latencies were significantly longer as compared to controls. Thus, the method of VSEP could contribute to the important differential diagnosis of AD and MD in elderly patients.

Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended) and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN) and error positivity (Pe)) originating from the medial prefrontal cortex (mPFC). Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS). Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

Background/Aims: Scientists proposed that patients with depression favour negative interpretations when appraising ambiguity. As self-report measures seem prone to response bias, implicit measures of emotional valence should be additionally used. Methods: A total of 16 patients with depression and 19 controls underwent an acoustic imagery task comprising neutral and negative words, as well as ambiguous words that could be understood either way. Affective startle modulation and direct interrogation were used to assess implicit and explicit emotional valence, respectively. We expected a negative bias for ambiguous words in the patient group, resulting in augmented startle magnitudes and preference for negative interpretations of the ambiguous words in the interrogation. Results: Surprisingly, both groups preferred neutral interpretations and showed augmented startle magnitudes to ambiguous words. Furthermore, both groups displayed an emotional startle potentiation for negative words. Conclusion: In summary, our results do not confirm a negative interpretation bias or a blunted emotional response in patients with major depression. The mismatch between self-report and affective startle reaction to ambiguous targets might reflect defensive mobilization or attention effects., OA-Komponente aus Allianzlizenz

An approach bias for alcohol stimuli (i.e. faster approach than avoidance reactions) might facilitate relapses in alcohol dependence. Neurobiological models suggest hypersensitivity in the reward system [inter alia nucleus accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced approach impulses towards alcohol stimuli. At the same time, in alcohol dependence, these structures are only insufficiently controlled by a hypoactive dorsolateral prefrontal cortex (DLPFC). The present study investigated the cortical aspects of this model with functional near-infrared spectroscopy in 21 alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age, gender and education) during performance of the Approach-Avoidance Task (AAT) for the first time. Complementing previous findings, in reaction times (RTs), patients showed stronger approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in HC. Group differences in activity of the OFC were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures. Probable awareness of the behavioural hypotheses due to explicit task instructions and patients' deficient prefrontal function might account for this equally aligned pattern. Results are discussed with regard to recent findings revealing a reduced behavioural approach bias and risk for relapse by applying a retraining version of the AAT. Functional measurements might serve as a method for monitoring the corresponding neurobiological changes and-possibly-predicting the success of such a training.

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.

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.

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.

Neurotoxic effects of alcohol consumption are well-known. There is plenty of literature on frontal lobe impairment on the behavioural and structural brain imaging level. However, only few functional imaging studies investigated altered neural patterns and even less abstinence-related neural recovery.In a cross-sectional design three patient groups (acute withdrawal, detoxified, abstinent) and healthy controls (each n = 20) performed a phonological and semantic verbal fluency task (VFT) while brain activity was measured with near-infrared spectroscopy (NIRS).First, for the phonological condition withdrawal patients and detoxified patients showed less fluency-related frontal lobe activation compared to controls despite equal performance. Second, significant linear trend effects from withdrawal patients over detoxified and abstinent patients up to healthy controls indicated more normal activation patterns in the abstinent group that did not differ significantly from the controls. In the detoxified group brain activation increased with time since detoxification.Our results are compatible with an increase in frontal brain activity from alcohol dependence over abstinence up to normal functioning. However, as cross-sectional designs do not allow to assess causal relations, results have to be considered preliminary and longitudinal studies are needed to further elucidate recovery processes in alcohol dependence.

Introduction Vagus somatosensory evoked potentials (VSEP) were proposed as a means of early and differential diagnosis of Alzheimers disease (AD) with prolonged VSEP latencies reflecting disease-specific changes in the lower brainstem. Heart rate variability (HRV), too is a marker supposed to be influenced by autonomic brainstem nuclei. With the presented study we aimed at testing the hypothesis that prolonged VSEP latencies correlate with changes in HRV parameters in subjects with Mild cognitive impairment (MCI) as a potential state of early AD and healthy controls (HC). Methods In 27 subjects with MCI and 191 HC (age 74 ± 1.4 years), VSEP and HRV were measured according to standard procedures and correlation analyses as well as univariate analyses of variance (ANOVA) to compare VSEP and HRV parameters between the MCI and the HC group were calculated. Results In frontocentral recordings (C4F4), all VSEP latencies correlated negatively with HRV parameters, most strongly P1 with longer latencies coinciding with significantly lower parasympathic tone (respiratory sinus arrhythmia RSA, high frequency power HF). While difference in HRV parameters between the MCI and the HC group did not reach statistical significant difference, there was a significant difference in VSEP parameters with longer P2 latencies in the MCI group. Conclusion Correlation of VSEP latencies with brainstem-regulated HRV is a further hint for VSEP being generated in autonomic brainstem structures. Follow up examination of participants will reveal if subjects who present at baseline with longer VSEP latencies and less HRV will more often develop AD in the future than subjects who do not.

A new method for the assessment of vagus nerve function has recently been introduced into clinical practice. In the present study we could show that, contrary to our results in Alzheimer's disease (AD), in patients with vascular dementia (VaD) vagus sensory evoked potentials (VSEP) did not show statistically significant differences as compared to healthy controls. Thus, we hypothesize that the new method of VSEP could possibly contribute to a differential diagnosis between early cases of AD and VaD.

ZusammenfassungBei der elektrischen Stimulation des N. vagus über einen sensiblen Hautast am äußeren Ohr lassen sich spezifische neuronale Antworten als bipolar evozierte Fernfeldpotenziale an der Schädelkalotte abgreifen, die als Vagus-evozierte Potenziale bezeichnet werden. Latenzen im Bereich weniger Millisekunden wie bei akustisch Evozierten Potenzialen (AEP) und Veränderungen nach Lokalanästhesie im Stimulationsgebiet, sind Hinweise für ihre neurogene Entstehung im Bereich der Vagus-Kerngebiete im Hirnstamm. Wir präsentieren die Daten von fünf Einzelfalluntersuchungen von verschiedenen neuropsychiatrischen Erkrankungen und diskutieren sie hinsichtlich der betroffenen neuroanatomischen Strukturen. Diese neue Methode wäre gerade im Hinblick auf eine Früherkennung neurodegenerativer Erkrankungen wie M. Parkinson oder Alzheimer-Erkrankung von großem Nutzen für den frühzeitigen und zielgerichteten Einsatz neuroprotektiver Behandlungsmöglichkeiten. Im Vergleich zur bisherigen operativen Vorgehensweise bei der Stimulation des Vagus-Hauptstammes wäre eine nebenwirkungsfreie und minimalinvasive Stimulationsweise auch ein bedeutender Fortschritt im Hinblick auf den therapeutischen Einsatz bei therapieresistenten Epilepsien und Depressionen.

Vagus somatosensory-evoked potentials (VSEP) were proposed as a neurophysiological indicator of brainstem dysfunction based on prolonged latencies found in Alzheimer's dementia and Parkinson's disease. We now aimed at a further confirmation of this view independent from neurodegenerative diseases and hypothesized that VSEP in multiple sclerosis with brainstem affection show prolonged latencies, too. In 15 patients with multiple sclerosis according to McDonald and 15 healthy controls after stimulation of the auricular branch of the vagus nerve at the tragus (electrical square impulses, impulse width 0.1 ms, interstimulus interval 2 s, intensity 8 mA), evoked potentials were recorded from electrode positions C3-F3, C4-F4, Fz-F3 and Fz-F4. Analysis of variance showed a significant main effect of the factor diagnosis on latency P1 (F(1,24)=7.067, P=0.001), no significant effect for latencies N1 and P2 nor for the amplitudes. A subgroup of patients with signs of brainstem affection showed a trend for longer P1 latencies (F(1,11)=5916, P=0.033) as compared with the group without. We take this result as further hint for VSEP to be generated at brainstem level which needs confirmation in larger-scale studies and other brainstem-affecting diseases. The method could be suitable for the demonstration of the involvement of differential brainstem nuclei in various neurodegenerative diseases.

Based on a recent report on the relatedness between depressed mood, as assessed by the Beck Depression Inventory (BDI), and personality according to Cloninger’s Temperament and Character Inventory (TCI), we attempted to replicate those findings in a sample of normal subjects (n=850) and depressive inpatients (n=353) taking into account age, gender and various aspects of depressive symptoms by means of BDI factors. ‘Harm Avoidance’ and ‘Self-Directedness’ were found closely related with depressive mood in both samples. Furthermore, ‘Exploratory Excitability’ (NS 1) was consistently related with depressive mood. However, the occurred age and gender effects onto the relations of depressive mood and personality characteristics were very weak (trends for ‘Reward Dependence’ and ‘Persistence’ at P=0.10 exclusively in the normal sample). Most of the variance in depressive mood could be explained by changes in ‘Harm Avoidance’ and ‘Self-Directedness’ independent on effects of age and gender. Possibly, the latter factors are slightly influencing these relations for ‘Reward Dependence’ and ‘Persistence’.