Neurofunktionelle Aspekte von experimentell induzierter Angst bei Patienten mit phobischem Schwankschwindel

INTRODUCTION Vertigo and anxiety are frequent symptoms in both psychiatric and vertigo patients, especially in those with phobic postural vertigo (PPV). Vertigo is one of the most common causes for a visit in a neurological practice. Furthermore, PPV has one of the highest incidence rates among all types of vertigo. Patients suffering from PPV show many symptoms similar to anxiety disorders. On account of this, functional magnetic resonance and cholecystokinin tetrapeptide (CCK-4) were used as a valid model to experimentally induce anxiety symptoms, in order to investigate the neuronal correlates of anxiety in PPV patients in comparison to healthy controls (HC). This was done by addressing, among other things, the question to which extent the underlying fear-networks differ between those two groups. METHODS 15 PPV patients (average age: 43 years, 6 f, 9 m) and 15 gender and age (± 2 years) matched healthy controls underwent challenges with 50 µg bolus CCK-4 injections, not knowing the exact time point of the injection, for the purpose of distinguishing between anticipatory and CCK-4 induced anxiety. Simultaneously a functional MRI (3T Verio Siemens; echo-planar EPI sequence [TR = 3s; 36 slices; slice thickness: 3mm; interslice-gap: 0.75mm]) was recorded. The panic symptom scale was used before (PSS pre) and after (PSS post) the injection. In addition, psychiatric symptoms (e.g. depression, anxiety) as well as somatic symptoms (e.g. heart rate) were assessed. BrainVoyager™ and FSL Software were used to examine the functional MRI data (Independent Component Analysis and Region of Interest analysis). RESULTS During anticipatory anxiety, healthy controls showed functional responses mainly in fronto-temporal regions. In comparison to HC, patients suffering from PPV revealed pronounced BOLD responses e.g. in the insula, the amygdala, the inferior frontal gyrus (BA 13), the superior and medial temporal gyrus as well as the cuneus. CCK-4 induced anxiety (PPV vs. HC) was accompanied by activations, for example in the anterior cingulate gyrus (ACC), the amygdala, the putamen, the insula as well as the superior, medial, inferior frontal and temporal gyrus. In addition, a region of interest analysis demonstrated an increased number of activated voxels in the parietal, temporal and occipital lobe in patients after CCK-4 injection compared to healthy controls; the differences regarding amygdala and orbitofrontal cortex reached a trend level.With respect to the psychiatric symptoms, significantly increased scores were demonstrated in patients regarding depression and anxiety ratings (especially somatic symptoms), vertigo symptoms (VSS-D) and PSS values before the injection (PSS pre). The injection of CCK-4 led to an increase of heart rate in all subjects. CONCLUSIONS In patients suffering from phobic postural vertigo the application of CCK-4 led to pronounced BOLD responses in brain regions playing a central role in anxiety and cognition as seen in fear-related processes. These neuronal responses were more pronounced than in healthy subjects. Given this fact, these findings could provide evidence for common aspects of phobic postural vertigo and anxiety disorders

Neurofunktionelle Aspekte von experimentell induzierter Angst bei Patienten mit phobischem Schwankschwindel

INTRODUCTION Vertigo and anxiety are frequent symptoms in both psychiatric and vertigo patients, especially in those with phobic postural vertigo (PPV). Vertigo is one of the most common causes for a visit in a neurological practice. Furthermore, PPV has one of the highest incidence rates among all types of vertigo. Patients suffering from PPV show many symptoms similar to anxiety disorders. On account of this, functional magnetic resonance and cholecystokinin tetrapeptide (CCK-4) were used as a valid model to experimentally induce anxiety symptoms, in order to investigate the neuronal correlates of anxiety in PPV patients in comparison to healthy controls (HC). This was done by addressing, among other things, the question to which extent the underlying fear-networks differ between those two groups. METHODS 15 PPV patients (average age: 43 years, 6 f, 9 m) and 15 gender and age (± 2 years) matched healthy controls underwent challenges with 50 µg bolus CCK-4 injections, not knowing the exact time point of the injection, for the purpose of distinguishing between anticipatory and CCK-4 induced anxiety. Simultaneously a functional MRI (3T Verio Siemens; echo-planar EPI sequence [TR = 3s; 36 slices; slice thickness: 3mm; interslice-gap: 0.75mm]) was recorded. The panic symptom scale was used before (PSS pre) and after (PSS post) the injection. In addition, psychiatric symptoms (e.g. depression, anxiety) as well as somatic symptoms (e.g. heart rate) were assessed. BrainVoyager™ and FSL Software were used to examine the functional MRI data (Independent Component Analysis and Region of Interest analysis). RESULTS During anticipatory anxiety, healthy controls showed functional responses mainly in fronto-temporal regions. In comparison to HC, patients suffering from PPV revealed pronounced BOLD responses e.g. in the insula, the amygdala, the inferior frontal gyrus (BA 13), the superior and medial temporal gyrus as well as the cuneus. CCK-4 induced anxiety (PPV vs. HC) was accompanied by activations, for example in the anterior cingulate gyrus (ACC), the amygdala, the putamen, the insula as well as the superior, medial, inferior frontal and temporal gyrus. In addition, a region of interest analysis demonstrated an increased number of activated voxels in the parietal, temporal and occipital lobe in patients after CCK-4 injection compared to healthy controls; the differences regarding amygdala and orbitofrontal cortex reached a trend level.With respect to the psychiatric symptoms, significantly increased scores were demonstrated in patients regarding depression and anxiety ratings (especially somatic symptoms), vertigo symptoms (VSS-D) and PSS values before the injection (PSS pre). The injection of CCK-4 led to an increase of heart rate in all subjects. CONCLUSIONS In patients suffering from phobic postural vertigo the application of CCK-4 led to pronounced BOLD responses in brain regions playing a central role in anxiety and cognition as seen in fear-related processes. These neuronal responses were more pronounced than in healthy subjects. Given this fact, these findings could provide evidence for common aspects of phobic postural vertigo and anxiety disorders

Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study

The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity > 50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and betal (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a reduction of the Y-BOGS scores was identified. Our results suggest that measuring brain activity with LORETA could be an efficient and applicable technique to prospectively identify treatment responders in OCD

Just “Like Coffee” or Neuroenhancement by Stimulants?

Introduction: Pharmacological neuroenhancement (PN) is a topic of increasing importance and prevalence among students. However, there is a lack of differentiating PN substances, according to their psychoactive effects. In particular, there is a lack of data about PN by caffeinated drinks, even if coffee is a common and broadly used Neuroenhancer because of its cognitively enhancing effects regarding wakefulness, alertness and concentration. Materials and Methods: A web-survey was developed for German students and alumni about the non-medical use of caffeine for PN contained questions about coffee, caffeinated drinks and energy drinks, caffeine pills and methylxanthine tea regarding frequency and further contextual factors. Results: Six hundred and eighty-three participants completed the survey. Nearly all participants knew about PN (97.7%). 88.1% admitted using some over-the-counter substances. For PN purposes, coffee was used by 72.9% followed by energy drinks (68.2%) and cola drinks (62.4%). Methylxanthine containing tea was used for PN purposes, too (black tea 52.3%, green tea 51.7%). 1.8% admitted using illegal substances or prescription drugs, too. Discussion: Using legal methylxanthine containing drinks for PN seems to be extremely common with coffee and energy drinks being the preferred substances, while illegal and prescription drugs are only minimally used. Further studies should investigate the awareness of methylxanthine containing drinks as well as its character to be a flavoring drink or a neuroenhancer

Effect of smoking status on neuronal responses to graphic cigarette warning labels

Background Smoking is responsible for a large proportion of cancer, respiratory and cardiovascular deaths. Nevertheless the health risks of smoking are still underestimated in many smokers. The present study aimed to examine neurobiological responses to graphical warnings on cigarette packings in non-smokers and patients with tobacco dependence. Methods Twenty non-smokers and twenty-four patients with tobacco dependence participated in a functional MRI study during that pictures of different categories were presented ((a) EU-warning pictures, (b) text-only warnings, (c) neutral pictures with short information). Patients contributed twice in the experiment (after 10 hours nicotine withdrawal / about 5 minutes after nicotine consumption). Results Smokers during withdrawal demonstrated increased neuronal responses predominantly in subcortical, temporal and frontal brain regions that are associated with emotional and cognitive processes during the presentation of graphical warnings compared to neutral pictures. In smokers after smoking and non-smokers, the differences between graphical warnings and neutral pictures were increased compared to smokers during withdrawal. The comparison of the graphical warnings with text-only labels demonstrated the importance of affective brain regions especially in smokers after smoking and in non-smokers. During withdrawal, the neural responses associated with graphical warnings and text-only labels differed only marginally. Discussion and conclusion The results suggest that emotional and cognitive reactions to graphical warnings are predominantly seen in smokers after smoking and in non-smokers. The impact of these pictures during withdrawal seems to be less pronounced;in this case, more unspecific processes seem to be important, including the projection of sensory signals to the cerebral cortex

Neurofunctional differences and similarities between persistent postural-perceptual dizziness and anxiety disorder

Introduction: Persistent postural-perceptual dizziness (PPPD) (ICD-11) and anxiety disorders (ANX) share behavioural symptoms like anxiety, avoidance, social withdrawal, hyperarousal, or palpitation as well as neurological symptoms like vertigo, stance and gait disorders. Furthermore, previous studies have shown a bidirectional link between vestibulo-spatial and anxiety neural networks. So far, there have been no neuroimaging-studies comparing these groups. Objectives: The aim of this explorative study was to investigate differences and similarities of neural correlates between these two patient groups and to compare their findings with a healthy control group. Methods: 63 participants, divided in two patient groups (ANX = 20 and PPPD = 14) and two sex and age matched healthy control groups (HC-A = 16, HC-P = 13) were included. Anxiety and dizziness related pictures were shown during fMRI-measurements in a block-design in order to induce emotional responses. All subjects filled in questionnaires regarding vertigo (VSS, VHQ), anxiety (STAI), depression (BDI-II), alexithymia (TAS), and illness-perception (IPQ). After modelling the BOLD response with a standard canonical HRF, voxel-wise t-tests between conditions (emotional-negative vs neutral stimuli) were used to generate statistical contrast maps and identify relevant brain areas (pFDR 30 voxels). ROI-analyses were performed for amygdala, cingulate gyrus, hippocampus, inferior frontal gyrus, insula, supramarginal gyrus and thalamus (p ≤ 0.05). Results: Patient groups differed from both HC groups regarding anxiety, dizziness, depression and alexithymia scores; ratings of the PPPD group and the ANX group did differ significantly only in the VSS subscale ‘vertigo and related symptoms’ (VSS-VER). The PPPD group showed increased neural responses in the vestibulo-spatial network, especially in the supramarginal gyrus (SMG), and superior temporal gyrus (STG), compared to ANX and HC-P group. The PPPD group showed increased neural responses compared to the HC-P group in the anxiety network including amygdala, insula, lentiform gyrus, hippocampus, inferior frontal gyrus (IFG) and brainstem. Neuronal responses were enhanced in visual structures, e.g. fusiform gyrus, middle occipital gyrus, and in the medial orbitofrontal cortex (mOFC) in healthy controls compared to patients with ANX and PPPD, and in the ANX group compared to the PPPD group. Conclusions: These findings indicate that neuronal responses to emotional information in the PPPD and the ANX group are comparable in anxiety networks but not in vestibulo-spatial networks. Patients with PPPD revealed a stronger neuronal response especially in SMG and STG compared to the ANX and the HC group. These results might suggest higher sensitivity and poorer adaptation processes in the PPPD group to anxiety and dizziness related pictures. Stronger activation in visual processing areas in HC subjects might be due to less emotional and more visual processing strategies

Metabolic control of arginine and ornithine levels paces the progression of leaf senescence

Pools of arginine and ornithine generated during protein degradation can pace the progression of leaf senescence by affecting the TCA cycle, polyamine biosynthesis and the ethylene signaling pathway.Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts-likely due to the lack of induction of amino acids (AAs) transport-can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival

Real-Time fMRI Neurofeedback in Patients With Tobacco Use Disorder During Smoking Cessation: Functional Differences and Implications of the First Training Session in Regard to Future Abstinence or Relapse

One of the most prominent symptoms in addiction disorders is the strong desire to consume a particular substance or to show a certain behavior (craving). The strong association between craving and the probability of relapse emphasizes the importance of craving in the therapeutic process. Former studies have demonstrated that neuromodulation using real-time fMRI (rtfMRI) neurofeedback (NF) can be used as a treatment modality in patients with tobacco use disorder. The aim of the present project was to determine whether it is possible to predict the outcome of NF training plus group psychotherapy at the beginning of the treatment. For that purpose, neuronal responses during the first rtfMRI NF session of patients who remained abstinent for at least 3 months were compared to those of patients with relapse. All patients were included in a certified smoke-free course and took part in three NF sessions. During the rtfMRI NF sessions tobacco-associated and neutral pictures were presented. Subjects were instructed to reduce their neuronal responses during the presentation of smoking cues in an individualized region of interest for craving [anterior cingulate cortex (ACC), insula or dorsolateral prefrontal cortex]. Patients were stratified to different groups [abstinence (N = 10) vs. relapse (N = 12)] according to their individual smoking status 3 months after the rtfMRI NF training. A direct comparison of BOLD responses during the first NF-session of patients who had remained abstinent over 3 months after the NF training and patients who had relapsed after 3 months showed that patients of the relapse group demonstrated enhanced BOLD responses, especially in the ACC, the supplementary motor area as well as dorsolateral prefrontal areas, compared to abstinent patients. These results suggest that there is a probability of estimating a successful withdrawal in patients with tobacco use disorder by analyzing the first rtfMRI NF session: a pronounced reduction of frontal responses during NF training in patients might be the functional correlate of better therapeutic success. The results of the first NF sessions could be useful as predictor whether a patient will be able to achieve success after the behavioral group therapy and NF training in quitting smoking or not

Phase-transfer catalysis as a modern technique in organic synthesis

Phase-transfer catalysis (PTC) has been already known for 60 years and has an established position both on a laboratory and industrial scale. It is an energy-saving technique, ensuring high yields and selectivity under mild conditions. PTC is successfully used, among others, in the pharmaceutical, polymer, agrochemical industries, for the production of dyes, fragrances and flavors, to name a few. Currently, the development of phase-transfer catalysis is focused mainly on the search for active catalysts as well as extending the scope of its applications. In particular, catalysts immobilized on an insoluble carrier, which can be easily separated from the reaction mixture and recycled many times, are of great interest. The growing demand for chiral compounds has resulted in the development of phase-transfer catalysts which, while retaining the advantages of conventional PTC, will allow to obtain a product with high enantiomeric excess. This work characterizes the phase-transfer catalysis and presents examples of its applications in organic synthesis

Synthesis of Propylene Carbonate by Urea Alcoholysis&mdash;Recent Advances

Organic carbonates are considered the chemicals of the future. In particular, propylene carbonate is widely used as a non-reactive solvent, plasticizer, fuel additive, and reagent, especially in the production of environmentally friendly polymers that are not harmful to human health. This paper reviews recent literature findings regarding the development of propylene carbonate synthetic methods starting from propane-1,2-diol and urea. The ammonia formed during the synthesis is recycled to obtain urea from carbon dioxide