Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

Effects of physical activity on cognitive performance: a controlled clinical study in depressive patients.

Physical activity is a common adjunctive therapy in psychiatric and psychosomatic hospitals. In the present study, we assessed the effects of an exercise program, integrated into routine inpatient treatment, on cognitive performance and subjective severity of depression in a sample of patients suffering from major depression. We randomized n = 38 patients with unipolar depression to either physical exercise (n = 18) or occupational therapy as an active control treatment (n = 20). Both treatments were delivered in group format over a period of 3-4 weeks. Data indicate that there were significant improvements of cognitive functions and depressive symptoms in both groups, with specific treatment effects in reaction time and in short-term verbal memory favoring the physical activity group. In conclusion, we found physical exercise to be a feasible, easy-to-implement add-on therapy for depressive patients with promising effects on cognitive performance. However, these results need to be replicated in larger samples with an extended follow-up.

Influence of single-dose quetiapine on fear network activity - A pharmaco-imaging study.

OBJECTIVE: Anxiety disorders are among the most frequent psychiatric disorders. Current treatment guidelines recommend antidepressants, the calcium modulator gabapentin, and benzodiazepines as pharmacological treatments. However, delayed onset of action precludes the use of antidepressants as an acute treatment, while benzodiazepines can be recommended only as an emergency treatment due to their inherent risk of dependence. Therefore, an alternative pharmacological agent with acute efficacy is needed. Preliminary evidence points towards possible anxiolytic properties of the atypical antipsychotic quetiapine. The goals of this study were to test the acute anxiolytic properties of quetiapine in patients suffering from arachnophobia in a challenge paradigm, and to assess the effects of quetiapine on the central nervous fear network. METHODS: In a randomized, double-blind, placebo-controlled proof-of-concept study, n=58 arachnophobic patients underwent an fMRI scan while looking at phobia-related and neutral stimuli. Subjective anxiety was evaluated retrospectively in questionnaires. RESULTS: The functional imaging data revealed that patients showed stronger amygdala activation to phobia-related than to neutral stimuli. However, no effect of quetiapine on fear network activity was detected. Further, on questionnaire measures, quetiapine significantly reduced somatic anxiety symptoms, but had no effect on general psychological anxiety. CONCLUSION: Viewing phobic pictures resulted in a robust amygdala activation in arachnophobic patients. Quetiapine seems to have no influence on activation in anxiety-related brain areas but appears to reduce acute somatic anxiety symptoms in patients with specific phobia. The central nervous correlates of the anxiolytic effects of quetiapine remain to be clarified in future studies.

Is prepulse modification altered by continuous theta burst stimulation? DAT1 genotype and motor threshold interact on prepulse modification following brain stimulation.

Previous studies suggest an inhibitory top-down control of the amygdala by the prefrontal cortex (PFC). Both brain regions play a role in the modulation of prepulse modification (PPM) of the acoustic startle response by a pre-stimulus. Repetitive transcranial magnetic stimulation (rTMS) can modulate the activity of the PFC and might thus affect PPM. This study tested the effect of inhibitory rTMS on PPM accounting for a genetic variant of the dopamine transporter gene (DAT1). Healthy participants (N = 102) were stimulated with continuous theta burst stimulation (cTBS, an intense form of inhibitory rTMS) or sham treatment over the right PFC. Afterwards, during continuous presentation of a background white noise a louder noise burst was presented either alone (control startle) or preceded by a prepulse. Participants were genotyped for a DAT1 variable number tandem repeat (VNTR) polymorphism. Two succeeding sessions of cTBS over the right PFC (2 × 600 stimuli with a time lag of 15 min) attenuated averaged prepulse inhibition (PPI) in participants with a high resting motor threshold. An attenuation of PPI induced by prepulses with great distances to the pulse (480, 2000 ms) was observed following active cTBS in participants that were homozygous carriers of the 10-repeat-allele of the DAT1 genotype and had a high resting motor threshold. Our results confirm the importance of the prefrontal cortex for the modulation of PPM. The effects were observed in participants with a high resting motor threshold only, probably because they received a higher dose of cTBS. The effects in homozygous carriers of the DAT1 10-repeat allele confirm the relevance of dopamine for PPM. Conducting an exploratory study we decided against the use of a correction for multiple testing.

Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further.

Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia.

Preliminary evidence suggests beneficial effects of transcranial magnetic stimulation (TMS) on anxiety. The objective of this study was to investigate the effects of intermittent theta burst stimulation (iTBS) as a form of TMS on acute anxiety provoked by a virtual reality (VR) scenario. Participants with spider phobia (n=41) and healthy controls (n=42) were exposed to a spider scenario in VR after one session of iTBS over the prefrontal cortex or sham treatment. Participants with spider phobia reacted with more anxiety compared to healthy controls. Their heart rate and skin conductance increased compared to baseline. Contrary to expectations, iTBS did not influence these reactions, but modulated heart rate variability (HRV). Sympathetic influence on HRV showed an increase in the active iTBS group only. This study does not support the idea of beneficial effects of a single session of iTBS on anxiety, although other protocols or repeated sessions might be effective.

Spatial and temporal variability of source contributions to ambient PM10 during winter in Augsburg, Germany using organic and inorganic tracers.

Daily PM10 samples were collected during a one-month sampling campaign from February 13 to March 12, 2008 at eight different sampling sites in Augsburg, Southern Germany. Source apportionment was performed to identify the main sources and related contributions by analysis of organic and inorganic tracers. Nine factors were separated comprising: solid fuel combustion, traffic-related emissions, secondary inorganics, and mixed sources. Spatiotemporal variation of the source contributions was evaluated using the Pearson correlation coefficient (r) and coefficient of divergence (COD). All factors (except hopanes and mixed sources) showed moderate to high (0.60.8) correlation coefficients between the eight sites and were distributed heterogeneously. Secondary sulfate and secondary nitrate factors were relatively more uniformly distributed (compared to other factors) with lower medians of COD value (0.47 and 0.56, respectively) and higher correlation values (r=0.97 and 0.85, respectively). The maximum daily average contribution for coal & wood combustion factor was observed at the LfU suburban site (4.0 µg m(-3)); wood combustion factor at the LSW residential site (5.1 µg m(-3)) ; diesel & fuel oil consumption factor at the Bifa suburban and BP urban sites (both 2.5 µg m(-3)); road dust & tram factor at the KP traffic site (16.2 µg m(-3)) and the BP urban site (6.6 µg m(-3)); hopanes factor at the BP urban and Bifa suburban sites (both 0.7 µg m(-3)); and de-icing NaCl factor at the KP traffic site (4.8 µg m(-3)). Secondary sulfate and secondary nitrate factors had approximately similar contributions (6.2 µg m(-3) and 4.3 µg m(-3), respectively) at all sites. Mixed sources factor had the highest daily average contribution to PM10 mass at the KP traffic site (7.0 µg m(-3)).

[Repetitive transcranial magnetic stimulation (rTMS) for anxiety disorders--a possible therapeutic option?]. / Repetitive transkranielle Magnetstimulation (rTMS) bei Angsterkrankungen--eine mögliche Therapieoption?

Anxiety disorders rank among the most frequent psychiatric disorders. Effective psychotherapeutic and psychopharmacological interventions exist, although a considerable number of patients does not respond to standard interventions. Repetitive transcranial magnetic stimulation (rTMS) is capable of modulating cortical activity locally and non-invasively. Therefore, rTMS is discussed as a possible alternative treatment approach in psychiatric disorders. The present paper aims to provide a systematic review of randomised controlled studies, open studies, and case reports examining the potential therapeutic effects of rTMS in anxiety disorders. Overall, these studies suggest beneficial effects of rTMS on anxiety symptoms. Nevertheless, larger randomised controlled studies are warranted to allow a more comprehensive evaluation of the therapeutic efficacy of rTMS in anxiety disorders.

Auditory processing in remitted major depression: a long-term follow-up investigation using 3T-fMRI.

Major depression is accompanied by cortical dysfunction including impaired auditory processing of non-speech stimuli. In a previous study, we could show that potent antidepressant treatment with electroconvulsive therapy (ECT) did not lead to full functional normalization of altered fMRI activation patterns in response to sine tones although depressive symptoms improved and remission was achieved in the majority of patients. In a next step, a longitudinal follow-up investigation was conducted looking on neuronal activation over time along with full remission in a subgroup of patients of the previous study in order to address the question whether changes in neuronal activation patterns reflect a more state- or trait-dependent characteristic. Results showed that although clinically remitted, patients still exhibited an increased activity of the secondary auditory cortex and multimodal recruitment of the left cuneus, an area of the visual system. However, activity of recruited secondary visual network had decreased over time. A positive correlation was observed between the number of hospital admissions during the follow-up period and activity of the secondary visual area of the left cuneus at baseline prior to ECT. Thus, although the persistence of differences in activation patterns after sine tone presentation in this follow-up investigation could argue for a potential trait marker of depression characterized by alterations in auditory processing, attenuation of neuronal activation in some areas over time suggests that changes might in part also be state-dependent.

Therapy-refractory panic: current research areas as possible perspectives in the treatment of anxiety.

Panic disorder (PD) is characterized by recurrent panic attacks that are defined as distinct episodes of intense fear, accompanied by symptoms related to physical arousal. Because most patients interpret these symptoms as signs of serious somatic disease (e.g., a heart attack), utilization of healthcare services is high in PD sufferers. PD can become debilitating, interfering significantly with patients' lives. Fortunately, effective treatments are available, but a considerable proportion of patients do not respond sufficiently. The aim of this paper is to outline some promising research strategies aimed at improving established treatments.

Comparison of combined psycho- and pharmacotherapy with monotherapy in anxiety disorders: controversial viewpoints and clinical perspectives.

Anxiety disorders are among the most frequent psychiatric disorders. Experimental evidence supports both psychotherapy as well as pharmacotherapy as effective treatments. There is, however, a controversy concerning the efficacy of a combination of both approaches. While some studies suggest that combined treatment enhances efficacy, others report conflicting results. This article traces the positions in this debate. We present the results from two recent meta-analyses and discuss implications for clinical practice and further research. We suggest that a research strategy that strives to establish differential indications based on patient characteristics should be preferred over attempts to reach a global judgement of the question, which appears too simplistic given the complexity of the issue.

Economic impact of milk production in the State of New Mexico.

The goal of this study was to quantify the economic role of dairy farming in New Mexico and to identify its linkages with allied industries in terms of income, value added, and employment impacts. An input-output model was used to estimate the direct, indirect, and induced impacts of the dairy farm industry on the economy of New Mexico. The results showed that in 2005, New Mexico's dairy farm industry had a total economic impact of $1.98 billion and accounted for 14,313 jobs. Therefore, dairy farming in New Mexico had an output multiplier (income) of 1.92, a labor income multiplier of $248 thousand/$ million of gross sales, and an employment multiplier of 13.91 jobs/$ million of gross sales. Furthermore, the New Mexico dairy farms accounted for 13.1% of the total agricultural outputs, 20.5% of the agricultural jobs, 1.5% of total state economic activity, and $80 million in tax revenue. With the exception of Lea, Eddy, and Bernalillo counties, which are diversified, the dairy farms accounted for more than two-thirds of the agricultural outputs and for more than two-fifths of the agricultural employment in counties where dairy farms are concentrated.

Contribution to the certification of B, Cd, Cu, Mg and Pb in a synthetic water sample, by use of isotope-dilution ICP-MS, for Comparison 12 of the International Measurement Evaluation Programme.

The contribution of the Institute for Reference Materials and Measurements to the certification of the B, Cd, Cu, Mg, and Pb content of a synthetic water sample used in Comparison 12 of the International Measurement Evaluation Programme (IMEP-12) is described. The aim of the IMEP programme is to demonstrate objectively the degree of equivalence and quality of chemical measurements of individual laboratories on the international scene by comparing them with reference ranges traceable to the SI (Système International d'Unités). IMEP is organized in support of European Union policies and helps to improve the traceability of values produced by field chemical measurement laboratories. The analytical procedure used to establish the reference values for the B, Cd, Cu, Mg, and Pb content of the IMEP-12 sample is based on inductively coupled plasma-isotope-dilution mass spectrometry (ICP-IDMS) applied as a primary method of measurement. The measurements performed for the IMEP-12 study are described in detail. Focus is on the element boron, which is particularly difficult to analyze by ICP-MS because of potential problems of low sensitivity, high mass discrimination, memory effects, and abundance sensitivity. For each of the certified amount contents presented here a total uncertainty budget was calculated using the method of propagation of uncertainties according to ISO (International Organization for Standardization) and Eurachem guidelines. For all investigated elements with concentrations in the low micro g kg(-1) and mg kg(-1) range (corresponding to pmol kg(-1) to the high micro mol kg(-1) level), SI-traceable reference values with relative expanded uncertainties ( k=2) of less than 2 % were obtained.

SI-traceable certification of the amount content of cadium below the ng g(-1) level in blood samples by isotope dilution ICP-MS applied as a primary method of measurement.

The development and implementation of a method for the certification of cadmium in blood samples at low ng g(-1) and sub ng g(-1) levels is described. The analytical procedure is based on inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) applied as a primary method of measurement. Two different sample digestion methods, an optimized microwave digestion procedure using HNO3 and H2O2 as oxidizing agents and a high-pressure asher digestion procedure, were developed and compared. The very high salt content of the digests and the high molybdenum content, which can cause oxide-based interferences with the Cd isotopes, were reduced by a chromatographic matrix separation step using an anion-exchange resin. All isotope ratio measurements were performed by a quadrupole ICP-MS equipped with an ultrasonic nebulizer with membrane desolvator. This sample introduction set-up was used to increase sensitivity and minimize the formation of oxides (less MoO+ interference with the Cd isotopes). Because of the very low Cd concentrations in the samples and the resulting need to minimize the procedural blank as much as possible, all sample-processing steps were performed in a clean room environment. Detection limits of 0.005 ng g(-1) Cd were achieved using sample weights of 2.7 g. The method described was used to recertify the cadmium content of three different blood reference materials from the Community Bureau of Reference (BCR) of the European Commission (BCR-194, BCR-195, BCR- 196). Cadmium concentrations ranged between approximately 0.2 ng g(-1) and approximately 12 ng g(-1). For these materials, SI-traceable certified values including total uncertainty budgets according to ISO and Eurachem guidelines were established.

Development of an ICP-IDMS method for accurate routine analyses of toxic heavy metals in polyolefins and comparison with results by TI-IDMS.

An inductively coupled plasma isotope dilution mass spectrometric (ICP-IDMS) method was developed as a suitable method - with respect to its sensitivity, precision, accuracy, and time-consumption - for the analysis of toxic heavy metal traces (Pb, Cd, Cr, and Hg) in polyolefins. Results for Pb, Cd, and Cr were compared with those obtained by thermal ionization isotope dilution mass spectrometry (TI-IDMS), which was used as a reference method. Because of its high first ionization potential and its high volatility mercury could not be determined by TI-IDMS. A multi-element spike solution, containing isotopically enriched 206Pb, 116Cd, 53Cr, and 201Hg, was used for the isotope dilution step. Decomposition of the polyolefin samples was carried out with concentrated HNO3 at temperatures of about 300 degrees C in a high pressure asher (HPA). This procedure decomposes polyolefins completely and allows isotopic equilibration between sample and spike isotopes. Detection limits of 16 ng/g, 5 ng/g, 164 ng/g, and 9 ng/g were obtained for Pb, Cd, Cr, and Hg by ICP-IDMS using only sample weights of 0.25 g. In different commercially available polyethylene samples heavy metal concentrations in the range of < 5 ng/g to 4 x 10(3) ng/g were analyzed. Both mass spectrometric methods were applied within the EU project "Polymeric Elemental Reference Material (PERM)" for the certification of two polyethylene reference materials. The ICP-IDMS results agreed very well with those of TI-IDMS which demonstrates the accuracy of the ICP-IDMS method also suitable for routine analyses.

Analysis of biocide transport limitation in an artificial biofilm system.

An alginate gel bead artificial biofilm system was used to assay biofilm susceptibility to four biocides and to analyse the extent to which each agent penetrated the biofilm. Chlorine, glutaraldehyde, an isothiazolone, and a quaternary ammonium compound were tested on alginate-entrapped Enterobacter aerogenes in gel beads ranging from 1.8 to 6 mm in diameter. Gel-entrapped bacteria were less susceptible to all four antimicrobial agents than were planktonic micro-organisms. The degree of kill measured in artificial biofilm gel beads depended on the size of the gel bead and the cell density at which it was loaded. Disinfection efficacy decreased as gel bead radius or cell density increased. The manifest dependence of biofilm disinfection efficacy on the physical properties of the artificial biofilm (radius and cell density) suggests the impingement of transport limitation of biocide transport into the biofilm. A previously developed theory of biocide reaction and diffusion in biofilm was tested by calculating an appropriate Thiele modulus. In accordance with the theory, the efficacy of all four biocides decreased, albeit noisily, as the Thiele modulus exceeded 1. This result demonstrates that transport limitation can impact antimicrobial performance against biofilms not only of oxidizing biocides but also of nonoxidizing agents.

Should the exit of the artificial abutment tooth be positioned in the region of the attached gingiva?

The necessity of an area of attached gingiva around penetrating implants was examined in 26 patients. It was demonstrated that plaque corneal in the major factor in avoiding inflammatory reactions.