From the Cell to the Brain –Fear and Anxiety across the Levels of Neuroscience

The four studies presented in this thesis independently provided support for a dynamic multilevel account for anxiety-related phenomena (see Table 2). Study 1 showed how medial prefrontal cortex activity (i.e., Structure Level) measured with EEG was related to heart rate (PNS Level) and provided some evidence that this association was dynamically linked to trait anxiety: in conditions of negative but not positive feedback did trait anxiety increase the link between cortical and cardiac activity. This modulation is consistent with the functional definition of anxiety given that negative but not positive feedback is normally associated with increased danger in the future. Study 2 showed how dopaminergic genes (Molecule Level) and manipulations of dopamine (Synapse Level) presumably affected network states (Network Level), which then influenced brain activity at the AMC (Structure Level) and error-related behavior (Whole System Level). The unexpected finding that trait-anxiety was not related to error monitoring in that study can be explained post hoc by task characteristics (Olvet & Hajcak, 2009), again suggesting that some patterns of multilevel interactions are dynamically linked to anxiety. Study 3 tested individuals with GAD (manifest at the Whole System Level) using a neuropsychological test designed to measure future-orientation in patients with damage of the ventromedial prefrontal cortex (Structure Level) and resulting impairments in neurovisceral connectivity (Bechara et al., 1997) thus affecting the CNS and PNS-Levels. Consistent with (a) the assumed future-orientation of anxiety and (b) increased neurovisceral connectivity in anxiety (Study 1) individuals with GAD performed better in the IGT than non-anxious control participants. Finally, Study 4 manipulated intracellular signalling cascades (Molecule Level), thereby modulating synaptic learning and extinction learning (Synapse Level), which then affected fear-related reflex potentiation (CNS-Level and Whole Systems Level). In contrast to prior studies that found improved extinction learning of hippocampus-dependent fear memory (e.g., fear conditioned to a place), Study 4 found that rolipram disturbed extinction learning of presumably hippocampus independent fear-memory (e.g., fear conditioned to a sound). Together with these other studies, Study 4 thus provides further evidence that situational characteristics (place vs. sound as cue for present danger) may influence various levels (including the Molecule Level) with regard to fear processing. As can be seen in Table 2, some studies covered different levels than others. Of course, the herein proposed subdivision into eight levels of organization should be seen as a flexible framework used for illustrating the multilevel perspective rather than as a rigid model. Future research may uncover that much more levels of organization are needed to explain certain phenomena, and there may also be cases when good predictions can be made based on fewer than eight levels. However, Table 2 also shows that guesses for most empty cells can be made based on existing theories and research findings. A critical exception may be the network level, and it has been noted by others that this level is underrepresented in cognitive neuroscience research. However, the network level may be particularly critical for linking what we know about substances, cells, synapses and neurons (mostly based on in vitro work) to what we know about anxiety relevant structures (based on neuroimaging, EEG and lesion studies). From this perspective, future studies that include the neural network levels when investigating danger-reduction phenomena may be indispensable stations for achieving a wholistic understanding of fear and anxiety

Dissociable feedback valence effects on frontal midline theta during reward gain versus threat avoidance learning

While frontal midline theta (FMθ) has been associated with threat processing, with cognitive control in the context of anxiety, and with reinforcement learning, most reinforcement learning studies on FMθ have used reward rather than threat-related stimuli as reinforcer. Accordingly, the role of FMθ in threat-related reinforcement learning is largely unknown. Here, n = 23 human participants underwent one reward-, and one punishment-, based reversal learning task, which differed only with regard to the kind of reinforcers that feedback was tied to (i.e., monetary gain vs. loud noise burst, respectively). In addition to single-trial EEG, we assessed single-trial feedback expectations based on both a reinforcement learning computational model and trial-by-trial subjective feedback expectation ratings. While participants' performance and feedback expectations were comparable between the reward and punishment tasks, FMθ was more reliably amplified to negative vs. positive feedback in the reward vs. punishment task. Regressions with feedback valence, computationally derived, and self-reported expectations as predictors and FMθ as criterion further revealed that trial-by-trial variations in FMθ specifically relate to reward-related feedback-valence and not to threat-related feedback or to violated expectations/prediction errors. These findings suggest that FMθ as measured in reinforcement learning tasks may be less sensitive to the processing of events with direct relevance for fear and anxiety

Acute tryptophan depletion attenuates brain-heart coupling following external feedback

External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP). The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity) is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance tracing, CECT) indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon), the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD), attenuating brain serotonin (5-HT), decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind cross-over design, 12 healthy male participants received a tryptophan-free amino-acid drink at one session (TRP−) and a balanced amino-acid control-drink (TRP+) on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after TRP+, which was significantly attenuated following TRP−. Moreover, plasma tryptophan levels during TRP+ were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies on the relationship between 5-HT and anxiety

Estimating the value of watershed services following forest restoration

Declining forest health, climate change, and development threaten the sustainability of water supplies in the western United States. While forest restoration may buffer threats to watershed services, funding shortfalls for landscape-scale restoration efforts limit management action. The hydrologic response and reduction in risk to watersheds following forest restoration treatments could create significant nonmarket benefits for downstream water users. Historic experimental watershed studies indicate a significant and positive response from forest thinning by a reallocation of water from evapotranspiration to surface-water yield. In this study, we estimate the willingness to pay (WTP) for improved watershed services for one group of downstream users, irrigators, following forest restoration activities. We find a positive and statistically significant WTP within our sample of $183.50 per household, at an aggregated benefit of more than$400,000 annually for 2181 irrigators. Our benefit estimate provides evidence that downstream irrigators may be willing to invest in landscape-scale forest restoration to maintain watershed services

Synthesis of Molybdenum and Tungsten Alkylidene Complexes That Contain Sterically Demanding Arenethiolate Ligands

Imido alkylidene complexes of Mo and W and oxo alkylidene complexes of W that contain thiophenoxide ligands of the type S-2,3,5,6-Ph[subscript 4]C[subscript 6]H (STPP) and S-2,6-(mesityl)[subscript 2]C[subscript 6]H[subscript 3] (SHMT = S-hexamethylterphenyl) have been prepared in order to compare their metathesis activity with that of the analogous phenoxide complexes. All thiolate complexes were significantly slower (up to ∼10× slower) for the metathesis homocoupling of 1-octene or polymerization of 2,3-dicarbomethoxynorbornene, and none of them was Z-selective. The slower rates could be attributed to the greater σ-donating ability of a thiophenoxide versus the analogous phenoxide and consequently a higher electron density at the metal in the thiophenoxide complexes.National Institutes of Health (U.S.) (Grant GM-59426

High prevalence of unsuspected abdominal aortic aneurysms in patients hospitalised for surgical coronary revascularisation

Objectives: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known among patients with coronary artery disease (CAD) who are considered for surgical revascularisation. We evaluated the value of screening AAA among coronary patients admitted in our cardiovascular surgery unit. Methods: Over a 24-month period, an abdominal echography was proposed to male patients aged 60 or more while hospitalised for surgical coronary revascularisation. Patients with previous investigation of the aorta were excluded. The aorta was considered aneurysmal when the anterior-posterior diameter was of 30 mm or more. Results: Three hundred and ninety-five consecutive patients all accepted a proposed abdominal echographic screening for AAA. Forty unsuspected AAA were detected (10.1%). The mean diameter was 38.9±1.3 mm. Four AAA were larger than 50 mm and considered for surgery after the CABG procedure. Surveillance was proposed to the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients with AAA were significantly older than those without AAA (71.3±0.8 vs. 69.4±0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were also associated more frequently with AAA. More than 16% of the patients being smokers and suffering hypertension presented with unsuspected AAA. Conclusions: In-hospital screening of AAA is very efficient among patients with coronary artery disease. Therefore, patients with CAD may be considered for routine AAA screenin

Long term measurements of aerosol optical properties at a primary forest site in Amazonia

A long term experiment was conducted in a primary forest area in Amazonia, with continuous in-situ measurements of aerosol optical properties between February 2008 and April 2011, comprising, to our knowledge, the longest database ever in the Amazon Basin. Two major classes of aerosol particles, with significantly different optical properties were identified: coarse mode predominant biogenic aerosols in the wet season (January-June), naturally released by the forest metabolism, and fine mode dominated biomass burning aerosols in the dry season (July-December), transported from regional fires. Dry particle median scattering coefficients at the wavelength of 550 nm increased from 6.3 Mm(-1) to 22 Mm(-1), whereas absorption at 637 nm increased from 0.5 Mm(-1) to 2.8 Mm(-1) from wet to dry season. Most of the scattering in the dry season was attributed to the predominance of fine mode (PM2) particles (40-80% of PM10 mass), while the enhanced absorption coefficients are attributed to the presence of light absorbing aerosols from biomass burning. As both scattering and absorption increased in the dry season, the single scattering albedo (SSA) did not show a significant seasonal variability, in average 0.86 +/- 0.08 at 637 nm for dry aerosols. Measured particle optical properties were used to estimate the aerosol forcing efficiency at the top of the atmosphere. Results indicate that in this primary forest site the radiative balance was dominated by the cloud cover, particularly in the wet season. Due to the high cloud fractions, the aerosol forcing efficiency absolute values were below -3.5 Wm(-2) in 70% of the wet season days and in 46% of the dry season days. Besides the seasonal variation, the influence of out-of-Basin aerosol sources was observed occasionally. Periods of influence of the Manaus urban plume were detected, characterized by a consistent increase on particle scattering (factor 2.5) and absorption coefficients (factor 5). Episodes of biomass burning and mineral dust particles advected from Africa were observed between January and April, characterized by enhanced concentrations of crustal elements (Al, Si, Ti, Fe) and potassium in the fine mode. During these episodes, median particle absorption coefficients increased by a factor of 2, whereas median SSA values decreased by 7 %, in comparison to wet season conditions.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)European Integrated FP6 project on Aerosol Cloud Climate and Air Quality Interactions (EUCAARI) under the scope of LBA experimentUniversidade Federal de São Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Earth & Exact Sci, São Paulo, BrazilUniv São Paulo, Inst Phys, Dept Appl Phys, São Paulo, BrazilLeibniz Inst Tropospher Res, Leipzig, GermanyNatl Inst Amazonian Res INPA, Manaus, Amazonas, BrazilLund Univ, Inst Phys, Div Nucl Phys, Lund, SwedenHarvard Univ, Dept Earth & Planetary Sci, Div Engn & Appl Sci, Cambridge, MA 02138 USAUniv Helsinki, Div Atmospher Sci, Dept Phys Sci, Helsinki, FinlandUniversidade Federal de São Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Earth & Exact Sci, São Paulo, BrazilFAPESP: AEROCLIMA 08/58100-2European Integrated FP6 project on Aerosol Cloud Climate and Air Quality Interactions (EUCAARI) under the scope of LBA experiment: 34684Web of Scienc

A Revised Framework for the Investigation of Expectation Update Versus Maintenance in the Context of Expectation Violations: The ViolEx 2.0 Model

Expectations are probabilistic beliefs about the future that shape and influence our perception, affect, cognition, and behavior in many contexts. This makes expectations a highly relevant concept across basic and applied psychological disciplines. When expectations are confirmed or violated, individuals can respond by either updating or maintaining their prior expectations in light of the new evidence. Moreover, proactive and reactive behavior can change the probability with which individuals encounter expectation confirmations or violations. The investigation of predictors and mechanisms underlying expectation update and maintenance has been approached from many research perspectives. However, in many instances there has been little exchange between different research fields. To further advance research on expectations and expectation violations, collaborative efforts across different disciplines in psychology, cognitive (neuro)science, and other life sciences are warranted. For fostering and facilitating such efforts, we introduce the ViolEx 2.0 model, a revised framework for interdisciplinary research on cognitive and behavioral mechanisms of expectation update and maintenance in the context of expectation violations. To support different goals and stages in interdisciplinary exchange, the ViolEx 2.0 model features three model levels with varying degrees of specificity in order to address questions about the research synopsis, central concepts, or functional processes and relationships, respectively. The framework can be applied to different research fields and has high potential for guiding collaborative research efforts in expectation research

The Bolocam Galactic Plane Survey: Survey Description and Data Reduction

We present the Bolocam Galactic Plane Survey (BGPS), a 1.1 mm continuum survey at 33" effective resolution of 170 square degrees of the Galactic Plane visible from the northern hemisphere. The survey is contiguous over the range -10.5 < l < 90.5, |b| < 0.5 and encompasses 133 square degrees, including some extended regions |b| < 1.5. In addition to the contiguous region, four targeted regions in the outer Galaxy were observed: IC1396, a region towards the Perseus Arm, W3/4/5, and Gem OB1. The BGPS has detected approximately 8400 clumps over the entire area to a limiting non-uniform 1-sigma noise level in the range 11 to 53 mJy/beam in the inner Galaxy. The BGPS source catalog is presented in a companion paper (Rosolowsky et al. 2010). This paper details the survey observations and data reduction methods for the images. We discuss in detail the determination of astrometric and flux density calibration uncertainties and compare our results to the literature. Data processing algorithms that separate astronomical signals from time-variable atmospheric fluctuations in the data time-stream are presented. These algorithms reproduce the structure of the astronomical sky over a limited range of angular scales and produce artifacts in the vicinity of bright sources. Based on simulations, we find that extended emission on scales larger than about 5.9' is nearly completely attenuated (> 90%) and the linear scale at which the attenuation reaches 50% is 3.8'. Comparison with other millimeter-wave data sets implies a possible systematic offset in flux calibration, for which no cause has been discovered. This presentation serves as a companion and guide to the public data release through NASA's Infrared Processing and Analysis Center (IPAC) Infrared Science Archive (IRSA). New data releases will be provided through IPAC IRSA with any future improvements in the reduction.Comment: Accepted for publication in Astrophysical Journal Supplemen

Locomotor adaptability in persons with unilateral transtibial amputation

Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb