Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.

Visual exploration behaviour during clock reading in Alzheimer's disease

Eye movement behaviour during visual exploration of 24 patients with probable Alzheimer's disease and 24 age-matched controls was compared in a clock reading task. Controls were found to focus exploration on distinct areas at the end of each clock hand. The sum of these two areas of highest fixation density was defined as the informative region of interest (ROI). In Alzheimer's disease patients, visual exploration was less focused, with fewer fixations inside the ROI, and the time until the first fixation was inside the ROI was significantly delayed. Changes of fixation distribution correlated significantly with the ability to read the clock correctly, but did not correlate with dementia severity. In Alzheimer's disease patients, fixations were longer and saccade amplitudes were smaller. The altered visual exploration in Alzheimer's disease might be related to parietal dysfunction or to an imbalance between a degraded occipito-parietal and relatively preserved occipito-temporal visual network.

Perceptual and processing differences between physical and dichorhinic odor mixtures

Perceptual integration of sensory input from our two nostrils has received little attention in comparison to lateralized inputs for vision and hearing. Here, we investigated whether a binary odor mixture of eugenol and l-carvone (smells of cloves and caraway) would be perceived differently if presented as a mixture in one nostril (physical mixture), vs. the same two odorants in separate nostrils (dichorhinic mixture). In parallel, we investigated whether the different types of presentation resulted in differences in olfactory event-related potentials (OERP). Psychophysical ratings showed that the dichorhinic mixtures were perceived as more intense than the physical mixtures. A tendency for shift in perceived quality was also observed. In line with these perceptual changes, the OERP showed a shift in latencies and amplitudes for early (more "sensory") peaks P1 and N1 whereas no significant differences were observed for the later (more "cognitive") peak P2. The results altogether suggest that the peripheral level is a site of interaction between odorants. Both psychophysical ratings and, for the first time, electrophysiological measurements converge on this conclusion.

The Assessment of Multiple Processes Underlying the Attentional Blink: A Fixed - links Modeling Approach based on Behavioral and Electrophysiological Data

When observers are presented with two visual targets appearing in the same position in close temporal proximity, a marked reduction in detection performance of the second target has often been reported, the so-called attentional blink phenomenon. Several studies found a similar decrement of P300 amplitudes during the attentional blink period as observed with detection performances of the second target. However, whether the parallel courses of second target performances and corresponding P300 amplitudes resulted from the same underlying mechanisms remained unclear. The aim of our study was therefore to investigate whether the mechanisms underlying the AB can be assessed by fixed-links modeling and whether this kind of assessment would reveal the same or at least related processes in the behavioral and electrophysiological data. On both levels of observation three highly similar processes could be identified: an increasing, a decreasing and a u-shaped trend. Corresponding processes from the behavioral and electrophysiological data were substantially correlated, with the two u-shaped trends showing the strongest association with each other. Our results provide evidence for the assumption that the same mechanisms underlie attentional blink task performance at the electrophysiological and behavioral levels as assessed by fixed-links models.

Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain

Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It is characterized by the dysregulation of voltage-gated sodium channels (Navs) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying the altered expression of Na(v)s remain unknown. This study investigated the role of the E3 ubiquitin ligase NEDD4-2, which is known to ubiquitylate Navs, in the pathogenesis of neuropathic pain in mice. The spared nerve injury (SNI) model of traumatic nerve injury-induced neuropathic pain was used, and an Na(v)1.7-specific inhibitor, ProTxII, allowed the isolation of Na(v)1.7-mediated currents. SNI decreased NEDD4-2 expression in DRG cells and increased the amplitude of Na(v)1.7 and Na(v)1.8 currents. The redistribution of Na(v)1.7 channels toward peripheral axons was also observed. Similar changes were observed in the nociceptive DRG neurons of Nedd4L knockout mice (SNS-Nedd4L(-/-)). SNS-Nedd4L(-/-) mice exhibited thermal hypersensitivity and an enhanced second pain phase after formalin injection. Restoration of NEDD4-2 expression in DRG neurons using recombinant adenoassociated virus (rAAV2/6) not only reduced Na(v)1.7 and Na(v)1.8 current amplitudes, but also alleviated SNI-induced mechanical allodynia. These findings demonstrate that NEDD4-2 is a potent posttranslational regulator of Na(v)s and that downregulation of NEDD4-2 leads to the hyperexcitability of DRG neurons and contributes to the genesis of pathological pain.

Impact of loading displacements on SLR-derived parameters and on the consistency between GNSS and SLR results

Displacements of the Earth’s surface caused by tidal and non-tidal loading forces are relevant in high-precision space geodesy. Some of the corrections are recommended by the international scientific community to be applied at the observation level, e.g., ocean tidal loading (OTL) and atmospheric tidal loading (ATL). Non-tidal displacement corrections are in general recommended not to be applied in the products of the International Earth Rotation and Reference Systems Service, in particular atmospheric non-tidal loading (ANTL), oceanic and hydrological non-tidal corrections. We assess and compare the impact of OTL, ATL and ANTL on SLR-derived parameters by reprocessing 12 years of SLR data considering and ignoring individual corrections. We show that loading displacements have an influence not only on station long-term stability, but also on geocenter coordinates, Earth Rotation Parameters, and satellite orbits. Applying the loading corrections reduces the amplitudes of annual signals in the time series of geocenter and station coordinates. The general improvement of the SLR station 3D coordinate repeatability when applying OTL, ATL and ANTL corrections are 19.5 %, 0.2 % and 3.3 % respectively, w.r.t. the solutions without loading corrections. ANTL corrections play a crucial role in the combination of optical (SLR) and microwave (GNSS, VLBI, DORIS) space geodetic observation techniques, because of the so-called Blue-Sky effect: SLR measurements can be carried out only under cloudless sky conditions—typically during high air pressure conditions, when the Earth’s crust is deformed, whereas microwave observations are weather-independent. Thus, applying the loading corrections at the observation level improves SLR-derived products as well as the consistency with microwave-based results. We assess the Blue-Sky effect on SLR stations and the consistency improvement between GNSS and SLR solutions when ANTL corrections are included. The omission of ANTL corrections may lead to inconsistencies between SLR and GNSS solutions of up to 2.5 mm for inland stations. As a result, the estimated GNSS–SLR coordinate differences correspond better to the local ties at the co-located stations when applying ANTL corrections.

Time-variable gravity signal in Greenland revealed by high-low satellite-to-satellite tracking

[1] In the event of a termination of the Gravity Recovery and Climate Experiment (GRACE) mission before the launch of GRACE Follow-On (due for launch in 2017), high-low satellite-to-satellite tracking (hl-SST) will be the only dedicated observing system with global coverage available to measure the time-variable gravity field (TVG) on a monthly or even shorter time scale. Until recently, hl-SST TVG observations were of poor quality and hardly improved the performance of Satellite Laser Ranging observations. To date, they have been of only very limited usefulness to geophysical or environmental investigations. In this paper, we apply a thorough reprocessing strategy and a dedicated Kalman filter to Challenging Minisatellite Payload (CHAMP) data to demonstrate that it is possible to derive the very long-wavelength TVG features down to spatial scales of approximately 2000 km at the annual frequency and for multi-year trends. The results are validated against GRACE data and surface height changes from long-term GPS ground stations in Greenland. We find that the quality of the CHAMP solutions is sufficient to derive long-term trends and annual amplitudes of mass change over Greenland. We conclude that hl-SST is a viable source of information for TVG and can serve to some extent to bridge a possible gap between the end-of-life of GRACE and the availability of GRACE Follow-On.

Cardiomyocyte growth and sarcomerogenesis at the intercalated disc

Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts.

Climatic drivers of hourly to yearly tree radius variations along a 6°C natural warming gradient

Climate affects the timing, rate and dynamics of tree growth, over time scales ranging from seconds to centuries. Monitoring how a tree's stem radius varies over these time scales can provide insight into intra-annual stem dynamics and improve our understanding of climate impacts on tree physiology and growth processes. Here, we quantify the response of radial conifer stem size to environmental fluctuations via a novel assessment of tree circadian cycles. We analyze four years of sub-hourly data collected from 56 larch and spruce trees growing along a natural temperature gradient of ∼6 °C in the central Swiss Alps. During the growing season, tree stem diameters were greatest at mid-morning and smallest in the late evening, reflecting the daily cycle of water uptake and loss. Along the gradient, amplitudes calculated from the stem radius cycle were ∼50% smaller at the upper site (∼2200 m a.s.l.) relative to the lower site (∼800 m a.s.l.). We show changes in precipitation, temperature and cloud cover have a substantial effect on typical growing season diurnal cycles; amplitudes were nine times smaller on rainy days (>10 mm), and daily amplitudes are approximately 40% larger when the mean daily temperature is 15–20 °C than when it is 5–10 °C. We find that over the growing season in the sub-alpine forests, spruce show greater daily stem water movement than larch. However, under projected future warming, larch could experience up to 50% greater stem water use, which may severely affect future growth on already dry sites. Our data further indicate that because of the confounding influences of radial growth and short-term water dynamics on stem size, conventional methodology probably overstates the effect of water-linked meteorological variables (i.e. precipitation and relative humidity) on intra-annual tree growth. We suggest future studies use intra-seasonal measurements of cell development and consider whether climatic factors produce reversible changes in stem diameter. These study design elements may help researchers more accurately quantify and attribute changes in forest productivity in response to future warming.

Warm Conveyor Belts in the ERA-Interim Dataset (1979–2010): Part I: Climatology and Potential Vorticity Evolution

A global climatology of warm conveyor belts (WCBs) is presented for the years 1979–2010, based on trajectories calculated with Interim ECMWF Re-Analysis (ERA-Interim) data. WCB trajectories are identified as strongly ascending air parcels (600 hPa in 2 days) near extratropical cyclones. Corroborating earlier studies, WCBs are more frequent during winter than summer and they ascend preferentially in the western ocean basins between 25° and 50° latitude. Before ascending, WCB trajectories typically approach from the subtropics in summer and from more midlatitude regions in winter. Considering humidity, cloud water, and potential temperature along WCBs confirms that they experience strong condensation and integrated latent heating during the ascent (typically >20 K). Liquid and ice water contents along WCBs peak at about 700 and 550 hPa, respectively. The mean potential vorticity (PV) evolution shows typical tropospheric values near 900 hPa, followed by an increase to almost 1 potential vorticity unit (PVU) at 700 hPa, and a decrease to less than 0.5 PVU at 300 hPa. These low PV values in the upper troposphere constitute significant negative anomalies with amplitudes of 1–3 PVU, which can strongly influence the downstream flow. Considering the low-level diabatic PV production, (i) WCBs starting at low latitudes (<40°) are unlikely to attain high PV (due to weak planetary vorticity) although they exhibit the strongest latent heating, and (ii) for those ascending at higher latitudes, a strong vertical heating gradient and high absolute vorticity are both important. This study therefore provides climatological insight into the cloud diabatic formation of significant positive and negative PV anomalies in the extratropical lower and upper troposphere, respectively.

A Wavelet Analysis of Pliopleistocene Climate Indicators: A New View of Periodicity Evolution

Wavelet analysis offers an alternative to Fourier based time-series analysis, and is particularly useful when the amplitudes and periods of dominant cycles are time dependent. We analyse climatic records derived from oxygen isotopic ratios of marine sediment cores with modified Morlet wavelets. We use a normalization of the Morlet wavelets which allows direct correspondence with Fourier analysis. This provides a direct view of the oscillations at various frequencies, and illustrates the nature of the time-dependence of the dominant cycles.

Spatial Patterns of Intraseasonal Variability of Chlorophyll and Sea Surface Temperature in the California Current

Six years of daily satellite data are used to quantify and map intraseasonal variability of chlorophyll and sea surface temperature (SST) in the California Current. We define intraseasonal variability as temporal variation remaining after removal of interannual variability and stationary seasonal cycles. Semivariograms are used to quantify the temporal structure of residual time series. Empirical orthogonal function (EOF) analyses of semivariograms calculated across the region isolate dominant scales and corresponding spatial patterns of intraseasonal variability. The mode 1 EOFs for both chlorophyll and SST semivariograms indicate a dominant timescale of similar to 60 days. Spatial amplitudes and patterns of intraseasonal variance derived from mode 1 suggest dominant forcing of intraseasonal variability through distortion of large scale chlorophyll and SST gradients by mesoscale circulation. Intraseasonal SST variance is greatest off southern Baja and along southern Oregon and northern California. Chlorophyll variance is greatest over the shelf and slope, with elevated values closely confined to the Baja shelf and extending farthest from shore off California and the Pacific Northwest. Intraseasonal contributions to total SST variability are strongest near upwelling centers off southern Oregon and northern California, where seasonal contributions are weak. Intraseasonal variability accounts for the majority of total chlorophyll variance in most inshore areas save for southern Baja, where seasonal cycles dominate. Contributions of higher EOF modes to semivariogram structure indicate the degree to which intraseasonal variability is shifted to shorter timescales in certain areas. Comparisons of satellite-derived SST semivariograms to those calculated from co-located and concurrent buoy SST time series show similar features.

A Model Study of the Circulation in the Pearl River Estuary (PRE) and Its Adjacent Coastal Waters: 1. Simulations and Comparison with Observations

The Princeton Ocean Model is used to study the circulation features in the Pearl River Estuary and their responses to tide, river discharge, wind, and heat flux in the winter dry and summer wet seasons. The model has an orthogonal curvilinear grid in the horizontal plane with variable spacing from 0.5 km in the estuary to 1 km on the shelf and 15 sigma levels in the vertical direction. The initial conditions and the subtidal open boundary forcing are obtained from an associated larger-scale model of the northern South China Sea. Buoyancy forcing uses the climatological monthly heat fluxes and river discharges, and both the climatological monthly wind and the realistic wind are used in the sensitivity experiments. The tidal forcing is represented by sinusoidal functions with the observed amplitudes and phases. In this paper, the simulated tide is first examined. The simulated seasonal distributions of the salinity, as well as the temporal variations of the salinity and velocity over a tidal cycle are described and then compared with the in situ survey data from July 1999 and January 2000. The model successfully reproduces the main hydrodynamic processes, such as the stratification, mixing, frontal dynamics, summer upwelling, two-layer gravitational circulation, etc., and the distributions of hydrodynamic parameters in the Pearl River Estuary and coastal waters for both the winter and the summer season.

The quasi 16-day wave in mesospheric water vapor during boreal winter 2011/2012

This study investigates the characteristics of the quasi 16-day wave in the mesosphere during boreal winter 2011/2012 using observations of water vapor from ground-based microwave radiometers and satellite data. The ground-based microwave radiometers are located in Seoul (South Korea, 37° N), Bern (Switzerland, 47° N) and Sodankylä (Finland, 67° N). The quasi 16-day wave is observed in the mesosphere at all three locations, while the dominant period increases with latitude from 15 days at Seoul to 20 days at Sodankylä. The observed evolution of the quasi 16-day wave confirms that the wave activity is strongly decreased during a sudden stratospheric warming that occurred in mid-January 2012. Using satellite data from the Microwave Limb Sounder on the Aura satellite, we examine the zonal characteristics of the quasi 16-day wave and conclude that the observed waves above the mid-latitudinal stations Seoul and Bern are eastward-propagating s=−1 planetary waves with periods of 15 to 16 days, while the observed oscillation above the polar station Sodankylä is a standing oscillation with a period of approximately 20 days. The strongest relative wave amplitudes in water vapor during the investigated time period are approximately 15%. The wave activity varies strongly along a latitude circle. The activity of the quasi 16-day wave in mesospheric water vapor during boreal winter 2011/2012 is strongest over Northern Europe, the North Atlantic ocean and North-West Canada. The region of highest wave activity seems to be related to the position of the polar vortex. We conclude that the classic approach to characterize planetary waves zonally averaged along a latitude circle is not sufficient to explain the local observations because of the strong longitudinal dependence of the wave activity.

Diurnal variations in middle-atmospheric water vapor by ground-based microwave radiometry

Abstract. In this paper, we compare the diurnal variations in middle-atmospheric water vapor as measured by two ground-based microwave radiometers in the Alpine region near Bern, Switzerland. The observational data set is also compared to data from the chemistry–climate model WACCM. Due to the small diurnal variations of usually less than 1%, averages over extended time periods are required. Therefore, two time periods of five months each, December to April and June to October, were taken for the comparison. The diurnal variations from the observational data agree well with each other in amplitude and phase. The linear correlation coefficients range from 0.8 in the upper stratosphere to 0.5 in the upper mesosphere. The observed diurnal variability is significant at all pressure levels within the sensitivity of the instruments. Comparing our observations with WACCM, we find that the agreement of the phase of the diurnal cycle between observations and model is better from December to April than from June to October. The amplitudes of the diurnal variations for both time periods increase with altitude in WACCM, but remain approximately constant at 0.05 ppm in the observations. The WACCM data are used to separate the processes that lead to diurnal variations in middle-atmospheric water vapor above Bern. The dominating processes were found to be meridional advection below 0.1 hPa, vertical advection between 0.1 and 0.02 hPa and (photo-)chemistry above 0.02 hPa. The contribution of zonal advection is small. The highest diurnal variations in water vapor as seen in the WACCM data are found in the mesopause region during the time period from June to October with diurnal amplitudes of 0.2 ppm (approximately 5% in relative units).