Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

The AMPA receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have both been implicated in motor neurone vulnerability in Amyotrophic Lateral Sclerosis/Motor Neurone Disease. TNF alpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNF alpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/ml, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using Fura-2 AM microfluorimetry we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggests that TNF alpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in ALS

Using the variogram to explore imagery of two different spatial resolutions

The resolution of remotely sensed data is becoming increasingly fine, and there are now many sources of data with a pixel size of 1 m x 1 m. This produces huge amounts of data that have to be stored, processed and transmitted. For environmental applications this resolution possibly provides far more data than are needed: data overload. This poses the question: how much is too much? We have explored two resolutions of data-20 in pixel SPOT data and I in pixel Computerized Airborne Multispectral Imaging System (CAMIS) data from Fort A. P. Hill (Virginia, USA), using the variogram of geostatistics. For both we used the normalized difference vegetation index (NDVI). Three scales of spatial variation were identified in both the SPOT and 1 in data: there was some overlap at the intermediate spatial scales of about 150 in and of 500 m-600 in. We subsampled the I in data and scales of variation of about 30 in and of 300 in were identified consistently until the separation between pixel centroids was 15 in (or 1 in 225pixels). At this stage, spatial scales of about 100m and 600m were described, which suggested that only now was there a real difference in the amount of spatial information available from an environmental perspective. These latter were similar spatial scales to those identified from the SPOT image. We have also analysed I in CAMIS data from Fort Story (Virginia, USA) for comparison and the outcome is similar.:From these analyses it seems that a pixel size of 20m is adequate for many environmental applications, and that if more detail is required the higher resolution data could be sub-sampled to a 10m separation between pixel centroids without any serious loss of information. This reduces significantly the amount of data that needs to be stored, transmitted and analysed and has important implications for data compression.

Global scale water stages from SAR imagery (GlosSARi) to support global flood forecasting

Despite the success of studies attempting to integrate remotely sensed data and flood modelling and the need to provide near-real time data routinely on a global scale as well as setting up online data archives, there is to date a lack of spatially and temporally distributed hydraulic parameters to support ongoing efforts in modelling. Therefore, the objective of this project is to provide a global evaluation and benchmark data set of floodplain water stages with uncertainties and assimilation in a large scale flood model using space-borne radar imagery. An algorithm is developed for automated retrieval of water stages with uncertainties from a sequence of radar imagery and data are assimilated in a flood model using the Tewkesbury 2007 flood event as a feasibility study. The retrieval method that we employ is based on possibility theory which is an extension of fuzzy sets and that encompasses probability theory. In our case we first attempt to identify main sources of uncertainty in the retrieval of water stages from radar imagery for which we define physically meaningful ranges of parameter values. Possibilities of values are then computed for each parameter using a triangular ‘membership’ function. This procedure allows the computation of possible values of water stages at maximum flood extents along a river at many different locations. At a later stage in the project these data are then used in assimilation, calibration or validation of a flood model. The application is subsequently extended to a global scale using wide swath radar imagery and a simple global flood forecasting model thereby providing improved river discharge estimates to update the latter.

Estimating discharge from inundation imagery

Remote sensing from space-borne platforms is often seen as an appealing method of monitoring components of the hydrological cycle, including river discharge, due to its spatial coverage. However, data from these platforms is often less than ideal because the geophysical properties of interest are rarely measured directly and the measurements that are taken can be subject to significant errors. This study assimilated water levels derived from a TerraSAR-X synthetic aperture radar image and digital aerial photography with simulations from a two dimensional hydraulic model to estimate discharge, inundation extent, depths and velocities at the confluence of the rivers Severn and Avon, UK. An ensemble Kalman filter was used to assimilate spot heights water levels derived by intersecting shorelines from the imagery with a digital elevation model. Discharge was estimated from the ensemble of simulations using state augmentation and then compared with gauge data. Assimilating the real data reduced the error between analyzed mean water levels and levels from three gauging stations to less than 0.3 m, which is less than typically found in post event water marks data from the field at these scales. Measurement bias was evident, but the method still provided a means of improving estimates of discharge for high flows where gauge data are unavailable or of poor quality. Posterior estimates of discharge had standard deviations between 63.3 m3s-1 and 52.7 m3s-1, which were below 15% of the gauged flows along the reach. Therefore, assuming a roughness uncertainty of 0.03-0.05 and no model structural errors discharge could be estimated by the EnKF with accuracy similar to that arguably expected from gauging stations during flood events. Quality control prior to assimilation, where measurements were rejected for being in areas of high topographic slope or close to tall vegetation and trees, was found to be essential. The study demonstrates the potential, but also the significant limitations of currently available imagery to reduce discharge uncertainty in un-gauged or poorly gauged basins when combined with model simulations in a data assimilation framework.

Can we harness computerised cognitive bias modification to treat anxiety in schizophrenia? A first step highlighting the role of mental imagery

A new wave of computerised therapy is under development which, rather than simulating talking therapies, uses bias modification techniques to target the core psychological process underlying anxiety. Such interventions are aimed at anxiety disorders, and are yet to be adapted for co-morbid anxiety in psychosis. The cognitive bias modification (CBM) paradigm delivers repeated exposure to stimuli in order to train individuals to resolve ambiguous information in a positive, rather than anxiety provoking, manner. The current study is the first to report data from a modified form of CBM which targets co-morbid anxiety within individuals diagnosed with schizophrenia. Our version of CBM involved exposure to one hundred vignettes presented over headphones. Participants were instructed to actively simulate the described scenarios via visual imagery. Twenty-one participants completed both a single session of CBM and a single control condition session in counter-balanced order. Within the whole sample, there was no significant improvement on interpretation bias of CBM or state anxiety, relative to the control condition. However, in line with previous research, those participants who engage in higher levels of visual imagery exhibited larger changes in interpretation bias. We discuss the implications for harnessing computerised CBM therapy developments for co-morbid anxiety in schizophrenia.

Coding of visual space during motor preparation: approaching objects rapidly modulate corticospinal excitability in hand-centered coordinates

Defensive behaviors, such as withdrawing your hand to avoid potentially harmful approaching objects, rely on rapid sensorimotor transformations between visual and motor coordinates. We examined the reference frame for coding visual information about objects approaching the hand during motor preparation. Subjects performed a simple visuomanual task while a task-irrelevant distractor ball rapidly approached a location either near to or far from their hand. After the distractor ball appearance, single pulses of transcranial magnetic stimulation were delivered over the subject's primary motor cortex, eliciting motor evoked potentials (MEPs) in their responding hand. MEP amplitude was reduced when the ball approached near the responding hand, both when the hand was on the left and the right of the midline. Strikingly, this suppression occurred very early, at 70-80ms after ball appearance, and was not modified by visual fixation location. Furthermore, it was selective for approaching balls, since static visual distractors did not modulate MEP amplitude. Together with additional behavioral measurements, we provide converging evidence for automatic hand-centered coding of visual space in the human brain.

Posttraumatic stress symptoms in London school children following September 11, 2001: an exploratory investigation of peri-traumatic reactions and intrusive imagery

Threatening intrusive images are central to posttraumatic stress disorder. It has been suggested that intrusive imagery in the context of a sense of threat leads to the development and persistence of posttraumatic stress symptoms. This study investigates London school children's (N = 76; age 10-11 years) self-reported posttraumatic stress symptoms in response to viewing the attacks of September 11, 2001 on television. Assessments were made at two time points. A minority of participants reported moderate-severe symptoms with functional impairment at 2 months (14.5%) and 6 months (9.2%) after viewing the September 11events. After controlling for symptom stability, persistent symptoms were associated with peri-traumatic factors, notably perceiving that one's life was in danger. The combined effect of intrusive imagery and peri-traumatic life threat was associated with symptom persistence. Assessments of intrusive image content via checklist and free-report indicated that the images were directly related to September 11 and were fairly stable over time. Implications for treating children's intrusive images following stressful events are explored. (C) 2007 Elsevier Ltd. All rights reserved.

Exploring block construction and mental imagery: evidence of atypical orientation discrimination in Williams syndrome

The visuospatial perceptual abilities of individuals with Williams syndrome (WS) were investigated in two experiments. Experiment I measured the ability of participants to discriminate between oblique and between nonoblique orientations. Individuals with WS showed a smaller effect of obliqueness in response time, when compared to controls matched for nonverbal mental age. Experiment 2 investigated the possibility that this deviant pattern of orientation discrimination accounts for the poor ability to perform mental rotation in WS (Farran, Jarrold, & Gathercole, 2001). A size transformation task was employed, which shares the image transformation requirements of mental rotation, but not the orientation discrimination demands. Individuals with WS performed at the same level as controls. The results suggest a deviance at the perceptual level in WS, in processing orientation, which fractionates from the ability to mentally transform images.

Motor brain regions are involved in the encoding of delayed intentions: a fMRI study

In studies of prospective memory, recall of the content of delayed intentions is normally excellent, probably because they contain actions that have to be enacted at a later time. Action words encoded for later enactment are more accessible from memory than those encoded for later verbal report [Freeman, J.E., and Ellis, J.A. 2003a. The representation of delayed intentions: A prospective subject-performed task? Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 976-992.]. As this higher assessibility is lost when the intended actions have to be enacted during encoding, or when a motor interference task is introduced concurrent to intention encoding, Freeman and Ellis suggested that the advantage of to-be-enacted actions is due to additional preparatory motor operations during encoding. Accordingly, in a fMRI study with 10 healthy young participants, we investigated whether motor brain regions are differentially activated during verbal encoding of actions for later enactment with the right hand in contrast to verbal encoding of actions for later verbal report. We included an additional condition of verbal encoding of abstract verbs for later verbal report to investigate whether the semantic motor information inherent in action verbs in contrast to abstract verbs activates motor brain regions different from those involved in the verbal encoding of actions for later enactment. Differential activation for the verbal encoding of to-be-enacted actions in contrast to to-be-reported actions was found in brain regions known to be involved in covert motor preparation for hand movements, i.e. the postcentral gyrus, the precuneus, the dorsal and ventral premotor cortex, the posterior middle temporal gyrus and the inferior parietal lobule. There was no overlap between these brain regions and those differentially activated during the verbal encoding of actions in contrast to abstract verbs for later verbal report. Consequently, the results of this fMRI study suggest the presence of preparatory motor operations during the encoding of delayed intentions requiring a future motor response, which cannot be attributed to semantic information inherent to action verbs. (c) 2006 Elsevier B.V. All rights reserved.

Changing patterns of cognitive-motor interference (CMI) over time during recovery from stroke

Objective: To explore the extent and nature of change in cognitive-motor interference (CMI) among rehabilitating stroke patients who showed dual-task gait decrement at initial assessment. Design: Experimental, with in-subjects, repeated measures design. Setting: Rehabilitation centre for adults with acquired, nonprogressive brain injury. Subjects: Ten patients with unilateral stroke, available for reassessment 1-9 months following their participation in a study of CMI after brain injury. Measures: Median stride duration; mean word generation. Methods: Two x one-minute walking trials, two x one-minute word generation trials, two x one-minute trials of simultaneous walking and word generation; 10-metre walking time; Barthel ADL Scale score. Results: Seven out of ten patients showed reduction over time in dual-task gait decrement. Three out of ten showed reduction in cognitive decrement. Only one showed concomitant reduction in gait and word generation decrement. Conclusion: Extent of CMI during relearning to walk after a stroke reduced over time in the majority of patients. Effects were more evident in improved stride duration than improved cognitive performance. Measures of multiple task performance should be included in assessment for functional recovery.