Prior knowledge of illumination for 3D perception in the human brain

In perceiving 3D shape from ambiguous shading patterns, humans use the prior knowledge that the light is located above their head and slightly to the left. Although this observation has fascinated scientists and artists for a long time, the neural basis of this “light from above left” preference for the interpretation of 3D shape remains largely unexplored. Combining behavioral and functional MRI measurements coupled with multivoxel pattern analysis, we show that activations in early visual areas predict best the light source direction irrespective of the perceived shape, but activations in higher occipitotemporal and parietal areas predict better the perceived 3D shape irrespective of the light direction. These findings demonstrate that illumination is processed earlier than the representation of 3D shape in the visual system. In contrast to previous suggestions, we propose that prior knowledge about illumination is processed in a bottom-up manner and influences the interpretation of 3D structure at higher stages of processing.     

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Mutations in β-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the gene's exons. Four mutations previously associated with Gaucher disease and/or Parkinson's disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28–13.82), suggesting that GBA mutations may modify age of onset for PD.     

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the β-frequency band (15–35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in β-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in β-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or β-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.     

Illness representations and psychological adjustment of Greek couples dealing with a recently-diagnosed cancer: dyadic,interaction and perception-dissimilarity effects

The aim was to examine the impact of the dyadic, interaction and dissimilarity effects of the illness representations on the psychological health of recently diagnosed cancer patients and spouses in Greece. The sample consisted of 298 individuals nested in 149 couples. Effects were examined with the Actor–Partner Interdependence Model. Both actor (i.e., within person) and partner (i.e., between partners) effects were detected for both patients’ and spouses’ psychological symptoms. The negative association of patients’ psychological symptoms with their representations of illness coherence was weak at the higher and medium levels, and stronger at the lower levels of spouse corresponding representations. Patient–partner discrepancy in perceived illness consequences was associated with more psychological symptoms in patients. Adaptation to cancer is a dyadic process within the context of which patient and partner psychological well-being is affected by each other’s understanding of illness. Thus, the parallel examination of the illness representations of both partners is needed from the early phases of the illness trajectory.     

Object-selective responses in the human motion area MT/MST.

The perception of moving objects and our successful interaction with them entail that the visual system integrates shape and motion information about objects. However, neuroimaging studies have implicated different human brain regions in the analysis of visual motion (medial temporal cortex; MT/MST) and shape (lateral occipital complex; LOC), consistent with traditional approaches in visual processing that attribute shape and motion processing to anatomically and functionally separable neural mechanisms. Here we demonstrate object-selective fMRI responses (higher responses for intact than for scrambled images of objects) in MT/MST, and especially in a ventral subregion of MT/MST, suggesting that human brain regions involved mainly in the processing of visual motion are also engaged in the analysis of object shape.     

Toward experimental assessment of receptor occupancy: TGN1412 revisited

In March 2006, 6 healthy volunteers experienced serious adverse reactions during a first-in-human clinical trial of the superagonistic anti-CD28 mAb TGN1412. A first investigation excluded contaminations of the drug product or protocol irregularities as the root cause. Later, an expert scientific group convened in the United Kingdom to develop recommendations pertinent to minimizing risks of first-in-human clinical trials. The expert scientific group concluded from in silico calculations that at the initial dose of 0.1 mg/kg, which was adjusted on the basis of the no observed adverse effect level, approximately 86.2% to 90.9% CD28 receptor occupancy was obtained. Here we developed a flow cytometric method that revealed receptor occupancy of approximately 45% to 80% under the above conditions. Thus we present a method to experimentally determine receptor occupancy that can be taken as one parameter to define the minimal anticipated biological effect level as the basis for calculating safer starting doses for first-in-human clinical trials for products in which a potential risk has been identified. Additional measures are being discussed that will help to significantly improve safety of first-in-human clinical trials.     

Stability of lyophilised specimens for the molecular detection of viral DNA/RNA.

BACKGROUND: The range of nucleic acid-based technologies for the molecular detection of pathogens has grown rapidly in recent years. The influx of new testing methods into the clinical laboratory, demands for evaluation and standardisation of methods, interpretation of results and evaluation of laboratory performance have highlighted the need for internal and External Quality Assessment (EQA) systems more than ever before. External Quality Assessment panels demand reproducible, stable specimens of consistent form, suitable for transportation. OBJECTIVES: To determine the stability of freeze-dried viral specimens in terms of molecular detection. STUDY DESIGN: When EQA specimens are prepared, they undergo long-term storage and testing as part of the quality control (QC) process. The frequency and nature of testing is dependent on the resources and methodologies available at the time. A range of virus preparations used for EQA was monitored over a period of months to years in a retrospective study; the available quality monitoring data for the five viruses, including storage temperature and method of detection were analysed. RESULTS: The nucleic acid (DNA or RNA) of the freeze-dried viruses included in the study was readily detectable over a long period of time. Quantitative analysis indicated that detectable concentrations of nucleic acid post-freeze drying were similarly maintained. Storage temperature was an important factor in the stability of HCV, but other viruses were unaffected by storage at different temperatures. CONCLUSIONS: In summary, the molecular detection of nucleic acid (DNA or RNA) in freeze-dried specimens of HSV1, HSV2, HBV, HCV and HIV is possible even after prolonged storage, in some cases at a range of temperatures. Freeze drying allows large-scale production of viral specimens of high quality for EQA, which are stable in varying storage and shipment conditions. Furthermore, detection of each virus was possible with a range of commonly used molecular diagnostic methods.