In visual search, 30-40% of targets with a prevalence rate of 2% are missed, compared to 7% of targets with a prevalence rate of 50% (Wolfe, Horowitz & Kenner, 2005). This 'Low Prevalence' (LP) effect is thought to occur as participants are making motor errors, changing their response criteria and/or quitting their search too soon. We investigate whether color and spatial cues, known to improve visual search when the target has a high prevalence (HP), benefit search when the target is rare. Experiment 1 and 2 showed that although knowledge of the target's color reduces miss errors overall, it does not eliminate the LP effect as more targets were missed at LP than at HP. Furthermore, detection of a rare target is significantly impaired if it appears in an unexpected color -more so than if the prevalence of the target is high (Experiment 2). Experiment 3 showed that, if a rare target is exogenously cued, target detection is improved but still impaired relative to high prevalence conditions. Furthermore, if the cue is absent or invalid, the percentage of missed targets increase. Participants were given the option to correct motor errors in all three experiments, which reduced but did not eliminate the LP effect. The results suggest that although valid color and spatial cues improve target detection, participants still miss more targets at LP than at HP. Furthermore, invalid cues at LP are very costly in terms of miss errors. We discuss our findings in relation to current theories and applications of LP search.3
BackgroundFunctional neuroimaging research in autism spectrum disorder has reported patterns of decreased long-range, within-network, and interhemispheric connectivity. Research has also reported increased corticostriatal connectivity and between-network connectivity for default and attentional networks. Past studies have excluded individuals with autism and low verbal and cognitive performance (LVCP), so connectivity in individuals more significantly affected with autism has not yet been studied. This represents a critical gap in our understanding of brain function across the autism spectrum.MethodsUsing behavioral support procedures adapted from Nordahl, et al. (J Neurodev Disord 8:20–20, 2016), we completed non-sedated structural and functional MRI scans of 56 children ages 7–17, including LVCP children (n = 17, mean IQ = 54), children with autism and higher performance (HVCP, n = 20, mean IQ = 106), and neurotypical children (NT, n = 19, mean IQ = 111). Preparation included detailed intake questionnaires, video modeling, behavioral and anxiety reduction techniques, active noise-canceling headphones, and in-scan presentation of the Inscapes movie paradigm from Vanderwal et al. (Neuroimage 122:222–32, 2015). A high temporal resolution multiband echoplanar fMRI protocol analyzed motion-free time series data, extracted from concatenated volumes to mitigate the influence of motion artifact. All participants had > 200 volumes of motion-free fMRI scanning. Analyses were corrected for multiple comparisons.ResultsLVCP showed decreased within-network connectivity in default, salience, auditory, and frontoparietal networks (LVCP < HVCP) and decreased interhemispheric connectivity (LVCP < HVCP=NT). Between-network connectivity was higher for LVCP than NT between default and dorsal attention and frontoparietal networks. Lower IQ was associated with decreased connectivity within the default network and increased connectivity between default and dorsal attention networks.ConclusionsThis study demonstrates that with moderate levels of support, including readily available techniques, information about brain similarities and differences in LVCP individuals can be further studied. This initial study suggested decreased network segmentation and integration in LVCP individuals. Further imaging studies of LVCP individuals with larger samples will add to understanding of origins and effects of autism on brain function and behavior.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0248-y) contains supplementary material, which is available to authorized users.
Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Prior strategies have employed cardio-pulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus or plasmid DNA. While single stranded adeno-associated virus vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented by using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated virus vectors to the canine myocardium. Four vectors were evaluated—single stranded adeno-associated virus 9, self-complementary adeno-associated virus 9, self-complementary adeno-associated virus 8, self-complementary adeno-associated virus 6—so that comparison could be made between single stranded and self complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that self-complementary adeno-associated virus is superior to single stranded adeno-associated virus and that adeno-associated virus 6 is superior to other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15 to 4000 times more abundant in the heart than in any other organ for self-complementary adeno-associated virus 6. Percutaneous transendocardial injection of self-complementary adeno-associated virus 6 is a safe, effective method for achieving efficient cardiac gene transfer.
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