A scoping review and critique of the Input-Output subtyping dimension of spatial neglect.

Spatial neglect is a common and debilitating disorder after stroke whereby individuals have difficulty reporting, orienting, and/or responding to the contralesional side of space. Given the heterogeneity of neglect symptom presentation, various neglect subtypes have been proposed to better characterize the disorder. This review focuses on the distinction between Input neglect (i.e., difficulty perceiving and/or attending to contralesional stimuli) and Output neglect (i.e., difficulty planning and/or executing movements toward contralesional stimuli). Conceptualizations of Input and Output neglect have varied considerably. We provide a novel summary of the terminology, measurement approaches, and neural correlates of these subtypes. A protocol detailing our systematic scoping review strategy is registered on the Open Science Framework (https://osf.io/bvtxf/). For feasibility and greater comparability across studies, we limited our inclusion criteria to tasks focused on visual stimuli and upper-limb movements. A total of 110 articles were included in the review. Subtyping tasks were categorized based on whether they mainly manipulated aspects of the input (i.e., congruence of visual input with motor output, presence of visual input) or the output (i.e., modality, goal, or direction of output) to produce an Input-Output subtype dissociation. We used our review results to identify four main critiques of this literature: 1) lack of consistency/clarity in conceptual models; 2) methodological issues of dissociating Input and Output subtypes; 3) a need for updated neural theories; and 4) barriers to clinical application. We discuss the lessons learned from this subtyping dimension that can be applied to future research on neglect subtype assessment and treatment.

Changes in the Networks of Attention across the Lifespan: A Graphical Meta-Analysis.

Three Posnerian networks of attention (alerting, orienting, and executive control) have been distinguished on the bases of behavioural, neuropsychological, and neuroscientific evidence. Here, we examined the trajectories of these networks throughout the human lifespan using the various Attention Network Tests (ANTs), which were specifically developed to measure the efficacy of these networks. The ANT Database was used to identify relevant research, resulting in the inclusion of 36 publications. We conducted a graphical meta-analysis using network scores from each study, based on reaction time plotted as a function of age group. Evaluation of attentional networks from childhood to early adulthood suggests that the alerting network develops relatively quickly, and reaches near-adult level by the age of 12. The developmental pattern of the orienting network seems to depend on the information value of the spatial cues. Executive control network scores show a consistent decrease (improvement) with age in childhood. During adulthood (ages 19-75), changes in alerting depend on the modality of the warning signal, while a moderate increase in orienting scores was seen with increasing age. Whereas executive control scores, as measured in reaction time, increase (deterioration) from young adulthood into later adulthood an opposite trend is seen when scores are based on error rates.

MEK inhibition reduced vascular tumor growth and coagulopathy in a mouse model with hyperactive GNAQ.

Activating non-inherited mutations in the guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene family have been identified in childhood vascular tumors. Patients experience extensive disfigurement, chronic pain and severe complications including a potentially lethal coagulopathy termed Kasabach-Merritt phenomenon. Animal models for this class of vascular tumors do not exist. This has severely hindered the discovery of the molecular consequences of GNAQ mutations in the vasculature and, in turn, the preclinical development of effective targeted therapies. Here we report a mouse model expressing hyperactive mutant GNAQ in endothelial cells. Mutant mice develop vascular and coagulopathy phenotypes similar to those seen in patients. Mechanistically, by transcriptomic analysis we demonstrate increased mitogen activated protein kinase signaling in the mutant endothelial cells. Targeting of this pathway with Trametinib suppresses the tumor growth by reducing vascular cell proliferation and permeability. Trametinib also prevents the development of coagulopathy and improves mouse survival.

Role of aging and working memory in performance on a naturalistic visual search task.

Studying age-related changes in working memory (WM) and visual search can provide insights into mechanisms of visuospatial attention. In visual search, WM is used to remember previously inspected objects/locations and to maintain a mental representation of the target to guide the search. We sought to extend this work, using aging as a case of reduced WM capacity. The present study tested whether various domains of WM would predict visual search performance in both young (n = 47; aged 18-35 yrs) and older (n = 48; aged 55-78) adults. Participants completed executive and domain-specific WM measures, and a naturalistic visual search task with (single) feature and triple-conjunction (three-feature) search conditions. We also varied the WM load requirements of the search task by manipulating whether a reference picture of the target (i.e., target template) was displayed during the search, or whether participants needed to search from memory. In both age groups, participants with better visuospatial executive WM were faster to locate complex search targets. Working memory storage capacity predicted search performance regardless of target complexity; however, visuospatial storage capacity was more predictive for young adults, whereas verbal storage capacity was more predictive for older adults. Displaying a target template during search diminished the involvement of WM in search performance, but this effect was primarily observed in young adults. Age-specific interactions between WM and visual search abilities are discussed in the context of mechanisms of visuospatial attention and how they may vary across the lifespan.