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People perceive individual objects as being closer when they have the ability to interact with the objects than when they do not. We asked how interaction with multiple objects impacts representations of the environment. Participants studied multiple-object layouts, by manually exploring or simply observing each object, and then drew a scaled version of the environment (Exp. 1) or reconstructed a copy of the environment and its boundaries (Exp. 2) from memory. The participants who interacted with multiple objects remembered these objects as being closer together and reconstructed smaller environment boundaries than did the participants who looked without touching. These findings provide evidence that action-based perceptual distortions endure in memory over a moving observer’s multiple interactions, compressing not only representations between touched objects, but also untouched environmental boundaries.

Neurofibromatosis type-1 (NF1), resulting from NF1 gene loss of function, is characterized by an increased risk of developing benign and malignant peripheral nerve sheath tumors (MPNSTs). Whereas the cellular heterogeneity of NF1-associated tumors has been well studied, the molecular heterogeneity of MPNSTs is still poorly understood. Mutational heterogeneity within these malignant tumors greatly complicates the study of the underlying mechanisms of tumorigenesis. We have explored this molecular heterogeneity by performing loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, PTEN, and CDKN2A genes on sections of 10 MPNSTs derived from 10 unrelated NF1 patients. LOH data for the TP53 gene was found to correlate with the results of p53 immunohistochemical analysis in the same tumor sections. Further, approximately 70% of MPNSTs were found to display intra-tumoral molecular heterogeneity as evidenced by differences in the level of LOH between different sections of the same tumor samples. This study constitutes the first systematic analysis of molecular heterogeneity within MPNSTs derived from NF1 patients. Appreciation of the existence of molecular heterogeneity in NF1-associated tumors is important not only for optimizing somatic mutation detection, but also for understanding the mechanisms of NF1 tumorigenesis, a prerequisite for the development of specifically targeted cancer therapeutics.

Neurofibromatosis type-1 (NF1) is caused by constitutional mutations of the NF1 tumor-suppressor gene. Although ∼85% of inherited NF1 microlesions constitute truncating mutations, the remaining ∼15% are missense mutations whose pathological relevance is often unclear. The GTPase-activating protein-related domain (GRD) of the NF1-encoded protein, neurofibromin, serves to define its major function as a negative regulator of the Ras-MAPK (mitogen-activated protein kinase) signaling pathway. We have established a functional assay to assess the potential pathogenicity of 15 constitutional nonsynonymous NF1 missense mutations (11 novel and 4 previously reported but not functionally characterized) identified in the NF1- GRD (p.R1204G, p.R1204W, p.R1276Q, p.L1301R, p.I1307V, p.T1324N, p.E1327G, p.Q1336R, p.E1356G, p.R1391G, p.V1398D, p.K1409E, p.P1412R, p.K1436Q, p.S1463F). Individual mutations were introduced into an NF1-GRD expression vector and activated Ras was assayed by an enzyme-linked immunosorbent assay (ELISA). Ten NF1-GRD variants were deemed to be potentially pathogenic by virtue of significantly elevated levels of activated GTP-bound Ras in comparison to wild-type NF1 protein. The remaining five NF1-GRD variants were deemed less likely to be of pathological significance as they exhibited similar levels of activated Ras to the wild-type protein. These conclusions received broad support from both bioinformatic analysis and molecular modeling and serve to improve our understanding of NF1-GRD structure and function. HumMutat 33:1687–1696, 2012. C � 2012 Wiley Periodicals, Inc.

Neurofibromatosis type-1 (NF1) is associated with the growth of benign and malignant tumors. Approximately 15% of NF1 patients develop malignant peripheral nerve sheath tumors (MPNSTs), underlining the need to identify specific diagnostic/prognostic biomarkers associated with MPNST development. The Affymetrix Genome-Wide Human single-nucleotide polymorphism (SNP) Array 6.0 was used to perform SNP genotyping and copy number alteration (CNA), loss-of-heterozygosity (LOH), and copy number neutral–LOH (CNN–LOH) analyses of DNA isolated from 15 MPNSTs, five benign plexiform neurofibromas (PNFs), and patient-matched lymphocyte DNAs. MPNSTs exhibited high-level CNN-LOH, with recurrent changes occurring in MPNSTs but not PNFs. CNN–LOH was evident in MPNSTs but occurred less frequently than genomic deletions. CNAs involving the ITGB8, PDGFA, Ras-related C3 botulinum toxin substrate 1 (RAC1) (7p21-p22), PDGFRL (8p22-p21.3), and matrix metallopeptidase 12 (MMP12) (11q22.3) genes were specific to MPNSTs. Pathway analysis revealed the MPNST-specific amplification of seven Rho–GTPase pathway genes and several cytoskeletal remodeling/cell adhesion genes. In knockdown experiments employing short-hairpin RAC1, ROCK2, PTK2, and LIMK1 RNAs to transfect both control and MPNST-derived cell lines, cell adhesion was significantly increased in the MPNST cell lines, whereas wound healing, cell migration, and invasiveness were reduced, consistent with a role for these Rho–GTPase pathway genes in MPNST development and metastasis. These results suggest new targets for therapeutic intervention in relation to MPNSTs. Hum Mutat 33:763–776, 2012. © 2012 Wiley Periodicals, Inc.

Perhaps walking and chewing gum is effortless, but walking and tracking moving objects is not. Multiple object tracking is impaired by walking from one location to another, suggesting that updating location of the self puts demands on object tracking processes. Here, we quantified the cost of self-motion in terms of the tracking load. Participants in a virtual environment tracked a variable number of targets (1-5) among distractors while either staying in one place or moving along a path that was similar to the objects’ motion. At the end of each trial, participants decided whether a probed dot was a target or distractor. As in our previous work, self-motion significantly impaired performance in tracking multiple targets. Quantifying tracking capacity for each individual under move versus stay conditions further revealed that self-motion during tracking produced a cost to capacity of about 0.8 (±0.2) objects. Tracking your own motion is worth about one object, suggesting that updating the location of the self is similar, but perhaps slightly easier, than updating locations of objects.

When a visual target is displaced during a saccade, the perception of its displacement is suppressed. Its movement can usually only be detected if the displacement is quite large. This suppression can be eliminated by introducing a short blank period after the saccade and before the target reappears in a new location. This has been termed the blanking effect and has been attributed to the use of otherwise ignored extraretinal information. We examined whether similar effects occur with eyeblinks and other visual distractions. We found that suppression of displacement perception can also occur due to a blink (both immediately prior to the blink and during the blink), and that introducing a blank period after a blink reduces the displacement suppression in much the same way as after a saccade. The blanking effect does not occur when other visual distractions are used. This provides further support for the conclusion that the blanking effect arises from extraretinal signals about eye position.

Investigations of multiple-object tracking aim to further our understanding of how people perform common activities such as driving in traffic. However, tracking tasks in the laboratory have overlooked a crucial component of much real-world object tracking: self-motion. We investigated the hypothesis that keeping track of one's own movement impairs the ability to keep track of other moving objects. Participants attempted to track multiple targets while either moving around the tracking area or remaining in a fixed location. Participants' tracking performance was impaired when they moved to a new location during tracking, even when they were passively moved and when they did not see a shift in viewpoint. Self-motion impaired multiple-object tracking in both an immersive virtual environment and a real-world analog, but did not interfere with a difficult non-spatial tracking task. These results suggest that people use a common mechanism to track changes both to the location of moving objects around them and to keep track of their own location.

Inhibition of return facilitates visual search, biasing attention away from previously examined locations. Prior research has shown that, as a result of inhibitory tags associated with rejected distractor items, observers are slower to detect small probes presented at these tagged locations than they are to detect probes presented at locations that were unoccupied during visual search, but only when the search stimuli remain visible during the probe-detection task. Using an interrupted visual search task, in which search displays alternated with blank displays, we found that inhibitory tagging occurred in the absence of the search array when probes were presented during these blank displays. Furthermore, by manipulating participants’ attentional set, we showed that these inhibitory tags were associated only with items that the participants actively searched. Finally, by probing before the search was completed, we also showed that, early in search, processing at distractor locations was actually facilitated, and only as the search progressed did evidence for inhibitory tagging arise at those locations. These results suggest that the context of a visual search determines the presence or absence of inhibitory tagging, as well as demonstrating for the first time the temporal dynamics of location prioritization while search is ongoing.

University of Illinois at Urbana-Champaign, Urbana, Illinois Recent research has shown that saccadic eye movements interfere with dorsal-stream tasks such as judgments of object orientation, but not with ventral-stream tasks such as object recognition. Because saccade programming and execution also rely on the dorsal stream, it has been hypothesized that cognitive saccadic suppression occurs as a result of dual-task interference within the dorsal stream. Judging whether one number is larger or smaller than another (magnitude comparison) is a dorsal-stream task that relies especially on the right parietal cortex. In contrast, judging whether a number is odd or even (parity judgment) does not involve the dorsal stream. In the present study, one group of subjects judged whether two-digit numbers were greater than or less than 65, whereas another group judged whether two-digit numbers were odd or even. Subjects in both groups made these judgments while making no, short, or long saccades. Saccade distance had no effect on parity judgments, but reaction times to make magnitude comparison judgments increased with saccade distance when the eyes moved from right to left. Because the right parietal cortex is instrumental in generating leftward saccades, these results provide further evidence for the hypothesis that cognitive suppression during saccades occurs as a result of dual-task interference within the dorsal stream.

Observers use facial appearance to predict social behavior and individuals' personality traits. We examined the possibility that social contexts can also influence face perception. To investigate the relationship between competitive social contexts and perceived appearance, we leveraged a known link between aggression and a simple physiognomic cue: the facial width-to-height ratio (WHR). Faces with higher WHRs are perceived as being more aggressive (Carre, McCormick, & Mondloch, 2009) and individuals with naturally higher WHRs exhibit more aggressive behavior (Carre & McCormick, 2008). Participants played a simple skill game either in competition (N=30) or cooperation (N=30) with a confederate prior to reconstructing the facial appearance of their opponent/partner and a refereeing third party by arranging segmented facial features on a screen until they had produced a best likeness of the target individual. We anticipated that higher perceived aggression during competition would lead to higher reconstructed WHRs than cooperation. The results supported this prediction: participants' reconstructions had significantly higher WHRs (p Language: en

In the present research, we investigated whether eyeblinks interfere with cognitive processing. In Experiment 1, the participants performed a partial-report iconic memory task in which a letter array was presented for 106 msec, followed 50, 150, or 750 msec later by a tone that cued recall of one row of the array. At a cue delay of 50 msec between array offset and cue onset, letter report accuracy was lower when the participants blinked following array presentation than under no-blink conditions; the participants made more mislocation errors under blink conditions. This result suggests that blinking interferes with the binding of object identity and object position in iconic memory. Experiment 2 demonstrated that interference due to blinks was not due merely to changes in light intensity. Experiments 3 and 4 demonstrated that other motor responses did not interfere with iconic memory. We propose a new phenomenon,cognitive blink suppression, in which blinking inhibits cognitive processing. This phenomenon may be due to neural interference. Blinks reduce activation in area V1, which may interfere with the representation of information in iconic memory. nt]mis|This research was supported by NSF Grant BCS 01-32292.

Farrell & Robertson. (1998). Mental rotation and the automatic updating of body-centered spatial relationships. Journal of Experimental Psychology: Learning, Memory, and Cognition, 24(1), 227-233. Farrell &Thomson. (1998). Automatic spatial updating during locomotion without vision. Quarterly Journal of Experimental Psychology, Sect A-Human Experimental Psychology, 51(3), 637-654. Foo, Warren, Douchon & Tarr. (2005). Do humans integrate routes into a cognitive map? Mapversus landmark-based navigation of novel shortcuts. Journal of Experimental Psychology: Learning, Memory, and Cognition, 31, 195–215 Pick, Heinrichs, Montello, Smith, Sullivan, & Thompson. (1995). Topographic map reading. In P. Hancock, J. Flach, J. Caird and K. Vicente (eds.), Local Applications of the Ecological Approach to Human-Machine Systems (pp. 255–284). Hillsdale, NJ: Erlbaum Riecke & Bulthoff. (2004). Spatial updating in real and virtual environments: contribution and interaction of visual and vestibular cues. Applied Perception in Graphics and Visualization, 73, 9-17. Riecke, von der Heyde, & Bulthoff. (2009). Visual cues can be sufficient for triggering automatic, reflexlike spatial updating. ACM Transactions on Applied Perception, 2(3), 183-215. Thorndyke & Hayes-Roth. (1982). Differences in spatial knowledge acquired from maps and navigation. Cognitive Psychology, 14(4), 560-589. Waller, Loomis, Golledge, & Beall. (2000). Place learning in humans: The role of distance and direction information. Spatial Cognition and Computation, 2, 333–354. People are impaired at tracking when they simultaneously move through the environment • Object tracking and spatial updating rely on the same spatial process

Background Neurofibromatosis type-1 (NF1) is a complex neurogenetic disorder characterised by the development of benign and malignant tumours of the peripheral nerve sheath (MPNSTs). Whilst biallelic NF1 gene inactivation contributes to benign tumour formation, additional cellular changes in gene structure and/or expression are required to induce malignant transformation. Although few molecular profiling studies have been performed on the process of progression of pre-existing plexiform neurofibromas to MPNSTs, the integrated analysis of copy number alterations (CNAs) and gene expression is likely to be key to understanding the molecular mechanisms underlying NF1-MPNST tumorigenesis. In a pilot study, we employed this approach to identify genes differentially expressed between benign and malignant NF1 tumours. Results SPP1 (osteopontin) was the most differentially expressed gene (85-fold increase in expression), compared to benign plexiform neurofibromas. Short hairpin RNA (shRNA) knockdown of SPP1 in NF1-MPNST cells reduced tumour spheroid size, wound healing and invasion in four different MPNST cell lines. Seventy-six genes were found to exhibit concordance between CNA and gene expression level. Conclusions Pathway analysis of these genes suggested that glutathione metabolism and Wnt signalling may be specifically involved in NF1-MPNST development. SPP1 is associated with malignant transformation in NF1-associated MPNSTs and could prove to be an important target for therapeutic intervention. Electronic supplementary material The online version of this article (doi:10.1186/s40246-015-0025-3) contains supplementary material, which is available to authorized users.