Loes van Dam

The role of saccades in exerting voluntary control in perceptual and binocular rivalry

We have investigated the role of saccades and fixation positions in two perceptual rivalry paradigms (slant rivalry and Necker cube) and in two binocular rivalry paradigms (grating and house-face rivalry), and we compared results obtained from two different voluntary control conditions (natural viewing and hold percept). We found that for binocular rivalry, rather than for perceptual rivalry, there is a marked positive temporal correlation between saccades and perceptual flips at about the moment of the flip. Across different voluntary control conditions the pattern of temporal correlation did not change (although the amount of correlation did frequently, but not always, change), indicating that subjects do not use different temporal eye movement schemes to exert voluntary control. Analysis of the fixation positions at about the moment of the flips indicates that the fixation position by itself does not determine the percept but that subjects prefer to fixate at different positions when asked to hold either of the different percepts.

Bi-stability in perceived slant when binocular disparity and monocular perspective specify different slants.

We examined how much depth we perceive when viewing a depiction of a slanted plane in which binocular disparity and monocular perspective provide different slant information. We exposed observers to a grid stimulus in which the monocular--and binocular-specified grid orientations were varied independently across stimulus presentations. The grids were slanted about the vertical axis and observers estimated the slant relative to the frontal plane. We were particularly interested in the metrical aspects of perceived slant for a broad spectrum of possible combinations of disparity--and perspective-specified slants. We found that observers perceived only one grid orientation when the two specified orientations were similar. More interestingly, when the monocular--and binocular-specified orientations were rather different, observers experienced perceptual bi-stability (they were able to select either a perspective--or a disparity-dominated percept).

The role of (micro)saccades and blinks in perceptual bi-stability from slant rivalry

We exposed the visual system to an ambiguous 3D slant rivalry stimulus consisting of a grid for which monocular (perspective) and binocular (disparity) cues independently specified a slant about a horizontal axis. When those cues specified similar slants, observers perceived a single slant. When the difference between the specified slants was large, observers alternatively perceived a perspective- or a disparity-dominated slant. Eye movement measurements revealed that there was no positive correlation between a perceptual flip and both saccades (microsaccades as well as larger saccades) and blinks that occurred prior to a perceptual flip. We also found that changes in horizontal vergence were not responsible for perceptual flips. Thus, eye movements were not essential to flip from one percept to the other. After the moment of a perceptual flip the occurrence probabilities of both saccades and blinks were reduced. The reduced probability of saccades mainly occurred for larger voluntary saccades, rather than for involuntary microsaccades. We suggest that the reduced probability of voluntary saccades reflects a reset of saccade planning.

Predictability is necessary for closed-loop visual feedback delay adaptation

In case of delayed visual feedback during visuomotor tasks, like in some sluggish computer games, humans can modulate their behavior to compensate for the delay. However, opinions on the nature of this compensation diverge. Some studies suggest that humans adapt to feedback delays with lasting changes in motor behavior (aftereffects) and a recalibration of time perception. Other studies have shown little or no evidence for such semipermanent recalibration in the temporal domain. We hypothesize that predictability of the reference signal (target to be tracked) is necessary for semipermanent delay adaptation. To test this hypothesis, we trained participants with a 200 ms visual feedback delay in a visually guided manual tracking task, varying the predictability of the reference signal between conditions, but keeping reference motion and feedback delay constant. In Experiment 1, we focused on motor behavior. Only training in the predictable condition brings about all of the adaptive changes and aftereffects expected from delay adaptation. In Experiment 2, we used a synchronization task to investigate perceived simultaneity (perceptuomotor learning). Supporting the hypothesis, participants recalibrated subjective visuomotor simultaneity only when trained in the predictable condition. Such a shift in perceived simultaneity was also observed in Experiment 3, using an interval estimation task. These results show that delay adaptation in motor control can modulate the perceived temporal alignment of vision and kinesthetically sensed movement. The coadaptation of motor prediction and target prediction (reference extrapolation) seems necessary for such genuine delay adaptation. This offers an explanation for divergent results in the literature.

The eyes grasp, the hands see: Metric category knowledge transfers between vision and touch

Categorization of seen objects is often determined by the shapes of objects. However, shape is not exclusive to the visual modality: The haptic system also is expert at identifying shapes. Hence, an important question for understanding shape processing is whether humans store separate modality-dependent shape representations, or whether information is integrated into one multisensory representation. To answer this question, we created a metric space of computer-generated novel objects varying in shape. These objects were then printed using a 3-D printer, to generate tangible stimuli. In a categorization experiment, participants first explored the objects visually and haptically. We found that both modalities led to highly similar categorization behavior. Next, participants were trained either visually or haptically on shape categories within the metric space. As expected, visual training increased visual performance, and haptic training increased haptic performance. Importantly, however, we found that visual training also improved haptic performance, and vice versa. Two additional experiments showed that the location of the categorical boundary in the metric space also transferred across modalities, as did heightened discriminability of objects adjacent to the boundary. This observed transfer of metric category knowledge across modalities indicates that visual and haptic forms of shape information are integrated into a shared multisensory representation.

Preexposure disrupts learning of location-contingent perceptual biases for ambiguous stimuli

The perception of a bistable stimulus as one or the other interpretation can be biased by prior presentations of that stimulus. Such learning effects have been found to be long lasting even after small amounts of training. The effectiveness of training may be influenced by preexposure to the ambiguous stimulus. Here we investigate the role of preexposure for learning a position-dependent perceptual bias. We used rotating Necker Cubes as the bistable stimuli, which were presented at two locations: above or below fixation. On training trials, additional depth cues disambiguated the rotation direction contingent on the location. On test trials, the rotating cube was presented without disambiguation cues. Without preexposure to the ambiguous stimulus, subjects learned to perceive the cube to be rotating in the trained direction for both locations. However, subjects that were preexposed to the ambiguous stimulus did not learn the trained percept-location contingency, even though the preexposure was very short compared to the subsequent training. Preexposure to the disambiguated stimulus did not interfere with learning. This indicates a fundamental difference between ambiguous test and disambiguated training trials for learning a perceptual bias. In short, small variations in paradigm can have huge effects for the learning of perceptual biases for ambiguous stimuli.

Statistically Optimal Multisensory Cue Integration: A Practical Tutorial

Humans combine redundant multisensory estimates into a coherent multimodal percept. Experiments in cue integration have shown for many modality pairs and perceptual tasks that multisensory information is fused in a statistically optimal manner: observers take the unimodal sensory reliability into consideration when performing perceptual judgments. They combine the senses according to the rules of Maximum Likelihood Estimation to maximize overall perceptual precision. This tutorial explains in an accessible manner how to design optimal cue integration experiments and how to analyse the results from these experiments to test whether humans follow the predictions of the optimal cue integration model. The tutorial is meant for novices in multisensory integration and requires very little training in formal models and psychophysical methods. For each step in the experimental design and analysis, rules of thumb and practical examples are provided. We also publish Matlab code for an example experiment on cue integration and a Matlab toolbox for data analysis that accompanies the tutorial online. This way, readers can learn about the techniques by trying them out themselves. We hope to provide readers with the tools necessary to design their own experiments on optimal cue integration and enable them to take part in explaining when, why and how humans combine multisensory information optimally.

Two-way communication between the metabolic and cell cycle machineries: the molecular basis.

The relationship between cellular metabolism and the cell cycle machinery is by no means unidirectional. The ability of a cell to enter the cell cycle critically depends on the availability of metabolites. Conversely, the cell cycle machinery commits to regulating metabolic networks in order to support cell survival and proliferation. In this review, we will give an account of how the cell cycle machinery and metabolism are interconnected. Acquiring information on how communication takes place among metabolic signaling networks and the cell cycle controllers is crucial to increase our understanding of the deregulation thereof in disease, including cancer.

Switching between visuomotor mappings: Learning absolute mappings or relative shifts

Adaptation to specific visuomotor mappings becomes faster when switching back and forth between them. What is learned when repeatedly switching between the visuomotor mappings: the absolute mappings or the relative shift between the mappings? To test this, we trained participants in a rapid pointing task using a unique color cue as context for each mapping between pointing location and visual feedback. After extensive training, participants adapted to a new mapping using a neutral contextual cue. For catch trials (a change in cue and no visual feedback) different adaptation performances are predicted depending on how the mappings are encoded. When encoding an absolute mapping for each cue, participants would fall back to the mapping associated with the cue irrespective of the state they are currently in. In contrast, when a shift in mapping is encoded for the cue, pointing performance will shift relative to the current mapping by an amount equal to the difference between the previously learned mappings. Results indicate that the contextual cues signal absolute visuomotor mappings rather than relative shifts between mappings.

Analysis of gene expression in 3D spheroids highlights a survival role for ASS1 in mesothelioma

To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. A total of 209 genes were differentially expressed in common by the three cell lines in 3D (138 upregulated and 71 downregulated), although a clear resistance pathway was not apparent. We then compared the list of 3D genes with two publicly available datasets of gene expression of 56 pleural mesotheliomas compared to normal tissues. Interestingly, only three genes were increased in both 3D spheroids and human tumors: argininosuccinate synthase 1 (ASS1), annexin A4 (ANXA4) and major vault protein (MVP); of these, ASS1 was the only consistently upregulated of the three genes by qRT-PCR. To measure ASS1 protein expression, we stained 2 sets of tissue microarrays (TMA): one with 88 pleural mesothelioma samples and the other with additional 88 pleural mesotheliomas paired with matched normal tissues. Of the 176 tumors represented on the two TMAs, ASS1 was expressed in 87 (50%; staining greater than 1 up to 3+). For the paired samples, ASS1 expression in mesothelioma was significantly greater than in the normal tissues. Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance.