Biology subjects

van den Berg, R.

Publications and source records attributed to van den Berg, R..

10 recordsLinked to original sources

bioRxiv2024

Working memory representations are spatially transferred in cortex during mental manipulations

Working Memory (WM) enables us to maintain and directly manipulate mental representations, yet we know little about the neural implementation of this privileged online format. We recorded electroencephalography data as human subjects engaged in a task requiring continuous updates to the locations of objects retained in WM as well as in a visually identical task with WM demands removed. Analysis of neural data suggested WM-related contralateral delay activity reversed polarity as objects held in WM moved to the opposite hemifield. This was partially but not fully explained by visual attention demands. Thus, the cortical location of activity related to both attention and WM was updated to meet behavioral demands as the spatial location of remembered objects changed.

neuroscience↗

bioRxiv2023

Protein generation with evolutionary diffusion: sequence is all you need

Deep generative models are increasingly powerful tools for the in silico design of novel proteins. Recently, a family of generative models called diffusion models has demonstrated the ability to generate biologically plausible proteins that are dissimilar to any actual proteins seen in nature, enabling unprecedented capability and control in de novo protein design. However, current state-of-the-art diffusion models generate protein structures, which limits the scope of their training data and restricts generations to a small and biased subset of protein design space. Here, we introduce a general-purpose diffusion framework, EvoDiff, that combines evolutionary-scale data with the distinct conditioning capabilities of diffusion models for controllable protein generation in sequence space. EvoDiff generates high-fidelity, diverse, and structurally-plausible proteins that cover natural sequence and functional space. We show experimentally that EvoDiff generations express, fold, and exhibit expected secondary structure elements. Critically, EvoDiff can generate proteins inaccessible to structure-based models, such as those with disordered regions, while maintaining the ability to design scaffolds for functional structural motifs. We validate the universality of our sequence-based formulation by experimentally characterizing intrinsically-disordered mitochondrial targeting signals, metal-binding proteins, and protein binders designed using EvoDiff. We envision that EvoDiff will expand capabilities in protein engineering beyond the structure-function paradigm toward programmable, sequence-first design.

bioengineering↗

bioRxiv2021

Re-oxidation of cytosolic NADH is a major contributor to the high oxygen requirements of the thermotolerant yeast Ogataea parapolymorpha in oxygen-limited cultures

Thermotolerance is an attractive feature for yeast-based industrial ethanol production. However, incompletely understood oxygen requirements of known thermotolerant yeasts are incompatible with process requirements. To study the magnitude and molecular basis of these oxygen requirements in the facultatively fermentative, thermotolerant yeast Ogataea parapolymorpha, chemostat studies were performed under defined oxygen-sufficient and oxygen-limited cultivation regimes. The minimum oxygen requirements of O. parapolymorpha were found to be at least an order of magnitude larger than those of the thermotolerant yeast Kluyveromyces marxianus. This high oxygen requirement coincided with absence of glycerol formation, which plays a key role in NADH reoxidation in oxygen-limited cultures of other facultatively fermentative yeasts. Co-feeding of acetoin, whose reduction to 2,3-butanediol can reoxidize cytosolic NADH, supported a 2.5-fold higher biomass concentration in oxygen-limited cultures. The apparent inability of O. parapolymorpha to produce glycerol correlated with absence of orthologs of the S. cerevisiae genes encoding glycerol-3P phosphatase (ScGPP1, ScGPP2). Glycerol production was observed in aerobic batch cultures of a strain in which genes including key enzymes in mitochondrial reoxidation of NADH were deleted. However, transcriptome analysis did not identify a clear candidate for the responsible phosphatase. Expression of ScGPD2, encoding NAD+-dependent glycerol-3P dehydrogenase, and ScGPP1 in O. parapolymorpha resulted in increased glycerol production in oxygen-limited chemostats, but glycerol production rates remained substantially lower than observed in S. cerevisiae and K. marxianus. These results identify a dependency on aerobic respiration for reoxidation of NADH generated in biosynthesis as a key factor in the unexpectedly high oxygen requirements of O. parapolymorpha. ImportanceThermotolerant yeasts hold great potential for anaerobic fermentation processes but their application is so far hampered by incompletely understood oxygen requirements. Based on quantitative physiological studies in oxygen-limited chemostat cultures, this study shows that the thermotolerant yeast Ogataea parapolymorpha has a much higher oxygen requirement than other, previously investigated facultatively fermentative yeasts. The large oxygen requirement of O. parapolymorpha was linked to an inability of oxygen-limited cultures to efficiently reoxidize NADH formed in biosynthetic processes by glycerol formation. These results provide a basis for reducing the oxygen requirements of O. parapolymorpha by targeted metabolic engineering. In addition, this study shows that diversity of oxygen requirements should be taken into account in selecting yeast species for application in anaerobic or oxygen-limited industrial processes.

physiology↗

bioRxiv2021

On the generality and cognitive basis of base-rate neglect

Base rate neglect refers to peoples apparent tendency to underweight or even ignore base rate information when estimating posterior probabilities for events, such as the probability that a person with a positive cancer-test outcome actually does have cancer. While often replicated, almost all evidence for the phenomenon comes from studies that used problems with extremely low base rates, high hit rates, and low false alarm rates. It is currently unclear whether the effect generalizes to reasoning problems outside this "corner" of the entire problem space. Another limitation of previous studies is that they have focused on describing empirical patterns of the effect at the group level and not so much on the underlying strategies and individual differences. Here, we address these two limitations by testing participants on a broader problem space and modelling their responses at a single-participant level. We find that the empirical patterns that have served as evidence for base-rate neglect generalize to a larger problem space, albeit with large individual differences in the extent with which participants "neglect" base rates. In particular, we find a bi-modal distribution consisting of one group of participants who almost entirely ignore the base rate and another group who almost entirely account for it. This heterogeneity is reflected in the cognitive modeling results: participants in the former group were best captured by a linear-additive model, while participants in the latter group were best captured by a Bayesian model. We find little evidence for heuristic models. Altogether, these results suggest that the effect known as "base-rate neglect" generalizes to a large set of reasoning problems, but varies largely across participants and may need a reinterpretation in terms of the underlying cognitive mechanisms.

animal behavior and cognition↗

bioRxiv2020

Further perceptions of probability: in defence of trial-by-trial updating models

Extensive research in the behavioural sciences has addressed peoples ability to learn stationary probabilities, which stay constant over time, but only recently have there been attempts to model the cognitive processes whereby people learn - and track - non-stationary probabilities. In this context, the old debate on whether learning occurs by gradual formation of associations or by occasional shifts between hypotheses representing beliefs about distal states of the world has resurfaced. Gallistel et al. (2014) pitched the two theories against each other in a non-stationary probability learning task. They concluded that various qualitative patterns in their data were incompatible with trial-by-trial associative learning and could only be explained by a hypothesis-testing model. Here, we contest that claim and demonstrate that it was premature. First, we argue that their experimental paradigm consisted of two distinct tasks: probability tracking (an estimation task) and change detection (a decision-making task). Next, we present a model that uses the (associative) delta learning rule for the probability tracking task and bounded evidence accumulation for the change-detection task. We find that this combination of two highly established theories accounts well for all qualitative phenomena and outperforms the alternative model proposed by Gallistel et al. in a quantitative model comparison. In the spirit of cumulative science, we conclude that current experimental data on human learning of non-stationary probabilities can be explained as a combination of associative learning and bounded evidence accumulation and does not require a new model.

animal behavior and cognition↗

bioRxiv2020

More motivated but equally good: no effect of gamification on visual working memory performance

Gamification refers to the introduction of gaming elements such as scores and leaderboards in non-gaming contexts. While there is growing evidence that gamification has positive effects on intrinsic motivation and engagement, it is largely unknown whether these effects translate to improved cognitive performance. Here, we examine whether gamification affects performance on a visual working memory (VWM) task. In Experiment 1, we gamified a standard delayed-estimation task by introducing scores and a leveling system. On each trial, the subjects estimation error was mapped to a score between -100 and +100 and added to their total score. Subjects started at a set size of 1 and "leveled up" to the next set size each time they had accumulated 1,500 points. Post-experiment questionnaire data confirmed that subjects who performed the gamified version of the task were more motivated than control subjects. However, we found no difference in VWM performance between these two groups, nor between below-median and above-median motivated subjects. In Experiment 2, we tested for effects of trial-by-trial manipulations of motivation on VWM performance, by varying the scoring function across trials. Three scoring functions were used, with maxima of 7, 21, and 101 points. At the beginning of each trial, the subject was informed whether the potential reward was "low", "medium", or "high". Post-questionnaire data showed that subjects were more motivated on high-reward trials. However, we found no evidence for a difference in performance between the three reward levels. Our results suggest that gamification increases peoples motivation to carry out visual working memory tasks, but it does not necessarily increase their performance.

animal behavior and cognition↗

bioRxiv2019

Does monetary reward increase visual working memory performance?

Previous work has shown that humans distribute their visual working memory (VWM) resources flexibly across items: the higher the importance of an item, the better it is remembered. A related, but much less studied question is whether people also have control over the total amount of VWM resource allocated to a task. Here, we approach this question by testing whether increasing monetary incentives results in better overall VWM performance. In three experiments, subjects performed a delayed-estimation task on the Amazon Turk platform. In the first two experiments, four groups of subjects received a bonus payment based on their performance, with the maximum bonus ranging from $0 to $10 between groups. We found no effect of the amount of bonus on intrinsic motivation or on VWM performance in either experiment. In the third experiment, reward was manipulated on a trial-by-trial basis using a within-subjects design. Again, no evidence was found that VWM performance depended on the magnitude of potential reward. These results suggest that encoding quality in visual working memory is insensitive to monetary reward, which has implications for resource-rational theories of VWM.

animal behavior and cognition↗

bioRxiv2018

Grouping effects in numerosity perception under prolonged viewing conditions

Humans can estimate numerosities - such as the number sheep in a flock - without deliberate counting. A number of biases have been identified in these estimates, which seem primarily rooted in the spatial organization of objects (grouping, symmetry, etc). Most previous studies on the number sense used static stimuli with extremely brief exposure times. However, outside the laboratory, visual scenes are often dynamic and freely viewed for prolonged durations (e.g., a flock of moving sheep). The purpose of the present study is to examine grouping-induced numerosity biases in stimuli that more closely mimic these conditions. To this end, we designed two experiments with limited-dot-lifetime displays (LDDs), in which each dot is visible for a brief period of time and replaced by a new dot elsewhere after its disappearance. The dynamic nature of LDDs prevents subjects from counting even when they are free-viewing a stimulus under prolonged presentation. Subjects estimated the number of dots in arrays that were presented either as a single group or were segregated into two groups by spatial clustering, dot size, dot color, or dot motion. Grouping by color and motion reduced perceived numerosity compared to viewing them as a single group. Moreover, the grouping effect sizes between these two features were correlated, which suggests that the effects may share a common, feature-invariant mechanism. Finally, we find that dot size and total stimulus area directly affect perceived numerosity, which makes it difficult to draw reliable conclusions about grouping effects induced by spatial clustering and dot size. Our results provide new insights into biases in numerosity estimation and they demonstrate that the use of LDDs is an effective method to study the human number sense under prolonged viewing.

animal behavior and cognition↗

bioRxiv2018

Computational imperfections in human visual search

Optimal Bayesian models have been highly successful in describing human performance on perceptual decision-making tasks, such as cue combination and visual search. However, recent studies have argued that these models are often overly flexible and therefore lack explanatory power. Moreover, there are indications that neural computation is inherently imprecise, which makes it implausible that humans would perform optimally on any non-trivial task. Here, we reconsider human performance on a visual search task by using an approach that constrains model flexibility and tests for computational imperfections. Subjects performed a target detection task in which targets and distractors were tilted ellipses with orientations drawn from Gaussian distributions with different means. We varied the amount of overlap between these distributions to create multiple levels of external uncertainty. We also varied the level of sensory noise, by testing subjects under both short and unlimited display times. On average, empirical performance - measured as d - fell 18.1% short of optimal performance. We found no evidence that the magnitude of this suboptimality was affected by the level of internal or external uncertainty. The data were well accounted for by a Bayesian model with imperfections in its computations. This "imperfect Bayesian" model convincingly outperformed the "flawless Bayesian" model as well as all ten heuristic models that we tested. These results suggest that perception is founded on Bayesian principles, but with suboptimalities in the implementation of these principles. The view of perception as imperfect Bayesian inference can provide a middle ground between traditional Bayesian and anti-Bayesian views. Author summaryThe main task of perceptual systems is to make truthful inferences about the environment. The sensory input to these systems is often astonishingly imprecise, which makes human perception prone to error. Nevertheless, numerous studies have reported that humans often perform as accurately as is possible given these sensory imprecisions. This suggests that the brain makes optimal use of the sensory input and computes without error. The validity of this claim has recently been questioned for two reasons. First, it has been argued that a lot of the evidence for optimality comes from studies that used overly flexible models. Second, optimality in human perception is implausible due to limitations inherent to neural systems. In this study, we reconsider optimality in a standard visual perception task by devising a research method that addresses both concerns. In contrast to previous studies, we find clear indications of suboptimalities. Our data are best explained by a model that is based on the optimal decision strategy, but with imperfections in its execution.

neuroscience↗

bioRxiv2017

A rational theory of the limitations of working memory and attention

Encoding precision in visual working memory decreases with the number of encoded items. Here, we propose a normative theory for such set size effects: the brain minimizes a weighted sum of an error-based behavioral cost and a neural encoding cost. We construct a model from this theory and find that it predicts set size effects. Notably, these effects are mediated by probing probability, which aligns with previous empirical findings. The model accounts well for effects of both set size and probing probability on encoding precision in nine delayed-estimation experiments. Moreover, we find support for the prediction that the total amount of invested resource can vary non-monotonically with set size. Finally, we show that it is sometimes optimal to encode only a subset or even none of the relevant items in a task. Our findings raise the possibility that cognitive \"limitations\" arise from rational cost minimization rather than from constraints.

neuroscience↗