PersonID,Abstract
1,"Perceptual events derive their significance to an animal from their meaning about the world, that is from the information they carry about their causes. The brain should thus be able to efficiently infer the causes underlying our sensory events. Here we use multisensory cue combination to study causal inference in perception. We formulate an ideal-observer model that infers whether two sensory cues originate from the same location and that also estimates their location(s). This model accurately predicts the nonlinear integration of cues by human subjects in two auditory-visual localization tasks. The results show that indeed humans can efficiently infer the causal structure as well as the location of causes. By combining insights from the study of causal inference with the ideal-observer approach to sensory cue combination, we show that the capacity to infer causal structure is not limited to conscious, high-level cognition; it is also performed continually and effortlessly in perception."
2,"We use graphical models and structure learning to explore how people learn policies in sequential decision making tasks. Studies of sequential decision-making in humans frequently find suboptimal performance relative to an ideal actor that knows the graph model that generates reward in the environment. We argue that the learning problem humans face also involves learning the graph structure for reward generation in the environment. We formulate the structure learning problem using mixtures of reward models, and solve the optimal action selection problem using Bayesian Reinforcement Learning. We show that structure learning in one and two armed bandit problems produces many of the qualitative behaviors deemed suboptimal in previous studies. Our argument is supported by the results of experiments that demonstrate humans rapidly learn and exploit new reward structure."
3,"A large number of experiments have asked to what degree human reaching movements can be understood as being close to optimal in a statistical sense. However, little is known about whether these principles are relevant for other classes of movements. Here we analyzed movement in a task that is similar to surfing or snowboarding. Human subjects stand on a force plate that measures their center of pressure. This center of pressure affects the acceleration of a cursor that is displayed in a noisy fashion (as a cloud of dots) on a projection screen while the subject is incentivized to keep the cursor close to a fixed position. We find that salient aspects of observed behavior are well-described by optimal control models where a Bayesian estimation model (Kalman filter) is combined with an optimal controller (either a Linear-Quadratic-Regulator or Bang-bang controller). We find evidence that subjects integrate information over time taking into account uncertainty. However, behavior in this continuous steering task appears to be a highly non-linear function of the visual feedback. While the nervous system appears to implement Bayes-like mechanisms for a full-body, dynamic task, it may additionally take into account the specific costs and constraints of the task."
4,"Rhythmic brain activity, measured by magnetoencephalography (MEG), is modulated during stimulation and task performance. Here, we introduce an oscillatory response function (ORF) to predict the dynamic suppression rebound modulation of brain rhythms during a stimulus sequence. We derived a class of parametric models for the ORF in a generalized convolution framework. The model parameters were estimated from MEG data acquired from 10 subjects during bilateral tactile stimulation of fingers (stimulus rates of 4 Hz and 10 Hz in blocks of 0.5, 1, 2, and 4 s). The envelopes of the 17 to 23 Hz rhythmic activity, computed for sensors above the rolandic region, correlated 25% to 43% better with the envelopes predicted by the models than by the stimulus time course (boxcar). A linear model with separate convolution kernels for onset and offset responses gave the best prediction. We studied the generalizability of this model with data from 5 different subjects during a separate bilateral tactile sequence by first identifying neural sources of the 17 to 23 Hz activity using cortically constrained minimum norm estimates.Both the model and the boxcar predicted strongest modulation in the primary motor cortex. For short-duration stimulus blocks, the model predicted the envelope of the cortical currents 20% better than the boxcar did. These results suggest that ORFs could concisely describe brain rhythms during different stimuli, tasks, and pathologies"
5,"A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a molecular ticker tape, in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales"
6,"Cancer and healthy cells have distinct distributions of molecular properties and thus respond differently to drugs. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in both cancer and healthy cell populations increases the difficulty of selective drug action. Here we formalize a classification framework based on the idea that an ideal cancer drug should maximally discriminate between cancer and healthy cells. More specifically, this discrimination should be performed on the basis of measurable cell markers. We divide the problem into three parts which we explore with examples. First, molecular markers should discriminate cancer cells from healthy cells at the single-cell level. Second, the effects of drugs should be statistically predicted by these molecular markers. Third, drugs should be optimized for classification performance. We find that expression levels of a handful of genes suffice to discriminate well between individual cells in cancer and healthy tissue. We also find that gene expression predicts the efficacy of some cancer drugs, suggesting that these cancer drugs act as suboptimal classifiers using gene profiles. Finally, we formulate a framework that defines an optimal drug, and predicts drug cocktails that may target cancer more accurately than the individual drugs alone. Conceptualizing cancer drugs as solving a discrimination problem in the high-dimensional space of molecular markers promises to inform the design of new cancer drugs and drug cocktails."
7,"For rehabilitation and diagnoses, an understanding of patient activities and movements is important. Modern smartphones have built in accelerometers which promise to enable quantifying minute-by-minute what patients do (e.g. walk or sit). Such a capability could inform recommendations of physical activities and improve medical diagnostics. However, a major problem is that during everyday life, we carry our phone in different ways, e.g. on our belt, in our pocket, in our hand, or in a bag. The recorded accelerations are not only affected by our activities but also by the phone's location. Here we develop a method to solve this kind of problem, based on the intuition that activities change rarely, and phone locations change even less often. A hidden Markov model (HMM) tracks changes across both activities and locations, enabled by a static support vector machine (SVM) classifier that probabilistically identifies activity–location pairs. We find that this approach improves tracking accuracy on healthy subjects as compared to a static classifier alone. The obtained method can be readily applied to patient populations. Our research enables the use of phones as activity tracking devices, without the need of previous approaches to instruct subjects to always carry the phone in the same location."