Data-driven benchmarks have led to significant progress in key scientific modeling domains including weather and structural biology. Here, we introduce the Zebrafish Activity Prediction Benchmark (ZAPBench) to measure progress on the problem of predicting cellular-resolution neural activity throughout an entire vertebrate brain. The benchmark is based on a novel dataset containing 4d light-sheet microscopy recordings of over 70,000 neurons in a larval zebrafish brain, along with motion stabilized and voxel-level cell segmentations of these data that facilitate development of a variety of forecasting methods. Initial results from a selection of time series and volumetric video modeling approaches achieve better performance than naive baseline methods, but also show room for further improvement. The specific brain used in the activity recording is also undergoing synaptic-level anatomical mapping, which will enable future integration of detailed structural information into forecasting methods.

Predicting future neural activity is a core challenge in modeling brain dynamics, with applications ranging from scientific investigation to closed-loop neurotechnology. While recent models of population activity emphasize interpretability and behavioral decoding, neural forecasting—particularly across multi-session, spontaneous recordings—remains underexplored. We introduce POCO, a unified forecasting model that combines a lightweight univariate forecaster with a population-level encoder to capture both neuron-specific and brain-wide dynamics. Trained across five calcium imaging datasets spanning zebrafish, mice, and *C. elegans*, POCO achieves state-of-the-art accuracy at cellular resolution in spontaneous behaviors. After pre-training, POCO rapidly adapts to new recordings with minimal fine-tuning. Notably, POCO's learned unit embeddings recover biologically meaningful structure—such as brain region clustering—without any anatomical labels. Our comprehensive analysis reveals several key factors influencing performance, including context length, session diversity, and preprocessing. Together, these results position POCO as a scalable and adaptable approach for cross-session neural forecasting and offer actionable insights for future model design. By enabling accurate, generalizable forecasting models of neural dynamics across individuals and species, POCO lays the groundwork for adaptive neurotechnologies and large-scale efforts for neural foundation models. Code is available at [https://github.com/yuvenduan/POCO](https://github.com/yuvenduan/POCO).

Differentiable simulations of optical systems can be combined with deep learning-based reconstruction networks to enable high performance computational imaging via end-to-end (E2E) optimization of both the optical encoder and the deep decoder. This has enabled imaging applications such as 3D localization microscopy, depth estimation, and lensless photography via the optimization of local optical encoders. More challenging computational imaging applications, such as 3D snapshot microscopy which compresses 3D volumes into single 2D images, require a highly non-local optical encoder. We show that existing deep network decoders have a locality bias which prevents the optimization of such highly non-local optical encoders. We address this with a decoder based on a shallow neural network architecture using global kernel Fourier convolutional neural networks (FourierNets). We show that FourierNets surpass existing deep network based decoders at reconstructing photographs captured by the highly non-local DiffuserCam optical encoder. Further, we show that FourierNets enable E2E optimization of highly non-local optical encoders for 3D snapshot microscopy. By combining FourierNets with a large-scale multi-GPU differentiable optical simulation, we are able to optimize non-local optical encoders 170$\times$ to 7372$\times$ larger than prior state of the art, and demonstrate the potential for ROI-type specific optical encoding with a programmable microscope.

Multiple time series data occur in many real applications and the alignment among them is usually a fundamental step of data analysis. Frequently, these multiple time series are inter-dependent, which provides extra information for the alignment task and this information cannot be well utilized in the conventional pairwise alignment methods. Recently, the joint alignment was modeled as a max-flow problem, in which both the profile similarity between the aligned time series and the distance between adjacent warping functions are jointly optimized. However, despite the new model having elegant mathematical formulation and superior alignment accuracy, the long computation time and large memory usage, due to the use of the existing general-purpose max-flow algorithms, limit significantly its well-deserved wide use. In this report, we present BIdirectional pushing with Linear Component Operations (BILCO), a novel algorithm that solves the joint alignment max-flow problems efficiently and exactly. We develop the strategy of linear component operations that integrates dynamic programming technique and the push-relabel approach. This strategy is motivated by the fact that the joint alignment max-flow problem is a generalization of dynamic time warping (DTW) and numerous individual DTW problems are embedded. Further, a bidirectional-pushing strategy is proposed to introduce prior knowledge and reduce unnecessary computation, by leveraging another fact that good initialization can be easily computed for the joint alignment max-flow problem. We demonstrate the efficiency of BILCO using both synthetic and real experiments. Tested on thousands of datasets under various simulated scenarios and in three distinct application categories, BILCO consistently achieves at least 10 and averagely 20-folds increase in speed, and uses at most 1/8 and averagely 1/10 memory compared with the best existing max-flow method. Our source code can be found at https://github.com/yu-lab-vt/BILCO.

Progress in modern neuroscience critically depends on our ability to observe the activity of large neuronal populations with cellular spatial and high temporal resolution. However, two bottlenecks constrain efforts towards fast imaging of large populations. First, the resulting large video data is challenging to analyze. Second, there is an explicit tradeoff between imaging speed, signal-to-noise, and field of view: with current recording technology we cannot image very large neuronal populations with simultaneously high spatial and temporal resolution. Here we describe multi-scale approaches for alleviating both of these bottlenecks. First, we show that spatial and temporal decimation techniques based on simple local averaging provide order-of-magnitude speedups in spatiotemporally demixing calcium video data into estimates of single-cell neural activity. Second, once the shapes of individual neurons have been identified at fine scale (e.g., after an initial phase of conventional imaging with standard temporal and spatial resolution), we find that the spatial/temporal resolution tradeoff shifts dramatically: after demixing we can accurately recover denoised fluorescence traces and deconvolved neural activity of each individual neuron from coarse scale data that has been spatially decimated by an order of magnitude. This offers a cheap method for compressing this large video data, and also implies that it is possible to either speed up imaging significantly, or to "zoom out" by a corresponding factor to image order-of-magnitude larger neuronal populations with minimal loss in accuracy or temporal resolution.

Many perceptual processes and neural computations, such as speech recognition, motor control and learning, depend on the ability to measure and mark the passage of time. However, the processes that make such temporal judgements possible are unknown. A number of different hypothetical mechanisms have been advanced, all of which depend on the known, temporally predictable evolution of a neural or psychological state, possibly through oscillations or the gradual decay of a memory trace. Alternatively, judgements of elapsed time might be based on observations of temporally structured, but stochastic processes. Such processes need not be specific to the sense of time; typical neural and sensory processes contain at least some statistical structure across a range of time scales. Here, we investigate the statistical properties of an estimator of elapsed time which is based on a simple family of stochastic process.

Our understanding of the input-output function of single cells has been substantially advanced by biophysically accurate multi-compartmental models. The large number of parameters needing hand tuning in these models has, however, somewhat hampered their applicability and interpretability. Here we propose a simple and well-founded method for automatic estimation of many of these key parameters: 1) the spatial distribution of channel densities on the cell's membrane; 2) the spatiotemporal pattern of synaptic input; 3) the channels' reversal potentials; 4) the intercompartmental conductances; and 5) the noise level in each compartment. We assume experimental access to: a) the spatiotemporal voltage signal in the dendrite (or some contiguous subpart thereof, e.g. via voltage sensitive imaging techniques), b) an approximate kinetic description of the channels and synapses present in each compartment, and c) the morphology of the part of the neuron under investigation. The key observation is that, given data a)-c), all of the parameters 1)-4) may be simultaneously inferred by a version of constrained linear regression; this regression, in turn, is efficiently solved using standard algorithms, without any "local minima" problems despite the large number of parameters and complex dynamics. The noise level 5) may also be estimated by standard techniques. We demonstrate the method's accuracy on several model datasets, and describe techniques for quantifying the uncertainty in our estimates.