Michał Januszewski

Jan-Matthis Lueckmann, Viren Jain, Michał Januszewski

Constructing mechanistic models of neural circuits is a fundamental goal of neuroscience, yet verifying such models is limited by the lack of ground truth. To rigorously test model discovery, we establish an in silico testbed using neuromechanical simulations of a larval zebrafish as a transparent ground truth. We find that LLM-based tree search autonomously discovers predictive models that significantly outperform established forecasting baselines. Conditioning on sensory drive is necessary but not sufficient for faithful system identification, as models exploit statistical shortcuts. Structural priors prove essential for enabling robust out-of-distribution generalization and recovery of interpretable mechanistic models. Our insights provide guidance for modeling real-world neural recordings and offer a broader template for AI-driven scientific discovery.

Jan-Matthis Lueckmann, Alexander Immer, Alex Bo-Yuan Chen et al.

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.

Alexander Immer, Jan-Matthis Lueckmann, Alex Bo-Yuan Chen et al.

Large-scale neuronal activity recordings with fluorescent calcium indicators are increasingly common, yielding high-resolution 2D or 3D videos. Traditional analysis pipelines reduce this data to 1D traces by segmenting regions of interest, leading to inevitable information loss. Inspired by the success of deep learning on minimally processed data in other domains, we investigate the potential of forecasting neuronal activity directly from volumetric videos. To capture long-range dependencies in high-resolution volumetric whole-brain recordings, we design a model with large receptive fields, which allow it to integrate information from distant regions within the brain. We explore the effects of pre-training and perform extensive model selection, analyzing spatio-temporal trade-offs for generating accurate forecasts. Our model outperforms trace-based forecasting approaches on ZAPBench, a recently proposed benchmark on whole-brain activity prediction in zebrafish, demonstrating the advantages of preserving the spatial structure of neuronal activity.

Michał Januszewski, Jeremy Maitin-Shepard, Peter Li et al.

State-of-the-art image segmentation algorithms generally consist of at least two successive and distinct computations: a boundary detection process that uses local image information to classify image locations as boundaries between objects, followed by a pixel grouping step such as watershed or connected components that clusters pixels into segments. Prior work has varied the complexity and approach employed in these two steps, including the incorporation of multi-layer neural networks to perform boundary prediction, and the use of global optimizations during pixel clustering. We propose a unified and end-to-end trainable machine learning approach, flood-filling networks, in which a recurrent 3d convolutional network directly produces individual segments from a raw image. The proposed approach robustly segments images with an unknown and variable number of objects as well as highly variable object sizes. We demonstrate the approach on a challenging 3d image segmentation task, connectomic reconstruction from volume electron microscopy data, on which flood-filling neural networks substantially improve accuracy over other state-of-the-art methods. The proposed approach can replace complex multi-step segmentation pipelines with a single neural network that is learned end-to-end.