Active learning of neural population dynamics using two-photon holographic optogenetics

Recent advances in techniques for monitoring and perturbing neural populations have greatly enhanced our ability to study circuits in the brain. In particular, two-photon holographic optogenetics now enables precise photostimulation of experimenter-specified groups of individual neurons, while simultaneous two-photon calcium imaging enables the measurement of ongoing and induced activity across the neural population. Despite the enormous space of potential photostimulation patterns and the time-consuming nature of photostimulation experiments, very little algorithmic work has been done to determine the most effective photostimulation patterns for identifying the neural population dynamics. Here, we develop methods to efficiently select which neurons to stimulate such that the resulting neural responses will best inform a dynamical model of the neural population activity. Using neural population responses to photostimulation in mouse motor cortex, we demonstrate the efficacy of a low-rank linear dynamical systems model, and develop an active learning procedure which takes advantage of low-rank structure to determine informative photostimulation patterns. We demonstrate our approach on both real and synthetic data, obtaining in some cases as much as a two-fold reduction in the amount of data required to reach a given predictive power. Our active stimulation design method is based on a novel active learning procedure for low-rank regression, which may be of independent interest.

Energy-Based Concept Bottleneck Models: Unifying Prediction, Concept Intervention, and Conditional Interpretations

Existing methods, such as concept bottleneck models (CBMs), have been successful in providing concept-based interpretations for black-box deep learning models. They typically work by predicting concepts given the input and then predicting the final class label given the predicted concepts. However, (1) they often fail to capture the high-order, nonlinear interaction between concepts, e.g., correcting a predicted concept (e.g., "yellow breast") does not help correct highly correlated concepts (e.g., "yellow belly"), leading to suboptimal final accuracy; (2) they cannot naturally quantify the complex conditional dependencies between different concepts and class labels (e.g., for an image with the class label "Kentucky Warbler" and a concept "black bill", what is the probability that the model correctly predicts another concept "black crown"), therefore failing to provide deeper insight into how a black-box model works. In response to these limitations, we propose Energy-based Concept Bottleneck Models (ECBMs). Our ECBMs use a set of neural networks to define the joint energy of candidate (input, concept, class) tuples. With such a unified interface, prediction, concept correction, and conditional dependency quantification are then represented as conditional probabilities, which are generated by composing different energy functions. Our ECBMs address both limitations of existing CBMs, providing higher accuracy and richer concept interpretations. Empirical results show that our approach outperforms the state-of-the-art on real-world datasets.

Attention for Causal Relationship Discovery from Biological Neural Dynamics

This paper explores the potential of the transformer models for learning Granger causality in networks with complex nonlinear dynamics at every node, as in neurobiological and biophysical networks. Our study primarily focuses on a proof-of-concept investigation based on simulated neural dynamics, for which the ground-truth causality is known through the underlying connectivity matrix. For transformer models trained to forecast neuronal population dynamics, we show that the cross attention module effectively captures the causal relationship among neurons, with an accuracy equal or superior to that for the most popular Granger causality analysis method. While we acknowledge that real-world neurobiology data will bring further challenges, including dynamic connectivity and unobserved variability, this research offers an encouraging preliminary glimpse into the utility of the transformer model for causal representation learning in neuroscience.

Learning Time-Invariant Representations for Individual Neurons from Population Dynamics

Neurons can display highly variable dynamics. While such variability presumably supports the wide range of behaviors generated by the organism, their gene expressions are relatively stable in the adult brain. This suggests that neuronal activity is a combination of its time-invariant identity and the inputs the neuron receives from the rest of the circuit. Here, we propose a self-supervised learning based method to assign time-invariant representations to individual neurons based on permutation-, and population size-invariant summary of population recordings. We fit dynamical models to neuronal activity to learn a representation by considering the activity of both the individual and the neighboring population. Our self-supervised approach and use of implicit representations enable robust inference against imperfections such as partial overlap of neurons across sessions, trial-to-trial variability, and limited availability of molecular (transcriptomic) labels for downstream supervised tasks. We demonstrate our method on a public multimodal dataset of mouse cortical neuronal activity and transcriptomic labels. We report > 35% improvement in predicting the transcriptomic subclass identity and > 20% improvement in predicting class identity with respect to the state-of-the-art.

LatticeGen: A Cooperative Framework which Hides Generated Text in a Lattice for Privacy-Aware Generation on Cloud

In the current user-server interaction paradigm of prompted generation with large language models (LLM) on cloud, the server fully controls the generation process, which leaves zero options for users who want to keep the generated text to themselves. We propose LatticeGen, a cooperative framework in which the server still handles most of the computation while the user controls the sampling operation. The key idea is that the true generated sequence is mixed with noise tokens by the user and hidden in a noised lattice. Considering potential attacks from a hypothetically malicious server and how the user can defend against it, we propose the repeated beam-search attack and the mixing noise scheme. In our experiments we apply LatticeGen to protect both prompt and generation. It is shown that while the noised lattice degrades generation quality, LatticeGen successfully protects the true generation to a remarkable degree under strong attacks (more than 50% of the semantic remains hidden as measured by BERTScore).

X-Ray2EM: Uncertainty-Aware Cross-Modality Image Reconstruction from X-Ray to Electron Microscopy in Connectomics

Comprehensive, synapse-resolution imaging of the brain will be crucial for understanding neuronal computations and function. In connectomics, this has been the sole purview of volume electron microscopy (EM), which entails an excruciatingly difficult process because it requires cutting tissue into many thin, fragile slices that then need to be imaged, aligned, and reconstructed. Unlike EM, hard X-ray imaging is compatible with thick tissues, eliminating the need for thin sectioning, and delivering fast acquisition, intrinsic alignment, and isotropic resolution. Unfortunately, current state-of-the-art X-ray microscopy provides much lower resolution, to the extent that segmenting membranes is very challenging. We propose an uncertainty-aware 3D reconstruction model that translates X-ray images to EM-like images with enhanced membrane segmentation quality, showing its potential for developing simpler, faster, and more accurate X-ray based connectomics pipelines.

The XPRESS Challenge: Xray Projectomic Reconstruction -- Extracting Segmentation with Skeletons

The wiring and connectivity of neurons form a structural basis for the function of the nervous system. Advances in volume electron microscopy (EM) and image segmentation have enabled mapping of circuit diagrams (connectomics) within local regions of the mouse brain. However, applying volume EM over the whole brain is not currently feasible due to technological challenges. As a result, comprehensive maps of long-range connections between brain regions are lacking. Recently, we demonstrated that X-ray holographic nanotomography (XNH) can provide high-resolution images of brain tissue at a much larger scale than EM. In particular, XNH is wellsuited to resolve large, myelinated axon tracts (white matter) that make up the bulk of long-range connections (projections) and are critical for inter-region communication. Thus, XNH provides an imaging solution for brain-wide projectomics. However, because XNH data is typically collected at lower resolutions and larger fields-of-view than EM, accurate segmentation of XNH images remains an important challenge that we present here. In this task, we provide volumetric XNH images of cortical white matter axons from the mouse brain along with ground truth annotations for axon trajectories. Manual voxel-wise annotation of ground truth is a time-consuming bottleneck for training segmentation networks. On the other hand, skeleton-based ground truth is much faster to annotate, and sufficient to determine connectivity. Therefore, we encourage participants to develop methods to leverage skeleton-based training. To this end, we provide two types of ground-truth annotations: a small volume of voxel-wise annotations and a larger volume with skeleton-based annotations. Entries will be evaluated on how accurately the submitted segmentations agree with the ground-truth skeleton annotations.

im2nerf: Image to Neural Radiance Field in the Wild

We propose im2nerf, a learning framework that predicts a continuous neural object representation given a single input image in the wild, supervised by only segmentation output from off-the-shelf recognition methods. The standard approach to constructing neural radiance fields takes advantage of multi-view consistency and requires many calibrated views of a scene, a requirement that cannot be satisfied when learning on large-scale image data in the wild. We take a step towards addressing this shortcoming by introducing a model that encodes the input image into a disentangled object representation that contains a code for object shape, a code for object appearance, and an estimated camera pose from which the object image is captured. Our model conditions a NeRF on the predicted object representation and uses volume rendering to generate images from novel views. We train the model end-to-end on a large collection of input images. As the model is only provided with single-view images, the problem is highly under-constrained. Therefore, in addition to using a reconstruction loss on the synthesized input view, we use an auxiliary adversarial loss on the novel rendered views. Furthermore, we leverage object symmetry and cycle camera pose consistency. We conduct extensive quantitative and qualitative experiments on the ShapeNet dataset as well as qualitative experiments on Open Images dataset. We show that in all cases, im2nerf achieves the state-of-the-art performance for novel view synthesis from a single-view unposed image in the wild.

Subgraph Frequency Distribution Estimation using Graph Neural Networks

Small subgraphs (graphlets) are important features to describe fundamental units of a large network. The calculation of the subgraph frequency distributions has a wide application in multiple domains including biology and engineering. Unfortunately due to the inherent complexity of this task, most of the existing methods are computationally intensive and inefficient. In this work, we propose GNNS, a novel representational learning framework that utilizes graph neural networks to sample subgraphs efficiently for estimating their frequency distribution. Our framework includes an inference model and a generative model that learns hierarchical embeddings of nodes, subgraphs, and graph types. With the learned model and embeddings, subgraphs are sampled in a highly scalable and parallel way and the frequency distribution estimation is then performed based on these sampled subgraphs. Eventually, our methods achieve comparable accuracy and a significant speedup by three orders of magnitude compared to existing methods.

Revisiting Latent-Space Interpolation via a Quantitative Evaluation Framework

Latent-space interpolation is commonly used to demonstrate the generalization ability of deep latent variable models. Various algorithms have been proposed to calculate the best trajectory between two encodings in the latent space. In this work, we show how data labeled with semantically continuous attributes can be utilized to conduct a quantitative evaluation of latent-space interpolation algorithms, for variational autoencoders. Our framework can be used to complement the standard qualitative comparison, and also enables evaluation for domains (such as graph) in which the visualization is difficult. Interestingly, our experiments reveal that the superiority of interpolation algorithms could be domain-dependent. While normalised interpolation works best for the image domain, spherical linear interpolation achieves the best performance in the graph domain. Next, we propose a simple-yet-effective method to restrict the latent space via a bottleneck structure in the encoder. We find that all interpolation algorithms evaluated in this work can benefit from this restriction. Finally, we conduct interpolation-aware training with the labeled attributes, and show that this explicit supervision can improve the interpolation performance.