Machine learning (ML) has emerged as a promising approach for improving diffusion MRI (dMRI) tractography, a task that remains limited by the intrinsic tension between local diffusion information and global anatomical plausibility. In this work, we systematically evaluate recurrent neural networks (RNNs) and Transformer models for iterative tractography, with particular attention to training strategies, input representations (including convolutional neural network (CNN)-based embeddings and end-of-sequence (EOS) tokens), and hyperparameter selection. We introduce a generation-validation phase enabling supervision at the streamline level during training, allowing supervision despite the mismatch between local loss functions and global streamline quality. Using the ISMRM2015 tractography challenge dataset, our models achieve the highest reported performance to date. Through controlled experiments, we quantify the impact of missing bundles, noisy or imperfect training streamlines, and invalid fibers in the training set. Finally, we demonstrate the applicability of our best-performing models for in vivo data from the Tractoinferno database. Overall, our results highlight both the potential and the limits of sequence-based deep learning models such as Transformers and RNNs for tractography, and emphasize the need for improved phantoms and evaluation methods for in vivo validation. We provide takeaways and recommendations for future researchers training and validating sequence-based supervised methods for tractography.

The cognitive sciences aim to understand intelligence by formalizing underlying operations as computational models. Traditionally, this follows a cycle of discovery where researchers develop paradigms, collect data, and test predefined model classes. However, this manual pipeline is fundamentally constrained by the slow pace of human intervention and a search space limited by researchers' background and intuition. Here, we propose a paradigm shift toward a fully automated, in silico science of the mind that implements every stage of the discovery cycle using Large Language Models (LLMs). In this framework, experimental paradigms exploring conceptually meaningful task structures are directly sampled from an LLM. High-fidelity behavioral data are then simulated using foundation models of cognition. The tedious step of handcrafting cognitive models is replaced by LLM-based program synthesis, which performs a high-throughput search over a vast landscape of algorithmic hypotheses. Finally, the discovery loop is closed by optimizing for ''interestingness'', a metric of conceptual yield evaluated by an LLM-critic. By enabling a fast and scalable approach to theory development, this automated loop functions as a high-throughput in-silico discovery engine, surfacing informative experiments and mechanisms for subsequent validation in real human populations.

Neural activity often exhibits multiple timescales that can vary with behavioral states and task conditions. Identifying these timescales from neural recordings is important for better understanding neural computation and function. However, traditional approaches based on autocorrelation fitting are difficult to scale to high-dimensional population recordings and can become unreliable when neural dynamics change with behavior. State-space models have been a powerful framework for modeling high-dimensional neural population activity through latent dynamical systems, but standard formulations and inference methods do not explicitly account for multiple timescales and therefore do not guarantee accurate recovery of the underlying temporal structure. Motivated by these questions, we introduce the Multi-Timescale Switching Linear Dynamical System (MTS-SLDS), a framework for identifying regime-specific latent timescales from continuous or spiking neural observations. MTS-SLDS combines a multi-lag moment initialization, which captures temporal structure across multiple observation lags, with \textit{regime-conditioned} Laplace-EM inference, which reduces mixing of dynamical statistics across uncertain regimes. Characteristic timescales can then be extracted directly from the eigenvalues of the learned latent transition matrices. In synthetic and neural experiments with Gaussian and Poisson spike observations, MTS-SLDS accurately recovers timescales and switching structure over multiple datasets.