A fine-grained account of functional selectivity in the cortex is essential for understanding how visual information is processed and represented in the brain. Classical studies using designed experiments have identified multiple category-selective regions; however, these approaches rely on preconceived hypotheses about categories. Subsequent data-driven discovery methods have sought to address this limitation but are often limited by simple, typically linear encoding models. We propose an in silico approach for data-driven discovery of novel category-selectivity hypotheses based on an encoder-decoder transformer model. The architecture incorporates a brain-region to image-feature cross-attention mechanism, enabling nonlinear mappings between high-dimensional deep network features and semantic patterns encoded in the brain activity. We further introduce a method to characterize the selectivity of individual parcels by leveraging diffusion-based image generative models and large-scale datasets to synthesize and select images that maximally activate each parcel. Our approach reveals regions with complex, compositional selectivity involving diverse semantic concepts, which we validate in silico both within and across subjects. Using a brain encoder as a "digital twin" offers a powerful, data-driven framework for generating and testing hypotheses about visual selectivity in the human brain--hypotheses that can guide future fMRI experiments.

A major goal of neuroscience is to understand brain computations during visual processing in naturalistic settings. A dominant approach is to use image-computable deep neural networks trained with different task objectives as a basis for linear encoding models. However, in addition to requiring estimation of a large number of linear encoding parameters, this approach ignores the structure of the feature maps both in the brain and the models. Recently proposed alternatives factor the linear mapping into separate sets of spatial and feature weights, thus finding static receptive fields for units, which is appropriate only for early visual areas. In this work, we employ the attention mechanism used in the transformer architecture to study how retinotopic visual features can be dynamically routed to category-selective areas in high-level visual processing. We show that this computational motif is significantly more powerful than alternative methods in predicting brain activity during natural scene viewing, across different feature basis models and modalities. We also show that this approach is inherently more interpretable as the attentionrouting signals for different high-level categorical areas can be easily visualized for any input image. Given its high performance at predicting brain responses to novel images, the model deserves consideration as a candidate mechanistic model of how visual information from retinotopic maps is routed in the human brain based on the relevance of the input content to different category-selective regions.

A fine-grained account of functional selectivity in the cortex is essential for understanding how visual information is processed and represented in the brain. Classical studies using designed experiments have identified multiple category-selective regions; however, these approaches rely on preconceived hypotheses about categories. Subsequent data-driven discovery methods have sought to address this limitation but are often limited by simple, typically linear encoding models. We propose an in silico approach for data-driven discovery of novel category-selectivity hypotheses based on an encoder-decoder transformer model. The architecture incorporates a brain-region to image-feature cross-attention mechanism, enabling nonlinear mappings between high-dimensional deep network features and semantic patterns encoded in the brain activity. We further introduce a method to characterize the selectivity of individual parcels by leveraging diffusion-based image generative models and large-scale datasets to synthesize and select images that maximally activate each parcel. Our approach reveals regions with complex, compositional selectivity involving diverse semantic concepts, which we validate in silico both within and across subjects. Using a brain encoder as a "digital twin" offers a powerful, data-driven framework for generating and testing hypotheses about visual selectivity in the human brain--hypotheses that can guide future fMRI experiments.

Recent advances in Structure-based Drug Design (SBDD) have leveraged generative models for 3D molecular generation, predominantly evaluating model performance by binding affinity to target proteins. However, practical drug discovery necessitates high binding affinity along with synthetic feasibility and selectivity, critical properties that were largely neglected in previous evaluations. To address this gap, we identify fundamental limitations of conventional diffusion-based generative models in effectively guiding molecule generation toward these diverse pharmacological properties. We propose CBYG, a novel framework extending Bayesian Flow Network into a gradient-based conditional generative model that robustly integrates property-specific guidance. Additionally, we introduce a comprehensive evaluation scheme incorporating practical benchmarks for binding affinity, synthetic feasibility, and selectivity, overcoming the limitations of conventional evaluation methods. Extensive experiments demonstrate that our proposed CBYG framework significantly outperforms baseline models across multiple essential evaluation criteria, highlighting its effectiveness and practicality for real-world drug discovery applications.

Encoding models using word embeddings or artificial neural network (ANN) features reliably predict brain responses to naturalistic stimuli, yet interpreting these models remains challenging. A central limitation is superposition: distinct semantic features become entangled along correlated directions in dense embeddings when latent features outnumber embedding dimensions. This entanglement renders regression weights non-identifiable--different combinations of semantic directions can produce identical predictions, precluding principled interpretation of voxel selectivity. To address this, we introduce the Sparse Concept Encoding Model, which transforms dense embeddings into a higher-dimensional, sparse, non-negative space of learned concept atoms.

Recent advances in Structure-based Drug Design (SBDD) have leveraged generative models for 3D molecular generation, predominantly evaluating model performance by binding affinity to target proteins. However, practical drug discovery necessitates high binding affinity along with synthetic feasibility and selectivity, critical properties that were largely neglected in previous evaluations. To address this gap, we identify fundamental limitations of conventional diffusion-based generative models in effectively guiding molecule generation toward these diverse pharmacological properties. We propose $\texttt{CByG}$, a novel framework extending Bayesian Flow Network into a gradient-based conditional generative model that robustly integrates property-specific guidance. Additionally, we introduce a comprehensive evaluation scheme incorporating practical benchmarks for binding affinity, synthetic feasibility, and selectivity, overcoming the limitations of conventional evaluation methods. Extensive experiments demonstrate that our proposed $\texttt{CByG}$, framework significantly outperforms baseline models across multiple essential evaluation criteria, highlighting its effectiveness and practicality for real-world drug discovery applications.

Encoding models using word embeddings or artificial neural network (ANN) features reliably predict brain responses to naturalistic stimuli, yet interpreting these models remains challenging. A central limitation is superposition: distinct semantic features become entangled along correlated directions in dense embeddings when latent features outnumber embedding dimensions. This entanglement renders regression weights non-identifiable--different combinations of semantic directions can produce identical predictions, precluding principled interpretation of voxel selectivity. To address this, we introduce the Sparse Concept Encoding Model, which transforms dense embeddings into a higher-dimensional, sparse, non-negative space of learned concept atoms.

Neural Information Processing Systems http://nips.cc/

A long standing goal in neuroscience has been to elucidate the functional organization of the brain. Within higher visual cortex, functional accounts have remained relatively coarse, focusing on regions of interest (ROIs) and taking the form of selectivity for broad categories such as faces, places, bodies, food, or words. Because the identification of such ROIs has typically relied on manually assembled stimulus sets consisting of isolated objects in non-ecological contexts, exploring functional organization without robust a priori hypotheses has been challenging. To overcome these limitations, we introduce a data-driven approach in which we synthesize images predicted to activate a given brain region using paired natural images and fMRI recordings, bypassing the need for category-specific stimuli. Our approach - Brain Diffusion for Visual Exploration ("BrainDiVE") - builds on recent generative methods by combining large-scale diffusion models with brain-guided image synthesis. Validating our method, we demonstrate the ability to synthesize preferred images with appropriate semantic specificity for well-characterized category-selective ROIs. We then show that BrainDiVE can characterize differences between ROIs selective for the same high-level category. Finally we identify novel functional subdivisions within these ROIs, validated with behavioral data. These results advance our understanding of the fine-grained functional organization of human visual cortex, and provide well-specified constraints for further examination of cortical organization using hypothesis-driven methods.

The variables of the low-level model (left) are divided into partitions (center) such that each low-level partition corresponds to a high level variable from the high-level model (right). The circles represent variables and the arrows represent causal dependencies. Blue circles are variables that are not being intervened on and red circles are variables that are being intervened on. Observe that a low-level causal dependence between partitions does not necessarily result in a high-level causal dependence between variables and that not every low-level intervention results in a high level intervention.