Deep neural networks have brought remarkable breakthroughs in medical image analysis. However, due to their data-hungry nature, the modest dataset sizes in medical imaging projects might be hindering their full potential. Generating synthetic data provides a promising alternative, allowing to complement training datasets and conducting medical image research at a larger scale. Diffusion models recently have caught the attention of the computer vision community by producing photorealistic synthetic images. In this study, we explore using Latent Diffusion Models to generate synthetic images from high-resolution 3D brain images. We used T1w MRI images from the UK Biobank dataset (N=31,740) to train our models to learn about the probabilistic distribution of brain images, conditioned on covariables, such as age, sex, and brain structure volumes. We found that our models created realistic data, and we could use the conditioning variables to control the data generation effectively. Besides that, we created a synthetic dataset with 100,000 brain images and made it openly available to the scientific community.

Representational Similarity Analysis (RSA) is a popular method for analyzing neuroimaging and behavioral data. Here we evaluate the accuracy and reliability of RSA in the context of model selection, and compare it to that of regression. Although RSA offers flexibility in handling high-dimensional, cross-modal, and cross-species data, its reliance on a transformation of raw data into similarity structures may result in the loss of critical stimulus-response information. Across extensive simulation studies and empirical analyses, we show that RSA leads to lower model selection accuracy, regardless of sample size, noise level, feature dimensionality, or multicollinearity, relative to regression. While principal component analysis and feature reweighting mitigate RSA's deficits driven by multicollinearity, regression remains superior in accurately distinguishing between models. Empirical data and a follow-up fMRI simulation further support these conclusions. Our findings suggest that researchers should carefully consider which approach to use: RSA is less effective than linear regression for model selection and fitting when direct stimulus-response mappings are available.

In randomized controlled trials, covariate adjustment can improve statistical power and reduce the required sample size compared with unadjusted estimators. Several regulatory agencies have released guidance on covariate adjustment, which has recently attracted attention in biopharmaceutical research. Analysis of covariance (ANCOVA) is often used to adjust for baseline covariates when outcomes are continuous. To design a sample size based on ANCOVA, it is necessary to prespecify the association between the outcome and baseline covariates, as well as among the baseline covariates themselves. However, determining these parameters at the design stage is challenging. Although it may be possible to adaptively assess these during the trial and recalculate the required sample size, existing sample size recalculation methods assume that the joint distribution of the outcome and baseline covariates is multivariate normal, which is not always the case in practice. In this study, we propose a blinded sample size recalculation method for the ANCOVA estimator based on the asymptotic relative efficiency under minimal distributional assumptions, thus accommodating arbitrary model misspecification. The proposed method is able to achieve the nominal power and reduce the required sample size without inflating the type I error rate in the final analysis. We conducted simulations to evaluate the performance of the proposed method under various scenarios and applied it to data from an HIV clinical trial. We provide R and SAS macro codes to implement the proposed method.

Scientific discoveries often hinge on synthesizing decades of research, a task that potentially outstrips human information processing capacities. Large language models (LLMs) offer a solution. LLMs trained on the vast scientific literature could potentially integrate noisy yet interrelated findings to forecast novel results better than human experts. To evaluate this possibility, we created BrainBench, a forward-looking benchmark for predicting neuroscience results. We find that LLMs surpass experts in predicting experimental outcomes. BrainGPT, an LLM we tuned on the neuroscience literature, performed better yet. Like human experts, when LLMs were confident in their predictions, they were more likely to be correct, which presages a future where humans and LLMs team together to make discoveries. Our approach is not neuroscience-specific and is transferable to other knowledge-intensive endeavors.

Reservoir computing (RC) establishes the basis for the processing of time-series data by exploiting the high-dimensional spatiotemporal response of a recurrent neural network to an input signal. In particular, RC trains only the output layer weights. This simplicity has drawn attention especially in Edge Artificial Intelligence (AI) applications. Edge AI enables time-series anomaly detection in real time, which is important because detection delays can lead to serious incidents. However, achieving adequate anomaly-detection performance with RC alone may require an unacceptably large reservoir on resource-constrained edge devices. Without enlarging the reservoir, attention mechanisms can improve accuracy, although they may require substantial computation and undermine the learning efficiency of RC. In this study, to improve the anomaly detection performance of RC without sacrificing learning efficiency, we propose a spectral residual RC (SR-RC) that integrates the spectral residual (SR) method - a learning-free, bottom-up attention mechanism - with RC. We demonstrated that SR-RC outperformed conventional RC and logistic-regression models based on values extracted by the SR method across benchmark tasks and real-world time-series datasets. Moreover, because the SR method, similarly to RC, is well suited for hardware implementation, SR-RC suggests a practical direction for deploying RC as Edge AI for time-series anomaly detection.

A central goal in the cognitive sciences is the development of numerical models for mental representations of object concepts. This paper introduces Variational Interpretable Concept Embeddings (VICE), an approximate Bayesian method for embedding object concepts in a vector space using data collected from humans in a triplet odd-one-out task. VICE uses variational inference to obtain sparse, non-negative representations of object concepts with uncertainty estimates for the embedding values. These estimates are used to automatically select the dimensions that best explain the data. We derive a PAC learning bound for VICE that can be used to estimate generalization performance or determine a sufficient sample size for experimental design. VICE rivals or outperforms its predecessor, SPoSE, at predicting human behavior in the triplet odd-one-out task. Furthermore, VICE's object representations are more reproducible and consistent across random initializations, highlighting the unique advantage of using VICE for deriving interpretable embeddings from human behavior.

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: 1) MRI-to-CT and 2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (>0.87/0.90) and gamma pass rates for photon (>98.1%/99.0%) and proton (>97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy.

This roadmap provides a comprehensive and forward-looking perspective on the individualized application and safety of non-ionizing radiation (NIR) dosimetry in diagnostic and therapeutic medicine. Covering a wide range of frequencies, i.e., from low-frequency to terahertz, this document provides an overview of the current state of the art and anticipates future research needs in selected key topics of NIR-based medical applications. It also emphasizes the importance of personalized dosimetry, rigorous safety evaluation, and interdisciplinary collaboration to ensure safe and effective integration of NIR technologies in modern therapy and diagnosis.

A wealth of studies report evidence that occipitotemporal cortex tessellates into "category-selective" brain regions that are apparently specialized for representing ecologically important visual stimuli like faces, bodies, scenes, and tools. Here, we argue that while valuable insights have been gained through the lens of category-selectivity, a more complete view of visual function in occipitotemporal cortex requires centering the behavioral relevance of visual properties in real-world environments rather than stimulus category. Focusing on behavioral relevance challenges a simple mapping between stimulus and visual function in occipitotemporal cortex because the environmental properties relevant to a behavior are visually diverse and how a given property is represented is modulated by our goals. Grounding our thinking in behavioral relevance rather than category-selectivity raises a host of theoretical and empirical issues that we discuss while providing proposals for how existing tools can be harnessed in this light to better understand visual function in occipitotemporal cortex.

State-space graphical models and the variational autoencoder framework provide a principled apparatus for learning dynamical systems from data. State-of-the-art probabilistic approaches are often able to scale to large problems at the cost of flexibility of the variational posterior or expressivity of the dynamics model. However, those consolidations can be detrimental if the ultimate goal is to learn a generative model capable of explaining the spatiotemporal structure of the data and making accurate forecasts. We introduce a low-rank structured variational autoencoding framework for nonlinear Gaussian state-space graphical models capable of capturing dense covariance structures that are important for learning dynamical systems with predictive capabilities. Our inference algorithm exploits the covariance structures that arise naturally from sample based approximate Gaussian message passing and low-rank amortized posterior updates -- effectively performing approximate variational smoothing with time complexity scaling linearly in the state dimensionality. In comparisons with other deep state-space model architectures our approach consistently demonstrates the ability to learn a more predictive generative model. Furthermore, when applied to neural physiological recordings, our approach is able to learn a dynamical system capable of forecasting population spiking and behavioral correlates from a small portion of single trials.

Despite the impact of psychiatric disorders on clinical health, early-stage diagnosis remains a challenge. Machine learning studies have shown that classifiers tend to be overly narrow in the diagnosis prediction task. The overlap between conditions leads to high heterogeneity among participants that is not adequately captured by classification models. To address this issue, normative approaches have surged as an alternative method. By using a generative model to learn the distribution of healthy brain data patterns, we can identify the presence of pathologies as deviations or outliers from the distribution learned by the model. In particular, deep generative models showed great results as normative models to identify neurological lesions in the brain. However, unlike most neurological lesions, psychiatric disorders present subtle changes widespread in several brain regions, making these alterations challenging to identify. In this work, we evaluate the performance of transformer-based normative models to detect subtle brain changes expressed in adolescents and young adults. We trained our model on 3D MRI scans of neurotypical individuals (N=1,765). Then, we obtained the likelihood of neurotypical controls and psychiatric patients with early-stage schizophrenia from an independent dataset (N=93) from the Human Connectome Project. Using the predicted likelihood of the scans as a proxy for a normative score, we obtained an AUROC of 0.82 when assessing the difference between controls and individuals with early-stage schizophrenia. Our approach surpassed recent normative methods based on brain age and Gaussian Process, showing the promising use of deep generative models to help in individualised analyses.

The evolution of biological neural systems has led to both modularity and sparse coding, which enables energy efficiency and robustness across the diversity of tasks in the lifespan. In contrast, standard neural networks rely on dense, non-specialized architectures, where all model parameters are simultaneously updated to learn multiple tasks, leading to interference. Current sparse neural network approaches aim to alleviate this issue but are hindered by limitations such as 1) trainable gating functions that cause representation collapse, 2) disjoint experts that result in redundant computation and slow learning, and 3) reliance on explicit input or task IDs that limit flexibility and scalability. In this paper we propose Conditionally Overlapping Mixture of ExperTs (COMET), a general deep learning method that addresses these challenges by inducing a modular, sparse architecture with an exponential number of overlapping experts. COMET replaces the trainable gating function used in Sparse Mixture of Experts with a fixed, biologically inspired random projection applied to individual input representations. This design causes the degree of expert overlap to depend on input similarity, so that similar inputs tend to share more parameters. This results in faster learning per update step and improved out-of-sample generalization. We demonstrate the effectiveness of COMET on a range of tasks, including image classification, language modeling, and regression, using several popular deep learning architectures.

To study how mental object representations are related to behavior, we estimated sparse, non-negative representations of objects using human behavioral judgments on images representative of 1,854 object categories. These representations predicted a latent similarity structure between objects, which captured most of the explainable variance in human behavioral judgments. Individual dimensions in the low-dimensional embedding were found to be highly reproducible and interpretable as conveying degrees of taxonomic membership, functionality, and perceptual attributes. We further demonstrated the predictive power of the embeddings for explaining other forms of human behavior, including categorization, typicality judgments, and feature ratings, suggesting that the dimensions reflect human conceptual representations of objects beyond the specific task.

Objective: The concurrent recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is a technique that has received much attention due to its potential for combined high temporal and spatial resolution. However, the ballistocardiogram (BCG), a large-amplitude artifact caused by cardiac induced movement contaminates the EEG during EEG-fMRI recordings. Removal of BCG in software has generally made use of linear decompositions of the corrupted EEG. This is not ideal as the BCG signal is non-stationary and propagates in a manner which is non-linearly dependent on the electrocardiogram (ECG). In this paper, we present a novel method for BCG artifact suppression using recurrent neural networks (RNNs). Methods: EEG signals were recovered by training RNNs on the nonlinear mappings between ECG and the BCG corrupted EEG. We evaluated our model's performance against the commonly used Optimal Basis Set (OBS) method at the level of individual subjects, and investigated generalization across subjects. Results: We show that our algorithm can generate larger average power reduction of the BCG at critical frequencies, while simultaneously improving task relevant EEG based classification. Conclusion: The presented deep learning architecture can be used to reduce BCG related artifacts in EEG-fMRI recordings. Significance: We present a deep learning approach that can be used to suppress the BCG artifact in EEG-fMRI without the use of additional hardware. This method may have scope to be combined with current hardware methods, operate in real-time and be used for direct modeling of the BCG.

Understanding how neural dynamics shape cognitive experiences remains a central challenge in neuroscience and psychiatry. Here, we present a novel framework leveraging state-to-output controllability from dynamical systems theory to model the interplay between cognitive perturbations, neural activity, and subjective experience. We demonstrate that large-scale fMRI signals are constrained to low-dimensional manifolds, where affective and cognitive states are naturally organized. Furthermore, we provide a theoretically robust method to estimate the controllability Gramian from steady-state neural responses, offering a direct measure of the energy required to steer cognitive outcomes. In five healthy participants viewing 2,185 emotionally evocative short videos, our analyses reveal a strong alignment between neural activations and affective ratings, with an average correlation of $r \approx 0.7$. In a clinical cohort of 255 patients with major depressive disorder, biweekly Hamilton Rating Scale trajectories over 11 weeks significantly mapped onto these manifolds, explaining approximately 20% more variance than chance (p < 10^{-10}, numerically better than chance in 93% reaching statistical significance in one-third of subjects). Our work bridges dynamical systems theory and clinical neuroscience, providing a principled approach to optimize mental health treatments by targeting the most efficient neural pathways for cognitive change.

Maximum entropy estimation is of broad interest for inferring properties of systems across many different disciplines. In this work, we significantly extend a technique we previously introduced for estimating the maximum entropy of a set of random discrete variables when conditioning on bivariate mutual informations and univariate entropies. Specifically, we show how to apply the concept to continuous random variables and vastly expand the types of information-theoretic quantities one can condition on. This allows us to establish a number of significant advantages of our approach over existing ones. Not only does our method perform favorably in the undersampled regime, where existing methods fail, but it also can be dramatically less computationally expensive as the cardinality of the variables increases. In addition, we propose a nonparametric formulation of connected informations and give an illustrative example showing how this agrees with the existing parametric formulation in cases of interest. We further demonstrate the applicability and advantages of our method to real world systems for the case of resting-state human brain networks. Finally, we show how our method can be used to estimate the structural network connectivity between interacting units from observed activity and establish the advantages over other approaches for the case of phase oscillator networks as a generic example.