Daily Papers

Neurological diseases are the leading global cause of disability, yet most lack disease-modifying treatments. We present PROTON, a heterogeneous graph transformer that generates testable hypotheses across molecular, organoid, and clinical systems. To evaluate PROTON, we apply it to Parkinson's disease (PD), bipolar disorder (BD), and Alzheimer's disease (AD). In PD, PROTON linked genetic risk loci to genes essential for dopaminergic neuron survival and predicted pesticides toxic to patient-derived neurons, including the insecticide endosulfan, which ranked within the top 1.29% of predictions. In silico screens performed by PROTON reproduced six genome-wide α-synuclein experiments, including a split-ubiquitin yeast two-hybrid system (normalized enrichment score [NES] = 2.30, FDR-adjusted p < 1 times 10^{-4}), an ascorbate peroxidase proximity labeling assay (NES = 2.16, FDR < 1 times 10^{-4}), and a high-depth targeted exome sequencing study in 496 synucleinopathy patients (NES = 2.13, FDR < 1 times 10^{-4}). In BD, PROTON predicted calcitriol as a candidate drug that reversed proteomic alterations observed in cortical organoids derived from BD patients. In AD, we evaluated PROTON predictions in health records from n = 610,524 patients at Mass General Brigham, confirming that five PROTON-predicted drugs were associated with reduced seven-year dementia risk (minimum hazard ratio = 0.63, 95% CI: 0.53-0.75, p < 1 times 10^{-7}). PROTON generated neurological hypotheses that were evaluated across molecular, organoid, and clinical systems, defining a path for AI-driven discovery in neurological disease.

In this paper, we identify a sparse reward subsystem within the hidden states of Large Language Models (LLMs), drawing an analogy to the biological reward subsystem in the human brain. We demonstrate that this subsystem contains value neurons that represent the model's internal expectation of state value, and through intervention experiments, we establish the importance of these neurons for reasoning. Our experiments reveal that these value neurons are robust across diverse datasets, model scales, and architectures; furthermore, they exhibit significant transferability across different datasets and models fine-tuned from the same base model. By examining cases where value predictions and actual rewards diverge, we identify dopamine neurons within the reward subsystem which encode reward prediction errors (RPE). These neurons exhibit high activation when the reward is higher than expected and low activation when the reward is lower than expected.

Safety fine-tuning algorithms are commonly used to fine-tune language models to reduce harmful outputs, but the exact internal mechanisms of how those models achieve this remain unclear. In studying direct preference optimisation (DPO) for toxicity reduction, current explanations claim that DPO works by dampening the most toxic MLP neurons to learn an offset to avert toxic regions in the residual stream. However, by ablating the most toxic neurons and applying activation patching, we find this explanation incomplete. By projecting neuron activation changes onto a toxicity probe, we find that only 31.8\% of toxicity reduction comes from dampened toxic neurons. Instead, DPO reduces toxicity by accumulating effects across multiple neuron groups, both reducing writing in the toxic direction and promoting anti-toxicity in the residual stream. Moreover, DPO gives noisy adjustments to neuron activations, with many neurons actually increasing toxicity. This indicates that DPO is a balancing process between opposing neuron effects to achieve toxicity reduction.

The primary obstacle for applying reinforcement learning (RL) to real-world robotics is the design of effective reward functions. While recently learning-based Process Reward Models (PRMs) are a promising direction, they are often hindered by two fundamental limitations: their reward models lack step-aware understanding and rely on single-view perception, leading to unreliable assessments of fine-grained manipulation progress; and their reward shaping procedures are theoretically unsound, often inducing a semantic trap that misguides policy optimization. To address these, we introduce Dopamine-Reward, a novel reward modeling method for learning a general-purpose, step-aware process reward model from multi-view inputs. At its core is our General Reward Model (GRM), trained on a vast 3,400+ hour dataset, which leverages Step-wise Reward Discretization for structural understanding and Multi-Perspective Reward Fusion to overcome perceptual limitations. Building upon Dopamine-Reward, we propose Dopamine-RL, a robust policy learning framework that employs a theoretically-sound Policy-Invariant Reward Shaping method, which enables the agent to leverage dense rewards for efficient self-improvement without altering the optimal policy, thereby fundamentally avoiding the semantic trap. Extensive experiments across diverse simulated and real-world tasks validate our approach. GRM achieves state-of-the-art accuracy in reward assessment, and Dopamine-RL built on GRM significantly improves policy learning efficiency. For instance, after GRM is adapted to a new task in a one-shot manner from a single expert trajectory, the resulting reward model enables Dopamine-RL to improve the policy from near-zero to 95% success with only 150 online rollouts (approximately 1 hour of real robot interaction), while retaining strong generalization across tasks. Project website: https://robo-dopamine.github.io

Learning and decision making in the brain are key processes critical to survival, and yet are processes implemented by non-ideal biological building blocks which can impose significant error. We explore quantitatively how the brain might cope with this inherent source of error by taking advantage of two ubiquitous mechanisms, redundancy and synchronization. In particular we consider a neural process whose goal is to learn a decision function by implementing a nonlinear gradient dynamics. The dynamics, however, are assumed to be corrupted by perturbations modeling the error which might be incurred due to limitations of the biology, intrinsic neuronal noise, and imperfect measurements. We show that error, and the associated uncertainty surrounding a learned solution, can be controlled in large part by trading off synchronization strength among multiple redundant neural systems against the noise amplitude. The impact of the coupling between such redundant systems is quantified by the spectrum of the network Laplacian, and we discuss the role of network topology in synchronization and in reducing the effect of noise. A range of situations in which the mechanisms we model arise in brain science are discussed, and we draw attention to experimental evidence suggesting that cortical circuits capable of implementing the computations of interest here can be found on several scales. Finally, simulations comparing theoretical bounds to the relevant empirical quantities show that the theoretical estimates we derive can be tight.

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge, focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Large Language Models have demonstrated impressive fluency across diverse tasks, yet their tendency to produce toxic content remains a critical challenge for AI safety and public trust. Existing toxicity mitigation approaches primarily manipulate individual neuron activations, but these methods suffer from instability, context dependence, and often compromise the model's core language abilities. To address these shortcomings, we investigate three key questions: the stability of neuron-level toxicity indicators, the advantages of structural (layer-wise) representations, and the interpretability of mechanisms driving toxic generation. Through extensive experiments on Jigsaw and ToxiCN datasets, we show that aggregated layer-wise features provide more robust signals than single neurons. Moreover, we observe conceptual limitations in prior works that conflate toxicity detection experts and generation experts within neuron-based interventions. To mitigate this, we propose a novel principled intervention technique, EigenShift, based on eigen-decomposition of the language model's final output layer. This method selectively targets generation-aligned components, enabling precise toxicity suppression without impairing linguistic competence. Our method requires no additional training or fine-tuning, incurs minimal computational cost, and is grounded in rigorous theoretical analysis.

Histopathological images contain rich phenotypic information that can be used to monitor underlying mechanisms contributing to diseases progression and patient survival outcomes. Recently, deep learning has become the mainstream methodological choice for analyzing and interpreting cancer histology images. In this paper, we present a comprehensive review of state-of-the-art deep learning approaches that have been used in the context of histopathological image analysis. From the survey of over 130 papers, we review the fields progress based on the methodological aspect of different machine learning strategies such as supervised, weakly supervised, unsupervised, transfer learning and various other sub-variants of these methods. We also provide an overview of deep learning based survival models that are applicable for disease-specific prognosis tasks. Finally, we summarize several existing open datasets and highlight critical challenges and limitations with current deep learning approaches, along with possible avenues for future research.

This study quantifies the association between non-adherence to antipsychotic medications and adverse outcomes in individuals with schizophrenia. We frame the problem using survival analysis, focusing on the time to the earliest of several adverse events (early death, involuntary hospitalization, jail booking). We extend standard causal inference methods (T-learner, S-learner, nearest neighbor matching) to utilize various survival models to estimate individual and average treatment effects, where treatment corresponds to medication non-adherence. Analyses are repeated using different amounts of longitudinal information (3, 6, 9, and 12 months). Using data from Allegheny County in western Pennsylvania, we find strong evidence that non-adherence advances adverse outcomes by approximately 1 to 4 months. Ablation studies confirm that county-provided risk scores adjust for key confounders, as their removal amplifies the estimated effects. Subgroup analyses by medication formulation (injectable vs. oral) and medication type consistently show that non-adherence is associated with earlier adverse events. These findings highlight the clinical importance of adherence in delaying psychiatric crises and show that integrating survival analysis with causal inference tools can yield policy-relevant insights. We caution that although we apply causal inference, we only make associative claims and discuss assumptions needed for causal interpretation.

Parkinsons disease (PD) alters cortical neural dynamics, yet reliable non-invasive electrophysiological biomarkers remain elusive. This study examined whether interpretable EEG features capturing complementary aspects of neural dynamics can discriminate Parkinsonian neural states. A comprehensive set of interpretable features was extracted and grouped into Standard descriptors (spectral power, phase synchronization, time-domain statistics) and Dynamical descriptors (aperiodic activity, cross-frequency coupling, scale-free dynamics, neuronal avalanche statistics, and instantaneous frequency measures). A multi-head attention transformer classifier was trained using strict LOSO validation. Group-level comparisons were performed to identify electrophysiological differences associated with disease and medication state. Standard feature sets achieved strongest performance in discriminating medication states (PDoff vs PDon), whereas Dynamical performed competitively in contrasts between PD patients and healthy controls. Random feature ablation analyses indicated that Dynamical descriptors provide complementary information distributed across features while correlation analysis revealed low redundancy within both feature sets. Group-level comparisons revealed medication-sensitive reductions in delta power and voltage variance, modulation of neuronal avalanche statistics, persistent increases in theta phase synchronization in PD patients, and disease-related alterations in cross-frequency interactions. Traditional spectral and synchronization features primarily reflect medication-related neural modulation, whereas dynamical descriptors reveal broader alterations in cortical network organization associated with disease but also with medication. These findings support multivariate EEG representations as a promising framework for developing non-invasive biomarkers of PD.

In this work we identify the dormant neuron phenomenon in deep reinforcement learning, where an agent's network suffers from an increasing number of inactive neurons, thereby affecting network expressivity. We demonstrate the presence of this phenomenon across a variety of algorithms and environments, and highlight its effect on learning. To address this issue, we propose a simple and effective method (ReDo) that Recycles Dormant neurons throughout training. Our experiments demonstrate that ReDo maintains the expressive power of networks by reducing the number of dormant neurons and results in improved performance.

Offline reinforcement learning (RL) aims to learn an optimal policy from pre-collected data. However, it faces challenges of distributional shift, where the learned policy may encounter unseen scenarios not covered in the offline data. Additionally, numerous applications suffer from a scarcity of labeled reward data. Relying on labeled data alone often leads to a narrow state-action distribution, further amplifying the distributional shift, and resulting in suboptimal policy learning. To address these issues, we first recognize that the volume of unlabeled data is typically substantially larger than that of labeled data. We then propose a semi-pessimistic RL method to effectively leverage abundant unlabeled data. Our approach offers several advantages. It considerably simplifies the learning process, as it seeks a lower bound of the reward function, rather than that of the Q-function or state transition function. It is highly flexible, and can be integrated with a range of model-free and model-based RL algorithms. It enjoys the guaranteed improvement when utilizing vast unlabeled data, but requires much less restrictive conditions. We compare our method with a number of alternative solutions, both analytically and numerically, and demonstrate its clear competitiveness. We further illustrate with an application to adaptive deep brain stimulation for Parkinson's disease.

Analyzing outcomes in long-term cancer survivor studies can be complex. The effects of predictors on the failure process may be difficult to assess over longer periods of time, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. In this manuscript, we compare seven different survival models that estimate the hazard rate and the effects of proportional and non-proportional covariates. In particular, we focus on an extension of the the multi-resolution hazard (MRH) estimator, combining a non-proportional hierarchical MRH approach with a data-driven pruning algorithm that allows for computational efficiency and produces robust estimates even in times of few observed failures. Using data from a large-scale randomized prostate cancer clinical trial, we examine patterns of biochemical failure and estimate the time-varying effects of androgen deprivation therapy treatment and other covariates. We compare the impact of different modeling strategies and smoothness assumptions on the estimated treatment effect. Our results show that the benefits of treatment diminish over time, possibly with implications for future treatment protocols.

Large language models (LLMs) frequently generate hallucinations -- plausible but factually incorrect outputs -- undermining their reliability. While prior work has examined hallucinations from macroscopic perspectives such as training data and objectives, the underlying neuron-level mechanisms remain largely unexplored. In this paper, we conduct a systematic investigation into hallucination-associated neurons (H-Neurons) in LLMs from three perspectives: identification, behavioral impact, and origins. Regarding their identification, we demonstrate that a remarkably sparse subset of neurons (less than 0.1% of total neurons) can reliably predict hallucination occurrences, with strong generalization across diverse scenarios. In terms of behavioral impact, controlled interventions reveal that these neurons are causally linked to over-compliance behaviors. Concerning their origins, we trace these neurons back to the pre-trained base models and find that these neurons remain predictive for hallucination detection, indicating they emerge during pre-training. Our findings bridge macroscopic behavioral patterns with microscopic neural mechanisms, offering insights for developing more reliable LLMs.

Within the complex neuroarchitecture of the brain, astrocytes play crucial roles in development, structure, and metabolism. These cells regulate neural activity through tripartite synapses, directly impacting cognitive processes such as learning and memory. Despite the growing recognition of astrocytes' significance, traditional Spiking Neural Network (SNN) models remain predominantly neuron-centric, overlooking the profound influence of astrocytes on neural dynamics. Inspired by these biological insights, we have developed an Astrocyte-Modulated Spiking Unit (AM-SU), an innovative framework that integrates neuron-astrocyte interactions into the computational paradigm, demonstrating wide applicability across various hardware platforms. Our Astrocyte-Modulated Spiking Neural Network (AstroSNN) exhibits exceptional performance in tasks involving memory retention and natural language generation, particularly in handling long-term dependencies and complex linguistic structures. The design of AstroSNN not only enhances its biological authenticity but also introduces novel computational dynamics, enabling more effective processing of complex temporal dependencies. Furthermore, AstroSNN shows low latency, high throughput, and reduced memory usage in practical applications, making it highly suitable for resource-constrained environments. By successfully integrating astrocytic dynamics into intelligent neural networks, our work narrows the gap between biological plausibility and neural modeling, laying the groundwork for future biologically-inspired neural computing research that includes both neurons and astrocytes.

The increasing complexity and parameter count of Convolutional Neural Networks (CNNs) and Transformers pose challenges in terms of computational efficiency and resource demands. Pruning has been identified as an effective strategy to address these challenges by removing redundant elements such as neurons, channels, or connections, thereby enhancing computational efficiency without heavily compromising performance. This paper builds on the foundational work of Optimal Brain Damage (OBD) by advancing the methodology of parameter importance estimation using the Hessian matrix. Unlike previous approaches that rely on approximations, we introduce Optimal Brain Apoptosis (OBA), a novel pruning method that calculates the Hessian-vector product value directly for each parameter. By decomposing the Hessian matrix across network layers and identifying conditions under which inter-layer Hessian submatrices are non-zero, we propose a highly efficient technique for computing the second-order Taylor expansion of parameters. This approach allows for a more precise pruning process, particularly in the context of CNNs and Transformers, as validated in our experiments including VGG19, ResNet32, ResNet50, and ViT-B/16 on CIFAR10, CIFAR100 and Imagenet datasets. Our code is available at https://github.com/NEU-REAL/OBA.

We show that in a drive-response coupling framework extreme events are suppressed in the response system by the dominance of a single driving signal. We validate this approach across three distinct response network topologies, namely (i) a pair of coupled neurons, (ii) a monolayer network of N coupled neurons and (iii) a two-layer multiplex network each composed of FitzHugh-Nagumo neuronal units. The response networks inherently exhibit extreme events. Our results demonstrate that influencing just one neuron in the response network with an appropriately tuned driving signal is sufficient to control extreme events across all three configurations. In the two-neuron case, suppression of extreme events occurs due to the breaking of phase-locking between the driving neuron and the targeted response neuron. In the case of monolayer and multiplex networks, suppression of extreme events results from the disruption of protoevent frequency dynamics and a subsequent frequency decoupling of the driven neuron from the rest of the network. We also observe that when the size of the neurons in response network connected to the drive increases, the onset of control occurs earlier indicating a scaling advantage of the method.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

I investigate a stronger form of regularization by deactivating neurons for extended periods, a departure from the temporary changes of methods like Dropout. However, this long-term dynamism introduces a critical challenge: severe training instability when neurons are revived with random weights. To solve this, I propose the Lifecycle (LC) principle, a regularization mechanism centered on a key innovation: state memory. Instead of re-initializing a revived neuron, my method restores its parameters to their last known effective state. This process preserves learned knowledge and avoids destructive optimization shocks. My theoretical analysis reveals that the LC principle smooths the loss landscape, guiding optimization towards flatter minima associated with better generalization. Experiments on image classification benchmarks demonstrate that my method improves generalization and robustness. Crucially, ablation studies confirm that state memory is essential for achieving these gains.

We analyze a family of large language models in such a lightweight manner that can be done on a single GPU. Specifically, we focus on the OPT family of models ranging from 125m to 66b parameters and rely only on whether an FFN neuron is activated or not. First, we find that the early part of the network is sparse and represents many discrete features. Here, many neurons (more than 70% in some layers of the 66b model) are "dead", i.e. they never activate on a large collection of diverse data. At the same time, many of the alive neurons are reserved for discrete features and act as token and n-gram detectors. Interestingly, their corresponding FFN updates not only promote next token candidates as could be expected, but also explicitly focus on removing the information about triggering them tokens, i.e., current input. To the best of our knowledge, this is the first example of mechanisms specialized at removing (rather than adding) information from the residual stream. With scale, models become more sparse in a sense that they have more dead neurons and token detectors. Finally, some neurons are positional: them being activated or not depends largely (or solely) on position and less so (or not at all) on textual data. We find that smaller models have sets of neurons acting as position range indicators while larger models operate in a less explicit manner.

Glioblastomas are the most aggressive type of glioma, having a 5-year survival rate of 6.9%. Treatment typically involves surgery, followed by radiotherapy and chemotherapy, and frequent magnetic resonance imaging (MRI) scans to monitor disease progression. To assess treatment response, radiologists use the Response Assessment in Neuro-Oncology (RANO) criteria to categorize the tumor into one of four labels based on imaging and clinical features: complete response, partial response, stable disease, and progressive disease. This assessment is very complex and time-consuming. Since deep learning (DL) has been widely used to tackle classification problems, this work aimed to implement the first DL pipeline for the classification of RANO criteria based on two consecutive MRI acquisitions. The models were trained and tested on the open dataset LUMIERE. Five approaches were tested: 1) subtraction of input images, 2) different combinations of modalities, 3) different model architectures, 4) different pretraining tasks, and 5) adding clinical data. The pipeline that achieved the best performance used a Densenet264 considering only T1-weighted, T2-weighted, and Fluid Attenuated Inversion Recovery (FLAIR) images as input without any pretraining. A median Balanced Accuracy of 50.96% was achieved. Additionally, explainability methods were applied. Using Saliency Maps, the tumor region was often successfully highlighted. In contrast, Grad-CAM typically failed to highlight the tumor region, with some exceptions observed in the Complete Response and Progressive Disease classes, where it effectively identified the tumor region. These results set a benchmark for future studies on glioblastoma treatment response assessment based on the RANO criteria while emphasizing the heterogeneity of factors that might play a role when assessing the tumor's response to treatment.

Biological nervous systems are created in a fundamentally different way than current artificial neural networks. Despite its impressive results in a variety of different domains, deep learning often requires considerable engineering effort to design high-performing neural architectures. By contrast, biological nervous systems are grown through a dynamic self-organizing process. In this paper, we take initial steps toward neural networks that grow through a developmental process that mirrors key properties of embryonic development in biological organisms. The growth process is guided by another neural network, which we call a Neural Developmental Program (NDP) and which operates through local communication alone. We investigate the role of neural growth on different machine learning benchmarks and different optimization methods (evolutionary training, online RL, offline RL, and supervised learning). Additionally, we highlight future research directions and opportunities enabled by having self-organization driving the growth of neural networks.

Uncovering the fundamental neural correlates of biological intelligence, developing mathematical models, and conducting computational simulations are critical for advancing new paradigms in artificial intelligence (AI). In this study, we implemented a comprehensive visual decision-making model that spans from visual input to behavioral output, using a neural dynamics modeling approach. Drawing inspiration from the key components of the dorsal visual pathway in primates, our model not only aligns closely with human behavior but also reflects neural activities in primates, and achieving accuracy comparable to convolutional neural networks (CNNs). Moreover, magnetic resonance imaging (MRI) identified key neuroimaging features such as structural connections and functional connectivity that are associated with performance in perceptual decision-making tasks. A neuroimaging-informed fine-tuning approach was introduced and applied to the model, leading to performance improvements that paralleled the behavioral variations observed among subjects. Compared to classical deep learning models, our model more accurately replicates the behavioral performance of biological intelligence, relying on the structural characteristics of biological neural networks rather than extensive training data, and demonstrating enhanced resilience to perturbation.

The static synaptic connectivity of neuronal circuits stands in direct contrast to the dynamics of their function. As in changing community interactions, different neurons can participate actively in various combinations to effect behaviors at different times. We introduce an unsupervised approach to learn the dynamic affinities between neurons in live, behaving animals, and to reveal which communities form among neurons at different times. The inference occurs in two major steps. First, pairwise non-linear affinities between neuronal traces from brain-wide calcium activity are organized by non-negative tensor factorization (NTF). Each factor specifies which groups of neurons are most likely interacting for an inferred interval in time, and for which animals. Finally, a generative model that allows for weighted community detection is applied to the functional motifs produced by NTF to reveal a dynamic functional connectome. Since time codes the different experimental variables (e.g., application of chemical stimuli), this provides an atlas of neural motifs active during separate stages of an experiment (e.g., stimulus application or spontaneous behaviors). Results from our analysis are experimentally validated, confirming that our method is able to robustly predict causal interactions between neurons to generate behavior. Code is available at https://github.com/dyballa/dynamic-connectomes.

There is renewed interest in modeling and understanding the nervous system of the nematode Caenorhabditis elegans (C. elegans), as this small model system provides a path to bridge the gap between nervous system structure (connectivity) and function (physiology). However, existing physiology datasets, whether involving passive recording or stimulation, are in distinct formats, and connectome datasets require preprocessing before analysis can commence. Here we compile and homogenize datasets of neural activity and connectivity. Our neural activity dataset is derived from 11 C. elegans neuroimaging experiments, while our connectivity dataset is compiled from 9 connectome annotations based on 3 primary electron microscopy studies and 1 signal propagation study. Physiology datasets, collected under varying protocols, measure calcium fluorescence in labeled subsets of the worm's 300 neurons. Our preprocessing pipeline standardizes these datasets by consistently ordering labeled neurons and resampling traces to a common sampling rate, yielding recordings from approximately 900 worms and 250 uniquely labeled neurons. The connectome datasets, collected from electron microscopy reconstructions, represent the entire nervous system as a graph of connections. Our collection is accessible on HuggingFace, facilitating analysis of the structure-function relationship in biology using modern neural network architectures and enabling cross-lab and cross-animal comparisons.

Identifying key pathological features in brain MRIs is crucial for the long-term survival of glioma patients. However, manual segmentation is time-consuming, requiring expert intervention and is susceptible to human error. Therefore, significant research has been devoted to developing machine learning methods that can accurately segment tumors in 3D multimodal brain MRI scans. Despite their progress, state-of-the-art models are often limited by the data they are trained on, raising concerns about their reliability when applied to diverse populations that may introduce distribution shifts. Such shifts can stem from lower quality MRI technology (e.g., in sub-Saharan Africa) or variations in patient demographics (e.g., children). The BraTS-2024 challenge provides a platform to address these issues. This study presents our methodology for segmenting tumors in the BraTS-2024 SSA and Pediatric Tumors tasks using MedNeXt, comprehensive model ensembling, and thorough postprocessing. Our approach demonstrated strong performance on the unseen validation set, achieving an average Dice Similarity Coefficient (DSC) of 0.896 on the BraTS-2024 SSA dataset and an average DSC of 0.830 on the BraTS Pediatric Tumor dataset. Additionally, our method achieved an average Hausdorff Distance (HD95) of 14.682 on the BraTS-2024 SSA dataset and an average HD95 of 37.508 on the BraTS Pediatric dataset. Our GitHub repository can be accessed here: Project Repository : https://github.com/python-arch/BioMbz-Optimizing-Brain-Tumor-Segmentation-with-MedNeXt-BraTS-2024-SSA-and-Pediatrics

Prior studies on the emergence in large models have primarily focused on how the functional capabilities of large language models (LLMs) scale with model size. Our research, however, transcends this traditional paradigm, aiming to deepen our understanding of the emergence within LLMs by placing a special emphasis not just on the model size but more significantly on the complex behavior of neuron interactions during the training process. By introducing the concepts of "self-organization" and "multifractal analysis," we explore how neuron interactions dynamically evolve during training, leading to "emergence," mirroring the phenomenon in natural systems where simple micro-level interactions give rise to complex macro-level behaviors. To quantitatively analyze the continuously evolving interactions among neurons in large models during training, we propose the Neuron-based Multifractal Analysis (NeuroMFA). Utilizing NeuroMFA, we conduct a comprehensive examination of the emergent behavior in LLMs through the lens of both model size and training process, paving new avenues for research into the emergence in large models.

Availability of large and diverse medical datasets is often challenged by privacy and data sharing restrictions. For successful application of machine learning techniques for disease diagnosis, prognosis, and precision medicine, large amounts of data are necessary for model building and optimization. To help overcome such limitations in the context of brain MRI, we present NeuroSynth: a collection of generative models of normative regional volumetric features derived from structural brain imaging. NeuroSynth models are trained on real brain imaging regional volumetric measures from the iSTAGING consortium, which encompasses over 40,000 MRI scans across 13 studies, incorporating covariates such as age, sex, and race. Leveraging NeuroSynth, we produce and offer 18,000 synthetic samples spanning the adult lifespan (ages 22-90 years), alongside the model's capability to generate unlimited data. Experimental results indicate that samples generated from NeuroSynth agree with the distributions obtained from real data. Most importantly, the generated normative data significantly enhance the accuracy of downstream machine learning models on tasks such as disease classification. Data and models are available at: https://huggingface.co/spaces/rongguangw/neuro-synth.

Historically, artificial intelligence has drawn much inspiration from neuroscience to fuel advances in the field. However, current progress in reinforcement learning is largely focused on benchmark problems that fail to capture many of the aspects that are of interest in neuroscience today. We illustrate this point by extending a T-maze task from neuroscience for use with reinforcement learning algorithms, and show that state-of-the-art algorithms are not capable of solving this problem. Finally, we point out where insights from neuroscience could help explain some of the issues encountered.

The Wilson-Cowan model for metapopulation, a Neural Mass Network Model, treats different subcortical regions of the brain as connected nodes, with connections representing various types of structural, functional, or effective neuronal connectivity between these regions. Each region comprises interacting populations of excitatory and inhibitory cells, consistent with the standard Wilson-Cowan model. By incorporating stable attractors into such a metapopulation model's dynamics, we transform it into a learning algorithm capable of achieving high image and text classification accuracy. We test it on MNIST and Fashion MNIST, in combination with convolutional neural networks, on CIFAR-10 and TF-FLOWERS, and, in combination with a transformer architecture (BERT), on IMDB, always showing high classification accuracy. These numerical evaluations illustrate that minimal modifications to the Wilson-Cowan model for metapopulation can reveal unique and previously unobserved dynamics.

Breast cancer is a prevalent form of cancer among women, with over 1.5 million women being diagnosed each year. Unfortunately, the survival rates for breast cancer patients in certain third-world countries, like South Africa, are alarmingly low, with only 40% of diagnosed patients surviving beyond five years. The inadequate availability of resources, including qualified pathologists, delayed diagnoses, and ineffective therapy planning, contribute to this low survival rate. To address this pressing issue, medical specialists and researchers have turned to domain-specific AI approaches, specifically deep learning models, to develop end-to-end solutions that can be integrated into computer-aided diagnosis (CAD) systems. By improving the workflow of pathologists, these AI models have the potential to enhance the detection and diagnosis of breast cancer. This research focuses on evaluating the performance of various cutting-edge convolutional neural network (CNN) architectures in comparison to a relatively new model called the Vision Trans-former (ViT). The objective is to determine the superiority of these models in terms of their accuracy and effectiveness. The experimental results reveal that the ViT models outperform the other selected state-of-the-art CNN architectures, achieving an impressive accuracy rate of 95.15%. This study signifies a significant advancement in the field, as it explores the utilization of data augmentation and other relevant preprocessing techniques in conjunction with deep learning models for the detection and diagnosis of breast cancer using datasets of Breast Cancer Histopathological Image Classification.

Recurrent neural networks (RNNs) are widely used throughout neuroscience as models of local neural activity. Many properties of single RNNs are well characterized theoretically, but experimental neuroscience has moved in the direction of studying multiple interacting areas, and RNN theory needs to be likewise extended. We take a constructive approach towards this problem, leveraging tools from nonlinear control theory and machine learning to characterize when combinations of stable RNNs will themselves be stable. Importantly, we derive conditions which allow for massive feedback connections between interacting RNNs. We parameterize these conditions for easy optimization using gradient-based techniques, and show that stability-constrained "networks of networks" can perform well on challenging sequential-processing benchmark tasks. Altogether, our results provide a principled approach towards understanding distributed, modular function in the brain.

The Spiking Neural Network (SNN) has attracted more and more attention recently. It adopts binary spike signals to transmit information. Benefitting from the information passing paradigm of SNNs, the multiplications of activations and weights can be replaced by additions, which are more energy-efficient. However, its ``Hard Reset" mechanism for the firing activity would ignore the difference among membrane potentials when the membrane potential is above the firing threshold, causing information loss. Meanwhile, quantifying the membrane potential to 0/1 spikes at the firing instants will inevitably introduce the quantization error thus bringing about information loss too. To address these problems, we propose to use the ``Soft Reset" mechanism for the supervised training-based SNNs, which will drive the membrane potential to a dynamic reset potential according to its magnitude, and Membrane Potential Rectifier (MPR) to reduce the quantization error via redistributing the membrane potential to a range close to the spikes. Results show that the SNNs with the ``Soft Reset" mechanism and MPR outperform their vanilla counterparts on both static and dynamic datasets.

We propose a novel nonlinear bidirectionally coupled heterogeneous chain network whose dynamics evolve in discrete time. The backbone of the model is a pair of popular map-based neuron models, the Chialvo and the Rulkov maps. This model is assumed to proximate the intricate dynamical properties of neurons in the widely complex nervous system. The model is first realized via various nonlinear analysis techniques: fixed point analysis, phase portraits, Jacobian matrix, and bifurcation diagrams. We observe the coexistence of chaotic and period-4 attractors. Various codimension-1 and -2 patterns for example saddle-node, period-doubling, Neimark-Sacker, double Neimark-Sacker, flip- and fold-Neimark Sacker, and 1:1 and 1:2 resonance are also explored. Furthermore, the study employs two synchronization measures to quantify how the oscillators in the network behave in tandem with each other over a long number of iterations. Finally, a time series analysis of the model is performed to investigate its complexity in terms of sample entropy.

Recurrent Neural Networks (RNNs) are popular models of brain function. The typical training strategy is to adjust their input-output behavior so that it matches that of the biological circuit of interest. Even though this strategy ensures that the biological and artificial networks perform the same computational task, it does not guarantee that their internal activity dynamics match. This suggests that the trained RNNs might end up performing the task employing a different internal computational mechanism, which would make them a suboptimal model of the biological circuit. In this work, we introduce a novel training strategy that allows learning not only the input-output behavior of an RNN but also its internal network dynamics, based on sparse neural recordings. We test the proposed method by training an RNN to simultaneously reproduce internal dynamics and output signals of a physiologically-inspired neural model. Specifically, this model generates the multiphasic muscle-like activity patterns typically observed during the execution of reaching movements, based on the oscillatory activation patterns concurrently observed in the motor cortex. Remarkably, we show that the reproduction of the internal dynamics is successful even when the training algorithm relies on the activities of a small subset of neurons sampled from the biological network. Furthermore, we show that training the RNNs with this method significantly improves their generalization performance. Overall, our results suggest that the proposed method is suitable for building powerful functional RNN models, which automatically capture important computational properties of the biological circuit of interest from sparse neural recordings.

The neurons of artificial neural networks were originally invented when much less was known about biological neurons than is known today. Our work explores a modification to the core neuron unit to make it more parallel to a biological neuron. The modification is made with the knowledge that biological dendrites are not simply passive activation funnels, but also compute complex non-linear functions as they transmit activation to the cell body. The paper explores a novel system of "Perforated" backpropagation empowering the artificial neurons of deep neural networks to achieve better performance coding for the same features they coded for in the original architecture. After an initial network training phase, additional "Dendrite Nodes" are added to the network and separately trained with a different objective: to correlate their output with the remaining error of the original neurons. The trained Dendrite Nodes are then frozen, and the original neurons are further trained, now taking into account the additional error signals provided by the Dendrite Nodes. The cycle of training the original neurons and then adding and training Dendrite Nodes can be repeated several times until satisfactory performance is achieved. Our algorithm was successfully added to modern state-of-the-art PyTorch networks across multiple domains, improving upon original accuracies and allowing for significant model compression without a loss in accuracy.

How neuronal circuits achieve credit assignment remains a central unsolved question in systems neuroscience. Various studies have suggested plausible solutions for back-propagating error signals through multi-layer networks. These purely functionally motivated models assume distinct neuronal compartments to represent local error signals that determine the sign of synaptic plasticity. However, this explicit error modulation is inconsistent with phenomenological plasticity models in which the sign depends primarily on postsynaptic activity. Here we show how a plausible microcircuit model and Hebbian learning rule derived within an adaptive control theory framework can resolve this discrepancy. Assuming errors are encoded in top-down dis-inhibitory synaptic afferents, we show that error-modulated learning emerges naturally at the circuit level when recurrent inhibition explicitly influences Hebbian plasticity. The same learning rule accounts for experimentally observed plasticity in the absence of inhibition and performs comparably to back-propagation of error (BP) on several non-linearly separable benchmarks. Our findings bridge the gap between functional and experimentally observed plasticity rules and make concrete predictions on inhibitory modulation of excitatory plasticity.

In theoretical neuroscience, recent work leverages deep learning tools to explore how some network attributes critically influence its learning dynamics. Notably, initial weight distributions with small (resp. large) variance may yield a rich (resp. lazy) regime, where significant (resp. minor) changes to network states and representation are observed over the course of learning. However, in biology, neural circuit connectivity could exhibit a low-rank structure and therefore differs markedly from the random initializations generally used for these studies. As such, here we investigate how the structure of the initial weights -- in particular their effective rank -- influences the network learning regime. Through both empirical and theoretical analyses, we discover that high-rank initializations typically yield smaller network changes indicative of lazier learning, a finding we also confirm with experimentally-driven initial connectivity in recurrent neural networks. Conversely, low-rank initialization biases learning towards richer learning. Importantly, however, as an exception to this rule, we find lazier learning can still occur with a low-rank initialization that aligns with task and data statistics. Our research highlights the pivotal role of initial weight structures in shaping learning regimes, with implications for metabolic costs of plasticity and risks of catastrophic forgetting.

An important issue with Large Language Models (LLMs) is their undesired ability to generate toxic language. In this work, we show that the neurons responsible for toxicity can be determined by their power to discriminate toxic sentences, and that toxic language can be mitigated by reducing their activation levels proportionally to this power. We propose AUROC adaptation (AurA), an intervention that can be applied to any pre-trained LLM to mitigate toxicity. As the intervention is proportional to the ability of each neuron to discriminate toxic content, it is free of any model-dependent hyperparameters. We show that AurA can achieve up to 2.2 times reduction in toxicity with only a 0.72 perplexity increase. We also show that AurA is effective with models of different scale (from 1.5B to 40B parameters), and its effectiveness in mitigating toxic language, while preserving common-sense zero-shot abilities, holds across all scales. AurA can be combined with pre-prompting strategies, boosting its average mitigation potential from 1.28times to 2.35times. Moreover, AurA can counteract adversarial pre-prompts that maliciously elicit toxic content, making it an effective method for deploying safer and less toxic models.

Refusal refers to the functional behavior enabling safety-aligned language models to reject harmful or unethical prompts. Following the growing scientific interest in mechanistic interpretability, recent work encoded refusal behavior as a single direction in the model's latent space; e.g., computed as the difference between the centroids of harmful and harmless prompt representations. However, emerging evidence suggests that concepts in LLMs often appear to be encoded as a low-dimensional manifold embedded in the high-dimensional latent space. Motivated by these findings, we propose a novel method leveraging Self-Organizing Maps (SOMs) to extract multiple refusal directions. To this end, we first prove that SOMs generalize the prior work's difference-in-means technique. We then train SOMs on harmful prompt representations to identify multiple neurons. By subtracting the centroid of harmless representations from each neuron, we derive a set of multiple directions expressing the refusal concept. We validate our method on an extensive experimental setup, demonstrating that ablating multiple directions from models' internals outperforms not only the single-direction baseline but also specialized jailbreak algorithms, leading to an effective suppression of refusal. Finally, we conclude by analyzing the mechanistic implications of our approach.

The ability to predict upcoming events has been hypothesized to comprise a key aspect of natural and machine cognition. This is supported by trends in deep reinforcement learning (RL), where self-supervised auxiliary objectives such as prediction are widely used to support representation learning and improve task performance. Here, we study the effects predictive auxiliary objectives have on representation learning across different modules of an RL system and how these mimic representational changes observed in the brain. We find that predictive objectives improve and stabilize learning particularly in resource-limited architectures, and we identify settings where longer predictive horizons better support representational transfer. Furthermore, we find that representational changes in this RL system bear a striking resemblance to changes in neural activity observed in the brain across various experiments. Specifically, we draw a connection between the auxiliary predictive model of the RL system and hippocampus, an area thought to learn a predictive model to support memory-guided behavior. We also connect the encoder network and the value learning network of the RL system to visual cortex and striatum in the brain, respectively. This work demonstrates how representation learning in deep RL systems can provide an interpretable framework for modeling multi-region interactions in the brain. The deep RL perspective taken here also suggests an additional role of the hippocampus in the brain -- that of an auxiliary learning system that benefits representation learning in other regions.

The out-of-distribution (OOD) problem generally arises when neural networks encounter data that significantly deviates from the training data distribution, i.e., in-distribution (InD). In this paper, we study the OOD problem from a neuron activation view. We first formulate neuron activation states by considering both the neuron output and its influence on model decisions. Then, to characterize the relationship between neurons and OOD issues, we introduce the neuron activation coverage (NAC) -- a simple measure for neuron behaviors under InD data. Leveraging our NAC, we show that 1) InD and OOD inputs can be largely separated based on the neuron behavior, which significantly eases the OOD detection problem and beats the 21 previous methods over three benchmarks (CIFAR-10, CIFAR-100, and ImageNet-1K). 2) a positive correlation between NAC and model generalization ability consistently holds across architectures and datasets, which enables a NAC-based criterion for evaluating model robustness. Compared to prevalent InD validation criteria, we show that NAC not only can select more robust models, but also has a stronger correlation with OOD test performance.

Artificial neural networks for motor control usually adopt generic architectures like fully connected MLPs. While general, these tabula rasa architectures rely on large amounts of experience to learn, are not easily transferable to new bodies, and have internal dynamics that are difficult to interpret. In nature, animals are born with highly structured connectivity in their nervous systems shaped by evolution; this innate circuitry acts synergistically with learning mechanisms to provide inductive biases that enable most animals to function well soon after birth and learn efficiently. Convolutional networks inspired by visual circuitry have encoded useful biases for vision. However, it is unknown the extent to which ANN architectures inspired by neural circuitry can yield useful biases for other AI domains. In this work, we ask what advantages biologically inspired ANN architecture can provide in the domain of motor control. Specifically, we translate C. elegans locomotion circuits into an ANN model controlling a simulated Swimmer agent. On a locomotion task, our architecture achieves good initial performance and asymptotic performance comparable with MLPs, while dramatically improving data efficiency and requiring orders of magnitude fewer parameters. Our architecture is interpretable and transfers to new body designs. An ablation analysis shows that constrained excitation/inhibition is crucial for learning, while weight initialization contributes to good initial performance. Our work demonstrates several advantages of biologically inspired ANN architecture and encourages future work in more complex embodied control.

Finding a code to unravel the population of neural responses that leads to a distinct animal behavior has been a long-standing question in the field of neuroscience. With the recent advances in machine learning, it is shown that the hierarchically Deep Neural Networks (DNNs) perform optimally in decoding unique features out of complex datasets. In this study, we utilize the power of a DNN to explore the computational principles in the mammalian brain by exploiting the Neuropixel data from Allen Brain Institute. We decode the neural responses from mouse visual cortex to predict the presented stimuli to the animal for natural (bear, trees, cheetah, etc.) and artificial (drifted gratings, orientated bars, etc.) classes. Our results indicate that neurons in mouse visual cortex encode the features of natural and artificial objects in a distinct manner, and such neural code is consistent across animals. We investigate this by applying transfer learning to train a DNN on the neural responses of a single animal and test its generalized performance across multiple animals. Within a single animal, DNN is able to decode the neural responses with as much as 100% classification accuracy. Across animals, this accuracy is reduced to 91%. This study demonstrates the potential of utilizing the DNN models as a computational framework to understand the neural coding principles in the mammalian brain.

We propose and test the LLM Brain Rot Hypothesis: continual exposure to junk web text induces lasting cognitive decline in large language models (LLMs). To causally isolate data quality, we run controlled experiments on real Twitter/X corpora, constructing junk and reversely controlled datasets via two orthogonal operationalizations: M1 (engagement degree) and M2 (semantic quality), with matched token scale and training operations across conditions. Contrary to the control group, continual pre-training of 4 LLMs on the junk dataset causes non-trivial declines (Hedges' g>0.3) on reasoning, long-context understanding, safety, and inflating "dark traits" (e.g., psychopathy, narcissism). The gradual mixtures of junk and control datasets also yield dose-response cognition decay: for example, under M1, ARC-Challenge with Chain Of Thoughts drops 74.9 rightarrow 57.2 and RULER-CWE 84.4 rightarrow 52.3 as junk ratio rises from 0% to 100%. Error forensics reveal several key insights. First, we identify thought-skipping as the primary lesion: models increasingly truncate or skip reasoning chains, explaining most of the error growth. Second, partial but incomplete healing is observed: scaling instruction tuning and clean data pre-training improve the declined cognition yet cannot restore baseline capability, suggesting persistent representational drift rather than format mismatch. Finally, we discover that the popularity, a non-semantic metric, of a tweet is a better indicator of the Brain Rot effect than the length in M1. Together, the results provide significant, multi-perspective evidence that data quality is a causal driver of LLM capability decay, reframing curation for continual pretraining as a training-time safety problem and motivating routine "cognitive health checks" for deployed LLMs.

We introduce Continual Learning via Neural Pruning (CLNP), a new method aimed at lifelong learning in fixed capacity models based on neuronal model sparsification. In this method, subsequent tasks are trained using the inactive neurons and filters of the sparsified network and cause zero deterioration to the performance of previous tasks. In order to deal with the possible compromise between model sparsity and performance, we formalize and incorporate the concept of graceful forgetting: the idea that it is preferable to suffer a small amount of forgetting in a controlled manner if it helps regain network capacity and prevents uncontrolled loss of performance during the training of future tasks. CLNP also provides simple continual learning diagnostic tools in terms of the number of free neurons left for the training of future tasks as well as the number of neurons that are being reused. In particular, we see in experiments that CLNP verifies and automatically takes advantage of the fact that the features of earlier layers are more transferable. We show empirically that CLNP leads to significantly improved results over current weight elasticity based methods.

This work aims to tackle the Parkinson's disease (PD) detection problem from the speech signal in a bilingual setting by proposing an ad-hoc dual-head deep neural architecture for type-based binary classification. One head is specialized for diadochokinetic patterns. The other head looks for natural speech patterns present in continuous spoken utterances. Only one of the two heads is operative accordingly to the nature of the input. Speech representations are extracted from self-supervised learning (SSL) models and wavelet transforms. Adaptive layers, convolutional bottlenecks, and contrastive learning are exploited to reduce variations across languages. Our solution is assessed against two distinct datasets, EWA-DB, and PC-GITA, which cover Slovak and Spanish languages, respectively. Results indicate that conventional models trained on a single language dataset struggle with cross-linguistic generalization, and naive combinations of datasets are suboptimal. In contrast, our model improves generalization on both languages, simultaneously.

The liquid state machine (LSM) combines low training complexity and biological plausibility, which has made it an attractive machine learning framework for edge and neuromorphic computing paradigms. Originally proposed as a model of brain computation, the LSM tunes its internal weights without backpropagation of gradients, which results in lower performance compared to multi-layer neural networks. Recent findings in neuroscience suggest that astrocytes, a long-neglected non-neuronal brain cell, modulate synaptic plasticity and brain dynamics, tuning brain networks to the vicinity of the computationally optimal critical phase transition between order and chaos. Inspired by this disruptive understanding of how brain networks self-tune, we propose the neuron-astrocyte liquid state machine (NALSM) that addresses under-performance through self-organized near-critical dynamics. Similar to its biological counterpart, the astrocyte model integrates neuronal activity and provides global feedback to spike-timing-dependent plasticity (STDP), which self-organizes NALSM dynamics around a critical branching factor that is associated with the edge-of-chaos. We demonstrate that NALSM achieves state-of-the-art accuracy versus comparable LSM methods, without the need for data-specific hand-tuning. With a top accuracy of 97.61% on MNIST, 97.51% on N-MNIST, and 85.84% on Fashion-MNIST, NALSM achieved comparable performance to current fully-connected multi-layer spiking neural networks trained via backpropagation. Our findings suggest that the further development of brain-inspired machine learning methods has the potential to reach the performance of deep learning, with the added benefits of supporting robust and energy-efficient neuromorphic computing on the edge.

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

Instance segmentation of neurons in volumetric light microscopy images of nervous systems enables groundbreaking research in neuroscience by facilitating joint functional and morphological analyses of neural circuits at cellular resolution. Yet said multi-neuron light microscopy data exhibits extremely challenging properties for the task of instance segmentation: Individual neurons have long-ranging, thin filamentous and widely branching morphologies, multiple neurons are tightly inter-weaved, and partial volume effects, uneven illumination and noise inherent to light microscopy severely impede local disentangling as well as long-range tracing of individual neurons. These properties reflect a current key challenge in machine learning research, namely to effectively capture long-range dependencies in the data. While respective methodological research is buzzing, to date methods are typically benchmarked on synthetic datasets. To address this gap, we release the FlyLight Instance Segmentation Benchmark (FISBe) dataset, the first publicly available multi-neuron light microscopy dataset with pixel-wise annotations. In addition, we define a set of instance segmentation metrics for benchmarking that we designed to be meaningful with regard to downstream analyses. Lastly, we provide three baselines to kick off a competition that we envision to both advance the field of machine learning regarding methodology for capturing long-range data dependencies, and facilitate scientific discovery in basic neuroscience.

Gradient descent has proven to be a powerful and effective technique for optimization in numerous machine learning applications. Recent advances in computational neuroscience have shown that learning in standard gradient descent optimization formulation is not consistent with learning in biological systems. This has opened up interesting avenues for building biologically inspired learning techniques. One such approach is inspired by Dale's law, which states that inhibitory and excitatory synapses do not swap roles during the course of learning. The resulting exponential gradient descent optimization scheme leads to log-normally distributed synaptic weights. Interestingly, the density that satisfies the Fokker-Planck equation corresponding to the stochastic differential equation (SDE) with geometric Brownian motion (GBM) is the log-normal density. Leveraging this connection, we start with the SDE governing geometric Brownian motion, and show that discretizing the corresponding reverse-time SDE yields a multiplicative update rule, which surprisingly, coincides with the sampling equivalent of the exponential gradient descent update founded on Dale's law. Furthermore, we propose a new formalism for multiplicative denoising score-matching, subsuming the loss function proposed by Hyvaerinen for non-negative data. Indeed, log-normally distributed data is positive and the proposed score-matching formalism turns out to be a natural fit. This allows for training of score-based models for image data and results in a novel multiplicative update scheme for sample generation starting from a log-normal density. Experimental results on MNIST, Fashion MNIST, and Kuzushiji datasets demonstrate generative capability of the new scheme. To the best of our knowledge, this is the first instance of a biologically inspired generative model employing multiplicative updates, founded on geometric Brownian motion.

High-resolution brain imaging can now capture not just synapse locations but their molecular composition, with the cost of such mapping falling exponentially. Yet such ultrastructural data has so far told us little about local neuronal physiology - specifically, the parameters (e.g., synaptic efficacies, local conductances) that govern neural dynamics. We propose to translate molecularly annotated ultrastructure into physiology, introducing the concept of an ultrastructure-to-dynamics compiler: a learned mapping from molecularly annotated ultrastructure to simulator-ready, uncertainty-aware physiological parameters. The requirement is paired training data, with jointly acquired ultrastructure from imaging, and dynamical responses to perturbations from physiological experiments. With this data we can train models that predict local physiology directly from structure. Such a compiler would support biophysical simulations by turning anatomical maps into models of circuit dynamics, shifting structure-to-function from a descriptive program to a predictive one and opening routes to understanding neural computation and forecasting intervention effects.

State-of-the-art systems neuroscience experiments yield large-scale multimodal data, and these data sets require new tools for analysis. Inspired by the success of large pretrained models in vision and language domains, we reframe the analysis of large-scale, cellular-resolution neuronal spiking data into an autoregressive spatiotemporal generation problem. Neuroformer is a multimodal, multitask generative pretrained transformer (GPT) model that is specifically designed to handle the intricacies of data in systems neuroscience. It scales linearly with feature size, can process an arbitrary number of modalities, and is adaptable to downstream tasks, such as predicting behavior. We first trained Neuroformer on simulated datasets, and found that it both accurately predicted simulated neuronal circuit activity, and also intrinsically inferred the underlying neural circuit connectivity, including direction. When pretrained to decode neural responses, the model predicted the behavior of a mouse with only few-shot fine-tuning, suggesting that the model begins learning how to do so directly from the neural representations themselves, without any explicit supervision. We used an ablation study to show that joint training on neuronal responses and behavior boosted performance, highlighting the model's ability to associate behavioral and neural representations in an unsupervised manner. These findings show that Neuroformer can analyze neural datasets and their emergent properties, informing the development of models and hypotheses associated with the brain.

In the artificial neuron, I replace the dot product with the weighted Lehmer mean, which may emulate different cases of a generalized mean. The single neuron instance is replaced by a multiplet of neurons which have the same averaging weights. A group of outputs feed forward, in lieu of the single scalar. The generalization parameter is typically set to a different value for each neuron in the multiplet. I further extend the concept to a multiplet taken from the Gini mean. Derivatives with respect to the weight parameters and with respect to the two generalization parameters are given. Some properties of the network are investigated, showing the capacity to emulate the classical exclusive-or problem organically in two layers and perform some multiplication and division. The network can instantiate truncated power series and variants, which can be used to approximate different functions, provided that parameters are constrained. Moreover, a mean case slope score is derived that can facilitate a learning-rate novelty based on homogeneity of the selected elements. The multiplet neuron equation provides a way to segment regularization timeframes and approaches.

PURPOSE: Subarachnoid hemorrhage (SAH) entails high morbidity and mortality rates. Convolutional neural networks (CNN), a form of deep learning, are capable of generating highly accurate predictions from imaging data. Our objective was to predict mortality in SAH patients by processing the initial CT scan on a CNN based algorithm. METHODS: Retrospective multicentric study of a consecutive cohort of patients with SAH between 2011-2022. Demographic, clinical and radiological variables were analyzed. Pre-processed baseline CT scan images were used as the input for training a CNN using AUCMEDI Framework. Our model's architecture leverages the DenseNet-121 structure, employing transfer learning principles. The output variable was mortality in the first three months. Performance of the model was evaluated by statistical parameters conventionally used in studies involving artificial intelligence methods. RESULTS: Images from 219 patients were processed, 175 for training and validation of the CNN and 44 for its evaluation. 52%(115/219) of patients were female, and the median age was 58(SD=13.06) years. 18.5%(39/219) were idiopathic SAH. Mortality rate was 28.5%(63/219). The model showed good accuracy at predicting mortality in SAH patients exclusively using the images of the initial CT scan (Accuracy=74%, F1=75% and AUC=82%). CONCLUSION: Modern image processing techniques based on AI and CNN make possible to predict mortality in SAH patients with high accuracy using CT scan images as the only input. These models might be optimized by including more data and patients resulting in better training, development and performance on tasks which are beyond the skills of conventional clinical knowledge.

A hallmark of intelligence is the ability to autonomously learn new flexible, cognitive behaviors - that is, behaviors where the appropriate action depends not just on immediate stimuli (as in simple reflexive stimulus-response associations), but on contextual information that must be adequately acquired, stored and processed. While many meta-learning algorithms can design agents that autonomously learn new tasks, cognitive tasks adds another level of learning and memory to typical ``learning-to-learn'' problems. Here we evolve neural networks, endowed with plastic connections and neuromodulation, over a sizable set of simple cognitive tasks adapted from a computational neuroscience framework. The resulting evolved networks can automatically modify their own connectivity to acquire a novel simple cognitive task, never seen during evolution, from stimuli and rewards alone, through the spontaneous operation of their evolved neural organization and plasticity system. Our results emphasize the importance of carefully considering the multiple learning loops involved in the emergence of intelligent behavior.