Research in computational neuroscience is increasingly organized around three methodological commitments: bridging scales through generative modeling, validating alignment claims with rigorous controls, and grounding neural inference in mechanistic constraints. Cross-subject neural alignment via latent spaces and multimodal topographic models exemplify the first trend, where variational autoencoders and self-supervised learning on naturalistic data replace stimulus-locked paradigms, enabling discovery of organizational principles that generalize across individuals and modalities. A second cluster addresses the sufficiency of standard evaluation metrics: representational similarity matrices, prediction scores, and behavioral decoding accuracies are shown to conflate functionally equivalent but geometrically distinct codes, to be explained by nuisance controls, or to mask distributional biases at the single-stimulus level, motivating auditable frameworks and mechanism-stripping tests that separate signal from artifact. The third commitment embeds neural models within biophysical and dynamical constraints, hybrid neural ODEs preserving conductance-based structure, state-space models respecting closed-loop brain-body coupling, and inverse planning models grounded in physics simulation, rather than treating neural data as substrate-agnostic pattern-matching problems. Across these themes, the field is moving from isolated predictive benchmarks toward integrated inference: asking not whether a model predicts held-out activity, but whether it recovers identifiable dynamics, preserves biological interpretability, and explains systematic variation across scales and contexts.
Cole Brennan
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Aligning neural activity across subjects offers the promise of discovering shared computational principles and generalizable decoders. However, traditional alignment methods require shared stimuli across subjects, a constraint that limits applicability to naturalistic paradigms with limited or non-overlapping data. We introduce a Multi-Encoder-Decoder Variational Autoencoder (MED-VAE) that achieves cross-subject alignment without shared stimuli by anchoring representations to a common scaffold provided by a pretrained ANN. Using the Natural Scenes Dataset, we show that MED-VAE creates common latent spaces with superior semantic organisation, achieving higher cross-subject alignment than common methods while maintaining robust generalisation to held-out stimuli where traditional methods degrade. Reconstructing from these common spaces back to each subject's original neural space, MED-VAE preserves equal stimulus-driven signal in its cross-subject latent space. Finally, we show that this superior alignment directly enables cross-subject neural prediction, as demonstrated via cross-subject image decoding. In summary, we introduce a framework to identify generalisable common subspaces for cross-subject predictions and downstream tasks, demonstrated here for visual cortex responses to static images.
Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications -- omitting channels or reducing morphological detail -- introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.
Automated sleep staging is a fundamental application of passive Brain-Computer Interfaces (pBCI), decoding spontaneous neural states to enable closed-loop interventions independent of user intent. This study evaluates criticality features derived from Detrended Fluctuation Analysis (DFA) for the specific identification of deep sleep (N3). We analyzed $347,232$ EEG epochs from $290$ older women using UMAP manifold learning to visualize state transitions. Subsequently, six classifiers were benchmarked via 10-fold cross-validation, using balanced accuracy to determine the optimal "state-sensing" engine for neurofeedback.Naive Bayes achieved the highest mean balanced accuracy ($87.17\% \pm 0.24\%$), significantly outperforming a fully connected deep neural network (FNN: $81.58\%$) and Random Forest ($80.97\%$). Linear models (LDA: $57.21\%$; SVM: $51.01\%$) performed poorly, indicating that DFA-derived criticality features reside on a distinct, non-linear manifold. Probabilistic decoding of EEG criticality provides a high-accuracy sensing mechanism for pBCIs. This robust classification pipeline supports the development of state-dependent neurofeedback, such as targeted auditory stimulation, to enhance cognitive recovery.
Neural recordings are often interpreted as local measurements, yet the signal at any one sensor can also reflect structured activity distributed across the broader network. This raises a basic question: to what extent does an electrode's signal reflect local versus distributed information in the underlying system? More specifically, how much of an electrode's activity is carried by its immediate neighborhood, and how much is embedded more broadly across the array? We address this with a Spatially Masked Regression (SMR) framework that reconstructs each electrode's timeseries from the remaining electrodes while excluding a configurable neighborhood around the target. By progressively increasing this mask, spatial locality becomes an experimental control for quantifying how much predictive information survives after nearby channels are withheld. We apply SMR to intracranial EEG with heterogeneous electrode coverage and to scalp EEG with standardized montages over sensorimotor cortex. Using distance correlation between original and reconstructed signals, we find strong within-subject reconstruction in both modalities, substantial residual predictability even when local neighbors are excluded, and markedly stronger cross-subject transfer in EEG than in iEEG. Masking shows that nearby electrodes contribute strongly to reconstruction but do not account for all of it, indicating that individual channels reflect both local redundancy and broader distributed structure. Surrogates that preserve selected marginal or spectral properties while disrupting phase structure or temporal ordering substantially reduce performance, supporting the conclusion that SMR depends on structured temporal and cross-channel organization rather than on marginal statistics alone. These results position SMR as an interpretable framework for quantifying the balance between local and distributed information in recordings.
The escalating demand for mental healthcare, driven by rising societal stress, highlights the limitations of traditional psychiatric diagnostics. Conventional methods - relying primarily on clinical interviews and patient self-reports - are inherently vulnerable to subjective bias and the varying empirical judgment of practitioners. To address the need for quantitative evaluation, biological signal-based detection, including electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS), has emerged as a promising objective alternative. Such technology is particularly vital for identifying latent depressive states that may be unrecognized by the subjects themselves. Furthermore, in aging populations, the high comorbidity between depression and dementia necessitates early differentiation to prevent mutual symptom exacerbation and maintain Quality of Life (QoL). This pilot study of eleven healthy students establishes a framework for biological signal-based depression detection, serving as a foundational step toward automated, objective diagnostic tools for clinical use.
Neural population geometry shapes downstream computation. Recent empirical findings in neurobiology suggest that a hyperbolic structure underlies population activity in the hippocampus. Here we provide a theoretical framework for this phenomenon. First, we propose a plausible construction of hippocampal tuning curves that statistically induces hyperbolic geometry. Next, we establish a connection between neural decoding and associative memory by demonstrating that the Modern Hopfield Network update rule computes the minimum mean-squared-error (MMSE) estimator. Finally, we introduce a novel associative memory model defined in hyperbolic space that yields significantly larger capacity than leading models. Our results suggest that animals encode spatial information as a latent hyperbolic cognitive map, improving both memory capacity and decoding accuracy.
Early detection of neurodegeneration remains a critical clinical challenge. This study investigates whether sleep EEG signal criticality, quantified via Multifractal Detrended Fluctuation Analysis (MFDFA), serves as a non-invasive biomarker for future cognitive decline. We analyzed longitudinal data from the National Sleep Research Resource (NSRR) Study of Osteoporotic Fractures (SOF) cohort, comparing baseline sleep EEG dynamics between women who remained cognitively normal and those who later progressed to dementia-related impairment ($3MS < 78$).Our results reveal significant group-level differences in Hurst exponent $H(q)$ distributions, particularly during non-REM stages N2 and N3. Cognitively healthy individuals exhibited signal dynamics significantly closer to an optimally critical state across all electrode locations ($p \leqslant 0.001$), supporting the Brain Criticality Hypothesis. Supervised UMAP projections confirmed clear spatial separation between groups throughout the overnight sleep architecture.The dementia group demonstrated a shift in DFA exponents toward $1.0$, suggesting that a reconfiguration of scale-free neural dynamics during sleep precedes clinical symptoms. These findings highlight the potential for MFDFA-derived measures to be integrated into automated, sleep-based screening tools, enabling earlier preventative interventions during the prodromal window of dementia.
Nearby neurons in cortex share similar response profiles, producing systematic spatial organization across sensory and cognitive systems. Recent topographic models reproduce aspects of this structure but remain unimodal and spatially constrain each layer separately, yielding fragmented maps that capture neither the contiguity of cortical processing streams nor their integration across modalities. We introduce Topo-Omni, a topographic multimodal model in which visual, auditory, and language/cognitive processing share a single contiguous in-silico sheet. Built by fine-tuning a pretrained foundation model with a spatial smoothness objective, this architecture develops clusters across modalities that are consistent with human neuroimaging, from sensory to cognitive systems. Driving or suppressing a cluster selectively biases or impairs perception, paralleling human intervention studies. Finally, we use our model to screen for novel clusters in-silico and discover new natural landscape and animal networks which we validate in human data. A single spatial principle thus organizes representations across modalities and processing stages, yielding testable hypotheses about cortical organization.
Neurodegenerative disorders such as Alzheimer's disease exhibit highly organized patterns of regional brain vulnerability, yet the biological mechanisms underlying this spatial selectivity remain incompletely understood. Existing imaging-transcriptomic studies have largely relied on correlation-based analyses between gene expression and neuroimaging phenotypes, limiting their ability to model how molecular organization gives rise to neurodegeneration. Here, we introduce a cross-scale spatially-aware generative framework for modeling transcriptomic programs underlying cortical neurodegeneration. Regional transcriptomic profiles were derived from the Allen Human Brain Atlas using 910 landmark genes across 68 cortical regions. Neurodegenerative vulnerability maps were constructed from ADNI FreeSurfer cortical thickness measurements by computing regional cortical thinning differences between cognitively normal controls (NC = 926) and Alzheimer's disease subjects (AD = 426). A variational generative architecture was used to learn latent biological programs linking regional gene-expression organization to cortical degeneration while incorporating graph-based spatial smoothness regularization to preserve cortical organization. The proposed framework achieved strong prediction of regional neurodegenerative vulnerability, yielding an explained variance of 0.8604 and a significant spatial correlation between predicted and observed cortical degeneration profiles (r = 0.9439, p < 0.001). The learned latent representations revealed structured transcriptomic organization associated with distributed disease susceptibility. These findings demonstrate that biologically constrained generative modeling can bridge microscale molecular organization with macroscale neurodegeneration, providing a foundation for spatially-aware generative neurobiology and computational neuroscience.
What can representational similarity matrices (RSMs) tell us about a neural code? As the popularity of these summary statistics grows, so too does the need for a more complete characterization of their properties. Here, we show that symmetries in network inputs can confound RSM-based analyses. Stimulus symmetries render many representations functionally equivalent, but these different configurations can lead to different RSMs. These different RSMs reflect qualitatively different representational geometries. We show that stochastic gradient descent or energetic regularization can generate sparse, drifting codes, leading in turn to drifting RSMs. Moreover, we demonstrate that these phenomena are present in networks trained to encode image data, where the symmetry is latent. Our results illustrate the challenges inherent in comparing nonlinear neural codes, when functionally-equivalent representations are not related by a simple rotation.
Brain-language model comparisons often interpret neural prediction scores as evidence that model representations capture brain-relevant language computation. We asked whether language models align with brains, and whether prediction scores are enough to support that claim, using L-PACT, a source-audited framework that evaluates predictive, relational, mechanism-stripping, and reliability-bounded evidence. Across primary naturalistic language neural datasets and derived language-model representations, L-PACT compared real model features with nuisance baselines and severe controls, tested whether model-to-brain profiles reproduced brain-to-brain patterns, recomputed held-out scores after mechanism stripping, and normalized evidence against brain-brain ceilings. The locked analysis set contains 414 predictive-control rows, 2304 relational profile rows, 4320 mechanism-stripping rows, 420 brain-brain ceiling rows, and 146 integrated decision rows. Assay-sensitivity checks showed that brain-brain reliability, brain-as-model run-to-run relational profiles, independent low-level neural and WAV-derived acoustic-envelope gates, and a deterministic implanted-signal simulation can produce positive evidence when expected. Nevertheless, no real model row passed the predictive, relational, mechanism-stripping, or operational Turing-bounded reliability gates; all 146 integrated rows were control-explained. Less stringent single-criterion rules would have counted raw positive predictive, relational, stripping-delta, and ceiling-normalized effects, but L-PACT downgraded them because controls explained the apparent evidence. In the analyzed derived artifact set, the tested language-model representations do not satisfy L-PACT alignment gates; apparent positives are converted into an auditable control-explained taxonomy rather than treated as structural alignment.
The spatial and functional organization of the primate visual cortex is a fundamental problem in neuroscience. While recent computational frameworks like the Topographic Deep Artificial Neural Network (TDANN) have successfully modeled spatial organization in the ventral stream, the computational origins of the dorsal stream's distinct topographies, such as direction-selective maps in the middle temporal (MT) area, remain largely unresolved. In this work, we present a spatiotemporal TDANN to investigate whether MT topography is governed by the same universal principles. By training a 3D ResNet on naturalistic videos via a Momentum Contrast (MoCo) self-supervised paradigm alongside a biologically inspired spatial loss, we demonstrate the spontaneous emergence of brain-like direction maps and topological pinwheel structures. Crucially, we reveal that MT tuning properties, characterized by strong direction selectivity paired with a residual axial component, arise from a strict optimization trade-off between task-driven discriminative pressure and spatial regularization. The model's representations quantitatively match in vivo macaque MT physiological baselines, including direction selectivity index, circular variance, and pinwheel density. These findings unify the computational origins of the ventral and dorsal streams, establishing a general mechanism for cortical self-organization.
AI chatbots are increasingly used for health advice, but their performance in psychiatric triage remains undercharacterized. Psychiatric triage is particularly challenging because urgency must often be inferred from thoughts, behavior, and context rather than from objective findings. We evaluated the performance of 15 frontier AI chatbots on psychiatric triage from realistic single-message disclosures using 112 clinical vignettes, each paired with 1 of 4 original benchmark triage labels: A, routine; B, assessment within 1 week; C, assessment within 24 to 48 hours; and D, emergency care now. Vignettes covered 9 psychiatric presentation clusters and 9 focal risk dimensions, organized into 28 presentation-by-risk groups. Each group contributed 4 distinct vignettes, with 1 vignette at each triage level. Each vignette was rendered as a realistic human-authored conversational query, and the AI chatbots were tasked with assigning a triage label from that disclosure. Emergency under-triage occurred in 23 of 410 level D trials (5.6%), and all under-triaged emergencies were reassigned to level C urgency. Across target models, average accuracy ranged from 42.0% to 71.8%. Accuracy was highest for level D vignettes (94.3%) and lowest for level B vignettes (19.7%). Mean signed ordinal error was positive (+0.47 triage levels), indicating net over-triage. Dispersion was highest around the middle triage levels. All results were confirmed relative to clinician consensus labels from 50 medical doctors. When presented with user messages containing sufficient clinical information, frontier AI chatbots thus recognized psychiatric emergencies as requiring urgent medical assessment with near-zero error rates, yet showed marked over-triage for low and intermediate risk presentations.
The relationship between brain lateralization and cognitive functions is well-documented. The left hemisphere primarily handles tasks such as language and arithmetic, while the right hemisphere is involved in creative activities like drawing and music perception. Eye-tracking technology has shown the potential to reveal cognitive states by measuring ocular metrics such as pupil diameter and fixation duration. However, the ability to distinguish lateralized brain activity using these ocular metrics remains underexplored. Here, we demonstrate that pupil diameter and fixation duration can effectively classify left and right brain hemisphere activities. We obtained a considerably high classification performance, with an F1 score of 0.894. The results suggest that ocular metrics are robust indicators of lateralized brain activity and can be applied in cognitive monitoring and neurorehabilitation. Our future work expands on this by integrating these methods into real-time applications EyeBrain, potentially broadening their use across various cognitive and neurological domains.
Large-scale neuroscience is generating rich datasets across animals, brain areas and behavioral contexts, yet our modeling efforts remains fragmented across isolated experiments. We argue that understanding behavior requires integrative neurocybernetic models: understandable dynamical models that capture the closed-loop coupling of brain, body and environment, treat the brain as a controller pursuing latent objectives, represent structured variation across scales, and scale to heterogeneous datasets. Such models shift the goal from predicting neural recordings in isolation to inferring the organizing principles that govern neural and behavioral dynamics. We outline a practical route toward this goal by combining nonlinear state-space models and meta-dynamical extensions with scalable inference, knowledge distillation, mixed open- and closed-loop training, and connectomics-informed architectures. By pooling complementary constraints from recordings, behavior, perturbations and anatomy, integrative neurocybernetic models can provide statistical amplification, few-shot generalization, and mechanistic insight into shared dynamical structure, individual variation, and the control objectives that govern behavior. This agenda offers a model-centric path from fragmented data to a mechanistic science of how brains produce behavior.
Neural networks exhibit a remarkable degree of representational convergence across diverse architectures, training objectives, and even data modalities. This convergence is predictive of alignment with brain representation. A recent hypothesis suggests this arises from learning the underlying structure in the environment in similar ways. However, it is unclear how individual stimuli elicit convergent representations across networks. An image can be perceived in multiple ways and expressed differently using words. Here, we introduce a methodology based on the Generalized Procrustes Algorithm to measure intra-modal representational convergence at the single-stimulus level. We applied this to vision models with distinct training objectives, selecting stimuli based on their degree of alignment (intra-modal dispersion). Crucially, we found that this intra-modal dispersion strongly modulates alignment between vision and language models (cross-modal convergence). Specifically, stimuli with low intra-modal dispersion (high agreement among vision models) elicited significantly higher cross-modal alignment than those with high dispersion, by up to a factor of two (e.g., in pairings of DINOv2 with language models). This effect was robust to stimulus selection criteria and generalized across different pairings of vision and language models. Measuring convergence at the single-stimulus level provides a path toward understanding the sources of convergence and divergence across modalities, and between neural networks and human neural representations.
Scaling data and artificial neural networks has transformed AI, driving breakthroughs in language and vision. Whether similar principles apply to modeling brain activity remains unclear. Here we leveraged a dataset of 3.1 million neurons from the visual cortex of 73 mice across 323 sessions, totaling more than 150 billion neural tokens recorded during natural movies, images and parametric stimuli, and behavior. We train multi-modal, multi-task models that support three regimes flexibly at test time: neural prediction, behavioral decoding, neural forecasting, or any combination of the three. OmniMouse achieves state-of-the-art performance, outperforming specialized baselines across nearly all evaluation regimes. We find that performance scales reliably with more data, but gains from increasing model size saturate. This inverts the standard AI scaling story: in language and computer vision, massive datasets make parameter scaling the primary driver of progress, whereas in brain modeling -- even in the mouse visual cortex, a relatively simple system -- models remain data-limited despite vast recordings. The observation of systematic scaling raises the possibility of phase transitions in neural modeling, where larger and richer datasets might unlock qualitatively new capabilities, paralleling the emergent properties seen in large language models. Code available at https://github.com/enigma-brain/omnimouse.
Recent studies reveal striking representational alignment between artificial neural networks (ANNs) and biological brains, leading to proposals that all sufficiently capable systems converge on universal representations of reality. Here, we argue that this claim of Universality is premature. We introduce the Umwelt Representation Hypothesis (URH), proposing that alignment arises not from convergence toward a single global optimum, but from overlap in ecological constraints under which systems develop. We review empirical evidence showing that representational differences between species, individuals, and ANNs are systematic and adaptive, which is difficult to reconcile with Universality. Finally, we reframe ANN model comparison as a method for mapping clusters of alignment in ecological constraint space rather than searching for a single optimal world model.
Forecasting neural activity in response to naturalistic stimuli remains a key challenge for understanding brain dynamics and enabling downstream neurotechnological applications. Here, we introduce a generative forecasting framework for modeling neural dynamics based on autoregressive flow matching (AFM). Building on recent advances in transport-based generative modeling, our approach probabilistically predicts neural responses at scale from multimodal sensory input. Specifically, we learn the conditional distribution of future neural activity given past neural dynamics and concurrent sensory input, explicitly modeling neural activity as a temporally evolving process in which future states depend on recent neural history. We evaluate our framework on the Algonauts project 2025 challenge functional magnetic resonance imaging dataset using subject-specific models. AFM significantly outperforms both a non-autoregressive flow-matching baseline and the official challenge general linear model baseline in predicting short-term parcel-wise blood oxygenation level-dependent (BOLD) activity, demonstrating improved generalization and widespread cortical prediction performance. Ablation analyses show that access to past BOLD dynamics is a dominant driver of performance, while autoregressive factorization yields consistent, modest gains under short-horizon, context-rich conditions. Together, these findings position autoregressive flow-based generative modeling as an effective approach for short-term probabilistic forecasting of neural dynamics with promising applications in closed-loop neurotechnology.
Parkinson's disease (PD) affects over ten million people worldwide. Although temporal interference (TI) and deep brain stimulation (DBS) are promising therapies, inter-individual variability limits empirical treatment selection, increasing non-negligible surgical risk and cost. Previous explorations either resort to limited statistical biomarkers that are insufficient to characterize variability, or employ AI-driven methods which is prone to overfitting and opacity. We bridge this gap with a pretraining-finetuning framework to predict outcomes directly from resting-state fMRI. Critically, a generative virtual brain foundation model, pretrained on a collective dataset (2707 subjects, 5621 sessions) to capture universal disorder patterns, was finetuned on PD cohorts receiving TI (n=51) or DBS (n=55) to yield individualized virtual brains with high fidelity to empirical functional connectivity (r=0.935). By constructing counterfactual estimations between pathological and healthy neural states within these personalized models, we predicted clinical responses (TI: AUPR=0.853; DBS: AUPR=0.915), substantially outperforming baselines. External and prospective validations (n=14, n=11) highlight the feasibility of clinical translation. Moreover, our framework provides state-dependent regional patterns linked to response, offering hypothesis-generating mechanistic insights.
Understanding how the brain processes linguistic constructions is a central challenge in cognitive neuroscience and linguistics. Recent computational studies show that artificial neural language models spontaneously develop differentiated representations of Argument Structure Constructions (ASCs), generating predictions about when and how construction-level information emerges during processing. The present study tests these predictions in human neural activity using electroencephalography (EEG). Ten native English speakers listened to 200 synthetically generated sentences across four construction types (transitive, ditransitive, caused-motion, resultative) while neural responses were recorded. Analyses using time-frequency methods, feature extraction, and machine learning classification revealed construction-specific neural signatures emerging primarily at sentence-final positions, where argument structure becomes fully disambiguated, and most prominently in the alpha band. Pairwise classification showed reliable differentiation, especially between ditransitive and resultative constructions, while other pairs overlapped. Crucially, the temporal emergence and similarity structure of these effects mirror patterns in recurrent and transformer-based language models, where constructional representations arise during integrative processing stages. These findings support the view that linguistic constructions are neurally encoded as distinct form-meaning mappings, in line with Construction Grammar, and suggest convergence between biological and artificial systems on similar representational solutions. More broadly, this convergence is consistent with the idea that learning systems discover stable regions within an underlying representational landscape - recently termed a Platonic representational space - that constrains the emergence of efficient linguistic abstractions.
People infer rich social information from others' actions. These inferences are often constrained by the physical world: what agents can do, what obstacles permit, and how the physical actions of agents causally change an environment and other agents' mental states and behavior. We propose that such rich social perception is more than visual pattern matching, but rather a reasoning process grounded in an integration of intuitive psychology with intuitive physics. To test this hypothesis, we introduced PHASE (PHysically grounded Abstract Social Events), a large dataset of procedurally generated animations, depicting physically simulated two-agent interactions on a 2D surface. Each animation follows the style of the Heider and Simmel movie, with systematic variation in environment geometry, object dynamics, agent capacities, goals, and relationships (friendly/adversarial/neutral). We then present a computational model, SIMPLE, a physics-grounded Bayesian inverse planning model that integrates planning, probabilistic planning, and physics simulation to infer agents' goals and relations from their trajectories. Our experimental results showed that SIMPLE achieved high accuracy and agreement with human judgments across diverse scenarios, while feedforward baseline models -- including strong vision-language models -- and physics-agnostic inverse planning failed to achieve human-level performance and did not align with human judgments. These results suggest that our model provides a computational account for how people understand physically grounded social scenes by inverting a generative model of physics and agents.
Connectivity structure shapes neural computation, but inferring this structure from population recordings is degenerate: multiple connectivity structures can generate identical dynamics. Recent work uses low-rank recurrent neural networks (lrRNNs) to infer low-dimensional latent dynamics and connectivity structure from observed activity, enabling a mechanistic interpretation of the dynamics. However, standard approaches for training lrRNNs can recover spurious structures irrelevant to the underlying dynamics. We first characterize the identifiability of connectivity structures in lrRNNs and determine conditions under which a unique solution exists. Then, to find such solutions, we develop an inference framework based on maximum entropy and continuous normalizing flows (CNFs), trained via flow matching. Instead of estimating a single connectivity matrix, our method learns the maximally unbiased distribution over connection weights consistent with observed dynamics. This approach captures complex yet necessary distributions such as heavy-tailed connectivity found in empirical data. We validate our method on synthetic datasets with connectivity structures that generate multistable attractors, limit cycles, and ring attractors, and demonstrate its applicability in recordings from rat frontal cortex during decision-making. Our framework shifts circuit inference from recovering connectivity to identifying which connectivity structures are computationally required, and which are artifacts of underconstrained inference.
Normalization is a critical operation in neural circuits. In the brain, there is evidence that normalization is implemented via inhibitory interneurons and allows neural populations to adjust to changes in the distribution of their inputs. In artificial neural networks (ANNs), normalization is used to improve learning in tasks that involve complex input distributions. However, it is unclear whether inhibition-mediated normalization in biological neural circuits also improves learning. Here, we explore this possibility using ANNs with separate excitatory and inhibitory populations trained on an image recognition task with variable luminosity. We find that inhibition-mediated normalization does not improve learning if normalization is applied only during inference. However, when this normalization is extended to include back-propagated errors, performance improves significantly. These results suggest that if inhibition-mediated normalization improves learning in the brain, it additionally requires the normalization of learning signals.
Autonomous LLM agents require structured long-term memory, yet current "append-and-evolve" systems like A-MEM face O(N^2) write-latency and excessive token costs. We introduce D-MEM (Dopamine-Gated Agentic Memory), a biologically inspired architecture that decouples short-term interaction from cognitive restructuring via a Fast/Slow routing system based on Reward Prediction Error (RPE). A lightweight Critic Router evaluates stimuli for Surprise and Utility. Routine, low-RPE inputs are bypassed or cached in an O(1) fast-access buffer. Conversely, high-RPE inputs, such as factual contradictions or preference shifts, trigger a "dopamine" signal, activating the O(N) memory evolution pipeline to reshape the agent's knowledge graph. To evaluate performance under realistic conditions, we introduce the LoCoMo-Noise benchmark, which injects controlled conversational noise into long-term sessions. Evaluations demonstrate that D-MEM reduces token consumption by over 80%, eliminates O(N^2) bottlenecks, and outperforms baselines in multi-hop reasoning and adversarial resilience. By selectively gating cognitive restructuring, D-MEM provides a scalable, cost-efficient foundation for lifelong agentic memory.
This study presents the development of the PsyCogMetrics AI Lab (psycogmetrics.ai), an integrated, cloud-based platform that operationalizes psychometric and cognitive-science methodologies for Large Language Model (LLM) evaluation. Framed as a three-cycle Action Design Science study, the Relevance Cycle identifies key limitations in current evaluation methods and unfulfilled stakeholder needs. The Rigor Cycle draws on kernel theories such as Popperian falsifiability, Classical Test Theory, and Cognitive Load Theory to derive deductive design objectives. The Design Cycle operationalizes these objectives through nested Build-Intervene-Evaluate loops. The study contributes a novel IT artifact, a validated design for LLM evaluation, benefiting research at the intersection of AI, psychology, cognitive science, and the social and behavioral sciences.
Animal brains flexibly and efficiently achieve many behavioral tasks with a single neural network. A core goal in modern neuroscience is to map the mechanisms of the brain's flexibility onto the dynamics underlying neural populations. However, identifying task-specific dynamical rules from limited, noisy, and high-dimensional experimental neural recordings remains a major challenge, as experimental data often provide only partial access to brain states and dynamical mechanisms. While recurrent neural networks (RNNs) directly constrained neural data have been effective in inferring underlying dynamical mechanisms, they are typically limited to single-task domains and struggle to generalize across behavioral conditions. Here, we introduce JEDI, a hierarchical model that captures neural dynamics across tasks and contexts by learning a shared embedding space over RNN weights. This model recapitulates individual samples of neural dynamics while scaling to arbitrarily large and complex datasets, uncovering shared structure across conditions in a single, unified model. Using simulated RNN datasets, we demonstrate that JEDI accurately learns robust, generalizable, condition-specific embeddings. By reverse-engineering the weights learned by JEDI, we show that it recovers ground truth fixed point structures and unveils key features of the underlying neural dynamics in the eigenspectra. Finally, we apply JEDI to motor cortex recordings during monkey reaching to extract mechanistic insight into the neural dynamics of motor control. Our work shows that joint learning of contextual embeddings and recurrent weights provides scalable and generalizable inference of brain dynamics from recordings alone.
Brains remain unrivaled in their ability to recognize and generate complex spatiotemporal patterns. While AI is able to reproduce some of these capabilities, deep learning algorithms remain largely at odds with our current understanding of brain circuitry and dynamics. This is prominently the case for backpropagation through time (BPTT), the go-to algorithm for learning complex temporal dependencies. In this work we propose a general formalism to approximate BPTT in a controlled, biologically plausible manner. Our approach builds on, unifies and extends several previous approaches to local, time-continuous, phase-free spatiotemporal credit assignment based on principles of energy conservation and extremal action. Our starting point is a prospective energy function of neuronal states, from which we calculate real-time error dynamics for time-continuous neuronal networks. In the general case, this provides a simple and straightforward derivation of the adjoint method result for neuronal networks, the time-continuous equivalent to BPTT. With a few modifications, we can turn this into a fully local (in space and time) set of equations for neuron and synapse dynamics. Our theory provides a rigorous framework for spatiotemporal deep learning in the brain, while simultaneously suggesting a blueprint for physical circuits capable of carrying out these computations. These results reframe and extend the recently proposed Generalized Latent Equilibrium (GLE) model.
Standard accounts of memory consolidation emphasise the stabilisation of stored representations, but struggle to explain representational drift, semanticisation, or the necessity of offline replay. Here we propose that high-capacity neocortical networks optimise stored representations for generalisation by reducing complexity via predictive forgetting, i.e. the selective retention of experienced information that predicts future outcomes or experience. We show that predictive forgetting formally improves information-theoretic generalisation bounds on stored representations. Under high-fidelity encoding constraints, such compression is generally unattainable in a single pass; high-capacity networks therefore benefit from temporally separated, iterative refinement of stored traces without re-accessing sensory input. We demonstrate this capacity dependence with simulations in autoencoder-based neocortical models, biologically plausible predictive coding circuits, and Transformer-based language models, and derive quantitative predictions for consolidation-dependent changes in neural representational geometry. These results identify a computational role for off-line consolidation beyond stabilisation, showing that outcome-conditioned compression optimises the retention-generalisation trade-off.
Reaching for grasping, and manipulating objects are essential motor functions in everyday life. Decoding human motor intentions is a central challenge for rehabilitation and assistive technologies. This study focuses on predicting intentions by inferring movement direction and target location from multichannel electromyography (EMG) signals, and investigating how spatially and temporally accurate such information can be detected relative to movement onset. We present a computational pipeline that combines data-driven temporal segmentation with classical and deep learning classifiers in order to analyse EMG data recorded during the planning, early execution, and target contact phases of a delayed reaching task. Early intention prediction enables devices to anticipate user actions, improving responsiveness and supporting active motor recovery in adaptive rehabilitation systems. Random Forest achieves $80\%$ accuracy and Convolutional Neural Network $75\%$ accuracy across $25$ spatial targets, each separated by $14^\circ$ azimuth/altitude. Furthermore, a systematic evaluation of EMG channels, feature sets, and temporal windows demonstrates that motor intention can be efficiently decoded even with drastically reduced data. This work sheds light on the temporal and spatial evolution of motor intention, paving the way for anticipatory control in adaptive rehabilitation systems and driving advancements in computational approaches to motor neuroscience.