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Quantitative Biology Neurons and Cognition

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Wednesday 7 October

Neurons and Cognition

Feedback to the primary visual cortex is highly concentrated on the central visual field representation

Retrograde tracer injections in marmoset monkeys revealed a striking feature of neural circuitry in primate visual system: among neurons projecting to the primary visual cortex (striate cortex, V1), the proportion of extrastriate feedback neurons relative to thalamic feedforward neurons decreases markedly with visual field eccentricity. This supports the Central-Peripheral Dichotomy theory, which proposes fundamentally distinct computational specializations — visual recognition and attentional selection, respectively — in the central and peripheral visual fields.
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All authors Piotr Majka, Emmanuel K L Cho, Karolina Łabuszewska, Thuy Vy Nguyen, Marcin Syc, Tomasz Walkiewicz, Katrina H Worthy, Li Zhaoping, Marcello Rosa

Neurons and Cognition · Cross-listed from cs.CV

Do Generative Priors Align with Human Naturalness Perception?

Visual generative models are trained to capture the probability distributions of natural images, yet whether their native priors reflect the regularities governing human perception of image naturalness remains an open question. Here, we probe these priors through native prediction errors across 25 open image and video generators. Because raw single-image losses are dominated by scene content and visual complexity, we evaluate directional loss differences using content-preserving, paired relational interventions that selectively disrupt facial configurations or physical illumination consistency while limiting changes in low-level image statistics. Across both domains, these loss differences reproduce human-like selective sensitivities and tolerances, capturing the classic Thatcher effect on faces and shape-dependent responses to illumination inconsistencies. Notably, these loss differences reliably track continuous gradations of human naturalness judgments across individual stimulus pairs (peaking at $r = .84$ on faces and $.64$ on physical scenes) and retain unique human-aligned signals even after controlling for feature distances from frozen vision encoders and standard image quality metrics. We also find that while overall sensitivity to these violations broadly covaries with human alignment across models, the two systematically decouple along denoising schedules, with alignment peaking earlier than sensitivity, revealing that human-like naturalness judgments dissociate from generic violation detection. Together, these findings demonstrate that learning visual distributions yields generative loss landscapes that capture distinct aspects of human naturalness perception.
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Neurons and Cognition · Cross-listed from q-bio.QM

CircuitATLAS: Agentic reasoning over a systems neuroscience knowledge graph for target discovery in circuitopathies

Drug discovery for neurological disease has traditionally centered on the molecules altered by disease. But the molecules that cause pathology are not necessarily the best points from which to reverse it. Here, we ask which otherwise unaltered molecular control points can be engaged to restore pathological neural circuits toward functional states. We present CircuitATLAS, a provenance-grounded systems-neuroscience knowledge graph and agentic framework for target discovery in circuitopathies. It structures literature-derived relationships across diseases, phenotypes, electrophysiology, circuits, brain regions, cell types and molecular effectors, while deliberately excluding direct disease-gene and disease-protein edges to reduce shortcut reasoning. The graph contains 3.83 million nodes and 7.66 million edges, including 5.31 million LLM-extracted relations, and incorporates structured datasets such as the Human Cell Atlas and new multimodal in vivo measurements. We then introduce an agentic workflow that reasons from measurable disease phenotypes through their circuit and cellular substrates to molecular interventions, therapeutic feasibility and clinical constraints. Finally, we introduce a human-governed in vivo lab-in-the-loop linking hypothesis generation to experimental iteration. Within this framework an agent nominated ATP1A3, the neuronal alpha3 Na+/K+-ATPase, as a control point on cortical excitability; interneuron-restricted expression of ATP1A3 abolished the beta- and gamma-band response to a focal 4-aminopyridine challenge in vivo, and the validated target was then carried into a structure-guided small-molecule campaign terminating in a defined assay to resolve the direction of modulation. CircuitATLAS thus provides a framework for discovering therapeutics based not only on what is molecularly disrupted in disease, but on what can be controlled to restore circuit function.
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Neurons and Cognition · Cross-listed from stat.AP

Predicting Long-Term ADAS-Cog Change From Early Response After Repetitive Transcranial Magnetic Stimulation in Alzheimer Disease

Early cognitive response after repetitive transcranial magnetic stimulation (rTMS) may predict later cognitive change in Alzheimer disease, but the incremental value of domain-specific response is unclear. We analyzed data from 112 randomized participants; 101 entered a Week-5 landmark cohort and 91 had complete predictors and outcomes at 8, 16, and 24 weeks post-treatment. Nested predictor-set comparisons used ridge regression to evaluate baseline information, trial variables, early total-score response, and domain-specific response. Model-class comparisons included ridge, multi-task elastic net, restricted random forest, and longitudinal mixed effects. Validation used repeated treatment-site-stratified 5-fold cross-validation with five repetitions, nested hyperparameter tuning, and paired participant-level bootstrap comparisons with 10,000 resamples. Adding Week-3 and Week-5 ADAS-Cog total-score response improved prediction. The early total-response ridge achieved overall MAE 3.067, RMSE 3.885, and $R^2=0.384$. Replacing two total-response variables with 22 component-level changes worsened performance (MAE 3.363, RMSE 4.269, $R^2=0.257$). The paired MAE difference was -0.297 points (95% CI -0.485 to -0.115). Mixed effects was competitive (MAE 3.162), with an uncertain overall difference from total-response ridge. Sensitivity analyses using absolute future scores and excluding Week-3 response supported the main findings. In this sample, early aggregate ADAS-Cog response was more informative than a higher-dimensional domain-specific representation. The model is an internally validated early-response updating tool, not a pretreatment selection model or evidence of causal rTMS efficacy.
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Neurons and Cognition

Connectome-Based Modeling of Mutation-Specific Amyloid-$\beta$ Aggregation in Familial Alzheimer's Disease

Familial amyloid-$\beta$ (A$\beta$) variants alter aggregation kinetics, but their interaction with structural brain connectivity remains incompletely understood. We developed a mutation-aware mechanistic model coupling a coarse-grained monomer–oligomer–fibril aggregation–fragmentation system to graph diffusion on the 540-node Budapest Reference Connectome component. Experimental A$\beta_{42}$ nucleation scores scaled primary nucleation rates for seven variants relative to wild type. Robustness was examined using mutation-score uncertainty, alternative kinetic mappings, global sensitivity analysis, seed and edge-weight perturbations, degree-preserving randomized connectomes, spatial propagation analysis, synthetic ABC-SMC parameter recovery, posterior prediction, and Chemical Langevin simulations. E22G showed the earliest threshold crossing and greatest cumulative oligomer burden, whereas A2V was delayed under the selected mapping. Mutation rankings persisted across tested network perturbations, although regional burden patterns depended on topology. Connectome distance from seed regions was associated with later oligomer arrival (Spearman $\rho\approx0.92$). Under inferred parameter uncertainty, the mean timing-rank correlation was 0.990 and cumulative-burden ordering was preserved in every posterior draw, while exact peak-amplitude ordering was less stable. Stochastic ensemble medians retained the deterministic ordering despite overlap among trajectories. Within this proof-of-concept framework, mutation-dependent kinetics primarily influence aggregation timing and cumulative burden, while connectivity shapes spatial propagation. Nominal background rates, model-time units, and synthetic parameter recovery limit interpretation to mechanistic comparisons rather than clinically calibrated prediction.
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Neurons and Cognition · Cross-listed from cs.HC

Many Brains, One Geometry: A Shared Visual-Semantic Space for Cross-Dataset fMRI Decoding

Visual decoding from fMRI is typically siloed by participant and experiment, obscuring whether heterogeneous neural measurements can be organized within a common computational geometry. Here we introduce BRAID-fMRI (Brain Representation Alignment across Individuals and Datasets), a shared CLIP-supervised decoding framework. BRAID-fMRI uses a single ROI-wise Transformer with optional participant conditioning across eight visual-fMRI datasets comprising 93 dataset-specific participant entries, 430,007 single-trial responses and 162,839 unique stimuli. Regional brain activity is aligned with 512-dimensional CLIP ViT-B/32 representations using a multi-positive contrastive objective that treats repeated stimuli across participants and datasets as positives. BRAID-fMRI supports retrieval across seven evaluation datasets. On eight matched participant entries, it achieves 35.0 +/- 11.1% Top-10 accuracy, exceeding the observed mean accuracy of the two evaluated baselines - the MindEye-style pooled-CLIP decoder (27.1 +/- 5.1%) and ridge regression (21.1 +/- 9.1%) - and attaining the highest observed accuracy for seven of eight entries. In separately trained participant-agnostic models, expanding the source pool increased target-dataset holdout accuracy by up to 92.1% relative to the initial source-training condition. The learned space preserves graded semantic structure, while ablations and saliency highlight ventral and early visual cortex and category-specific motion and attentional systems. These results support scalable cross-dataset decoding into a common CLIP-aligned space, with model sensitivity concentrated in ventral and early visual inputs.
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All authors Moein Khajehnejad, Michelangelo Tronti, Forough Habibollahi, Tommaso Boccato, Matteo Ferrante, Nicola Toschi

Neurons and Cognition · Cross-listed from cs.LG

MovieSTAGE: Scene, Transition, and Global Encoding for Movie-fMRI ADHD Classification

Naturalistic movie-fMRI provides a shared, temporally structured probe of brain dynamics, yet predictive models commonly rely on whole-run functional connectivity (FC) or temporally generic representations that are not aligned with narrative events. We introduce MovieSTAGE (Scene, Transition, and Global Encoding), a multiscale framework that combines hypergraph-structured FC-profile organization within scenes, unsigned FC-profile differences across adjacent scenes, and whole-movie FC. We evaluated 260 participants from the CMI-HBN Despicable Me cohort on case-control, ADHD-subtype, and three-class classification using 10 repetitions of stratified five-fold cross-validation, complete out-of-fold (OOF) predictions, and paired subject-cluster bootstrap and permutation tests. MovieSTAGE achieved AUROCs of 0.69, 0.73, and 0.75 and balanced accuracies of 67.6%, 69.8%, and 58.3%, respectively, yielding the highest mean point estimates among the evaluated methods. On the three-class task, the full model outperformed all two-branch variants, the HGNN scene encoder outperformed MLP, GAT, and BNT alternatives under matched settings, and the human-annotated partition outperformed duration-matched random and fixed-count GSBS controls. These controlled results support incremental predictive value from event-aligned scene and transition representations when combined with whole-movie FC in this cohort. Post-hoc model-derived analyses generated network-level hypotheses involving frontoparietal and default-mode systems.
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Neurons and Cognition

Scaling subjects in cross-modal alignment: video decoding with EEG foundation model

Naturalistic visual decoding from EEG has long been constrained by cohort size: existing scaling literature caps out at a few dozen subjects, leading prior work to conclude that scaling subject cohorts yields minimal performance gains. Training a cross-modal EEG–video contrastive encoder on a cohort larger by more than an order of magnitude, we find the axis is productive but has an onset. Below $S\approx50$ — the entirety of the range prior work occupies — no model improves meaningfully over an untrained encoder; above it, decoding rises log-linearly in subject count with no saturation at the top of our ladder, on a fitted stimulus-feature probe and on fit-free movie-moment retrieval alike, and the gain transfers to a second, unseen film. How far the axis carries then depends on initialisation more than on capacity: an encoder initialised from an EEG foundation model scales ${\sim}1.6\times$ faster per doubling of the cohort than randomly initialised encoders at two depths, is the only one still converting subjects into retrieval accuracy at the top of the ladder, and converges on a fraction of the alignment compute. Subject scaling on shared naturalistic stimuli is thus an effective and currently unsaturated frontier for scaling EEG foundation models.
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Tuesday 6 October

Neurons and Cognition · Cross-listed from cs.NE

A Connectome Test of the Fly Hashing Algorithm

Dasgupta, Stevens and Navlakha (2017) showed that the Drosophila olfactory circuit, modelled as a random sparse projection followed by winner-take-all, is a locality-sensitive hash that beats classical LSH. The projection was random because the wiring was unknown. We test it against four electron-microscopy connectomes (MaleCNS, hemibrain, FlyWire, BANC; four animals, seven hemispheres). First, the 2017 pattern holds in a reimplementation of its protocol on SIFT, MNIST and odour mixtures (GloVe is near chance at short codes for every method): the fly hash beats k Gaussian projections at short hash lengths (3.1x in AP@200 on MNIST at k = 4). Second, against the tested real-valued Gaussian baseline that advantage is per active cell, not per operation: Gaussian projections given the same projection arithmetic retrieve better on every dataset and input dimension tested. Third, across four connectomes the measured pairing of glomeruli gives no consistent retrieval advantage over degree-preserving rewiring: retrieval is slightly lower (median -1.6%), and the small odour deficits depend on how missing odour responses are treated. Separately, equalising glomerular fan-out at fixed connection count improves retrieval in the model in every hemisphere, while equalising inputs per cell lowers it on average. Yet the fan-out profile is similar across the four sampled animals (median between-animal Spearman rho = 0.86), structural synapse counts do not offset it, and its relation to odour tuning is weak. In the model that uneven allocation costs retrieval. For practice: measured wiring gives no consistent retrieval advantage over degree-preserving random wiring, so a fly hash needs no connectome data, and its advantage is per active unit, which may suit hardware where active units rather than arithmetic are the binding cost, a hypothesis we do not test.
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Neurons and Cognition · Cross-listed from cs.CL

Language-model ratings of depression reflect the rater more than the patient

Depression has no diagnostic blood test. Language models promise tireless, consistent assessment, but can accurate raters disagree about individuals? We pre-registered 880 language-model raters, crossing 11 open models with prompting and scoring choices, and applied them to 189 interviews against the eight-item Patient Health Questionnaire. Model choice explained 30.0% of summed-symptom score variance, stable participant differences 10.5%. Two randomly drawn raters with area under the receiver operating characteristic curve (AUC) >= 0.70 disagreed on screening decisions for 40% of participants, on average. Average over-rating governed how many were flagged, yet equal-capacity raters chose differently for about one participant in five. A locked analysis of 86 new interviews reproduced the main pre-registered findings. Exploratory recalibration with 40 labelled participants raised accuracy from about 60% to 75% and halved disagreement, leaving one participant in five decided differently. Calibration repaired much of the rater dependence without securing agreement about individuals.
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Neurons and Cognition · Cross-listed from cs.CV

From the Drosophila Visual Connectome to General-Purpose Computer Vision

Biological connectomes encode structured solutions to visual computation that may provide reusable inductive biases for artificial vision. We develop ConnectomeX around FlyVision, a trainable architecture that preserves parallel ON/OFF processing, recurrent computation and population-level graph interaction while scaling model capacity across tasks. FlyVision reached 99.34% accuracy on MNIST with 80,608 parameters and 78.03% on CIFAR-10 with 81,408 parameters. On ImageNet-1K, FlyVision Base and Large reached 60.79% and 66.25% top-1 accuracy with 1.8 and 3.7 million parameters, while a Large local-k7 model with a learned low-frequency branch reached 66.53%, compared with 69.25% for ResNet18 with 11.7 million parameters. On a 22-class skin-disease benchmark, FlyVision Large achieved 63.78% accuracy and 95.28% macro-AUROC with 2.99 million parameters. In four-class chest radiography, ImageNet-pretrained FlyVision Base and Large reached 92.60% and 92.76% accuracy with 1.33 and 2.97 million parameters, compared with 91.56% for ImageNet-pretrained ResNet18 with 11.18 million. BrainAGE extends FlyVision to volumetric T1-weighted MRI by applying a shared ImageNet-pretrained FlyVision Large encoder to 24 sagittal, coronal and axial slices per scan and combining slice-level age estimates by confidence-modulated Gaussian voting. On 433 held-out scans, three-axis fusion achieved a mean absolute error of 5.98 years and R^2 = 0.868. Across the 224x224 classification tasks, the best FlyVision configuration remained within three percentage points of ResNet18 on ImageNet-1K and skin-disease classification and exceeded it on chest radiography with substantially fewer parameters. These results show that a conserved connectome-informed computation can scale from compact recognition to large-scale natural and biomedical vision.
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All authors Zongyu Li, Akito Yamauchi, Huaizhi Liu, Vishwanatha Rao, Jia Guo, for the Frontotemporal Lobar Degeneration Neuroimaging Initiative, for the Alzheimer's Disease Neuroimaging Initiative

Neurons and Cognition

A Time-Resolved Framework for Quantifying Neuronal Network State Transitions

Electrophysiological recordings provide powerful tools for characterizing the dynamics of neuronal networks. In vitro neuronal cultures offer a controlled setting for investigating network responses to diverse interventions, including pharmacological and optogenetic stimulation. However, conventional analyses often reduce electrophysiological activity to aggregate measures calculated over fixed temporal windows, providing only a static representation of the network state. Here, we introduce a comprehensive, multiparametric analytical framework designed to characterize both the temporal evolution of network activity and the transitional states induced by external interventions. The framework combines multiple network discriminators with a compositional analysis that resolves electrode-level responses into excited, inhibited, and unchanged states over successive temporal segments. We apply the framework to electrophysiological recordings obtained under pharmacological interventions with 4-aminopyridine (4-AP), optogenetic stimulation, and additional benchmark conditions. The results demonstrate that the proposed analysis can reveal subtle and transient responses that may be difficult to detect using conventional aggregate measures, including responses to low-dose pharmacological interventions. These findings highlight the value of temporally resolved and compositional analyses for characterizing heterogeneous neuronal network responses in vitro.
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All authors Ilya Auslender, Yasaman Heydari, Asiye Malkoç, Clara Zaccaria, Yuri Bozzi, Lorenzo Pavesi

Neurons and Cognition · Cross-listed from cs.AI

Confidence-Ordering Reversal under Contextual Priors in Neural Decoding

Contextual priors improve neural-to-language decoding by reshaping candidate scores. However, confidence is read from the same reshaped scores, so the errors a prior leaves behind can become more confident with no change in accuracy to reveal it. We study how a prior shapes confidence in speech retrieval on MEG-MASC and MOUS using local decoding scores, a contextual prior combined by additive shallow fusion, and the fused top-two margin as confidence. Among initially incorrect predictions, we find a confidence-ordering reversal: a larger margin makes a repair more likely when the correct candidate starts near the top of the local ranking, but less likely when it starts lower. On MEG-MASC, pooled correctness AUROC is 0.87, yet AUROC separating repairs from residual errors falls from 0.70 at initial ranks 2-3 to 0.39 at ranks 21-50. Errors starting beyond rank 20, inside the reversed region, make up 46.6% of all post-fusion errors. We propose a score-level account: a repair must first close the correct candidate's initial deficit, limiting its final margin, whereas a residual error can build a large margin between two incorrect candidates. A causal intervention that changes only the fusion weight moves the reversal to deeper ranks as predicted. Under a word-level LM prior, it keeps moving after accuracy gain peaks, so a weight chosen for accuracy does not settle confidence. Reading local and prior scores separately improves selective decoding: the decoder answers on 74.5% of windows instead of 56.7%, while 92% of output sets still contain the correct candidate. Confidence after contextual fusion should retain the local and contextual evidence behind each prediction, not just the fused scores. Project website: https://confidencereversal.github.io/; Code: https://github.com/AmadeusFake/NeuDecodingConfReversal
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Neurons and Cognition

Neural networks as decision trees: an analytical solution for learning and neural selectivity

Nonlinear neural networks develop structured internal representations, yet how their geometry is determined by the tasks being learned remains poorly understood. Here, we develop an analytical framework for piecewise-linear feedforward and recurrent networks that links learning, activation-region structure, and neural selectivity. We show that, at any stationary point of gradient-aligned learning, a nonlinear network decomposes into local linear regressions over its activation regions. Deviations from the corresponding least-squares solutions are jointly constrained by network weights shared across regions and vanish in the low-error regime, yielding an approximate piecewise least-squares decomposition of the task. This structure admits a decision-tree interpretation, which we recover numerically by fitting trees to predict network activation patterns from the input. We further derive how the regions in which neurons are active determine the task statistics they capture, thereby organizing neural selectivity into distinct subpopulations. The resulting predictions closely match the selectivity geometry observed in simulated networks and two empirical neural datasets. Finally, we show that neural baseline regulates activation pattern diversity, placing networks along a continuum between coarse, generalizing representations and fine-grained, expressive representations. Together, these results establish activation regions as a unifying framework for describing how nonlinear networks decompose task structure into local computations and how those computations can be revealed through neural activity.
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Neurons and Cognition · Cross-listed from cs.NE

ReGraph: A Computational Account of Emergent Generalization in the "what" and "where" Dual Visual Streams

Where generalization capacity–the ability to extract context-invariant relational structures–first emerges remains a central question in AI and neuroscience. The foundation for this capacity lies upstream of the hippocampus, within the entorhinal cortex, where parallel pathways dissociate relational structure in the medial entorhinal cortex (MEC) from sensory content in the lateral entorhinal cortex. However, as Eichenbaum argued, such factorization likely originates earlier, driven by the segregation of the dorsal ('where') and ventral ('what') visual streams. Supporting this, grid-like firing patterns–a signature of MEC (context-invariant codes)–also appear in preceding neocortical regions along the dorsal pathway. Yet, how such representations are computationally formed along upstream pathways remains unknown. To investigate this in silico, we developed ReGraph, a recurrent dual-stream graph model with biological inductive biases, including retina-driven stream-specialized encoding, dorsal-to-ventral modulation, and dynamic lateral connectivity. Trained on the action benchmark Something-Something V2, ReGraph revealed a pathway-specific emergence of relational mapping: context-invariant codes and grid-like spatial bases uniquely co-emerged along the extended dorsal stream. In contrast, their absence in single-stream, unmodulated variants, and standard baselines implies that these inductive biases are prerequisites for relational structures. Crucially, our post-hoc analyses demonstrated that these grid-like bases serve as reusable routing templates for information processing via lateral connectivity. Together, our findings provide a computational account that generalization may not be a faculty that emerges abruptly within a dedicated region, but a property that already takes shape as sensory information is parsed into factorized streams of hierarchical visual processing.
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All authors Hyewon Kang, Jungmin Lee, Ilgyu Lee, Seok-Jun Hong

Neurons and Cognition · Cross-listed from cs.LG

CANDLE: Cortical Null-Space Decomposition for Noninvasive Brain Source Imaging

Electrophysiological source imaging (ESI) aims to estimate cortical source activity from noninvasive electrophysiological measurements such as electroencephalogram (EEG). However, ESI is fundamentally ill-posed because source activity is substantially higher-dimensional than sensor observations, resulting in non-unique solutions. Recent learning-based approaches address this ambiguity by learning data-driven source priors, yet they often struggle to generalize across subject-specific cortical geometries. To address this, we propose CANDLE, a learning-based ESI model that estimates source activity on subject-specific cortical geometries. CANDLE learns a prior over the null space induced by the source-to-sensor mapping derived from T1-weighted MRI, restricting learning to unobservable source components while preserving geometric constraints. To train CANDLE, we develop a whole-brain simulator spanning over 1,100 subject-specific cortical geometries with source configurations derived from over 26,000 statistical brain maps. Trained exclusively on simulated data, CANDLE outperformed prior ESI methods on simulated source activity estimation and generalized to two empirical tasks: (i) intracranial stimulation localization from simultaneously recorded scalp EEG and (ii) epileptogenic zone estimation from presurgical interictal EEG. Our project page is available at https://candle-esi.pages.dev}{https://candle-esi.pages.dev.
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Monday 5 October

Neurons and Cognition

Interplay between Excitability and Noise in Analog Spiking Neurons

A spiking neuron is a dynamical system exhibiting a limit cycle (a spike) when subject to sufficiently excitatory input. Famous neuroscience experiments by Bryant and Segundo as well as Mainen and Sejnowski revealed that the spike times of some biological neurons are more reliable when subject to time-varying stimuli compared to constant ones. Provided with an industrial physics-based transient noise SPICE simulation framework compatible with foundry transistor compact models, we have demonstrated similar behaviours for a CMOS analog spiking neuron designed for neuromorphic computing hardware platforms. Under constant excitation current, the neuron operates in oscillatory regime and the empirical periods (interspike intervals) suffer from accumulated phase noise (jitter) during successive cycles, mainly due to the thermal noise of transistors. A time-varying input is reported to be capable of triggering output spikes according to a controlled statetransition mechanism, thereby significantly reducing the spike time jitter in the excitability regime. The physical limitation of the oscillatory or rate-coding regime in terms of reliabilitydissipation tradeoff is further evidenced by a stochastic thermodynamic uncertainty relation, a theorem that applies to general overdamped dissipative stochastic dynamical systems.
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All authors Léopold Van Brandt, Alon Ascoli, Michele Bonnin, Grégoire Brandsteert, Denis Flandre, Jean-Charles Delvenne

Neurons and Cognition

COMPASS 2.0: psychometric representational similarity analysis distinguishes symptom structure from personal signal

Language models can score psychiatric questionnaires from speech, but agreement with self-report may reflect the questionnaire rather than the person. We introduce psychometric representational similarity analysis, a framework for comparing the structure of speech-derived scores, self-report, item wording and theory, and implement it alongside person-level construct scoring in COMPASS 2.0. We show how similarly worded items induce covariance without psychological signal. In pre-registered discovery and confirmation analyses of clinical interviews from 275 participants, language-derived symptom geometry resembled wording more than self-report, with no structure beyond wording detected by the registered tests. Geometric agreement with self-report survived assigning participants someone else's answers, whereas person-paired scores captured distress more than specific symptoms. Complementary analyses examined counselling quality and wording structure across 34 instruments and the Research Domain Criteria (RDoC) framework. These findings distinguish agreement about psychological structure from evidence that language-derived assessments track individual people.
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Neurons and Cognition · Cross-listed from cs.CV

NeuroCBIR: A Fast and Accurate Image Retrieval System for Whole-Brain and Region-Specific MRI

Content-based image retrieval (CBIR) in neuroimaging enables the identification of structurally similar brain scans, supporting diagnosis, prognosis, and treatment planning; however, existing methods are often limited to small datasets, single brain regions, or coarse class labels, thereby restricting their clinical utility and generalizability. Here, we present NeuroCBIR, a framework for fast and flexible retrieval of both whole-brain and region-specific 3D T1w MRI scans. A total of 103 cortical and subcortical regions are extracted to enable both whole-brain and region-level queries. NeuroCBIR leverages latent representations learned by a variational autoencoder (VAE) combined with contrastive learning, producing scan-specific embeddings that capture anatomical patterns. These embeddings were evaluated for subject re-identification, zero-shot age prediction, and zero-shot multi-class pathology stratification. Re-identification performance was high across both whole-brain and brain-region levels (mean average precision across the top-5 retrieved images (mAP@5) >= 98.4%), with robust generalization across datasets and acquisition conditions. While NeuroCBIR is not trained for age prediction or pathology stratification, zero-shot evaluations for these two tasks demonstrate that the embeddings encode meaningful information for downstream tasks. Embedding extraction on a 4-core CPU required approximately 18.7 s per scan, whereas similarity search was effectively instantaneous (less than 0.01 s). NeuroCBIR is publicly available for brain MRI with more than 26,000 precomputed T1w MRI embeddings. It supports reproducible research, region-specific flexibility, and clinically meaningful personalized diagnostic support. The software is available at https://github.com/minnelab/NeuroCBIR.
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All authors Felix Nieto-del-Amor, Jingru Fu, J.-Sebastian Muehlboeck, Eric Westman, Daniel Ferreira, Rodrigo Moreno

Neurons and Cognition

From communication to computation in neurons-on-a-chip: an in silico study of neurotopomorphic computing

Living neuronal networks transform inputs through recurrent cellular and population dynamics, yet it is unknown which network architecture supports which computation. Neurons-on-a-chip turn this question into a design problem because microchannels guide axonal growth and set the network architecture. We introduce IC$^3$, an Integrated Characterisation of Communication-Driven Computation, which characterizes network state through neuronal dynamics, functional communication, and structural support. We implemented nine architectures in silico as conductance-based spiking networks and tested each on frequency decoding, temporal-order discrimination, and fading memory. Predominantly feedforward circuits decoded best. Sequential Chain and Microchannel Diode had the lowest IC$^3$ and recruited a third of reachable neurons, yet achieved the two highest scores on both classification tasks. Across architectures, higher IC$^3$ went with lower classification scores. We term this new direction neurotopomorphic computing, in which the physical organisation of neuronal connectivity is engineered as part of the computing substrate.
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Neurons and Cognition · Cross-listed from cs.LG

CoHyFuse: Condition-wise Hypergraph Fusion with Global Connectome in Task-fMRI

Task-fMRI connectomes reveal state-dependent neural reconfigurations, yet conventional methods marginalize these signals by aggregating distinct conditions into static pairwise graphs, thereby obscuring condition-specific multi-ROI organization. We introduce CoHyFuse, a condition-aware ROI-centered hypergraph framework that constructs a task-state-specific incidence matrix from condition-wise functional connectivity (FC)-profile embeddings, allowing the same ROI to form different multi-ROI hyperedges across task phases. Condition-specific neighborhood sizes $K_q$ further adapt the hyperedge scale to each task state, and the resulting condition embeddings are fused with a complementary whole-session FC branch for prediction. In the AABC cohort (N=1,074), CoHyFuse achieved the best mean out-of-fold predictive performance among evaluated baselines on FACENAME Fluid Cognition Composite (FCC) prediction (7.83$\pm$0.10 MAE, 0.439$\pm$0.026 \(R^2\)) and VISMOTOR age prediction (7.52$\pm$0.37 MAE, 0.592$\pm$0.022 \(R^2\)). In an auxiliary CMI-HBN attention-deficit/hyperactivity disorder (ADHD) classification benchmark (N=223), CoHyFuse obtained 72.0$\pm$2.1% macro-AUC and 74.2$\pm$2.9% accuracy. Ablation studies support the contributions of condition-wise incidence construction and dual-view fusion, suggesting that state-resolved ROI-set structure provides complementary predictive information beyond whole-session FC alone. Occlusion analysis identifies the Distraction condition as the primary driver of model prediction, pointing toward the Salience/Ventral Attention Network (SAN)–FrontoParietal Network (FPN) and within-SAN hyperedge-defined ROI-set motifs as candidate model-relevant patterns. This framework provides an interpretable, state-resolved view of the connectome for downstream cohort analysis.
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Sunday 4 October

Neurons and Cognition · Cross-listed from cs.LG

Lightweight Semantic EEG Foundation Model for Frozen Cross-Disorder Transfer

Large-scale EEG foundation models have demonstrated promising transferability across neurological disorders, but often require millions of parameters and substantial computational resources. In this paper, we present the Universal Semantic EEG Foundation Model (USE-FM), a lightweight EEG foundation model that learns transferable neural representations through self-supervised signal reconstruction on the Temple University Hospital EEG Corpus (TUEG). After pretraining, the encoder is frozen and evaluated on two clinically distinct downstream tasks, abnormal EEG detection (TUAB) and epileptic seizure recognition (TUEP), using a unified frozen-transfer protocol against recent EEG foundation models, including LUNA-Base and CBraMod. With only 1.46 million parameters, approximately one-fifth the size of existing models, USE-FM achieves competitive overall performance, including strong sensitivity and F1-score on TUEP (SEN $75.00 \pm 14.14$, F1 $70.37 \pm 4.01$), while maintaining competitive performance on TUAB (AUC $85.24 \pm 5.61$). Beyond downstream classification, latent representation analysis using $k$-means clustering together with PCA and t-SNE demonstrates that USE-FM learns organized semantic EEG representations comparable to substantially larger foundation models. These results suggest that large-scale self-supervised pretraining enables lightweight architectures to learn transferable semantic EEG representations, providing a computationally efficient foundation for cross-disorder analysis and future clinical decision support in neurological disorders.
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Neurons and Cognition

Recurrent network dynamics explain the time course of perceptual grouping in natural scenes

How the brain groups image elements into coherent objects in natural scenes remains unclear. Existing models for grouping in biological vision rely on simplified stimuli with explicit boundaries and cannot explain human behavior in naturalistic settings. We propose a mechanistic framework in which recurrent interactions propagate enhanced neuronal activity within and between cortical areas. The framework links computational principles, neural circuitry and perceptual psychology. Local boundary signals govern early grouping, whereas later stages integrate top-down feedback carrying information about object identity, grouping features across internal edges into coherent object representations. We instantiated this framework as a brain-inspired recurrent neural network trained to group features in natural images. The network learned to propagate enhanced activity across a cued object's representation, mirroring the brain's perceptual grouping mechanisms. The network's dynamics also predicted human reaction times. The framework links cortical dynamics to human vision and generates testable predictions for neuro-physiological and psychophysical experiments.
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All authors Sami Mollard, Alekh K. Ashok, Lore Goetschalckx, Drew Linsley, Thomas Serre, Sander M. Bohte, Pieter R. Roelfsema

Saturday 3 October

Neurons and Cognition

Efficiency and robustness partition the solution space for memory in recurrent networks

In computational neuroscience, task-trained recurrent neural networks (RNNs) are commonly used as a testbed for exploring the space of recurrent circuit solutions compatible with a particular function. However, these networks are subject to inductive biases that may be misaligned with those of biological circuits, which operate under various efficiency and robustness constraints. Here, using a minimal stimulus recall task, we systematically characterize how the solution space of recurrent neural networks is shaped by the desiderata of weight efficiency, activity efficiency, and robustness to noise. We show that weight efficient solutions exhibit a low-rank bias that aligns with the inductive biases of task-trained networks and favors dynamical motifs involving slow, persistent dynamics, whereas activity efficiency encourages high-rank solutions that rely on transient amplification. Moreover, we find that activity efficient solutions exhibit a strong dissociation between high-variance modes of activity and those that causally influence network output. Unlike in static feedforward settings, we demonstrate that noise robustness and activity efficiency are generally in opposition, rather than synergistic. Using these findings, we propose a normative account of misaligned coding phenomena recently identified in premotor cortex.
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Neurons and Cognition

Heterarchy in the Brain: Control as a Spectrum, Not a Chain of Command

Neuroscience treats the brain as a control hierarchy, with cortical systems governing subcortical mechanisms. We argue that this mistakes a configuration for an architecture. Local asymmetries of influence are real, but control is relational and process-specific; because neural elements constrain one another across concurrent processes, relations can form cycles that resist a stable ranking. Evidence from learned action, cortico-cerebellar and thalamocortical loops, and defensive behavior shows that control changes with practice, task phase, urgency, viability demands, and affordances. Hierarchical order therefore characterizes time-bounded configurations, whereas heterarchy characterizes the architecture's repertoire across occasions. We propose a spectrum of control indexed by dynamical decoupling: how far behavior can depend on history, internal state, and anticipated consequences. The account yields experimentally testable predictions.
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Friday 2 October

Neurons and Cognition

Beyond Completion Time: A Multimodal Approach to Characterizing Eye-Hand Coordination During the Nine-Hole Peg Test in Multiple Sclerosis

Multiple sclerosis (MS) can impair upper-extremity function through motor, sensory, cognitive, and visual deficits. Although the Nine-Hole Peg Test (9-HPT) is widely used to assess dexterity, completion time alone provides limited insight into the eye-hand coordination underlying performance. We characterized 9-HPT performance in nine people with MS (PwMS) and nine healthy controls using simultaneous eye tracking, markerless hand tracking, and object detection. Each peg cycle was divided into transport, manipulation and insertion, and return-to-bin phases. PwMS had longer overall completion times. Transport was prolonged with the non-dominant hand, manipulation was prolonged with the dominant hand, and return-to-bin duration was longer with both hands, representing the largest phase difference. PwMS also made approximately one additional fixation per peg and showed greater variability in gaze landing position during dominant-hand performance. Saccadic amplitude and mean placement error did not differ significantly between groups, and gaze generally preceded hand movement in both groups. These exploratory findings suggest that MS-related slowing is concentrated in phases requiring precise manipulation and transition to the next peg. Multimodal assessment of the 9-HPT can reveal coordination deficits not captured by completion time alone.
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All authors Mahya Beheshti, Rajvardhan Gadde, Diana Maloku, Danae S. Manta, Bethany Lum, Silvana L. Costa, Todd E. Hudson, John-Ross Rizzo

Neurons and Cognition

Multimodal Physiological Decoding Reveals Individualized Arousal Dynamics in Closed-Loop Neurofeedback

Most arousal-based brain-computer interfaces (BCIs) use EEG to decode cognitive state. But arousal is an autonomic process. We examined if peripheral physiological signals give a better decode of task-related arousal. We used a public dataset from a difficult boundary-avoidance flight task. In this task, participants received EEG-based BCI neurofeedback, sham feedback, or no feedback. We trained a multimodal deep learning decoder on heart rate, heart rate variability (HRV), respiration, electrodermal activity, and pupil diameter. We compared it with an EEG-only decoder and with the original filter-bank common spatial pattern (FBCSP) decoder. All analyses were offline. The peripheral decoder had a within-subject AUC of 93.0%. The EEG-only decoder had 85.2% and the FBCSP decoder had 79.8%. Only the peripheral decoder showed the Yerkes-Dodson inverted-U relation between decoded arousal and performance. The feedback conditions did not change the arousal trajectories. Thus, the BCI benefit possibly comes from regulation at critical moments in the task, not from a continuous shift. We calculated a time-varying optimal arousal trajectory from control trials. Per-trial deviations from this trajectory predicted performance (r = -0.28 to -0.24, p < 0.01). Baseline HRV and gamma power changed the arousal-performance curve of each subject. We used these values to divide subjects into arousal-sensitive and arousal-tolerant groups. Control bands specific to each group increased trial separation (Cohen's d from 1.21 to 1.32 and from 0.85 to 1.10). These results show that peripheral signals are better than EEG for continuous arousal decoding. They also give a specification for individualized closed-loop arousal regulation. A prospective study must test this specification, for example with personalized transcutaneous vagus nerve stimulation.
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Neurons and Cognition

MEM as an Extension of Recurrent Processing Theory: Toward a Motivational Account of Consciousness

Victor Lamme's Recurrent Processing Theory (RPT) proposes that the feedforward sweep (FFS) can extract and categorize visual features unconsciously, while conscious vision emerges through recurrent processing and feedback interactions across representational levels. The Motivated Emotional Mind (MEM) model, developed by Wiesław L. Galus and Janusz A. Starzyk, retains this core principle but embeds it in an embodied architecture integrating multilayer networks, semi-hierarchical semblions, receptors, effectors, allostasis, emotional valuation, and memory-based sensory reconstruction. This article examines the substantive but limited relationship between RPT and MEM. While RPT explains the role of recurrence in perceptual organization and the transition to conscious vision, MEM addresses the content of recurrent processing, its grounding in receptor activity and bodily states, its interaction with memory and action, and the possible role of reconstructed sensory representations in phenomenal experience. Particular emphasis is placed on secondary perception: the top-down reconstruction of sensory and interoceptive maps through which memories, mental imagery, dreams, hallucinations, feelings, and observed scenarios acquire experiential form. MEM thus associates phenomenality not merely with recurrent activity or reportability, but with the reconstruction of modality-specific, receptor-grounded sensory and bodily content. The article also presents the mathematical model of MEM, formalizing re-entrant processing, representational competition, allostasis, affect, curiosity, procedural gaps, and action selection. We conclude that MEM can be viewed as an embodied and motivational extension of RPT. However, its distinctive claims, particularly the sufficiency of secondary perception for phenomenality and the proposed microstructure of semblions, remain hypotheses requiring causal testing.
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Neurons and Cognition

Stability of Phase-locked States of Weakly Coupled Izhikevich Neurons

The Izhikevich model is a computationally efficient neuron model that can exhibit a wide range of firing patterns observed in the brain. However, it is a discontinuous dynamical system, which means the methods for applying weakly coupled oscillator theory developed for continuous dynamical systems cannot be applied. Therefore, the collective behaviour of coupled Izhikevich model has not been fully studied. To our knowledge, we carry out the first computation of the phase model for an Izhikevich neuronal model with chemical synapses. Using the phase model we study the existence and stability of phase-locking states and how these vary with parameters. Moreover, we find an interesting connection between the stability of anti-phase states of the phase model and the bifurcation behaviour of the uncoupled Izhikevich model itself. The accuracy of the prediction of the phase model is supported by simulations of two weakly coupled Izhikevich neurons.
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Neurons and Cognition · Cross-listed from cs.CL

The Score Is Not the Structure: Brain Alignment and Cross-Lingual Transfer

Similarity scores are often offered as evidence that a model shares structure with the brain or across languages. We ask what such a score reads when that structure is removed, or when the instrument measuring it does not work, in two settings. Across seventeen languages, a grammaticality probe transfers worse between more distant languages (r = -0.66). But the probe's own accuracy falls along the same axis and is at chance in four languages, four of the five most distant. Dropping them halves the explained variance, and because it also narrows the range of distances, the design cannot say how much of the gradient is the instrument. Counting the 272 language pairs as independent gives p = 0.0006 for a steering effect that is null when the seventeen languages are the unit (p = 0.155). In brain alignment, a training objective raises a language model's similarity to fMRI responses from 0.10 to 0.34 (reliability ceiling 0.54), yet targets with the brain correspondence destroyed still reach 0.31. A shuffled target scores about k/n against the real one, for rank k and n sentences, a baseline that can be computed before any model is trained. Both interventions work, yet we detect no distance-graded steering effect and no syntactic benefit from alignment. Before reading a correspondence score, measure how much of it survives without the correspondence.
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