Eilif B. Muller

Henry Markram

Srikanth Ramaswamy

The function of the neocortex is fundamentally determined by its repeating microcircuit motif, but also by its rich, interregional connectiv… (see more)ity. We present a data-driven computational model of the anatomy of non-barrel primary somatosensory cortex of juvenile rat, integrating whole-brain scale data while providing cellular and subcellular specificity. The model consists of 4.2 million morphologically detailed neurons, placed in a digital brain atlas. They are connected by 14.2 billion synapses, comprising local, long-range and extrinsic connectivity. We delineated the limits of determining connectivity from anatomy, finding that it reproduces the targeting of PV+ and VIP+ interneurons only with explicitly added specificity, but the one of Sst+ neurons even without. Globally, connectivity was characterized by local clusters tied together through hub neurons in layer 5, demonstrating how local and interegional connectivity are complicit, inseparable networks. A 211,712 neuron subvolume of the model has been made freely and openly available to the community.

2026-01-19

eLife (published)

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

James B. Isbister

András Ecker

Christoph Pokorny

Sirio Bolaños-Puchet

Daniela Egas Santander

Alexis Arnaudon

Omar Awile

Natali Barros-Zulaica

Jorge Blanco Alonso

Elvis Boci

Giuseppe Chindemi

Jean-Denis Courcol

Tanguy Damart

Thomas Delemontex

Alexander Dietz

Gianluca Ficarelli

Michael Gevaert

Joni Herttuainen

Genrich Ivaska

Weina Ji … (see 22 more)

Daniel Keller

James King

Pramod Kumbhar

Samuel Lapere

Polina Litvak

Darshan Mandge

Fernando Pereira

Judit Planas

Rajnish Ranjan

Maria Reva

Armando Romani

Christian Rössert

Felix Schürmann

Vishal Sood

Aleksandra Teska

Anıl Tuncel

Werner Van Geit

Matthias Wolf

Henry Markram

Srikanth Ramaswamy

Michael W. Reimann

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which can be studied in large-scale, b… (see more)iophysically detailed models. We present a model comprising eight somatosensory cortex subregions, 4.2 million morpho-logical and electrically-detailed neurons, and 13.2 billion local and long-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. We reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s di-rect correspondence with biology generated predictions about how multiscale organisation shapes activity. We predict that structural and functional recurrency increases towards deeper layers and that stronger innervation by long-range connectivity increases local correlated activity. The model also predicts the role of inhibitory interneuron types in stimulus encoding, and of different layers in driving layer 2/3 stimulus responses. Simu-slation tools and a large subvolume of the model are made available.

2026-01-19

eLife (published)

Self-Supervised Learning from Structural Invariance

2025-09-22

UniReps @ Neural Information Processing Systems (oral)

seq-JEPA: Autoregressive Predictive Learning of Invariant-Equivariant World Models

Hafez Ghaemi

Shahab Bakhtiari

Current self-supervised algorithms commonly rely on transformations such as data augmentation and masking to learn visual representations. T… (see more)his is achieved by enforcing invariance or equivariance with respect to these transformations after encoding two views of an image. This dominant two-view paradigm often limits the flexibility of learned representations for downstream adaptation by creating performance trade-offs between high-level invariance-demanding tasks such as image classification and more fine-grained equivariance-related tasks. In this work, we proposes \emph{seq-JEPA}, a world modeling framework that introduces architectural inductive biases into joint-embedding predictive architectures to resolve this trade-off. Without relying on dual equivariance predictors or loss terms, seq-JEPA simultaneously learns two architecturally segregated representations: one equivariant to specified transformations and another invariant to them. To do so, our model processes short sequences of different views (observations) of inputs. Each encoded view is concatenated with an embedding of the relative transformation (action) that produces the next observation in the sequence. These view-action pairs are passed through a transformer encoder that outputs an aggregate representation. A predictor head then conditions this aggregate representation on the upcoming action to predict the representation of the next observation. Empirically, seq-JEPA demonstrates strong performance on both equivariant and invariant benchmarks without sacrificing one for the other. Furthermore, it excels at tasks that inherently require aggregating a sequence of observations, such as path integration across actions and predictive learning across eye movements.

2025-09-17

NeurIPS.cc/2025/Conference (poster)

Learning to combine top-down context and feed-forward representations under ambiguity with apical and basal dendrites

Guillaume Etter

Busra Tugce Gurbuz

One of the hallmark features of neocortical anatomy is the presence of extensive top-down projections into primary sensory areas, with many … (see more)impinging on the distal apical dendrites of pyramidal neurons. While it is known that they exert a modulatory effect, altering the gain of responses, their functional role remains an active area of research. It is hypothesized that these top-down projections carry contextual information that can help animals to resolve ambiguities in sensory data. One proposed mechanism of contextual integration is a non-linear integration of distinct input streams at apical and basal dendrites of pyramidal neurons. Computationally, however, it is yet to be demonstrated how such an architecture could leverage distinct compartments for flexible contextual integration and sensory processing when both sensory and context signals can be unreliable. Here, we implement an augmented deep neural network with distinct apical and basal compartments that integrates a) contextual information from top-down projections to apical compartments, and b) sensory representations driven by bottom-up projections to basal compartments, via a biophysically inspired rule. In addition, we develop a new multi-scenario contextual integration task using a generative image modeling approach. In addition to generalizing previous contextual integration tasks, it better captures the diversity of scenarios where neither contextual nor sensory information are fully reliable. To solve this task, this model successfully learns to select among integration strategies. We find that our model outperforms those without the "apical prior" when contextual information contradicts sensory input. Altogether, this suggests that the apical prior and biophysically inspired integration rule could be key components necessary for handling the ambiguities that animals encounter in the diverse contexts of the real world.

2025-06-22

Cerebral Cortex (New York, NY) (published)

arxiv.org

GitChameleon 2.0: Evaluating AI Code Generation Against Python Library Version Incompatibilities

Victor May

Samira Ebrahimi Kahou

Massimo Caccia

The rapid evolution of software libraries poses a considerable hurdle for code generation, necessitating continuous adaptation to frequent v… (see more)ersion updates while preserving backward compatibility. While existing code evolution benchmarks provide valuable insights, they typically lack execution-based evaluation for generating code compliant with specific library versions. To address this, we introduce GitChameleon 2.0, a novel, meticulously curated dataset comprising 328 Python code completion problems, each conditioned on specific library versions and accompanied by executable unit tests. GitChameleon 2.0 rigorously evaluates the capacity of contemporary large language models (LLMs), LLM-powered agents, code assistants, and RAG systems to perform version-conditioned code generation that demonstrates functional accuracy through execution. Our extensive evaluations indicate that state-of-the-art systems encounter significant challenges with this task; enterprise models achieving baseline success rates in the 48-51% range, underscoring the intricacy of the problem. By offering an execution-based benchmark emphasizing the dynamic nature of code libraries, GitChameleon 2.0 enables a clearer understanding of this challenge and helps guide the development of more adaptable and dependable AI code generation methods. We make the dataset and evaluation code publicly available at https://github.com/mrcabbage972/GitChameleonBenchmark.

2024-12-31

arXiv (preprint)

Specific inhibition and disinhibition in the higher-order structure of a cortical connectome

Michael W. Reimann

Daniela Egas Santander

András Ecker

Neurons are thought to act as parts of assemblies with strong internal excitatory connectivity. Conversely, inhibition is often reduced to b… (see more)lanket inhibition with no targeting specificity. We analyzed the structure of excitation and inhibition in the MICrONS mm 3 dataset, an electron microscopic reconstruction of a piece of cortical tissue. We found that excitation was structured around a feed-forward flow in large non-random neuron motifs with a structure of information flow from a small number of sources to a larger number of potential targets. Inhibitory neurons connected with neurons in specific sequential positions of these motifs, implementing targeted and symmetrical competition between them. None of these trends are detectable in only pairwise connectivity, demonstrating that inhibition is structured by these large motifs. While descriptions of inhibition in cortical circuits range from non-specific blanket-inhibition to targeted, our results describe a form of targeting specificity existing in the higher-order structure of the connectome. These findings have important implications for the role of inhibition in learning and synaptic plasticity.

2024-11-10

Cerebral Cortex (New York, NY) (published)

Top-down feedback matters: Functional impact of brainlike connectivity motifs on audiovisual integration

Mashbayar Tugsbayar

Mingze Li

Eilif B Muller

Blake Richards

Artificial neural networks (ANNs) are an important tool for studying neural computation, but many features of the brain are not captured by … (see more)standard ANN architectures. One notable missing feature in most ANN models is top-down feedback, i.e. projections from higher-order layers to lower-order layers in the network. Top-down feedback is ubiquitous in the brain, and it has a unique modulatory impact on activity in neocortical pyramidal neurons. However, we still do not understand its computational role. Here we develop a deep neural network model that captures the core functional properties of top-down feedback in the neocortex, allowing us to construct hierarchical recurrent ANN models that more closely reflect the architecture of the brain. We use this to explore the impact of different hierarchical recurrent architectures on an audiovisual integration task. We find that certain hierarchies, namely those that mimic the architecture of the human brain, impart ANN models with a light visual bias similar to that seen in humans. This bias does not impair performance on the audiovisual tasks. The results further suggest that different configurations of top-down feedback make otherwise identically connected models functionally distinct from each other, and from traditional feedforward and laterally recurrent models. Altogether our findings demonstrate that modulatory top-down feedback is a computationally relevant feature of biological brains, and that incorporating it into ANNs affects their behavior and constrains the solutions it’s likely to discover.

2024-10-02

bioRxiv (preprint)

Dhuruva Priyan Gowri Mariyappan

Assemblies, synapse clustering, and network topology interact with plasticity to explain structure-function relationships of the cortical connectome

András Ecker

Daniela Egas Santander

Marwan Abdellah

Jorge Blanco Alonso

Sirio Bolaños-Puchet

Giuseppe Chindemi

James B Isbister

James King

Pramod Kumbhar

Ioannis Magkanaris

Eilif B Muller

Michael W Reimann

Abstract Synaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have reve… (see more)aled mechanisms and protocols for the induction of plasticity between pairs of neurons, how these synaptic changes are coordinated in biological neuronal networks to ensure the emergence of learning remains poorly understood. Simulation and modeling have emerged as important tools to study learning in plastic networks, but have yet to achieve a scale that incorporates realistic network structure, active dendrites, and multi-synapse interactions, key determinants of synaptic plasticity. To rise to this challenge, we endowed an existing large-scale cortical network model, incorporating data-constrained dendritic processing and multi-synaptic connections, with a calcium-based model of functional plasticity that captures the diversity of excitatory connections extrapolated to in vivo-like conditions. This allowed us to study how dendrites and network structure interact with plasticity to shape stimulus representations at the microcircuit level. In our simulations, plasticity acted sparsely and specifically, firing rates and weight distributions remained stable without additional homeostatic mechanisms. At the circuit level, we found plasticity was driven by co-firing stimulus-evoked functional assemblies, spatial clustering of synapses on dendrites, and the topology of the network connectivity. As a result of the plastic changes, the network became more reliable with more stimulus-specific responses. We confirmed our testable predictions in the MICrONS datasets, an openly available electron microscopic reconstruction of a large volume of cortical tissue. Our results quantify at a large scale how the dendritic architecture and higher-order structure of cortical microcircuits play a central role in functional plasticity and provide a foundation for elucidating their role in learning.

2023-08-06

bioRxiv (preprint)

Community-based Reconstruction and Simulation of a Full-scale Model of Region CA1 of Rat Hippocampus

Armando Romani

Alberto Antonietti

Davide Bella

Julian Budd

Elisabetta Giacalone

Kerem Kurban

Sára Sáray

Marwan Abdellah

Alexis Arnaudon

Elvis Boci

Cristina Colangelo

Jean-Denis Courcol

Thomas Delemontex

András Ecker

Joanne Falck

Cyrille Favreau

Michael Gevaert

Juan B. Hernando

Joni Herttuainen

Genrich Ivaska … (see 28 more)

Lida Kanari

Anna-Kristin Kaufmann

James King

Pramod Kumbhar

Sigrun Lange

Huanxiang Lu

Carmen Alina Lupascu

Rosanna Migliore

Fabien Petitjean

Judit Planas

Pranav Rai

Srikanth Ramaswamy

Michael W. Reimann

Juan Luis Riquelme

Nadir Román Guerrero

Ying Shi

Vishal Sood

Mohameth François Sy

Werner Van Geit

Liesbeth Vanherpe

Tamás F. Freund

Audrey Mercer

Felix Schürmann

Alex M. Thomson

Michele Migliore

Szabolcs Káli

Henry Markram

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive fun… (see more)ctions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to reconcile information obtained from diverse experimental approaches. To address this challenge, we present a community-driven, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to address a range of scientific questions. In this article, we describe the methods used to set up simulations that reproduce and extend in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce and reconcile experimental findings. Finally, we make data, code and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This neuroscience community-driven model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

2023-05-16

bioRxiv (preprint)

COVI-AgentSim: an Agent-based Model for Evaluating Methods of Digital Contact Tracing

Prateek Gupta

Tegan Maharaj

Martin Weiss

Nasim Rahaman

Hannah Alsdurf

Abhinav Sharma

Nanor Minoyan

Soren Harnois Leblanc

Victor Schmidt

Pierre-Luc St. Charles

Akshay Patel

David Buckeridge … (see 9 more)

Joumana Ghosn

Yang Zhang

Bernhard Schölkopf

Jian Tang

Irina Rish

Christopher Pal

Joanna Merckx

Yoshua Bengio

The rapid global spread of COVID-19 has led to an unprecedented demand for effective methods to mitigate the spread of the disease, and vari… (see more)ous digital contact tracing (DCT) methods have emerged as a component of the solution. In order to make informed public health choices, there is a need for tools which allow evaluation and comparison of DCT methods. We introduce an agent-based compartmental simulator we call COVI-AgentSim, integrating detailed consideration of virology, disease progression, social contact networks, and mobility patterns, based on parameters derived from empirical research. We verify by comparing to real data that COVI-AgentSim is able to reproduce realistic COVID-19 spread dynamics, and perform a sensitivity analysis to verify that the relative performance of contact tracing methods are consistent across a range of settings. We use COVI-AgentSim to perform cost-benefit analyses comparing no DCT to: 1) standard binary contact tracing (BCT) that assigns binary recommendations based on binary test results; and 2) a rule-based method for feature-based contact tracing (FCT) that assigns a graded level of recommendation based on diverse individual features. We find all DCT methods consistently reduce the spread of the disease, and that the advantage of FCT over BCT is maintained over a wide range of adoption rates. Feature-based methods of contact tracing avert more disability-adjusted life years (DALYs) per socioeconomic cost (measured by productive hours lost). Our results suggest any DCT method can help save lives, support re-opening of economies, and prevent second-wave outbreaks, and that FCT methods are a promising direction for enriching BCT using self-reported symptoms, yielding earlier warning signals and a significantly reduced spread of the virus per socioeconomic cost.

2020-10-01

OpenReview.net/Anonymous_Preprint (unknown)