Framework
framework
Computational Mechanisms of Predictive Processing in Brains and Machines
Predictive processing offers a unifying view of neural computation, proposing that brains continuously anticipate sensory input and update internal models based on prediction errors. In this talk, I will present converging evidence for the computational mechanisms underlying this framework across human neuroscience and deep neural networks. I will begin with recent work showing that large-scale distributed prediction-error encoding in the human brain directly predicts how sensory representations reorganize through predictive learning. I will then turn to PredNet, a popular predictive coding inspired deep network that has been widely used to model real-world biological vision systems. Using dynamic stimuli generated with our Spatiotemporal Style Transfer algorithm, we demonstrate that PredNet relies primarily on low-level spatiotemporal structure and remains insensitive to high-level content, revealing limits in its generalization capacity. Finally, I will discuss new recurrent vision models that integrate top-down feedback connections with intrinsic neural variability, uncovering a dual mechanism for robust sensory coding in which neural variability decorrelates unit responses, while top-down feedback stabilizes network dynamics. Together, these results outline how prediction error signaling and top-down feedback pathways shape adaptive sensory processing in biological and artificial systems.
FLUXSynID: High-Resolution Synthetic Face Generation for Document and Live Capture Images
Synthetic face datasets are increasingly used to overcome the limitations of real-world biometric data, including privacy concerns, demographic imbalance, and high collection costs. However, many existing methods lack fine-grained control over identity attributes and fail to produce paired, identity-consistent images under structured capture conditions. In this talk, I will present FLUXSynID, a framework for generating high-resolution synthetic face datasets with user-defined identity attribute distributions and paired document-style and trusted live capture images. The dataset generated using FLUXSynID shows improved alignment with real-world identity distributions and greater diversity compared to prior work. I will also discuss how FLUXSynID’s dataset and generation tools can support research in face recognition and morphing attack detection (MAD), enhancing model robustness in both academic and practical applications.
Open SPM: A Modular Framework for Scanning Probe Microscopy
OpenSPM aims to democratize innovation in the field of scanning probe microscopy (SPM), which is currently dominated by a few proprietary, closed systems that limit user-driven development. Our platform includes a high-speed OpenAFM head and base optimized for small cantilevers, an OpenAFM controller, a high-voltage amplifier, and interfaces compatible with several commercial AFM systems such as the Bruker Multimode, Nanosurf DriveAFM, Witec Alpha SNOM, Zeiss FIB-SEM XB550, and Nenovision Litescope. We have created a fully documented and community-driven OpenSPM platform, with training resources and sourcing information, which has already enabled the construction of more than 15 systems outside our lab. The controller is integrated with open-source tools like Gwyddion, HDF5, and Pycroscopy. We have also engaged external companies, two of which are integrating our controller into their products or interfaces. We see growing interest in applying parts of the OpenSPM platform to related techniques such as correlated microscopy, nanoindentation, and scanning electron/confocal microscopy. To support this, we are developing more generic and modular software, alongside a structured development workflow. A key feature of the OpenSPM system is its Python-based API, which makes the platform fully scriptable and ideal for AI and machine learning applications. This enables, for instance, automatic control and optimization of PID parameters, setpoints, and experiment workflows. With a growing contributor base and industry involvement, OpenSPM is well positioned to become a global, open platform for next-generation SPM innovation.
Harnessing Big Data in Neuroscience: From Mapping Brain Connectivity to Predicting Traumatic Brain Injury
Neuroscience is experiencing unprecedented growth in dataset size both within individual brains and across populations. Large-scale, multimodal datasets are transforming our understanding of brain structure and function, creating opportunities to address previously unexplored questions. However, managing this increasing data volume requires new training and technology approaches. Modern data technologies are reshaping neuroscience by enabling researchers to tackle complex questions within a Ph.D. or postdoctoral timeframe. I will discuss cloud-based platforms such as brainlife.io, that provide scalable, reproducible, and accessible computational infrastructure. Modern data technology can democratize neuroscience, accelerate discovery and foster scientific transparency and collaboration. Concrete examples will illustrate how these technologies can be applied to mapping brain connectivity, studying human learning and development, and developing predictive models for traumatic brain injury (TBI). By integrating cloud computing and scalable data-sharing frameworks, neuroscience can become more impactful, inclusive, and data-driven..
Recent views on pre-registration
A discussion on some recent perspectives on pre-registration, which has become a growing trend in the past few years. This is not just limited to neuroimaging, and it applies to most scientific fields. We will start with this overview editorial by Simmons et al. (2021): https://faculty.wharton.upenn.edu/wp-content/uploads/2016/11/34-Simmons-Nelson-Simonsohn-2021a.pdf, and also talk about a more critical perspective by Pham & Oh (2021): https://www.researchgate.net/profile/Michel-Pham/publication/349545600_Preregistration_Is_Neither_Sufficient_nor_Necessary_for_Good_Science/links/60fb311e2bf3553b29096aa7/Preregistration-Is-Neither-Sufficient-nor-Necessary-for-Good-Science.pdf. I would like us to discuss the pros and cons of pre-registration, and if we have time, I may do a demonstration of how to perform a pre-registration through the Open Science Framework.
Relating circuit dynamics to computation: robustness and dimension-specific computation in cortical dynamics
Neural dynamics represent the hard-to-interpret substrate of circuit computations. Advances in large-scale recordings have highlighted the sheer spatiotemporal complexity of circuit dynamics within and across circuits, portraying in detail the difficulty of interpreting such dynamics and relating it to computation. Indeed, even in extremely simplified experimental conditions, one observes high-dimensional temporal dynamics in the relevant circuits. This complexity can be potentially addressed by the notion that not all changes in population activity have equal meaning, i.e., a small change in the evolution of activity along a particular dimension may have a bigger effect on a given computation than a large change in another. We term such conditions dimension-specific computation. Considering motor preparatory activity in a delayed response task we utilized neural recordings performed simultaneously with optogenetic perturbations to probe circuit dynamics. First, we revealed a remarkable robustness in the detailed evolution of certain dimensions of the population activity, beyond what was thought to be the case experimentally and theoretically. Second, the robust dimension in activity space carries nearly all of the decodable behavioral information whereas other non-robust dimensions contained nearly no decodable information, as if the circuit was setup to make informative dimensions stiff, i.e., resistive to perturbations, leaving uninformative dimensions sloppy, i.e., sensitive to perturbations. Third, we show that this robustness can be achieved by a modular organization of circuitry, whereby modules whose dynamics normally evolve independently can correct each other’s dynamics when an individual module is perturbed, a common design feature in robust systems engineering. Finally, we will recent work extending this framework to understanding the neural dynamics underlying preparation of speech.
Dimensionality reduction beyond neural subspaces
Over the past decade, neural representations have been studied from the lens of low-dimensional subspaces defined by the co-activation of neurons. However, this view has overlooked other forms of covarying structure in neural activity, including i) condition-specific high-dimensional neural sequences, and ii) representations that change over time due to learning or drift. In this talk, I will present a new framework that extends the classic view towards additional types of covariability that are not constrained to a fixed, low-dimensional subspace. In addition, I will present sliceTCA, a new tensor decomposition that captures and demixes these different types of covariability to reveal task-relevant structure in neural activity. Finally, I will close with some thoughts regarding the circuit mechanisms that could generate mixed covariability. Together this work points to a need to consider new possibilities for how neural populations encode sensory, cognitive, and behavioral variables beyond neural subspaces.
The Brain Prize winners' webinar
This webinar brings together three leaders in theoretical and computational neuroscience—Larry Abbott, Haim Sompolinsky, and Terry Sejnowski—to discuss how neural circuits generate fundamental aspects of the mind. Abbott illustrates mechanisms in electric fish that differentiate self-generated electric signals from external sensory cues, showing how predictive plasticity and two-stage signal cancellation mediate a sense of self. Sompolinsky explores attractor networks, revealing how discrete and continuous attractors can stabilize activity patterns, enable working memory, and incorporate chaotic dynamics underlying spontaneous behaviors. He further highlights the concept of object manifolds in high-level sensory representations and raises open questions on integrating connectomics with theoretical frameworks. Sejnowski bridges these motifs with modern artificial intelligence, demonstrating how large-scale neural networks capture language structures through distributed representations that parallel biological coding. Together, their presentations emphasize the synergy between empirical data, computational modeling, and connectomics in explaining the neural basis of cognition—offering insights into perception, memory, language, and the emergence of mind-like processes.
Brain circuits for spatial navigation
In this webinar on spatial navigation circuits, three researchers—Ann Hermundstad, Ila Fiete, and Barbara Webb—discussed how diverse species solve navigation problems using specialized yet evolutionarily conserved brain structures. Hermundstad illustrated the fruit fly’s central complex, focusing on how hardwired circuit motifs (e.g., sinusoidal steering curves) enable rapid, flexible learning of goal-directed navigation. This framework combines internal heading representations with modifiable goal signals, leveraging activity-dependent plasticity to adapt to new environments. Fiete explored the mammalian head-direction system, demonstrating how population recordings reveal a one-dimensional ring attractor underlying continuous integration of angular velocity. She showed that key theoretical predictions—low-dimensional manifold structure, isometry, uniform stability—are experimentally validated, underscoring parallels to insect circuits. Finally, Webb described honeybee navigation, featuring path integration, vector memories, route optimization, and the famous waggle dance. She proposed that allocentric velocity signals and vector manipulation within the central complex can encode and transmit distances and directions, enabling both sophisticated foraging and inter-bee communication via dance-based cues.
Decision and Behavior
This webinar addressed computational perspectives on how animals and humans make decisions, spanning normative, descriptive, and mechanistic models. Sam Gershman (Harvard) presented a capacity-limited reinforcement learning framework in which policies are compressed under an information bottleneck constraint. This approach predicts pervasive perseveration, stimulus‐independent “default” actions, and trade-offs between complexity and reward. Such policy compression reconciles observed action stochasticity and response time patterns with an optimal balance between learning capacity and performance. Jonathan Pillow (Princeton) discussed flexible descriptive models for tracking time-varying policies in animals. He introduced dynamic Generalized Linear Models (Sidetrack) and hidden Markov models (GLM-HMMs) that capture day-to-day and trial-to-trial fluctuations in choice behavior, including abrupt switches between “engaged” and “disengaged” states. These models provide new insights into how animals’ strategies evolve under learning. Finally, Kenji Doya (OIST) highlighted the importance of unifying reinforcement learning with Bayesian inference, exploring how cortical-basal ganglia networks might implement model-based and model-free strategies. He also described Japan’s Brain/MINDS 2.0 and Digital Brain initiatives, aiming to integrate multimodal data and computational principles into cohesive “digital brains.”
LLMs and Human Language Processing
This webinar convened researchers at the intersection of Artificial Intelligence and Neuroscience to investigate how large language models (LLMs) can serve as valuable “model organisms” for understanding human language processing. Presenters showcased evidence that brain recordings (fMRI, MEG, ECoG) acquired while participants read or listened to unconstrained speech can be predicted by representations extracted from state-of-the-art text- and speech-based LLMs. In particular, text-based LLMs tend to align better with higher-level language regions, capturing more semantic aspects, while speech-based LLMs excel at explaining early auditory cortical responses. However, purely low-level features can drive part of these alignments, complicating interpretations. New methods, including perturbation analyses, highlight which linguistic variables matter for each cortical area and time scale. Further, “brain tuning” of LLMs—fine-tuning on measured neural signals—can improve semantic representations and downstream language tasks. Despite open questions about interpretability and exact neural mechanisms, these results demonstrate that LLMs provide a promising framework for probing the computations underlying human language comprehension and production at multiple spatiotemporal scales.
Sensory cognition
This webinar features presentations from SueYeon Chung (New York University) and Srinivas Turaga (HHMI Janelia Research Campus) on theoretical and computational approaches to sensory cognition. Chung introduced a “neural manifold” framework to capture how high-dimensional neural activity is structured into meaningful manifolds reflecting object representations. She demonstrated that manifold geometry—shaped by radius, dimensionality, and correlations—directly governs a population’s capacity for classifying or separating stimuli under nuisance variations. Applying these ideas as a data analysis tool, she showed how measuring object-manifold geometry can explain transformations along the ventral visual stream and suggested that manifold principles also yield better self-supervised neural network models resembling mammalian visual cortex. Turaga described simulating the entire fruit fly visual pathway using its connectome, modeling 64 key cell types in the optic lobe. His team’s systematic approach—combining sparse connectivity from electron microscopy with simple dynamical parameters—recapitulated known motion-selective responses and produced novel testable predictions. Together, these studies underscore the power of combining connectomic detail, task objectives, and geometric theories to unravel neural computations bridging from stimuli to cognitive functions.
Understanding the complex behaviors of the ‘simple’ cerebellar circuit
Every movement we make requires us to precisely coordinate muscle activity across our body in space and time. In this talk I will describe our efforts to understand how the brain generates flexible, coordinated movement. We have taken a behavior-centric approach to this problem, starting with the development of quantitative frameworks for mouse locomotion (LocoMouse; Machado et al., eLife 2015, 2020) and locomotor learning, in which mice adapt their locomotor symmetry in response to environmental perturbations (Darmohray et al., Neuron 2019). Combined with genetic circuit dissection, these studies reveal specific, cerebellum-dependent features of these complex, whole-body behaviors. This provides a key entry point for understanding how neural computations within the highly stereotyped cerebellar circuit support the precise coordination of muscle activity in space and time. Finally, I will present recent unpublished data that provide surprising insights into how cerebellar circuits flexibly coordinate whole-body movements in dynamic environments.
Brain-Wide Compositionality and Learning Dynamics in Biological Agents
Biological agents continually reconcile the internal states of their brain circuits with incoming sensory and environmental evidence to evaluate when and how to act. The brains of biological agents, including animals and humans, exploit many evolutionary innovations, chiefly modularity—observable at the level of anatomically-defined brain regions, cortical layers, and cell types among others—that can be repurposed in a compositional manner to endow the animal with a highly flexible behavioral repertoire. Accordingly, their behaviors show their own modularity, yet such behavioral modules seldom correspond directly to traditional notions of modularity in brains. It remains unclear how to link neural and behavioral modularity in a compositional manner. We propose a comprehensive framework—compositional modes—to identify overarching compositionality spanning specialized submodules, such as brain regions. Our framework directly links the behavioral repertoire with distributed patterns of population activity, brain-wide, at multiple concurrent spatial and temporal scales. Using whole-brain recordings of zebrafish brains, we introduce an unsupervised pipeline based on neural network models, constrained by biological data, to reveal highly conserved compositional modes across individuals despite the naturalistic (spontaneous or task-independent) nature of their behaviors. These modes provided a scaffolding for other modes that account for the idiosyncratic behavior of each fish. We then demonstrate experimentally that compositional modes can be manipulated in a consistent manner by behavioral and pharmacological perturbations. Our results demonstrate that even natural behavior in different individuals can be decomposed and understood using a relatively small number of neurobehavioral modules—the compositional modes—and elucidate a compositional neural basis of behavior. This approach aligns with recent progress in understanding how reasoning capabilities and internal representational structures develop over the course of learning or training, offering insights into the modularity and flexibility in artificial and biological agents.
Decomposing motivation into value and salience
Humans and other animals approach reward and avoid punishment and pay attention to cues predicting these events. Such motivated behavior thus appears to be guided by value, which directs behavior towards or away from positively or negatively valenced outcomes. Moreover, it is facilitated by (top-down) salience, which enhances attention to behaviorally relevant learned cues predicting the occurrence of valenced outcomes. Using human neuroimaging, we recently separated value (ventral striatum, posterior ventromedial prefrontal cortex) from salience (anterior ventromedial cortex, occipital cortex) in the domain of liquid reward and punishment. Moreover, we investigated potential drivers of learned salience: the probability and uncertainty with which valenced and non-valenced outcomes occur. We find that the brain dissociates valenced from non-valenced probability and uncertainty, which indicates that reinforcement matters for the brain, in addition to information provided by probability and uncertainty alone, regardless of valence. Finally, we assessed learning signals (unsigned prediction errors) that may underpin the acquisition of salience. Particularly the insula appears to be central for this function, encoding a subjective salience prediction error, similarly at the time of positively and negatively valenced outcomes. However, it appears to employ domain-specific time constants, leading to stronger salience signals in the aversive than the appetitive domain at the time of cues. These findings explain why previous research associated the insula with both valence-independent salience processing and with preferential encoding of the aversive domain. More generally, the distinction of value and salience appears to provide a useful framework for capturing the neural basis of motivated behavior.
Use case determines the validity of neural systems comparisons
Deep learning provides new data-driven tools to relate neural activity to perception and cognition, aiding scientists in developing theories of neural computation that increasingly resemble biological systems both at the level of behavior and of neural activity. But what in a deep neural network should correspond to what in a biological system? This question is addressed implicitly in the use of comparison measures that relate specific neural or behavioral dimensions via a particular functional form. However, distinct comparison methodologies can give conflicting results in recovering even a known ground-truth model in an idealized setting, leaving open the question of what to conclude from the outcome of a systems comparison using any given methodology. Here, we develop a framework to make explicit and quantitative the effect of both hypothesis-driven aspects—such as details of the architecture of a deep neural network—as well as methodological choices in a systems comparison setting. We demonstrate via the learning dynamics of deep neural networks that, while the role of the comparison methodology is often de-emphasized relative to hypothesis-driven aspects, this choice can impact and even invert the conclusions to be drawn from a comparison between neural systems. We provide evidence that the right way to adjudicate a comparison depends on the use case—the scientific hypothesis under investigation—which could range from identifying single-neuron or circuit-level correspondences to capturing generalizability to new stimulus properties
On finding what you’re (not) looking for: prospects and challenges for AI-driven discovery
Recent high-profile scientific achievements by machine learning (ML) and especially deep learning (DL) systems have reinvigorated interest in ML for automated scientific discovery (eg, Wang et al. 2023). Much of this work is motivated by the thought that DL methods might facilitate the efficient discovery of phenomena, hypotheses, or even models or theories more efficiently than traditional, theory-driven approaches to discovery. This talk considers some of the more specific obstacles to automated, DL-driven discovery in frontier science, focusing on gravitational-wave astrophysics (GWA) as a representative case study. In the first part of the talk, we argue that despite these efforts, prospects for DL-driven discovery in GWA remain uncertain. In the second part, we advocate a shift in focus towards the ways DL can be used to augment or enhance existing discovery methods, and the epistemic virtues and vices associated with these uses. We argue that the primary epistemic virtue of many such uses is to decrease opportunity costs associated with investigating puzzling or anomalous signals, and that the right framework for evaluating these uses comes from philosophical work on pursuitworthiness.
Time perception in film viewing as a function of film editing
Filmmakers and editors have empirically developed techniques to ensure the spatiotemporal continuity of a film's narration. In terms of time, editing techniques (e.g., elliptical, overlapping, or cut minimization) allow for the manipulation of the perceived duration of events as they unfold on screen. More specifically, a scene can be edited to be time compressed, expanded, or real-time in terms of its perceived duration. Despite the consistent application of these techniques in filmmaking, their perceptual outcomes have not been experimentally validated. Given that viewing a film is experienced as a precise simulation of the physical world, the use of cinematic material to examine aspects of time perception allows for experimentation with high ecological validity, while filmmakers gain more insight on how empirically developed techniques influence viewers' time percept. Here, we investigated how such time manipulation techniques of an action affect a scene's perceived duration. Specifically, we presented videos depicting different actions (e.g., a woman talking on the phone), edited according to the techniques applied for temporal manipulation and asked participants to make verbal estimations of the presented scenes' perceived durations. Analysis of data revealed that the duration of expanded scenes was significantly overestimated as compared to that of compressed and real-time scenes, as was the duration of real-time scenes as compared to that of compressed scenes. Therefore, our results validate the empirical techniques applied for the modulation of a scene's perceived duration. We also found interactions on time estimates of scene type and editing technique as a function of the characteristics and the action of the scene presented. Thus, these findings add to the discussion that the content and characteristics of a scene, along with the editing technique applied, can also modulate perceived duration. Our findings are discussed by considering current timing frameworks, as well as attentional saliency algorithms measuring the visual saliency of the presented stimuli.
Predictive processing: a circuit approach to psychosis
Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In my talk, I will provide an overview of our progress in this endeavor.
Are integrative, multidisciplinary, and pragmatic models possible? The #PsychMapping experience
This presentation delves into the necessity for simplified models in the field of psychological sciences to cater to a diverse audience of practitioners. We introduce the #PsychMapping model, evaluate its merits and limitations, and discuss its place in contemporary scientific culture. The #PsychMapping model is the product of an extensive literature review, initially within the realm of sport and exercise psychology and subsequently encompassing a broader spectrum of psychological sciences. This model synthesizes the progress made in psychological sciences by categorizing variables into a framework that distinguishes between traits (e.g., body structure and personality) and states (e.g., heart rate and emotions). Furthermore, it delineates internal traits and states from the externalized self, which encompasses behaviour and performance. All three components—traits, states, and the externalized self—are in a continuous interplay with external physical, social, and circumstantial factors. Two core processes elucidate the interactions among these four primary clusters: external perception, encompassing the mechanism through which external stimuli transition into internal events, and self-regulation, which empowers individuals to become autonomous agents capable of exerting control over themselves and their actions. While the model inherently oversimplifies intricate processes, the central question remains: does its pragmatic utility outweigh its limitations, and can it serve as a valuable tool for comprehending human behaviour?
Trends in NeuroAI - Unified Scalable Neural Decoding (POYO)
Lead author Mehdi Azabou will present on his work "POYO-1: A Unified, Scalable Framework for Neural Population Decoding" (https://poyo-brain.github.io/). Mehdi is an ML PhD student at Georgia Tech advised by Dr. Eva Dyer. Paper link: https://arxiv.org/abs/2310.16046 Trends in NeuroAI is a reading group hosted by the MedARC Neuroimaging & AI lab (https://medarc.ai/fmri | https://groups.google.com/g/medarc-fmri).
Where Cognitive Neuroscience Meets Industry: Navigating the Intersections of Academia and Industry
In this talk, Mirta will share her journey from her education a mathematically-focused high school to her currently unconventional career in London, emphasizing the evolution from a local education in Croatia to international experiences in the US and UK. We will explore the concept of interdisciplinary careers in the modern world, viewing them through the framework of increasing demand, flexibility, and dynamism in the current workplace. We will underscore the significance of interdisciplinary research for launching careers outside of academia, and bolstering those within. I will challenge the conventional norm of working either in academia or industry, and encourage discussion about the opportunities for combining the two in a myriad of career opportunities. I’ll use examples from my own and others’ research to highlight opportunities for early career researchers to extend their work into practical applications. Such an approach leverages the strengths of both sectors, fostering innovation and practical applications of research findings. I hope these insights can offer valuable perspectives for those looking to navigate the evolving demands of the global job market, illustrating the advantages of a versatile skill set that spans multiple disciplines and allows extensions into exciting career options.
Reimagining the neuron as a controller: A novel model for Neuroscience and AI
We build upon and expand the efficient coding and predictive information models of neurons, presenting a novel perspective that neurons not only predict but also actively influence their future inputs through their outputs. We introduce the concept of neurons as feedback controllers of their environments, a role traditionally considered computationally demanding, particularly when the dynamical system characterizing the environment is unknown. By harnessing a novel data-driven control framework, we illustrate the feasibility of biological neurons functioning as effective feedback controllers. This innovative approach enables us to coherently explain various experimental findings that previously seemed unrelated. Our research has profound implications, potentially revolutionizing the modeling of neuronal circuits and paving the way for the creation of alternative, biologically inspired artificial neural networks.
Are integrative, multidisciplinary, and pragmatic models possible? The #PsychMapping experience
This presentation delves into the necessity for simplified models in the field of psychological sciences to cater to a diverse audience of practitioners. We introduce the #PsychMapping model, evaluate its merits and limitations, and discuss its place in contemporary scientific culture. The #PsychMapping model is the product of an extensive literature review, initially within the realm of sport and exercise psychology and subsequently encompassing a broader spectrum of psychological sciences. This model synthesizes the progress made in psychological sciences by categorizing variables into a framework that distinguishes between traits (e.g., body structure and personality) and states (e.g., heart rate and emotions). Furthermore, it delineates internal traits and states from the externalized self, which encompasses behaviour and performance. All three components—traits, states, and the externalized self—are in a continuous interplay with external physical, social, and circumstantial factors. Two core processes elucidate the interactions among these four primary clusters: external perception, encompassing the mechanism through which external stimuli transition into internal events, and self-regulation, which empowers individuals to become autonomous agents capable of exerting control over themselves and their actions. While the model inherently oversimplifies intricate processes, the central question remains: does its pragmatic utility outweigh its limitations, and can it serve as a valuable tool for comprehending human behaviour?
Characterising Representations of Goal Obstructiveness and Uncertainty Across Behavior, Physiology, and Brain Activity Through a Video Game Paradigm
The nature of emotions and their neural underpinnings remain debated. Appraisal theories such as the component process model propose that the perception and evaluation of events (appraisal) is the key to eliciting the range of emotions we experience. Here we study whether the framework of appraisal theories provides a clearer account for the differentiation of emotional episodes and their functional organisation in the brain. We developed a stealth game to manipulate appraisals in a systematic yet immersive way. The interactive nature of video games heightens self-relevance through the experience of goal-directed action or reaction, evoking strong emotions. We show that our manipulations led to changes in behaviour, physiology and brain activations.
Neuronal population interactions between brain areas
Most brain functions involve interactions among multiple, distinct areas or nuclei. Yet our understanding of how populations of neurons in interconnected brain areas communicate is in its infancy. Using a population approach, we found that interactions between early visual cortical areas (V1 and V2) occur through a low-dimensional bottleneck, termed a communication subspace. In this talk, I will focus on the statistical methods we have developed for studying interactions between brain areas. First, I will describe Delayed Latents Across Groups (DLAG), designed to disentangle concurrent, bi-directional (i.e., feedforward and feedback) interactions between areas. Second, I will describe an extension of DLAG applicable to three or more areas, and demonstrate its utility for studying simultaneous Neuropixels recordings in areas V1, V2, and V3. Our results provide a framework for understanding how neuronal population activity is gated and selectively routed across brain areas.
Event-related frequency adjustment (ERFA): A methodology for investigating neural entrainment
Neural entrainment has become a phenomenon of exceptional interest to neuroscience, given its involvement in rhythm perception, production, and overt synchronized behavior. Yet, traditional methods fail to quantify neural entrainment due to a misalignment with its fundamental definition (e.g., see Novembre and Iannetti, 2018; Rajandran and Schupp, 2019). The definition of entrainment assumes that endogenous oscillatory brain activity undergoes dynamic frequency adjustments to synchronize with environmental rhythms (Lakatos et al., 2019). Following this definition, we recently developed a method sensitive to this process. Our aim was to isolate from the electroencephalographic (EEG) signal an oscillatory component that is attuned to the frequency of a rhythmic stimulation, hypothesizing that the oscillation would adaptively speed up and slow down to achieve stable synchronization over time. To induce and measure these adaptive changes in a controlled fashion, we developed the event-related frequency adjustment (ERFA) paradigm (Rosso et al., 2023). A total of twenty healthy participants took part in our study. They were instructed to tap their finger synchronously with an isochronous auditory metronome, which was unpredictably perturbed by phase-shifts and tempo-changes in both positive and negative directions across different experimental conditions. EEG was recorded during the task, and ERFA responses were quantified as changes in instantaneous frequency of the entrained component. Our results indicate that ERFAs track the stimulus dynamics in accordance with the perturbation type and direction, preferentially for a sensorimotor component. The clear and consistent patterns confirm that our method is sensitive to the process of frequency adjustment that defines neural entrainment. In this Virtual Journal Club, the discussion of our findings will be complemented by methodological insights beneficial to researchers in the fields of rhythm perception and production, as well as timing in general. We discuss the dos and don’ts of using instantaneous frequency to quantify oscillatory dynamics, the advantages of adopting a multivariate approach to source separation, the robustness against the confounder of responses evoked by periodic stimulation, and provide an overview of domains and concrete examples where the methodological framework can be applied.
Great ape interaction: Ladyginian but not Gricean
Non-human great apes inform one another in ways that can seem very humanlike. Especially in the gestural domain, their behavior exhibits many similarities with human communication, meeting widely used empirical criteria for intentionality. At the same time, there remain some manifest differences. How to account for these similarities and differences in a unified way remains a major challenge. This presentation will summarise the arguments developed in a recent paper with Christophe Heintz. We make a key distinction between the expression of intentions (Ladyginian) and the expression of specifically informative intentions (Gricean), and we situate this distinction within a ‘special case of’ framework for classifying different modes of attention manipulation. The paper also argues that the attested tendencies of great ape interaction—for instance, to be dyadic rather than triadic, to be about the here-and-now rather than ‘displaced’—are products of its Ladyginian but not Gricean character. I will reinterpret video footage of great ape gesture as Ladyginian but not Gricean, and distinguish several varieties of meaning that are continuous with one another. We conclude that the evolutionary origins of linguistic meaning lie in gradual changes in not communication systems as such, but rather in social cognition, and specifically in what modes of attention manipulation are enabled by a species’ cognitive phenotype: first Ladyginian and in turn Gricean. The second of these shifts rendered humans, and only humans, ‘language ready’.
State-of-the-Art Spike Sorting with SpikeInterface
This webinar will focus on spike sorting analysis with SpikeInterface, an open-source framework for the analysis of extracellular electrophysiology data. After a brief introduction of the project (~30 mins) highlighting the basics of the SpikeInterface software and advanced features (e.g., data compression, quality metrics, drift correction, cloud visualization), we will have an extensive hands-on tutorial (~90 mins) showing how to use SpikeInterface in a real-world scenario. After attending the webinar, you will: (1) have a global overview of the different steps involved in a processing pipeline; (2) know how to write a complete analysis pipeline with SpikeInterface.
Identifying mechanisms of cognitive computations from spikes
Higher cortical areas carry a wide range of sensory, cognitive, and motor signals supporting complex goal-directed behavior. These signals mix in heterogeneous responses of single neurons, making it difficult to untangle underlying mechanisms. I will present two approaches for revealing interpretable circuit mechanisms from heterogeneous neural responses during cognitive tasks. First, I will show a flexible nonparametric framework for simultaneously inferring population dynamics on single trials and tuning functions of individual neurons to the latent population state. When applied to recordings from the premotor cortex during decision-making, our approach revealed that populations of neurons encoded the same dynamic variable predicting choices, and heterogeneous firing rates resulted from the diverse tuning of single neurons to this decision variable. The inferred dynamics indicated an attractor mechanism for decision computation. Second, I will show an approach for inferring an interpretable network model of a cognitive task—the latent circuit—from neural response data. We developed a theory to causally validate latent circuit mechanisms via patterned perturbations of activity and connectivity in the high-dimensional network. This work opens new possibilities for deriving testable mechanistic hypotheses from complex neural response data.
Brain network communication: concepts, models and applications
Understanding communication and information processing in nervous systems is a central goal of neuroscience. Over the past two decades, advances in connectomics and network neuroscience have opened new avenues for investigating polysynaptic communication in complex brain networks. Recent work has brought into question the mainstay assumption that connectome signalling occurs exclusively via shortest paths, resulting in a sprawling constellation of alternative network communication models. This Review surveys the latest developments in models of brain network communication. We begin by drawing a conceptual link between the mathematics of graph theory and biological aspects of neural signalling such as transmission delays and metabolic cost. We organize key network communication models and measures into a taxonomy, aimed at helping researchers navigate the growing number of concepts and methods in the literature. The taxonomy highlights the pros, cons and interpretations of different conceptualizations of connectome signalling. We showcase the utility of network communication models as a flexible, interpretable and tractable framework to study brain function by reviewing prominent applications in basic, cognitive and clinical neurosciences. Finally, we provide recommendations to guide the future development, application and validation of network communication models.
Learning to Express Reward Prediction Error-like Dopaminergic Activity Requires Plastic Representations of Time
The dominant theoretical framework to account for reinforcement learning in the brain is temporal difference (TD) reinforcement learning. The TD framework predicts that some neuronal elements should represent the reward prediction error (RPE), which means they signal the difference between the expected future rewards and the actual rewards. The prominence of the TD theory arises from the observation that firing properties of dopaminergic neurons in the ventral tegmental area appear similar to those of RPE model-neurons in TD learning. Previous implementations of TD learning assume a fixed temporal basis for each stimulus that might eventually predict a reward. Here we show that such a fixed temporal basis is implausible and that certain predictions of TD learning are inconsistent with experiments. We propose instead an alternative theoretical framework, coined FLEX (Flexibly Learned Errors in Expected Reward). In FLEX, feature specific representations of time are learned, allowing for neural representations of stimuli to adjust their timing and relation to rewards in an online manner. In FLEX dopamine acts as an instructive signal which helps build temporal models of the environment. FLEX is a general theoretical framework that has many possible biophysical implementations. In order to show that FLEX is a feasible approach, we present a specific biophysically plausible model which implements the principles of FLEX. We show that this implementation can account for various reinforcement learning paradigms, and that its results and predictions are consistent with a preponderance of both existing and reanalyzed experimental data.
How curiosity affects learning and information seeking via the dopaminergic circuit
Over the last decade, research on curiosity – the desire to seek new information – has been rapidly growing. Several studies have shown that curiosity elicits activity within the dopaminergic circuit and thereby enhances hippocampus-dependent learning. However, given this new field of research, we do not have a good understanding yet of (i) how curiosity-based learning changes across the lifespan, (ii) why some people show better learning improvements due to curiosity than others, and (iii) whether lab-based research on curiosity translates to how curiosity affects information seeking in real life. In this talk, I will present a series of behavioural and neuroimaging studies that address these three questions about curiosity. First, I will present findings on how curiosity and interest affect learning differently in childhood and adolescence. Second, I will show data on how inter-individual differences in the magnitude of curiosity-based learning depend on the strength of resting-state functional connectivity within the cortico-mesolimbic dopaminergic circuit. Third, I will present findings on how the level of resting-state functional connectivity within this circuit is also associated with the frequency of real-life information seeking (i.e., about Covid-19-related news). Together, our findings help to refine our recently proposed framework – the Prediction, Appraisal, Curiosity, and Exploration (PACE) framework – that attempts to integrate theoretical ideas on the neurocognitive mechanisms of how curiosity is elicited, and how curiosity enhances learning and information seeking. Furthermore, our findings highlight the importance of curiosity research to better understand how curiosity can be harnessed to improve learning and information seeking in real life.
The Effects of Movement Parameters on Time Perception
Mobile organisms must be capable of deciding both where and when to move in order to keep up with a changing environment; therefore, a strong sense of time is necessary, otherwise, we would fail in many of our movement goals. Despite this intrinsic link between movement and timing, only recently has research begun to investigate the interaction. Two primary effects that have been observed include: movements biasing time estimates (i.e., affecting accuracy) as well as making time estimates more precise. The goal of this presentation is to review this literature, discuss a Bayesian cue combination framework to explain these effects, and discuss the experiments I have conducted to test the framework. The experiments herein include: a motor timing task comparing the effects of movement vs non-movement with and without feedback (Exp. 1A & 1B), a transcranial magnetic stimulation (TMS) study on the role of the supplementary motor area (SMA) in transforming temporal information (Exp. 2), and a perceptual timing task investigating the effect of noisy movement on time perception with both visual and auditory modalities (Exp. 3A & 3B). Together, the results of these studies support the Bayesian cue combination framework, in that: movement improves the precision of time perception not only in perceptual timing tasks but also motor timing tasks (Exp. 1A & 1B), stimulating the SMA appears to disrupt the transformation of temporal information (Exp. 2), and when movement becomes unreliable or noisy there is no longer an improvement in precision of time perception (Exp. 3A & 3B). Although there is support for the proposed framework, more studies (i.e., fMRI, TMS, EEG, etc.) need to be conducted in order to better understand where and how this may be instantiated in the brain; however, this work provides a starting point to better understanding the intrinsic connection between time and movement
Internal representation of musical rhythm: transformation from sound to periodic beat
When listening to music, humans readily perceive and move along with a periodic beat. Critically, perception of a periodic beat is commonly elicited by rhythmic stimuli with physical features arranged in a way that is not strictly periodic. Hence, beat perception must capitalize on mechanisms that transform stimulus features into a temporally recurrent format with emphasized beat periodicity. Here, I will present a line of work that aims to clarify the nature and neural basis of this transformation. In these studies, electrophysiological activity was recorded as participants listened to rhythms known to induce perception of a consistent beat across healthy Western adults. The results show that the human brain selectively emphasizes beat representation when it is not acoustically prominent in the stimulus, and this transformation (i) can be captured non-invasively using surface EEG in adult participants, (ii) is already in place in 5- to 6-month-old infants, and (iii) cannot be fully explained by subcortical auditory nonlinearities. Moreover, as revealed by human intracerebral recordings, a prominent beat representation emerges already in the primary auditory cortex. Finally, electrophysiological recordings from the auditory cortex of a rhesus monkey show a significant enhancement of beat periodicities in this area, similar to humans. Taken together, these findings indicate an early, general auditory cortical stage of processing by which rhythmic inputs are rendered more temporally recurrent than they are in reality. Already present in non-human primates and human infants, this "periodized" default format could then be shaped by higher-level associative sensory-motor areas and guide movement in individuals with strongly coupled auditory and motor systems. Together, this highlights the multiplicity of neural processes supporting coordinated musical behaviors widely observed across human cultures.The experiments herein include: a motor timing task comparing the effects of movement vs non-movement with and without feedback (Exp. 1A & 1B), a transcranial magnetic stimulation (TMS) study on the role of the supplementary motor area (SMA) in transforming temporal information (Exp. 2), and a perceptual timing task investigating the effect of noisy movement on time perception with both visual and auditory modalities (Exp. 3A & 3B). Together, the results of these studies support the Bayesian cue combination framework, in that: movement improves the precision of time perception not only in perceptual timing tasks but also motor timing tasks (Exp. 1A & 1B), stimulating the SMA appears to disrupt the transformation of temporal information (Exp. 2), and when movement becomes unreliable or noisy there is no longer an improvement in precision of time perception (Exp. 3A & 3B). Although there is support for the proposed framework, more studies (i.e., fMRI, TMS, EEG, etc.) need to be conducted in order to better understand where and how this may be instantiated in the brain; however, this work provides a starting point to better understanding the intrinsic connection between time and movement
Distinct contributions of different anterior frontal regions to rule-guided decision-making in primates: complementary evidence from lesions, electrophysiology, and neurostimulation
Different prefrontal areas contribute in distinctly different ways to rule-guided behaviour in the context of a Wisconsin Card Sorting Test (WCST) analog for macaques. For example, causal evidence from circumscribed lesions in NHPs reveals that dorsolateral prefrontal cortex (dlPFC) is necessary to maintain a reinforced abstract rule in working memory, orbitofrontal cortex (OFC) is needed to rapidly update representations of rule value, and the anterior cingulate cortex (ACC) plays a key role in cognitive control and integrating information for correct and incorrect trials over recent outcomes. Moreover, recent lesion studies of frontopolar cortex (FPC) suggest it contributes to representing the relative value of unchosen alternatives, including rules. Yet we do not understand how these functional specializations relate to intrinsic neuronal activities nor the extent to which these neuronal activities differ between different prefrontal regions. After reviewing the aforementioned causal evidence I will present our new data from studies using multi-area multi-electrode recording techniques in NHPs to simultaneously record from four different prefrontal regions implicated in rule-guided behaviour. Multi-electrode micro-arrays (‘Utah arrays’) were chronically implanted in dlPFC, vlPFC, OFC, and FPC of two macaques, allowing us to simultaneously record single and multiunit activity, and local field potential (LFP), from all regions while the monkey performs the WCST analog. Rule-related neuronal activity was widespread in all areas recorded but it differed in degree and in timing between different areas. I will also present preliminary results from decoding analyses applied to rule-related neuronal activities both from individual clusters and also from population measures. These results confirm and help quantify dynamic task-related activities that differ between prefrontal regions. We also found task-related modulation of LFPs within beta and gamma bands in FPC. By combining this correlational recording methods with trial-specific causal interventions (electrical microstimulation) to FPC we could significantly enhance and impair animals performance in distinct task epochs in functionally relevant ways, further consistent with an emerging picture of regional functional specialization within a distributed framework of interacting and interconnected cortical regions.
Quasicriticality and the quest for a framework of neuronal dynamics
Critical phenomena abound in nature, from forest fires and earthquakes to avalanches in sand and neuronal activity. Since the 2003 publication by Beggs & Plenz on neuronal avalanches, a growing body of work suggests that the brain homeostatically regulates itself to operate near a critical point where information processing is optimal. At this critical point, incoming activity is neither amplified (supercritical) nor damped (subcritical), but approximately preserved as it passes through neural networks. Departures from the critical point have been associated with conditions of poor neurological health like epilepsy, Alzheimer's disease, and depression. One complication that arises from this picture is that the critical point assumes no external input. But, biological neural networks are constantly bombarded by external input. How is then the brain able to homeostatically adapt near the critical point? We’ll see that the theory of quasicriticality, an organizing principle for brain dynamics, can account for this paradoxical situation. As external stimuli drive the cortex, quasicriticality predicts a departure from criticality while maintaining optimal properties for information transmission. We’ll see that simulations and experimental data confirm these predictions and describe new ones that could be tested soon. More importantly, we will see how this organizing principle could help in the search for biomarkers that could soon be tested in clinical studies.
A new science of emotion: How brain-mind-body processes form functional neurological disorder
One of the most common medical conditions you’ve (maybe) never heard of – functional neurological disorder – lays at the interface of neurology and psychiatry and offers a window into fundamental brain-mind-body processes. Across ancient and modern times, functional neurological disorder has had a long and tumultuous history, with an evolving debate and understanding of how biopsychosocial factors contribute to the manifestation of the disorder. A central issue in contemporary discussions has revolved around questioning the extent to which emotions play a mechanistic and aetiological role in functional neurological disorder. Critical in this context, however, is that this ongoing debate has largely omitted the question of what emotions are in the first place. This talk first brings together advances in the understanding of working principles of the brain fundamental to introducing a new understanding of what emotions are. Building on recent theoretical frameworks from affective neuroscience, the idea of how the predictive process of emotion construction can be an integral component of the pathophysiology of functional neurological disorder is discussed.
The centrality of population-level factors to network computation is demonstrated by a versatile approach for training spiking networks
Neural activity is often described in terms of population-level factors extracted from the responses of many neurons. Factors provide a lower-dimensional description with the aim of shedding light on network computations. Yet, mechanistically, computations are performed not by continuously valued factors but by interactions among neurons that spike discretely and variably. Models provide a means of bridging these levels of description. We developed a general method for training model networks of spiking neurons by leveraging factors extracted from either data or firing-rate-based networks. In addition to providing a useful model-building framework, this formalism illustrates how reliable and continuously valued factors can arise from seemingly stochastic spiking. Our framework establishes procedures for embedding this property in network models with different levels of realism. The relationship between spikes and factors in such networks provides a foundation for interpreting (and subtly redefining) commonly used quantities such as firing rates.
Epigenomic (re)programming of the brain and behavior by ovarian hormones
Rhythmic changes in sex hormone levels across the ovarian cycle exert powerful effects on the brain and behavior, and confer female-specific risks for neuropsychiatric conditions. In this talk, Dr. Kundakovic will discuss the role of fluctuating ovarian hormones as a critical biological factor contributing to the increased depression and anxiety risk in women. Cycling ovarian hormones drive brain and behavioral plasticity in both humans and rodents, and the talk will focus on animal studies in Dr. Kundakovic’s lab that are revealing the molecular and receptor mechanisms that underlie this female-specific brain dynamic. She will highlight the lab’s discovery of sex hormone-driven epigenetic mechanisms, namely chromatin accessibility and 3D genome changes, that dynamically regulate neuronal gene expression and brain plasticity but may also prime the (epi)genome for psychopathology. She will then describe functional studies, including hormone replacement experiments and the overexpression of an estrous cycle stage-dependent transcription factor, which provide the causal link(s) between hormone-driven chromatin dynamics and sex-specific anxiety behavior. Dr. Kundakovic will also highlight an unconventional role that chromatin dynamics may have in regulating neuronal function across the ovarian cycle, including in sex hormone-driven X chromosome plasticity and hormonally-induced epigenetic priming. In summary, these studies provide a molecular framework to understand ovarian hormone-driven brain plasticity and increased female risk for anxiety and depression, opening new avenues for sex- and gender-informed treatments for brain disorders.
The Neural Race Reduction: Dynamics of nonlinear representation learning in deep architectures
What is the relationship between task, network architecture, and population activity in nonlinear deep networks? I will describe the Gated Deep Linear Network framework, which schematizes how pathways of information flow impact learning dynamics within an architecture. Because of the gating, these networks can compute nonlinear functions of their input. We derive an exact reduction and, for certain cases, exact solutions to the dynamics of learning. The reduction takes the form of a neural race with an implicit bias towards shared representations, which then govern the model’s ability to systematically generalize, multi-task, and transfer. We show how appropriate network architectures can help factorize and abstract knowledge. Together, these results begin to shed light on the links between architecture, learning dynamics and network performance.
From spikes to factors: understanding large-scale neural computations
It is widely accepted that human cognition is the product of spiking neurons. Yet even for basic cognitive functions, such as the ability to make decisions or prepare and execute a voluntary movement, the gap between spikes and computation is vast. Only for very simple circuits and reflexes can one explain computations neuron-by-neuron and spike-by-spike. This approach becomes infeasible when neurons are numerous the flow of information is recurrent. To understand computation, one thus requires appropriate abstractions. An increasingly common abstraction is the neural ‘factor’. Factors are central to many explanations in systems neuroscience. Factors provide a framework for describing computational mechanism, and offer a bridge between data and concrete models. Yet there remains some discomfort with this abstraction, and with any attempt to provide mechanistic explanations above that of spikes, neurons, cell-types, and other comfortingly concrete entities. I will explain why, for many networks of spiking neurons, factors are not only a well-defined abstraction, but are critical to understanding computation mechanistically. Indeed, factors are as real as other abstractions we now accept: pressure, temperature, conductance, and even the action potential itself. I use recent empirical results to illustrate how factor-based hypotheses have become essential to the forming and testing of scientific hypotheses. I will also show how embracing factor-level descriptions affords remarkable power when decoding neural activity for neural engineering purposes.
From cells to systems: multiscale studies of the epileptic brain
It is increasingly recognized that epilepsy affects human brain organization across multiple scales, ranging from cellular alterations in specific regions towards macroscale network imbalances. My talk will overview an emerging paradigm that integrates cellular, neuroimaging, and network modelling approaches to faithful characterize the extent of structural and functional alterations in the common epilepsies. I will also discuss how multiscale framework can help to derive clinically useful biomarkers of dysfunction, and how these methods may guide surgical planning and prognostics.
Autopoiesis and Enaction in the Game of Life
Enaction plays a central role in the broader fabric of so-called 4E (embodied, embedded, extended, enactive) cognition. Although the origin of the enactive approach is widely dated to the 1991 publication of the book "The Embodied Mind" by Varela, Thompson and Rosch, many of the central ideas trace to much earlier work. Over 40 years ago, the Chilean biologists Humberto Maturana and Francisco Varela put forward the notion of autopoiesis as a way to understand living systems and the phenomena that they generate, including cognition. Varela and others subsequently extended this framework to an enactive approach that places biological autonomy at the foundation of situated and embodied behavior and cognition. I will describe an attempt to place Maturana and Varela's original ideas on a firmer foundation by studying them within the context of a toy model universe, John Conway's Game of Life (GoL) cellular automata. This work has both pedagogical and theoretical goals. Simple concrete models provide an excellent vehicle for introducing some of the core concepts of autopoiesis and enaction and explaining how these concepts fit together into a broader whole. In addition, a careful analysis of such toy models can hone our intuitions about these concepts, probe their strengths and weaknesses, and move the entire enterprise in the direction of a more mathematically rigorous theory. In particular, I will identify the primitive processes that can occur in GoL, show how these can be linked together into mutually-supporting networks that underlie persistent bounded entities, map the responses of such entities to environmental perturbations, and investigate the paths of mutual perturbation that these entities and their environments can undergo.
Verb metaphors are processed as analogies
Metaphor is a pervasive phenomenon in language and cognition. To date, the vast majority of psycholinguistic research on metaphor has focused on noun-noun metaphors of the form An X is a Y (e.g., My job is a jail). Yet there is evidence that verb metaphor (e.g., I sailed through my exams) is more common. Despite this, comparatively little work has examined how verb metaphors are processed. In this talk, I will propose a novel account for verb metaphor comprehension: verb metaphors are understood in the same way that analogies are—as comparisons processed via structure-mapping. I will discuss the predictions that arise from applying the analogical framework to verb metaphor and present a series of experiments showing that verb metaphoric extension is consistent with those predictions.
A specialized role for entorhinal attractor dynamics in combining path integration and landmarks during navigation
During navigation, animals estimate their position using path integration and landmarks. In a series of two studies, we used virtual reality and electrophysiology to dissect how these inputs combine to generate the brain’s spatial representations. In the first study (Campbell et al., 2018), we focused on the medial entorhinal cortex (MEC) and its set of navigationally-relevant cell types, including grid cells, border cells, and speed cells. We discovered that attractor dynamics could explain an array of initially puzzling MEC responses to virtual reality manipulations. This theoretical framework successfully predicted both MEC grid cell responses to additional virtual reality manipulations, as well as mouse behavior in a virtual path integration task. In the second study (Campbell*, Attinger* et al., 2021), we asked whether these principles generalize to other navigationally-relevant brain regions. We used Neuropixels probes to record thousands of neurons from MEC, primary visual cortex (V1), and retrosplenial cortex (RSC). In contrast to the prevailing view that “everything is everywhere all at once,” we identified a unique population of MEC neurons, overlapping with grid cells, that became active with striking spatial periodicity while head-fixed mice ran on a treadmill in darkness. These neurons exhibited unique cue-integration properties compared to other MEC, V1, or RSC neurons: they remapped more readily in response to conflicts between path integration and landmarks; they coded position prospectively as opposed to retrospectively; they upweighted path integration relative to landmarks in conditions of low visual contrast; and as a population, they exhibited a lower-dimensional activity structure. Based on these results, our current view is that MEC attractor dynamics play a privileged role in resolving conflicts between path integration and landmarks during navigation. Future work should include carefully designed causal manipulations to rigorously test this idea, and expand the theoretical framework to incorporate notions of uncertainty and optimality.
Analogical inference in mathematics: from epistemology to the classroom (and back)
In this presentation, we will discuss adaptations of historical examples of mathematical research to bring out some of the intuitive judgments that accompany the working practice of mathematicians when reasoning by analogy. The main epistemological claim that we will aim to illustrate is that a central part of mathematical training consists in developing a quasi-perceptual capacity to distinguish superficial from deep analogies. We think of this capacity as an instance of Hadamard’s (1954) discriminating faculty of the mathematical mind, whereby one is led to distinguish between mere “hookings” (77) and “relay-results” (80): on the one hand, suggestions or ‘hints’, useful to raise questions but not to back up conjectures; on the other, more significant discoveries, which can be used as an evidentiary source in further mathematical inquiry. In the second part of the presentation, we will present some recent applications of this epistemological framework to mathematics education projects for middle and high schools in Italy.
Applying Structural Alignment theory to Early Verb Learning
Learning verbs is difficult and critical to learning one's native language. Children appear to benefit from seeing multiple events and comparing them to each other, and structural alignment theory provides a good theoretical framework to guide research into how preschool children may be comparing events as they learn new verbs. The talk will include 6 studies of early verb learning that make use of eye-tracking procedures as well as other behavioral (pointing) procedures, and that test key predictions from SA theory including the prediction that seeing similar examples before more varied examples helps observers learn how to compare (progressive alignment) and the prediction that when events have very low alignability with other events, that is one cue that the events should be ignored. Whether or how statistical learning may also be at work will be considered.
When to stop immune checkpoint inhibitor for malignant melanoma? Challenges in emulating target trials
Observational data have become a popular source of evidence for causal effects when no randomized controlled trial exists, or to supplement information provided by those. In practice, a wide range of designs and analytical choices exist, and one recent approach relies on the target trial emulation framework. This framework is particularly well suited to mimic what could be obtained in a specific randomized controlled trial, while avoiding time-related selection biases. In this abstract, we present how this framework could be useful to emulate trials in malignant melanoma, and the challenges faced when planning such a study using longitudinal observational data from a cohort study. More specifically, two questions are envisaged: duration of immune checkpoint inhibitors, and trials comparing treatment strategies for BRAF V600-mutant patients (targeted therapy as 1st line, followed by immunotherapy as 2nd line, vs. immunotherapy as 2nd line followed by targeted therapy as 1st line). Using data from 1027 participants to the MELBASE cohort, we detail the results for the emulation of a trial where immune checkpoint inhibitor would be stopped at 6 months vs. continued, in patients in response or with stable disease.
Implications of Vector-space models of Relational Concepts
Vector-space models are used frequently to compare similarity and dimensionality among entity concepts. What happens when we apply these models to relational concepts? What is the evidence that such models do apply to relational concepts? If we use such a model, then one implication is that maximizing surface feature variation should improve relational concept learning. For example, in STEM instruction, the effectiveness of teaching by analogy is often limited by students’ focus on superficial features of the source and target exemplars. However, in contrast to the prediction of the vector-space computational model, the strategy of progressive alignment (moving from perceptually similar to different targets) has been suggested to address this issue (Gentner & Hoyos, 2017), and human behavioral evidence has shown benefits from progressive alignment. Here I will present some preliminary data that supports the computational approach. Participants were explicitly instructed to match stimuli based on relations while perceptual similarity of stimuli varied parametrically. We found that lower perceptual similarity reduced accurate relational matching. This finding demonstrates that perceptual similarity may interfere with relational judgements, but also hints at why progressive alignment maybe effective. These are preliminary, exploratory data and I to hope receive feedback on the framework and to start a discussion in a group on the utility of vector-space models for relational concepts in general.
Extracting computational mechanisms from neural data using low-rank RNNs
An influential theory in systems neuroscience suggests that brain function can be understood through low-dimensional dynamics [Vyas et al 2020]. However, a challenge in this framework is that a single computational task may involve a range of dynamic processes. To understand which processes are at play in the brain, it is important to use data on neural activity to constrain models. In this study, we present a method for extracting low-dimensional dynamics from data using low-rank recurrent neural networks (lrRNNs), a highly expressive and understandable type of model [Mastrogiuseppe & Ostojic 2018, Dubreuil, Valente et al. 2022]. We first test our approach using synthetic data created from full-rank RNNs that have been trained on various brain tasks. We find that lrRNNs fitted to neural activity allow us to identify the collective computational processes and make new predictions for inactivations in the original RNNs. We then apply our method to data recorded from the prefrontal cortex of primates during a context-dependent decision-making task. Our approach enables us to assign computational roles to the different latent variables and provides a mechanistic model of the recorded dynamics, which can be used to perform in silico experiments like inactivations and provide testable predictions.
A framework for detecting noncoding rare variant associations of large-scale whole-genome sequencing studies
Versatile treadmill system for measuring locomotion and neural activity in head-fixed mice
Here, we present a protocol for using a versatile treadmill system to measure locomotion and neural activity at high temporal resolution in head-fixed mice. We first describe the assembly of the treadmill system. We then detail surgical implantation of the headplate on the mouse skull, followed by habituation of mice to locomotion on the treadmill system. The system is compact, movable, and simple to synchronize with other data streams, making it ideal for monitoring brain activity in diverse behavioral frameworks. https://dx.doi.org/10.1016/j.xpro.2022.101701
Neural networks in the replica-mean field limits
In this talk, we propose to decipher the activity of neural networks via a “multiply and conquer” approach. This approach considers limit networks made of infinitely many replicas with the same basic neural structure. The key point is that these so-called replica-mean-field networks are in fact simplified, tractable versions of neural networks that retain important features of the finite network structure of interest. The finite size of neuronal populations and synaptic interactions is a core determinant of neural dynamics, being responsible for non-zero correlation in the spiking activity and for finite transition rates between metastable neural states. Theoretically, we develop our replica framework by expanding on ideas from the theory of communication networks rather than from statistical physics to establish Poissonian mean-field limits for spiking networks. Computationally, we leverage our original replica approach to characterize the stationary spiking activity of various network models via reduction to tractable functional equations. We conclude by discussing perspectives about how to use our replica framework to probe nontrivial regimes of spiking correlations and transition rates between metastable neural states.
The future of neuropsychology will be open, transdiagnostic, and FAIR - why it matters and how we can get there
Cognitive neuroscience has witnessed great progress since modern neuroimaging embraced an open science framework, with the adoption of shared principles (Wilkinson et al., 2016), standards (Gorgolewski et al., 2016), and ontologies (Poldrack et al., 2011), as well as practices of meta-analysis (Yarkoni et al., 2011; Dockès et al., 2020) and data sharing (Gorgolewski et al., 2015). However, while functional neuroimaging data provide correlational maps between cognitive functions and activated brain regions, its usefulness in determining causal link between specific brain regions and given behaviors or functions is disputed (Weber et al., 2010; Siddiqiet al 2022). On the contrary, neuropsychological data enable causal inference, highlighting critical neural substrates and opening a unique window into the inner workings of the brain (Price, 2018). Unfortunately, the adoption of Open Science practices in clinical settings is hampered by several ethical, technical, economic, and political barriers, and as a result, open platforms enabling access to and sharing clinical (meta)data are scarce (e.g., Larivière et al., 2021). We are working with clinicians, neuroimagers, and software developers to develop an open source platform for the storage, sharing, synthesis and meta-analysis of human clinical data to the service of the clinical and cognitive neuroscience community so that the future of neuropsychology can be transdiagnostic, open, and FAIR. We call it neurocausal (https://neurocausal.github.io).
Universal function approximation in balanced spiking networks through convex-concave boundary composition
The spike-threshold nonlinearity is a fundamental, yet enigmatic, component of biological computation — despite its role in many theories, it has evaded definitive characterisation. Indeed, much classic work has attempted to limit the focus on spiking by smoothing over the spike threshold or by approximating spiking dynamics with firing-rate dynamics. Here, we take a novel perspective that captures the full potential of spike-based computation. Based on previous studies of the geometry of efficient spike-coding networks, we consider a population of neurons with low-rank connectivity, allowing us to cast each neuron’s threshold as a boundary in a space of population modes, or latent variables. Each neuron divides this latent space into subthreshold and suprathreshold areas. We then demonstrate how a network of inhibitory (I) neurons forms a convex, attracting boundary in the latent coding space, and a network of excitatory (E) neurons forms a concave, repellant boundary. Finally, we show how the combination of the two yields stable dynamics at the crossing of the E and I boundaries, and can be mapped onto a constrained optimization problem. The resultant EI networks are balanced, inhibition-stabilized, and exhibit asynchronous irregular activity, thereby closely resembling cortical networks of the brain. Moreover, we demonstrate how such networks can be tuned to either suppress or amplify noise, and how the composition of inhibitory convex and excitatory concave boundaries can result in universal function approximation. Our work puts forth a new theory of biologically-plausible computation in balanced spiking networks, and could serve as a novel framework for scalable and interpretable computation with spikes.
Nonlinear computations in spiking neural networks through multiplicative synapses
The brain efficiently performs nonlinear computations through its intricate networks of spiking neurons, but how this is done remains elusive. While recurrent spiking networks implementing linear computations can be directly derived and easily understood (e.g., in the spike coding network (SCN) framework), the connectivity required for nonlinear computations can be harder to interpret, as they require additional non-linearities (e.g., dendritic or synaptic) weighted through supervised training. Here we extend the SCN framework to directly implement any polynomial dynamical system. This results in networks requiring multiplicative synapses, which we term the multiplicative spike coding network (mSCN). We demonstrate how the required connectivity for several nonlinear dynamical systems can be directly derived and implemented in mSCNs, without training. We also show how to precisely carry out higher-order polynomials with coupled networks that use only pair-wise multiplicative synapses, and provide expected numbers of connections for each synapse type. Overall, our work provides an alternative method for implementing nonlinear computations in spiking neural networks, while keeping all the attractive features of standard SCNs such as robustness, irregular and sparse firing, and interpretable connectivity. Finally, we discuss the biological plausibility of mSCNs, and how the high accuracy and robustness of the approach may be of interest for neuromorphic computing.
Signal in the Noise: models of inter-trial and inter-subject neural variability
The ability to record large neural populations—hundreds to thousands of cells simultaneously—is a defining feature of modern systems neuroscience. Aside from improved experimental efficiency, what do these technologies fundamentally buy us? I'll argue that they provide an exciting opportunity to move beyond studying the "average" neural response. That is, by providing dense neural circuit measurements in individual subjects and moments in time, these recordings enable us to track changes across repeated behavioral trials and across experimental subjects. These two forms of variability are still poorly understood, despite their obvious importance to understanding the fidelity and flexibility of neural computations. Scientific progress on these points has been impeded by the fact that individual neurons are very noisy and unreliable. My group is investigating a number of customized statistical models to overcome this challenge. I will mention several of these models but focus particularly on a new framework for quantifying across-subject similarity in stochastic trial-by-trial neural responses. By applying this method to noisy representations in deep artificial networks and in mouse visual cortex, we reveal that the geometry of neural noise correlations is a meaningful feature of variation, which is neglected by current methods (e.g. representational similarity analysis).
Brian2CUDA: Generating Efficient CUDA Code for Spiking Neural Networks
Graphics processing units (GPUs) are widely available and have been used with great success to accelerate scientific computing in the last decade. These advances, however, are often not available to researchers interested in simulating spiking neural networks, but lacking the technical knowledge to write the necessary low-level code. Writing low-level code is not necessary when using the popular Brian simulator, which provides a framework to generate efficient CPU code from high-level model definitions in Python. Here, we present Brian2CUDA, an open-source software that extends the Brian simulator with a GPU backend. Our implementation generates efficient code for the numerical integration of neuronal states and for the propagation of synaptic events on GPUs, making use of their massively parallel arithmetic capabilities. We benchmark the performance improvements of our software for several model types and find that it can accelerate simulations by up to three orders of magnitude compared to Brian’s CPU backend. Currently, Brian2CUDA is the only package that supports Brian’s full feature set on GPUs, including arbitrary neuron and synapse models, plasticity rules, and heterogeneous delays. When comparing its performance with Brian2GeNN, another GPU-based backend for the Brian simulator with fewer features, we find that Brian2CUDA gives comparable speedups, while being typically slower for small and faster for large networks. By combining the flexibility of the Brian simulator with the simulation speed of GPUs, Brian2CUDA enables researchers to efficiently simulate spiking neural networks with minimal effort and thereby makes the advancements of GPU computing available to a larger audience of neuroscientists.
A predictive-processing account of psychosis
There has been increasing interest in the neurocomputational mechanisms underlying psychotic disorders in recent years. One promising approach is based on the theoretical framework of predictive processing, which proposes that inferences regarding the state of the world are made by combining prior beliefs with sensory signals. Delusions and hallucinations are the core symptoms of psychosis and often co-occur. Yet, different predictive-processing alterations have been proposed for these two symptom dimensions, according to which the relative weighting of prior beliefs in perceptual inference is decreased or increased, respectively. I will present recent behavioural, neuroimaging, and computational work that investigated perceptual decision-making under uncertainty and ambiguity to elucidate the changes in predictive processing that may give rise to psychotic experiences. Based on the empirical findings presented, I will provide a more nuanced predictive-processing account that suggests a common mechanism for delusions and hallucinations at low levels of the predictive-processing hierarchy, but still has the potential to reconcile apparently contradictory findings in the literature. This account may help to understand the heterogeneity of psychotic phenomenology and explain changes in symptomatology over time.
Adversarial-inspired autoencoder framework for salient sensory feature extraction
Bernstein Conference 2024
A connectome manipulation framework for the systematic and reproducible study of structure-function relationships through simulations
Bernstein Conference 2024
Correcting cortical output: a distributed learning framework for motor adaptation
Bernstein Conference 2024
A new framework for modeling innate capabilities in network with diverse types of spiking neurons: Probabilistic Skeleton
Bernstein Conference 2024
Plastic Arbor: a modern simulation framework for synaptic plasticity – from single synapses to networks of morphological neurons
Bernstein Conference 2024
Real-time detection of sharp-wave ripples with a closed-loop stimulation framework
Bernstein Conference 2024
A novel experimental framework for simultaneous measurement of excitatory and inhibitory conductances
COSYNE 2022
Multiscale Hierarchical Modeling Framework For Fully Mapping a Social Interaction
COSYNE 2022
Multiscale Hierarchical Modeling Framework For Fully Mapping a Social Interaction
COSYNE 2022
A novel experimental framework for simultaneous measurement of excitatory and inhibitory conductances
COSYNE 2022
SemiMultiPose: A Semi-supervised Multi-animal Pose Estimation Framework
COSYNE 2022
SemiMultiPose: A Semi-supervised Multi-animal Pose Estimation Framework
COSYNE 2022
Subcortical modulation of cortical dynamics for motor planning: a computational framework
COSYNE 2022
Subcortical modulation of cortical dynamics for motor planning: a computational framework
COSYNE 2022
Circuit-based framework for fine spatial scale clustering of orientation tuning in mouse V1
COSYNE 2023
Deep Neural Imputation: A Framework for Recovering Incomplete Brain Recordings
COSYNE 2023
Neuroformer: A Transformer Framework for Multimodal Neural Data Analysis
COSYNE 2023
A normative framework for balancing reward- and information-seeking behaviors in dynamic environments
COSYNE 2023
A probabilistic framework for task-aligned intra- and inter-area neural manifold estimation
COSYNE 2023
An adaptive state-space control framework for driving decision variables
COSYNE 2025
A computational framework for decoding active sensing
COSYNE 2025
Conditional Diffusion Framework for Analyzing Neural Dynamics Across Multiple Contexts
COSYNE 2025
Data-driven evaluation of interpretive framework for model-based planning
COSYNE 2025
A deep learning framework for center-periphery visual processing in mouse visual cortex
COSYNE 2025
Dual-Model Framework for Cerebellar Function: Integrating Reinforcement Learning and Adaptive Control
COSYNE 2025
FARMS: Framework for Animal and Robot Modeling and Simulation
COSYNE 2025
A connectome manipulation framework for the systematic and reproducible study of structure-function relationships through simulations
FENS Forum 2024
DeepD3 - A deep learning framework for detection of dendritic spines and dendrites
FENS Forum 2024
Enhancing hypothesis testing via interpretable machine learning frameworks
FENS Forum 2024
Membrane potential up/down-states enhance synaptic transmission in the human neocortex – A framework for memory consolidation during slow wave sleep
FENS Forum 2024
Metabolic dynamics shapes neural activity: A framework for control of epilepsy
FENS Forum 2024
Real-time detection of sharp-wave ripples with a closed-loop stimulation framework
FENS Forum 2024
Tactile perception and memory in rats and humans: A general framework across tasks and species
FENS Forum 2024