Light
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Dr. Erika Eggers
The Eggers Lab in the UArizona Departments of Physiology and Biomedical Engineering is seeking highly motivated candidates for the full-time position of Postdoctoral Research Associate I. Dr. Eggers’s NIH-funded research incorporates physiological light stimulation, electrophysiology, immunohistochemical and optogenetic approaches to identify cellular, synaptic and molecular mechanisms that underlie changes in retinal neurons in diabetes. The goal of current studies is to determine how retinal calcium and dopamine signaling are altered in multiple levels of the rod pathway during early stages of diabetes and to identify potential targets for treatment. More information on our current research interests can be found at: http://eggerslab.sites.arizona.edu/.
The SIMple microscope: Development of a fibre-based platform for accessible SIM imaging in unconventional environments
Advancements in imaging speed, depth and resolution have made structured illumination microscopy (SIM) an increasingly powerful optical sectioning (OS) and super-resolution (SR) technique, but these developments remain inaccessible to many life science researchers due to the cost, optical complexity and delicacy of these instruments. We address these limitations by redesigning the optical path using in-line fibre components that are compact, lightweight and easily assembled in a “Plug & Play” modality, without compromising imaging performance. They can be integrated into an existing widefield microscope with a minimum of optical components and alignment, making OS-SIM more accessible to researchers with less optics experience. We also demonstrate a complete SR-SIM imaging system with dimensions 300 mm × 300 mm × 450 mm. We propose to enable accessible SIM imaging by utilising its compact, lightweight and robust design to transport it where it is needed, and image in “unconventional” environments where factors such as temperature and biosafety considerations currently limit imaging experiments.
From Spiking Predictive Coding to Learning Abstract Object Representation
In a first part of the talk, I will present Predictive Coding Light (PCL), a novel unsupervised learning architecture for spiking neural networks. In contrast to conventional predictive coding approaches, which only transmit prediction errors to higher processing stages, PCL learns inhibitory lateral and top-down connectivity to suppress the most predictable spikes and passes a compressed representation of the input to higher processing stages. We show that PCL reproduces a range of biological findings and exhibits a favorable tradeoff between energy consumption and downstream classification performance on challenging benchmarks. A second part of the talk will feature our lab’s efforts to explain how infants and toddlers might learn abstract object representations without supervision. I will present deep learning models that exploit the temporal and multimodal structure of their sensory inputs to learn representations of individual objects, object categories, or abstract super-categories such as „kitchen object“ in a fully unsupervised fashion. These models offer a parsimonious account of how abstract semantic knowledge may be rooted in children's embodied first-person experiences.
Using Fast Periodic Visual Stimulation to measure cognitive function in dementia
Fast periodic visual stimulation (FPVS) has emerged as a promising tool for assessing cognitive function in individuals with dementia. This technique leverages electroencephalography (EEG) to measure brain responses to rapidly presented visual stimuli, offering a non-invasive and objective method for evaluating a range of cognitive functions. Unlike traditional cognitive assessments, FPVS does not rely on behavioural responses, making it particularly suitable for individuals with cognitive impairment. In this talk I will highlight a series of studies that have demonstrated its ability to detect subtle deficits in recognition memory, visual processing and attention in dementia patients using EEG in the lab, at home and in clinic. The method is quick, cost-effective, and scalable, utilizing widely available EEG technology. FPVS holds significant potential as a functional biomarker for early diagnosis and monitoring of dementia, paving the way for timely interventions and improved patient outcomes.
Rethinking brain mechanisms in the light of evolution
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.
Computational modelling of ocular pharmacokinetics
Pharmacokinetics in the eye is an important factor for the success of ocular drug delivery and treatment. Pharmacokinetic features determine the feasible routes of drug administration, dosing levels and intervals, and it has impact on eventual drug responses. Several physical, biochemical, and flow-related barriers limit drug exposure of anterior and posterior ocular target tissues during treatment during local (topical, subconjunctival, intravitreal) and systemic administration (intravenous, per oral). Mathematical models integrate joint impact of various barriers on ocular pharmacokinetics (PKs) thereby helping drug development. The models are useful in describing (top-down) and predicting (bottom-up) pharmacokinetics of ocular drugs. This is useful also in the design and development of new drug molecules and drug delivery systems. Furthermore, the models can be used for interspecies translation and probing of disease effects on pharmacokinetics. In this lecture, ocular pharmacokinetics and current modelling methods (noncompartmental analyses, compartmental, physiologically based, and finite element models) are introduced. Future challenges are also highlighted (e.g. intra-tissue distribution, prediction of drug responses, active transport).
Impact of High Fat Diet on Central Cardiac Circuits: When The Wanderer is Lost
Cardiac vagal motor drive originates in the brainstem's cardiac vagal motor neurons (CVNs). Despite well-established cardioinhibitory functions in health, our understanding of CVNs in disease is limited. There is a clear connection of cardiovascular regulation with metabolic and energy expenditure systems. Using high fat diet as a model, this talk will explore how metabolic dysfunction impacts the regulation of cardiac tissue through robust inhibition of CVNs. Specifically, it will present an often overlooked modality of inhibition, tonic gamma-aminobuytric acid (GABA) A-type neurotransmission using an array of techniques from single cell patch clamp electrophysiology to transgenic in vivo whole animal physiology. It also will highlight a unique interaction with the delta isoform of protein kinase C to facilitate GABA A-type receptor expression.
A Novel Neurophysiological Approach to Assessing Distractibility within the General Population
Vulnerability to distraction varies across the general population and significantly affects one’s capacity to stay focused on and successfully complete the task at hand, whether at school, on the road, or at work. In this talk, I will begin by discussing how distractibility is typically assessed in the literature and introduce our innovative ERP approach to measuring it. Since distractibility is a cardinal symptom of ADHD, I will introduce its most widely used paper-and-pencil screening tool for the general population as external validation. Following that, I will present the Load Theory of Attention and explain how we used perceptual load to test the reliability of our neural marker of distractibility. Finally, I will highlight potential future applications of this marker in clinical and educational settings.
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.
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.
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.”
Clonal analysis at single cell level helps to understand neural crest development
Recent research on the neural crest has revealed the multipotency and plasticity of nerve-associated Schwann cell precursors, which can differentiate into diverse cell types, including parasympathetic neurons, neuroendocrine cells, and mesenchymal stem cells. These findings challenge the traditional view of peripheral nerves, highlighting their role as niches for migratory progenitor cells that contribute to tissue formation and regeneration.
Optogenetic control of Nodal signaling patterns
Embryos issue instructions to their cells in the form of patterns of signaling activity. Within these patterns, the distribution of signaling in time and space directs the fate of embryonic cells. Tools to perturb developmental signaling with high resolution in space and time can help reveal how these patterns are decoded to make appropriate fate decisions. In this talk, I will present new optogenetic reagents and an experimental pipeline for creating designer Nodal signaling patterns in live zebrafish embryos. Our improved optoNodal reagents eliminate dark activity and improve response kinetics, without sacrificing dynamic range. We adapted an ultra-widefield microscopy platform for parallel light patterning in up to 36 embryos and demonstrated precise spatial control over Nodal signaling activity and downstream gene expression. Using this system, we demonstrate that patterned Nodal activation can initiate specification and internalization movements of endodermal precursors. Further, we used patterned illumination to generate synthetic signaling patterns in Nodal signaling mutants, rescuing several characteristic developmental defects. This study establishes an experimental toolkit for systematic exploration of Nodal signaling patterns in live embryos.
Light-gated membrane channels: Discovery and creation of diversity, principles from protein structure, and cell-function access to biology
Neural mechanisms governing the learning and execution of avoidance behavior
The nervous system orchestrates adaptive behaviors by intricately coordinating responses to internal cues and environmental stimuli. This involves integrating sensory input, managing competing motivational states, and drawing on past experiences to anticipate future outcomes. While traditional models attribute this complexity to interactions between the mesocorticolimbic system and hypothalamic centers, the specific nodes of integration have remained elusive. Recent research, including our own, sheds light on the midline thalamus's overlooked role in this process. We propose that the midline thalamus integrates internal states with memory and emotional signals to guide adaptive behaviors. Our investigations into midline thalamic neuronal circuits have provided crucial insights into the neural mechanisms behind flexibility and adaptability. Understanding these processes is essential for deciphering human behavior and conditions marked by impaired motivation and emotional processing. Our research aims to contribute to this understanding, paving the way for targeted interventions and therapies to address such impairments.
How to tell if someone is hiding something from you? An overview of the scientific basis of deception and concealed information detection
I my talk I will give an overview of recent research on deception and concealed information detection. I will start with a short introduction on the problems and shortcomings of traditional deception detection tools and why those still prevail in many recent approaches (e.g., in AI-based deception detection). I want to argue for the importance of more fundamental deception research and give some examples for insights gained therefrom. In the second part of the talk, I will introduce the Concealed Information Test (CIT), a promising paradigm for research and applied contexts to investigate whether someone actually recognizes information that they do not want to reveal. The CIT is based on solid scientific theory and produces large effects sizes in laboratory studies with a number of different measures (e.g., behavioral, psychophysiological, and neural measures). I will highlight some challenges a forensic application of the CIT still faces and how scientific research could assist in overcoming those.
Modelling the fruit fly brain and body
Through recent advances in microscopy, we now have an unprecedented view of the brain and body of the fruit fly Drosophila melanogaster. We now know the connectivity at single neuron resolution across the whole brain. How do we translate these new measurements into a deeper understanding of how the brain processes sensory information and produces behavior? I will describe two computational efforts to model the brain and the body of the fruit fly. First, I will describe a new modeling method which makes highly accurate predictions of neural activity in the fly visual system as measured in the living brain, using only measurements of its connectivity from a dead brain [1], joint work with Jakob Macke. Second, I will describe a whole body physics simulation of the fruit fly which can accurately reproduce its locomotion behaviors, both flight and walking [2], joint work with Google DeepMind.
The multi-phase plasticity supporting winner effect
Aggression is an innate behavior across animal species. It is essential for competing for food, defending territory, securing mates, and protecting families and oneself. Since initiating an attack requires no explicit learning, the neural circuit underlying aggression is believed to be genetically and developmentally hardwired. Despite being innate, aggression is highly plastic. It is influenced by a wide variety of experiences, particularly winning and losing previous encounters. Numerous studies have shown that winning leads to an increased tendency to fight while losing leads to flight in future encounters. In the talk, I will present our recent findings regarding the neural mechanisms underlying the behavioral changes caused by winning.
Exploring Lifespan Memory Development and Intervention Strategies for Memory Decline through a Unified Model-Based Assessment
Understanding and potentially reversing memory decline necessitates a comprehensive examination of memory's evolution throughout life. Traditional memory assessments, however, suffer from a lack of comparability across different age groups due to the diverse nature of the tests employed. Addressing this gap, our study introduces a novel, ACT-R model-based memory assessment designed to provide a consistent metric for evaluating memory function across a lifespan, from 5 to 85-year-olds. This approach allows for direct comparison across various tasks and materials tailored to specific age groups. Our findings reveal a pronounced U-shaped trajectory of long-term memory function, with performance at age 5 mirroring those observed in elderly individuals with impairments, highlighting critical periods of memory development and decline. Leveraging this unified assessment method, we further investigate the therapeutic potential of rs-fMRI-guided TBS targeting area 8AV in individuals with early-onset Alzheimer’s Disease—a region implicated in memory deterioration and mood disturbances in this population. This research not only advances our understanding of memory's lifespan dynamics but also opens new avenues for targeted interventions in Alzheimer’s Disease, marking a significant step forward in the quest to mitigate memory decay.
There’s more to timing than time: P-centers, beat bins and groove in musical microrhythm
How does the dynamic shape of a sound affect its perceived microtiming? In the TIME project, we studied basic aspects of musical microrhythm, exploring both stimulus features and the participants’ enculturated expertise via perception experiments, observational studies of how musicians produce particular microrhythms, and ethnographic studies of musicians’ descriptions of microrhythm. Collectively, we show that altering the microstructure of a sound (“what” the sound is) changes its perceived temporal location (“when” it occurs). Specifically, there are systematic effects of core acoustic factors (duration, attack) on perceived timing. Microrhythmic features in longer and more complex sounds can also give rise to different perceptions of the same sound. Our results shed light on conflicting results regarding the effect of microtiming on the “grooviness” of a rhythm.
Modeling human brain development and disease: the role of primary cilia
Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.
Roles of inhibition in stabilizing and shaping the response of cortical networks
Inhibition has long been thought to stabilize the activity of cortical networks at low rates, and to shape significantly their response to sensory inputs. In this talk, I will describe three recent collaborative projects that shed light on these issues. (1) I will show how optogenetic excitation of inhibition neurons is consistent with cortex being inhibition stabilized even in the absence of sensory inputs, and how this data can constrain the coupling strengths of E-I cortical network models. (2) Recent analysis of the effects of optogenetic excitation of pyramidal cells in V1 of mice and monkeys shows that in some cases this optogenetic input reshuffles the firing rates of neurons of the network, leaving the distribution of rates unaffected. I will show how this surprising effect can be reproduced in sufficiently strongly coupled E-I networks. (3) Another puzzle has been to understand the respective roles of different inhibitory subtypes in network stabilization. Recent data reveal a novel, state dependent, paradoxical effect of weakening AMPAR mediated synaptic currents onto SST cells. Mathematical analysis of a network model with multiple inhibitory cell types shows that this effect tells us in which conditions SST cells are required for network stabilization.
Executive functions in the brain of deaf individuals – sensory and language effects
Executive functions are cognitive processes that allow us to plan, monitor and execute our goals. Using fMRI, we investigated how early deafness influences crossmodal plasticity and the organisation of executive functions in the adult human brain. Results from a range of visual executive function tasks (working memory, task switching, planning, inhibition) show that deaf individuals specifically recruit superior temporal “auditory” regions during task switching. Neural activity in auditory regions predicts behavioural performance during task switching in deaf individuals, highlighting the functional relevance of the observed cortical reorganisation. Furthermore, language grammatical skills were correlated with the level of activation and functional connectivity of fronto-parietal networks. Together, these findings show the interplay between sensory and language experience in the organisation of executive processing in the brain.
Ganzflicker: Using light-induced hallucinations to predict risk factors of psychosis
Rhythmic flashing light, or “Ganzflicker”, can elicit altered states of consciousness and hallucinations, bringing your mind’s eye out into the real world. What do you experience if you have a super mind’s eye, or none at all? In this talk, I will discuss how Ganzflicker has been used to simulate psychedelic experiences, how it can help us predict symptoms of psychosis, and even tap into the neural basis of hallucinations.
Maintaining Plasticity in Neural Networks
Nonstationarity presents a variety of challenges for machine learning systems. One surprising pathology which can arise in nonstationary learning problems is plasticity loss, whereby making progress on new learning objectives becomes more difficult as training progresses. Networks which are unable to adapt in response to changes in their environment experience plateaus or even declines in performance in highly non-stationary domains such as reinforcement learning, where the learner must quickly adapt to new information even after hundreds of millions of optimization steps. The loss of plasticity manifests in a cluster of related empirical phenomena which have been identified by a number of recent works, including the primacy bias, implicit under-parameterization, rank collapse, and capacity loss. While this phenomenon is widely observed, it is still not fully understood. This talk will present exciting recent results which shed light on the mechanisms driving the loss of plasticity in a variety of learning problems and survey methods to maintain network plasticity in non-stationary tasks, with a particular focus on deep reinforcement learning.
Impact of personality profiles on emotion regulation efficiency: insights on experience, expressivity and physiological arousal
People are confronted every day with internal or external stimuli that can elicit emotions. In order to avoid negative ones, or to pursue individual aims, emotions are often regulated. The available emotion regulation strategies have been previously described as efficient or inefficient, but many studies highlighted that the strategies’ efficiency may be influenced by some different aspects such as personality. In this project, the efficiency of several strategies (e.g., reappraisal, suppression, distraction, …) has been studied according to personality profiles, by using the Big Five personality model and the Maladaptive Personality Trait Model. Moreover, the strategies’ efficiency has been tested according to the main emotional responses, namely experience, expressivity and physiological arousal. Results mainly highlighted the differential impact of strategies on individuals and a slight impact of personality. An important factor seems however to be the emotion parameter we are considering, potentially revealing a complex interplay between strategy, personality, and the considered emotion response. Based on these outcomes, further clinical aspects and recommendations will be also discussed.
Learning produces a hippocampal cognitive map in the form of an orthogonalized state machine
Cognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. Here, we employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different versions of linear tracks in virtual reality. The results provide a detailed view of the formation of a cognitive map in the hippocampus. Throughout learning, both the animal behavior and hippocampal neural activity progressed through multiple intermediate stages, gradually revealing improved task representation that mirrored improved behavioral efficiency. The learning process led to progressive decorrelations in initially similar hippocampal neural activity within and across tracks, ultimately resulting in orthogonalized representations resembling a state machine capturing the inherent struture of the task. We show that a Hidden Markov Model (HMM) and a biologically plausible recurrent neural network trained using Hebbian learning can both capture core aspects of the learning dynamics and the orthogonalized representational structure in neural activity. In contrast, we show that gradient-based learning of sequence models such as Long Short-Term Memory networks (LSTMs) and Transformers do not naturally produce such orthogonalized representations. We further demonstrate that mice exhibited adaptive behavior in novel task settings, with neural activity reflecting flexible deployment of the state machine. These findings shed light on the mathematical form of cognitive maps, the learning rules that sculpt them, and the algorithms that promote adaptive behavior in animals. The work thus charts a course toward a deeper understanding of biological intelligence and offers insights toward developing more robust learning algorithms in artificial intelligence.
Conversations with Caves? Understanding the role of visual psychological phenomena in Upper Palaeolithic cave art making
How central were psychological features deriving from our visual systems to the early evolution of human visual culture? Art making emerged deep in our evolutionary history, with the earliest art appearing over 100,000 years ago as geometric patterns etched on fragments of ochre and shell, and figurative representations of prey animals flourishing in the Upper Palaeolithic (c. 40,000 – 15,000 years ago). The latter reflects a complex visual process; the ability to represent something that exists in the real world as a flat, two-dimensional image. In this presentation, I argue that pareidolia – the psychological phenomenon of seeing meaningful forms in random patterns, such as perceiving faces in clouds – was a fundamental process that facilitated the emergence of figurative representation. The influence of pareidolia has often been anecdotally observed in Upper Palaeolithic art examples, particularly cave art where the topographic features of cave wall were incorporated into animal depictions. Using novel virtual reality (VR) light simulations, I tested three hypotheses relating to pareidolia in the caves of Upper Palaeolithic cave art in the caves of Las Monedas and La Pasiega (Cantabria, Spain). To evaluate this further, I also developed an interdisciplinary VR eye-tracking experiment, where participants were immersed in virtual caves based on the cave of El Castillo (Cantabria, Spain). Together, these case studies suggest that pareidolia was an intrinsic part of artist-cave interactions (‘conversations’) that influenced the form and placement of figurative depictions in the cave. This has broader implications for conceiving of the role of visual psychological phenomena in the emergence and development of figurative art in the Palaeolithic.
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.
Using Adversarial Collaboration to Harness Collective Intelligence
There are many mysteries in the universe. One of the most significant, often considered the final frontier in science, is understanding how our subjective experience, or consciousness, emerges from the collective action of neurons in biological systems. While substantial progress has been made over the past decades, a unified and widely accepted explanation of the neural mechanisms underpinning consciousness remains elusive. The field is rife with theories that frequently provide contradictory explanations of the phenomenon. To accelerate progress, we have adopted a new model of science: adversarial collaboration in team science. Our goal is to test theories of consciousness in an adversarial setting. Adversarial collaboration offers a unique way to bolster creativity and rigor in scientific research by merging the expertise of teams with diverse viewpoints. Ideally, we aim to harness collective intelligence, embracing various perspectives, to expedite the uncovering of scientific truths. In this talk, I will highlight the effectiveness (and challenges) of this approach using selected case studies, showcasing its potential to counter biases, challenge traditional viewpoints, and foster innovative thought. Through the joint design of experiments, teams incorporate a competitive aspect, ensuring comprehensive exploration of problems. This method underscores the importance of structured conflict and diversity in propelling scientific advancement and innovation.
Connectome-based models of neurodegenerative disease
Neurodegenerative diseases involve accumulation of aberrant proteins in the brain, leading to brain damage and progressive cognitive and behavioral dysfunction. Many gaps exist in our understanding of how these diseases initiate and how they progress through the brain. However, evidence has accumulated supporting the hypothesis that aberrant proteins can be transported using the brain’s intrinsic network architecture — in other words, using the brain’s natural communication pathways. This theory forms the basis of connectome-based computational models, which combine real human data and theoretical disease mechanisms to simulate the progression of neurodegenerative diseases through the brain. In this talk, I will first review work leading to the development of connectome-based models, and work from my lab and others that have used these models to test hypothetical modes of disease progression. Second, I will discuss the future and potential of connectome-based models to achieve clinically useful individual-level predictions, as well as to generate novel biological insights into disease progression. Along the way, I will highlight recent work by my lab and others that is already moving the needle toward these lofty goals.
Mathematical and computational modelling of ocular hemodynamics: from theory to applications
Changes in ocular hemodynamics may be indicative of pathological conditions in the eye (e.g. glaucoma, age-related macular degeneration), but also elsewhere in the body (e.g. systemic hypertension, diabetes, neurodegenerative disorders). Thanks to its transparent fluids and structures that allow the light to go through, the eye offers a unique window on the circulation from large to small vessels, and from arteries to veins. Deciphering the causes that lead to changes in ocular hemodynamics in a specific individual could help prevent vision loss as well as aid in the diagnosis and management of diseases beyond the eye. In this talk, we will discuss how mathematical and computational modelling can help in this regard. We will focus on two main factors, namely blood pressure (BP), which drives the blood flow through the vessels, and intraocular pressure (IOP), which compresses the vessels and may impede the flow. Mechanism-driven models translates fundamental principles of physics and physiology into computable equations that allow for identification of cause-to-effect relationships among interplaying factors (e.g. BP, IOP, blood flow). While invaluable for causality, mechanism-driven models are often based on simplifying assumptions to make them tractable for analysis and simulation; however, this often brings into question their relevance beyond theoretical explorations. Data-driven models offer a natural remedy to address these short-comings. Data-driven methods may be supervised (based on labelled training data) or unsupervised (clustering and other data analytics) and they include models based on statistics, machine learning, deep learning and neural networks. Data-driven models naturally thrive on large datasets, making them scalable to a plethora of applications. While invaluable for scalability, data-driven models are often perceived as black- boxes, as their outcomes are difficult to explain in terms of fundamental principles of physics and physiology and this limits the delivery of actionable insights. The combination of mechanism-driven and data-driven models allows us to harness the advantages of both, as mechanism-driven models excel at interpretability but suffer from a lack of scalability, while data-driven models are excellent at scale but suffer in terms of generalizability and insights for hypothesis generation. This combined, integrative approach represents the pillar of the interdisciplinary approach to data science that will be discussed in this talk, with application to ocular hemodynamics and specific examples in glaucoma research.
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.
Neuroinflammation in Epilepsy: what have we learned from human brain tissue specimens ?
Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum of genetic and acquired forms of focal epilepsies. Dissecting the cellular and molecular mediators of the pathological immune responses and their convergent and divergent mechanisms, is a major requisite for delineating their role in the establishment of epileptogenic networks. The role of small regulatory molecules involved in the regulation of specific pro- and anti-inflammatory pathways and the crosstalk between neuroinflammation and oxidative stress will be addressed. The observations supporting the activation of both innate and adaptive immune responses in human focal epilepsy will be discussed and elaborated, highlighting specific inflammatory pathways as potential targets for antiepileptic, disease-modifying therapeutic strategies.
Enhancing Qualitative Coding with Large Language Models: Potential and Challenges
Qualitative coding is the process of categorizing and labeling raw data to identify themes, patterns, and concepts within qualitative research. This process requires significant time, reflection, and discussion, often characterized by inherent subjectivity and uncertainty. Here, we explore the possibility to leverage large language models (LLM) to enhance the process and assist researchers with qualitative coding. LLMs, trained on extensive human-generated text, possess an architecture that renders them capable of understanding the broader context of a conversation or text. This allows them to extract patterns and meaning effectively, making them particularly useful for the accurate extraction and coding of relevant themes. In our current approach, we employed the chatGPT 3.5 Turbo API, integrating it into the qualitative coding process for data from the SWISS100 study, specifically focusing on data derived from centenarians' experiences during the Covid-19 pandemic, as well as a systematic centenarian literature review. We provide several instances illustrating how our approach can assist researchers with extracting and coding relevant themes. With data from human coders on hand, we highlight points of convergence and divergence between AI and human thematic coding in the context of these data. Moving forward, our goal is to enhance the prototype and integrate it within an LLM designed for local storage and operation (LLaMa). Our initial findings highlight the potential of AI-enhanced qualitative coding, yet they also pinpoint areas requiring attention. Based on these observations, we formulate tentative recommendations for the optimal integration of LLMs in qualitative coding research. Further evaluations using varied datasets and comparisons among different LLMs will shed more light on the question of whether and how to integrate these models into this domain.
NII Methods (journal club): NeuroQuery, comprehensive meta-analysis of human brain mapping
We will discuss a recent paper by Taylor et al. (2023): https://www.sciencedirect.com/science/article/pii/S1053811923002896. They discuss the merits of highlighting results instead of hiding them; that is, clearly marking which voxels and clusters pass a given significance threshold, but still highlighting sub-threshold results, with opacity proportional to the strength of the effect. They use this to illustrate how there in fact may be more agreement between researchers than previously thought, using the NARPS dataset as an example. By adopting a continuous, "highlighted" approach, it becomes clear that the majority of effects are in the same location and that the effect size is in the same direction, compared to an approach that only permits rejecting or not rejecting the null hypothesis. We will also talk about the implications of this approach for creating figures, detecting artifacts, and aiding reproducibility.
Diffuse coupling in the brain - A temperature dial for computation
The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of largescale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.
Brain Connectivity Workshop
Founded in 2002, the Brain Connectivity Workshop (BCW) is an annual international meeting for in-depth discussions of all aspects of brain connectivity research. By bringing together experts in computational neuroscience, neuroscience methodology and experimental neuroscience, it aims to improve the understanding of the relationship between anatomical connectivity, brain dynamics and cognitive function. These workshops have a unique format, featuring only short presentations followed by intense discussion. This year’s workshop is co-organised by Wellcome, putting the spotlight on brain connectivity in mental health disorders. We look forward to having you join us for this exciting, thought-provoking and inclusive event.
Anticipating behaviour through working memory (BACN Early Career Prize Lecture 2023)
Working memory is about the past but for the future. Adopting such a future-focused perspective shifts the narrative of working memory as a limited-capacity storage system to working memory as an anticipatory buffer that helps us prepare for potential and sequential upcoming behaviour. In my talk, I will present a series of our recent studies that have started to reveal emerging principles of a working memory that looks forward – highlighting, amongst others, how selective attention plays a vital role in prioritising internal contents for behaviour, and the bi-directional links between visual working memory and action. These studies show how studying the dynamics of working memory, selective attention, and action together paves way for an integrated understanding of how mind serves behaviour.
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.
Light-driven dopamine release in the adult and developing retina
Freeze or flee ? New insights from rodent models of autism
Individuals afflicted with certain types of autism spectrum disorder often exhibit impaired cognitive function alongside enhanced emotional symptoms and mood lability. However, current understanding of the pathogenesis of autism and intellectual disabilities is based primarily on studies in the hippocampus and cortex, brain areas involved in cognitive function. But, these disorders are also associated with strong emotional symptoms, which are likely to involve changes in the amygdala and other brain areas. In this talk I will highlight these issues by presenting analyses in rat models of ASD/ID lacking Nlgn3 and Frm1 (causing Fragile X Syndrome). In addition to identifying new circuit and cellular alterations underlying divergent patterns of fear expression, these findings also suggest novel therapeutic strategies.
From pecking order to ketamine - neural mechanism of social and emotional behavior
Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.
From pecking order to ketamine - neural mechanism of social and emotional behavior
Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.
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.
Walk the talk: concrete actions to promote diversity in neuroscience in Latin America
Building upon the webinar "What are the main barriers to succeed in brain sciences in Latin America?" (February 2021) and the paper "Addressing the opportunity gap in the Latin American neuroscience community" (Silva, A., Iyer, K., Cirulli, F. et al. Nat Neurosci August 2022), this ALBA-IBRO Webinar is the next chapter in our journey towards fostering inclusivity and diversity in neuroscience in Latin America. The webinar is designed to go beyond theoretical discussions and provide tangible solutions. We will showcase 3-4 best practice case studies, shining a spotlight on real-life actions and campaigns implemented at the institutional level, be it within government bodies, universities, or other organisations. Our goal is to empower neuroscientists across Latin America by equipping them with practical knowledge they can apply in their own institutions and countries.
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
How AI is advancing Clinical Neuropsychology and Cognitive Neuroscience
This talk aims to highlight the immense potential of Artificial Intelligence (AI) in advancing the field of psychology and cognitive neuroscience. Through the integration of machine learning algorithms, big data analytics, and neuroimaging techniques, AI has the potential to revolutionize the way we study human cognition and brain characteristics. In this talk, I will highlight our latest scientific advancements in utilizing AI to gain deeper insights into variations in cognitive performance across the lifespan and along the continuum from healthy to pathological functioning. The presentation will showcase cutting-edge examples of AI-driven applications, such as deep learning for automated scoring of neuropsychological tests, natural language processing to characeterize semantic coherence of patients with psychosis, and other application to diagnose and treat psychiatric and neurological disorders. Furthermore, the talk will address the challenges and ethical considerations associated with using AI in psychological research, such as data privacy, bias, and interpretability. Finally, the talk will discuss future directions and opportunities for further advancements in this dynamic field.
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.
Dynamic endocrine modulation of the nervous system
Sex hormones are powerful neuromodulators of learning and memory. In rodents and nonhuman primates estrogen and progesterone influence the central nervous system across a range of spatiotemporal scales. Yet, their influence on the structural and functional architecture of the human brain is largely unknown. Here, I highlight findings from a series of dense-sampling neuroimaging studies from my laboratory designed to probe the dynamic interplay between the nervous and endocrine systems. Individuals underwent brain imaging and venipuncture every 12-24 hours for 30 consecutive days. These procedures were carried out under freely cycling conditions and again under a pharmacological regimen that chronically suppresses sex hormone production. First, resting state fMRI evidence suggests that transient increases in estrogen drive robust increases in functional connectivity across the brain. Time-lagged methods from dynamical systems analysis further reveals that these transient changes in estrogen enhance within-network integration (i.e. global efficiency) in several large-scale brain networks, particularly Default Mode and Dorsal Attention Networks. Next, using high-resolution hippocampal subfield imaging, we found that intrinsic hormone fluctuations and exogenous hormone manipulations can rapidly and dynamically shape medial temporal lobe morphology. Together, these findings suggest that neuroendocrine factors influence the brain over short and protracted timescales.
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.
Retinal and brain circuits underlying the effects of light on behavior
Learning to see stuff
Humans are very good at visually recognizing materials and inferring their properties. Without touching surfaces, we can usually tell what they would feel like, and we enjoy vivid visual intuitions about how they typically behave. This is impressive because the retinal image that the visual system receives as input is the result of complex interactions between many physical processes. Somehow the brain has to disentangle these different factors. I will present some recent work in which we show that an unsupervised neural network trained on images of surfaces spontaneously learns to disentangle reflectance, lighting and shape. However, the disentanglement is not perfect, and we find that as a result the network not only predicts the broad successes of human gloss perception, but also the specific pattern of errors that humans exhibit on an image-by-image basis. I will argue this has important implications for thinking about appearance and vision more broadly.
Integrative Neuromodulation: from biomarker identification to optimizing neuromodulation
Why do we make decisions impulsively blinded in an emotionally rash moment? Or caught in the same repetitive suboptimal loop, avoiding fears or rushing headlong towards illusory rewards? These cognitive constructs underlying self-control and compulsive behaviours and their influence by emotion or incentives are relevant dimensionally across healthy individuals and hijacked across disorders of addiction, compulsivity and mood. My lab focuses on identifying theory-driven modifiable biomarkers focusing on these cognitive constructs with the ultimate goal to optimize and develop novel means of neuromodulation. Here I will provide a few examples of my group’s recent work to illustrate this approach. I describe a series of recent studies on intracranial physiology and acute stimulation focusing on risk taking and emotional processing. This talk highlights the subthalamic nucleus, a common target for deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder. I further describe recent translational work in non-invasive neuromodulation. Together these examples illustrate the approach of the lab highlighting modifiable biomarkers and optimizing neuromodulation.
Cognitive supports for analogical reasoning in rational number understanding
In cognitive development, learning more than the input provides is a central challenge. This challenge is especially evident in learning the meaning of numbers. Integers – and the quantities they denote – are potentially infinite, as are the fractional values between every integer. Yet children’s experiences of numbers are necessarily finite. Analogy is a powerful learning mechanism for children to learn novel, abstract concepts from only limited input. However, retrieving proper analogy requires cognitive supports. In this talk, I seek to propose and examine number lines as a mathematical schema of the number system to facilitate both the development of rational number understanding and analogical reasoning. To examine these hypotheses, I will present a series of educational intervention studies with third-to-fifth graders. Results showed that a short, unsupervised intervention of spatial alignment between integers and fractions on number lines produced broad and durable gains in fractional magnitudes. Additionally, training on conceptual knowledge of fractions – that fractions denote magnitude and can be placed on number lines – facilitates explicit analogical reasoning. Together, these studies indicate that analogies can play an important role in rational number learning with the help of number lines as schemas. These studies shed light on helpful practices in STEM education curricula and instructions.
Interplay between circuits that mediate spontaneous retinal waves and early light responses during retinal development
Understanding Machine Learning via Exactly Solvable Statistical Physics Models
The affinity between statistical physics and machine learning has a long history. I will describe the main lines of this long-lasting friendship in the context of current theoretical challenges and open questions about deep learning. Theoretical physics often proceeds in terms of solvable synthetic models, I will describe the related line of work on solvable models of simple feed-forward neural networks. I will highlight a path forward to capture the subtle interplay between the structure of the data, the architecture of the network, and the optimization algorithms commonly used for learning.
Unique features of oxygen delivery to the mammalian retina
Like all neural tissue, the retina has a high metabolic demand, and requires a constant supply of oxygen. Second and third order neurons are supplied by the retinal circulation, whose characteristics are similar to brain circulation. However, the photoreceptor region, which occupies half of the retinal thickness, is avascular, and relies on diffusion of oxygen from the choroidal circulation, whose properties are very different, as well as the retinal circulation. By fitting diffusion models to oxygen measurements made with oxygen microelectrodes, it is possible to understand the relative roles of the two circulations under normal conditions of light and darkness, and what happens if the retina is detached or the retinal circulation is occluded. Most of this work has been done in vivo in rat, cat, and monkey, but recent work in the isolated mouse retina will also be discussed.
Private oxytocin supply and its receptors in the hypothalamus for social avoidance learning
Many animals live in complex social groups. To survive, it is essential to know who to avoid and who to interact. Although naïve mice are naturally attracted to any adult conspecifics, a single defeat experience could elicit social avoidance towards the aggressor for days. The neural mechanisms underlying the behavior switch from social approach to social avoidance remains incompletely understood. Here, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin receptor (OXTR) expressing cells in the anterior subdivision of ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance learning. After defeat, aVMHvlOXTR cells drastically increase their responses to aggressor cues. This response change is functionally important as optogenetic activation of aVMHvlOXTR cells elicits time-locked social avoidance towards a benign social target whereas inactivating the cells suppresses defeat-induced social avoidance. Furthermore, OXTR in the aVMHvl is itself essential for the behavior change. Knocking out OXTR in the aVMHvl or antagonizing the receptor during defeat, but not during post-defeat social interaction, impairs defeat-induced social avoidance. aVMHvlOXTR receives its private supply of oxytocin from SOROXT cells. SOROXT is highly activated by the noxious somatosensory inputs associated with defeat. Oxytocin released from SOROXT depolarizes aVMHvlOXTR cells and facilitates their synaptic potentiation, and hence, increases aVMHvlOXTR cell responses to aggressor cues. Ablating SOROXT cells impairs defeat-induced social avoidance learning whereas activating the cells promotes social avoidance after a subthreshold defeat experience. Altogether, our study reveals an essential role of SOROXT-aVMHvlOXTR circuit in defeat-induced social learning and highlights the importance of hypothalamic oxytocin system in social ranking and its plasticity.
An insect vision-based flight control model with a plastic efference copy
COSYNE 2022
An insect vision-based flight control model with a plastic efference copy
COSYNE 2022
Moving bar of light evokes vectorial spatial selectivity in hippocampal place cells
COSYNE 2022
Moving bar of light evokes vectorial spatial selectivity in hippocampal place cells
COSYNE 2022
Exploring a neural circuit for estimating ambient wind direction in flight
COSYNE 2023
A computational map of flight control in Drosophila melanogaster
COSYNE 2025
Amygdalar regulation of memory engrams in the hippocampus: Spotlight on sex differences
FENS Forum 2024
Artificial light at night disrupts daily rhythms in blood-brain barrier permeability
FENS Forum 2024
Brain-wide in vivo dopamine dynamics revealed with next generation dLights
FENS Forum 2024
BrainTrawler Lite: Navigating through a multi-scale multi-modal gene transcriptomics data resource through a lightweight user interface
FENS Forum 2024
Combining electrophysiology, tissue clearing, and light sheet microscopy for an integrated approach towards brain circuit understanding
FENS Forum 2024
Decoding transcriptional regulation in response to sunlight in vertebrates: Circadian clocks and beyond
FENS Forum 2024
Deep cortical layers encode sustained changes in light conditions in freely moving mice
FENS Forum 2024
Dense reconstruction of mammalian brain tissue with light microscopy
FENS Forum 2024
Dense synapse-level reconstruction of brain tissue with super-resolution light microscopy
FENS Forum 2024
Differences in neural activation patterns within the action observation network during imitation of point-light displays and fully visible manipulative actions
FENS Forum 2024
Digital light processing of 3D structures for improved connectivity of hiPSC-derived neurons
FENS Forum 2024
Dissection of a neuronal integrator circuit through correlated light and electron microscopy in larval zebrafish. Part 1: Functional imaging and ultrastructure in the same animal
FENS Forum 2024
Dissection of a neuronal integrator circuit through correlated light and electron microscopy in larval zebrafish. Part 2: Correlating functional analyses and ultrastructure across different animals
FENS Forum 2024
The early light experience alters Stage II retinal waves via dopamine-modulated pathway in the developing mouse retina
FENS Forum 2024
Environment for precise EEG electrode localization on data from low-cost structured light projector cameras or MRI head scans
FENS Forum 2024
Facilitating memory consolidation through light exercise: The role of the coeruleo-hippocampal dopaminergic pathway
FENS Forum 2024
Green light exerts antinociceptive and anxiolytic effects via visual-somatosensory circuits
FENS Forum 2024
Impact of Alzheimer’s disease on non-visual light perception, suprachiasmatic nucleus connectivity, and sleep regulation
FENS Forum 2024
The influence of light exposure on Parkinson's disease progression
FENS Forum 2024
InLOV: Optogenetics for light-controlled insulin signaling modulates neuronal plasticity and cerebellar-driven behavior
FENS Forum 2024
Light-dependent cAMP modulation in astrocytes triggers synaptic potentiation, hemodynamic responses, and behavioural changes in mice: Role in Huntington’s disease
FENS Forum 2024
Light modulates central oxytocin and social memory via a retina-to-supraoptic nucleus circuit
FENS Forum 2024
Loss of neuroprotection in Alzheimer’s disease: Shedding light on BDNF receptor cleavage and its mirroring in extracellular vesicles
FENS Forum 2024
Macro2mesoSPIM light-sheet system and tissue-specific clearing strategies enable unobstructed 3D organ and organism interrogation
FENS Forum 2024
Mapping of neuronal populations with light-sheet fluorescence microscopy
FENS Forum 2024
Microcircuits in the marmoset prefrontal cortex: A large volume correlative light-electron microscopy study
FENS Forum 2024
NeuroDeblur: A novel software for fast deconvolution of large light-sheet, confocal, or bright-field microscopy stacks
FENS Forum 2024
A novel mouse model of light-mediated recanalization after stroke
FENS Forum 2024
Oblique light sheet tracking microscopy for whole brain functional imaging in a freely swimming zebrafish larva
FENS Forum 2024
pathoDISCO-HE: Light sheet microscopy and fluorescent labelling of glioblastoma multiforme for 3D virtual H&E imaging and improved pathohistological evaluation
FENS Forum 2024
Photopharmacology in the spotlight: Spatially selective adenosinergic modulation of hippocampal excitability in the pursuit of therapeutic innovation in temporal lobe epilepsy
FENS Forum 2024
Plasma neurofilament light chain in Chinese children with later-onset SMA under treatment with nusinersen
FENS Forum 2024
The pupillary light reflex drives evoked responses in retinal ganglion cells
FENS Forum 2024
The pupillary light response is mediated by direct retino-iridal projections together with iris intrinsic contraction in lampreys
FENS Forum 2024