The Gatsby Unit invites applications for a postdoctoral training fellowship under Dr Agostina Palmigiano, focussed on developing theoretical approaches to investigate the mechanisms underlying sensory, motor or cognitive computations. You will be responsible for the primary execution of the project (with opportunities for co-supervision of students), presentation of results at conferences and seminars, and publication in suitable media. This post is initially funded for 2 years with the possibility of a one-year extension at the end of the period. For detailed information on the role and how to apply, please visit www.ucl.ac.uk/gatsby/vacancies under 'Research Fellow (Palmigiano group)'. Agostina will also be at COSYNE 2024 between 29 February and 5 March. Please get in touch to set up informal chats with her if interested!

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.

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.

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.

This webinar on learning and memory features three experts—Nicolas Brunel, Ashok Litwin-Kumar, and Julijana Gjorgieva—who present theoretical and computational approaches to understanding how neural circuits acquire and store information across different scales. Brunel discusses calcium-based plasticity and how standard “Hebbian-like” plasticity rules inferred from in vitro or in vivo datasets constrain synaptic dynamics, aligning with classical observations (e.g., STDP) and explaining how synaptic connectivity shapes memory. Litwin-Kumar explores insights from the fruit fly connectome, emphasizing how the mushroom body—a key site for associative learning—implements a high-dimensional, random representation of sensory features. Convergent dopaminergic inputs gate plasticity, reflecting a high-dimensional “critic” that refines behavior. Feedback loops within the mushroom body further reveal sophisticated interactions between learning signals and action selection. Gjorgieva examines how activity-dependent plasticity rules shape circuitry from the subcellular (e.g., synaptic clustering on dendrites) to the cortical network level. She demonstrates how spontaneous activity during development, Hebbian competition, and inhibitory-excitatory balance collectively establish connectivity motifs responsible for key computations such as response normalization.

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.

The visual system faces a dual challenge. On the one hand, features of the natural visual environment should be stably processed - irrespective of ongoing wiring changes, representational drift, and behavior. On the other hand, eye, head, and body motion require a robust integration of pose and gaze shifts in visual computations for a stable perception of the world. We address these dimensions of stable visual processing by studying the circuit mechanism of long-term representational stability, focusing on the role of plasticity, network structure, experience, and behavioral state while recording large-scale neuronal activity with miniature two-photon microscopy.

Remembering events in the past is crucial to intelligent behaviour. Flexible memory retrieval, beyond simple recall, requires a model of how events relate to one another. Two key brain systems are implicated in this process: the hippocampal episodic memory (EM) system and the prefrontal working memory (WM) system. While an understanding of the hippocampal system, from computation to algorithm and representation, is emerging, less is understood about how the prefrontal WM system can give rise to flexible computations beyond simple memory retrieval, and even less is understood about how the two systems relate to each other. Here we develop a mathematical theory relating the algorithms and representations of EM and WM by showing a duality between storing memories in synapses versus neural activity. In doing so, we develop a formal theory of the algorithm and representation of prefrontal WM as structured, and controllable, neural subspaces (termed activity slots). By building models using this formalism, we elucidate the differences, similarities, and trade-offs between the hippocampal and prefrontal algorithms. Lastly, we show that several prefrontal representations in tasks ranging from list learning to cue dependent recall are unified as controllable activity slots. Our results unify frontal and temporal representations of memory, and offer a new basis for understanding the prefrontal representation of WM

When experts are immersed in a task, a natural assumption is that their brains prioritize task-related activity. Accordingly, most efforts to understand neural activity during well-learned tasks focus on cognitive computations and task-related movements. Surprisingly, we observed that during decision-making, the cortex-wide activity of multiple cell types is dominated by movements, especially “uninstructed movements”, that are spontaneously expressed. These observations argue that animals execute expert decisions while performing richly varied, uninstructed movements that profoundly shape neural activity. To understand the relationship between these movements and decision-making, we examined the movements more closely. We tested whether the magnitude or the timing of the movements was correlated with decision-making performance. To do this, we partitioned movements into two groups: task-aligned movements that were well predicted by task events (such as the onset of the sensory stimulus or choice) and task independent movement (TIM) that occurred independently of task events. TIM had a reliable, inverse correlation with performance in head-restrained mice and freely moving rats. This hinted that the timing of spontaneous movements could indicate periods of disengagement. To confirm this, we compared TIM to the latent behavioral states recovered by a hidden Markov model with Bernoulli generalized linear model observations (GLM-HMM) and found these, again, to be inversely correlated. Finally, we examined the impact of these behavioral states on neural activity. Surprisingly, we found that the same movement impacts neural activity more strongly when animals are disengaged. An intriguing possibility is that these larger movement signals disrupt cognitive computations, leading to poor decision-making performance. Taken together, these observations argue that movements and cognitionare closely intertwined, even during expert decision-making.

CCN is an annual conference that serves as a forum for cognitive science, neuroscience, and artificial intelligence researchers dedicated to understanding the computations that underlie complex behavior.

Neural computations are currently conceptualised using two separate approaches: sorting neurons into functional sub-populations or examining distributed collective dynamics. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from recurrent networks trained on neuroscience tasks, we show that the collective dynamics and sub-population structure play fundamentally complementary roles. Although various tasks can be implemented in networks with fully random population structure, we found that flexible input–output mappings instead require a non-random population structure that can be described in terms of multiple sub-populations. Our analyses revealed that such a sub-population organisation enables flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the collective dynamics.

The critical brain hypothesis states that the brain can benefit from operating close to a second-order phase transition. While it has been shown that several computational aspects of sensory information processing (e.g., sensitivity to input) are optimal in this regime, it is still unclear whether these computational benefits of criticality can be leveraged by neural systems performing behaviorally relevant computations. To address this question, we investigate signatures of criticality in networks optimized to perform efficient encoding. We consider a network of leaky integrate-and-fire neurons with synaptic transmission delays and input noise. Previously, it was shown that the performance of such networks varies non-monotonically with the noise amplitude. Interestingly, we find that in the vicinity of the optimal noise level for efficient coding, the network dynamics exhibits signatures of criticality, namely, the distribution of avalanche sizes follows a power law. When the noise amplitude is too low or too high for efficient coding, the network appears either super-critical or sub-critical, respectively. This result suggests that two influential, and previously disparate theories of neural processing optimization—efficient coding, and criticality—may be intimately related

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.

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.

Synaptic plasticity is known to be a key player in the brain’s life-long learning abilities. However, due to experimental limitations, the nature of the local changes at individual synapses and their link with emerging network-level computations remain unclear. I will present a numerical, meta-learning approach to deduce plasticity rules from either neuronal activity data and/or prior knowledge about the network's computation. I will first show how to recover known rules, given a human-designed loss function in rate networks, or directly from data, using an adversarial approach. Then I will present how to scale-up this approach to recurrent spiking networks using simulation-based inference.

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.

Memory is a key component of biological neural systems that enables the retention of information over a huge range of temporal scales, ranging from hundreds of milliseconds up to years. While Hebbian plasticity is believed to play a pivotal role in biological memory, it has so far been analyzed mostly in the context of pattern completion and unsupervised learning. Here, we propose that Hebbian plasticity is fundamental for computations in biological neural systems. We introduce a novel spiking neural network (SNN) architecture that is enriched by Hebbian synaptic plasticity. We experimentally show that our memory-equipped SNN model outperforms state-of-the-art deep learning mechanisms in a sequential pattern-memorization task, as well as demonstrate superior out-of-distribution generalization capabilities compared to these models. We further show that our model can be successfully applied to one-shot learning and classification of handwritten characters, improving over the state-of-the-art SNN model. We also demonstrate the capability of our model to learn associations for audio to image synthesis from spoken and handwritten digits. Our SNN model further presents a novel solution to a variety of cognitive question answering tasks from a standard benchmark, achieving comparable performance to both memory-augmented ANN and SNN-based state-of-the-art solutions to this problem. Finally we demonstrate that our model is able to learn from rewards on an episodic reinforcement learning task and attain near-optimal strategy on a memory-based card game. Hence, our results show that Hebbian enrichment renders spiking neural networks surprisingly versatile in terms of their computational as well as learning capabilities. Since local Hebbian plasticity can easily be implemented in neuromorphic hardware, this also suggests that powerful cognitive neuromorphic systems can be build based on this principle.

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).

Neural computations are currently investigated using two separate approaches: sorting neurons into functional subpopulations or examining the low-dimensional dynamics of collective activity. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from networks trained on neuroscience tasks, here we show that the dimensionality of the dynamics and subpopulation structure play fundamentally com- plementary roles. Although various tasks can be implemented by increasing the dimensionality in networks with fully random population structure, flexible input–output mappings instead require a non-random population structure that can be described in terms of multiple subpopulations. Our analyses revealed that such a subpopulation structure enables flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the collective dynamics. Our results lead to task-specific predictions for the structure of neural selectivity, for inactivation experiments and for the implication of different neurons in multi-tasking.

A central goal in neuroscience is to understand how orchestrated computations in the brain arise from the properties of single neurons and networks of such neurons. Answering this question requires theoretical advances that shine light into the ‘black box’ of representations in neural circuits. In this talk, we will demonstrate theoretical approaches that help describe how cognitive and behavioral task implementations emerge from the structure in neural populations and from biologically plausible neural networks. First, we will introduce an analytic theory that connects geometric structures that arise from neural responses (i.e., neural manifolds) to the neural population’s efficiency in implementing a task. In particular, this theory describes a perceptron’s capacity for linearly classifying object categories based on the underlying neural manifolds’ structural properties. Next, we will describe how such methods can, in fact, open the ‘black box’ of distributed neuronal circuits in a range of experimental neural datasets. In particular, our method overcomes the limitations of traditional dimensionality reduction techniques, as it operates directly on the high-dimensional representations, rather than relying on low-dimensionality assumptions for visualization. Furthermore, this method allows for simultaneous multi-level analysis, by measuring geometric properties in neural population data, and estimating the amount of task information embedded in the same population. These geometric frameworks are general and can be used across different brain areas and task modalities, as demonstrated in the work of ours and others, ranging from the visual cortex to parietal cortex to hippocampus, and from calcium imaging to electrophysiology to fMRI datasets. Finally, we will discuss our recent efforts to fully extend this multi-level description of neural populations, by (1) investigating how single neuron properties shape the representation geometry in early sensory areas, and by (2) understanding how task-efficient neural manifolds emerge in biologically-constrained neural networks. By extending our mathematical toolkit for analyzing representations underlying complex neuronal networks, we hope to contribute to the long-term challenge of understanding the neuronal basis of tasks and behaviors.

Flexible computation is a hallmark of intelligent behavior. Yet, little is known about how neural networks contextually reconfigure for different computations. Humans are able to perform a new task without extensive training, presumably through the composition of elementary processes that were previously learned. Cognitive scientists have long hypothesized the possibility of a compositional neural code, where complex neural computations are made up of constituent components; however, the neural substrate underlying this structure remains elusive in biological and artificial neural networks. Here we identified an algorithmic neural substrate for compositional computation through the study of multitasking artificial recurrent neural networks. Dynamical systems analyses of networks revealed learned computational strategies that mirrored the modular subtask structure of the task-set used for training. Dynamical motifs such as attractors, decision boundaries and rotations were reused across different task computations. For example, tasks that required memory of a continuous circular variable repurposed the same ring attractor. We show that dynamical motifs are implemented by clusters of units and are reused across different contexts, allowing for flexibility and generalization of previously learned computation. Lesioning these clusters resulted in modular effects on network performance: a lesion that destroyed one dynamical motif only minimally perturbed the structure of other dynamical motifs. Finally, modular dynamical motifs could be reconfigured for fast transfer learning. After slow initial learning of dynamical motifs, a subsequent faster stage of learning reconfigured motifs to perform novel tasks. This work contributes to a more fundamental understanding of compositional computation underlying flexible general intelligence in neural systems. We present a conceptual framework that establishes dynamical motifs as a fundamental unit of computation, intermediate between the neuron and the network. As more whole brain imaging studies record neural activity from multiple specialized systems simultaneously, the framework of dynamical motifs will guide questions about specialization and generalization across brain regions.

To move efficiently, animals must continuously work out their x,y,z positions with respect to real-world objects, and many animals have a pair of eyes to achieve this. How photoreceptors actively sample the eyes’ optical image disparity is not understood because this fundamental information-limiting step has not been investigated in vivo over the eyes’ whole sampling matrix. This integrative multiscale study will advance our current understanding of stereopsis from static image disparity comparison to a morphodynamic active sampling theory. It shows how photomechanical photoreceptor microsaccades enable Drosophila superresolution three-dimensional vision and proposes neural computations for accurately predicting these flies’ depth-perception dynamics, limits, and visual behaviors.

Many decisions under uncertainty entail dynamic belief updating: multiple pieces of evidence informing about the state of the environment are accumulated across time to infer the environmental state, and choose a corresponding action. Traditionally, this process has been conceptualized as a linear and perfect (i.e., without loss) integration of sensory information along purely feedforward sensory-motor pathways. Yet, natural environments can undergo hidden changes in their state, which requires a non-linear accumulation of decision evidence that strikes a tradeoff between stability and flexibility in response to change. How this adaptive computation is implemented in the brain has remained unknown. In this talk, I will present an approach that my laboratory has developed to identify evidence accumulation signatures in human behavior and neural population activity (measured with magnetoencephalography, MEG), across a large number of cortical areas. Applying this approach to data recorded during visual evidence accumulation tasks with change-points, we find that behavior and neural activity in frontal and parietal regions involved in motor planning exhibit hallmarks signatures of adaptive evidence accumulation. The same signatures of adaptive behavior and neural activity emerge naturally from simulations of a biophysically detailed model of a recurrent cortical microcircuit. The MEG data further show that decision dynamics in parietal and frontal cortex are mirrored by a selective modulation of the state of early visual cortex. This state modulation is (i) specifically expressed in the alpha frequency-band, (ii) consistent with feedback of evolving belief states from frontal cortex, (iii) dependent on the environmental volatility, and (iv) amplified by pupil-linked arousal responses during evidence accumulation. Together, our findings link normative decision computations to recurrent cortical circuit dynamics and highlight the adaptive nature of decision-related long-range feedback processing in the brain.

Reservoir computing is a promising framework to study cortical computation, as it is based on continuous, online processing and the requirements and operating principles are compatible with cortical circuit dynamics. However, the framework has issues that limit its scope as a generic model for cortical processing. The most obvious of these is that, in traditional models, learning is restricted to the output projections and takes place in a fully supervised manner. If such an output layer is interpreted at face value as downstream computation, this is biologically questionable. If it is interpreted merely as a demonstration that the network can accurately represent the information, this immediately raises the question of what would be biologically plausible mechanisms for transmitting the information represented by a reservoir and incorporating it in downstream computations. Another major issue is that we have as yet only modest insight into how the structural and dynamical features of a network influence its computational capacity, which is necessary not only for gaining an understanding of those features in biological brains, but also for exploiting reservoir computing as a neuromorphic application. In this talk, I will first demonstrate a method for quantifying the representational capacity of reservoirs without training them on tasks. Based on this technique, which allows systematic comparison of systems, I then present our recent work towards understanding the roles of heterogeneity and connectivity patterns in enhancing both the computational properties of a network and its ability to reliably transmit to downstream networks. Finally, I will give a brief taster of our current efforts to apply the reservoir computing framework to magnetic systems as an approach to neuromorphic computing.

From a workout at the gym to helping a colleague with their work, everyday we make decisions about whether we are willing to exert effort to obtain some sort of benefit. Increases in how effortful actions and cognitive processes are perceived to be has been linked to clinically severe impairments to motivation, such as apathy and fatigue, across many neurological and psychiatric conditions. However, the vast majority of neuroscience research has focused on understanding the benefits for acting, the rewards, and not on the effort required. As a result, the computational and neural mechanisms underlying how effort is processed are poorly understood. How do we compute how effortful we perceive a task to be? How does this feed into our motivation and decisions of whether to act? How are such computations implemented in the brain? and how do they change in different environments? I will present a series of studies examining these questions using novel behavioural tasks, computational modelling, fMRI, pharmacological manipulations, and testing in a range of different populations. These studies highlight how the brain represents the costs of exerting effort, and the dynamic processes underlying how our sensitivity to effort changes as a function of our goals, traits, and socio-cognitive processes. This work provides new computational frameworks for understanding and examining impaired motivation across psychiatric and neurological conditions, as well as why all of us, sometimes, can’t be bothered.

During perception the visual system integrates current sensory evidence with previously acquired knowledge of the visual world. Presumably this computation relies on internal recurrent interactions. We record populations of neurons from the primary visual cortex of cats and macaque monkeys and find evidence for adaptive internal responses to structured stimulation that change on both slow and fast timescales. In the first experiment, we present abstract images, only briefly, a protocol known to produce strong and persistent recurrent responses in the primary visual cortex. We show that repetitive presentations of a large randomized set of images leads to enhanced stimulus encoding on a timescale of minutes to hours. The enhanced encoding preserves the representational details required for image reconstruction and can be detected in post-exposure spontaneous activity. In a second experiment, we show that the encoding of natural scenes across populations of V1 neurons is improved, over a timescale of hundreds of milliseconds, with the allocation of spatial attention. Given the hierarchical organization of the visual cortex, contextual information from the higher levels of the processing hierarchy, reflecting high-level image regularities, can inform the activity in V1 through feedback. We hypothesize that these fast attentional boosts in stimulus encoding rely on recurrent computations that capitalize on the presence of high-level visual features in natural scenes. We design control images dominated by low-level features and show that, in agreement with our hypothesis, the attentional benefits in stimulus encoding vanish. We conclude that, in the visual system, powerful recurrent processes optimize neuronal responses, already at the earliest stages of cortical processing.

Timescales characterize how fast the observables change in time. In neuroscience, they can be estimated from the measured activity and can be used, for example, as a signature of the memory trace in the network. I will first discuss the inference of the timescales from the neuroscience data comprised of the short trials and introduce a new unbiased method. Then, I will apply the method to the data recorded from a local population of cortical neurons from the visual area V4. I will demonstrate that the ongoing spiking activity unfolds across at least two distinct timescales - fast and slow - and the slow timescale increases when monkeys attend to the location of the receptive field. Which models can give rise to such behavior? Random balanced networks are known for their fast timescales; thus, a change in the neurons or network properties is required to mimic the data. I will propose a set of models that can control effective timescales and demonstrate that only the model with strong recurrent interactions fits the neural data. Finally, I will discuss the timescales' relevance for behavior and cortical computations.

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We have engineered a suite of technologies to enable easy, robust access to much of the dorsal cortex of mice for optical and electrophysiological recordings. First, I will describe microsurgery robots that can programmed to perform delicate microsurgical procedures such as large bilateral craniotomies across the cortex and skull thinning in a semi-automated fashion. Next, I will describe digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (+300 days) optical access. These polymer skulls allow mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. We next engineered a widefield, miniaturized, head-mounted fluorescence microscope that is compatible with transparent polymer skull preparations. With a field of view of 8 × 10 mm2 and weighing less than 4 g, the ‘mini-mScope’ can image most of the mouse dorsal cortex with resolutions ranging from 39 to 56 µm. We used the mini-mScope to record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, social interactions and transitions from wakefulness to sleep.

Solving complex planning problems efficiently and flexibly requires reusing expensive previous computations. The brain can do this, but how? I present a new theory that addresses this question and connects planning to hitherto distinct areas within cognitive neuroscience, such as entorhinal representation of cognitive maps and cognitive control.

One of the fundamental functions of the brain is to flexibly plan and control movement production at different timescales to efficiently shape structured behaviors. I will present a model that clarifies how these complex computations could be performed in the mammalian brain, with an emphasis on the learning of an extendable library of autonomous motor motifs and the flexible stringing of these motifs in motor sequences. To build this model, we took advantage of the fact that the anatomy of the circuits involved is well known. Our results show how these architectural constraints lead to a principled understanding of how strategically positioned plastic connections located within motif-specific thalamocortical loops can interact with cortical dynamics that are shared across motifs to create an efficient form of modularity. This occurs because the cortical dynamics can be controlled by the activation of as few as one thalamic unit, which induces a low-rank perturbation of the cortical connectivity, and significantly expands the range of outputs that the network can produce. Finally, our results show that transitions between any motifs can be facilitated by a specific thalamic population that participates in preparing cortex for the execution of the next motif. Taken together, our model sheds light on the neural network mechanisms that can generate flexible sequencing of varied motor motifs.

Biological brains possess an exceptional ability to infer relevant behavioral responses to a wide range of stimuli from only a few examples. This capacity to generalize beyond the training set has been proven particularly challenging to realize in artificial systems. How neural processes enable this capacity to extrapolate to novel stimuli is a fundamental open question. A prominent but underexplored hypothesis suggests that generalization is facilitated by a low-dimensional organization of collective neural activity, yet evidence for the underlying neural mechanisms remains wanting. Combining network modeling, theory and neural data analysis, we tested this hypothesis in the framework of flexible timing tasks, which rely on the interplay between inputs and recurrent dynamics. We first trained recurrent neural networks on a set of timing tasks while minimizing the dimensionality of neural activity by imposing low-rank constraints on the connectivity, and compared the performance and generalization capabilities with networks trained without any constraint. We then examined the trained networks, characterized the dynamical mechanisms underlying the computations, and verified their predictions in neural recordings. Our key finding is that low-dimensional dynamics strongly increases the ability to extrapolate to inputs outside of the range used in training. Critically, this capacity to generalize relies on controlling the low-dimensional dynamics by a parametric contextual input. We found that this parametric control of extrapolation was based on a mechanism where tonic inputs modulate the dynamics along non-linear manifolds in activity space while preserving their geometry. Comparisons with neural recordings in the dorsomedial frontal cortex of macaque monkeys performing flexible timing tasks confirmed the geometric and dynamical signatures of this mechanism. Altogether, our results tie together a number of previous experimental findings and suggest that the low-dimensional organization of neural dynamics plays a central role in generalizable behaviors.

To efficiently process sensory information, the brain relies on statistical regularities in the input. While generally improving the reliability of sensory estimates, this strategy also induces perceptual illusions that help reveal the underlying computational principles. Focusing on auditory and visual perception, in my talk I will describe how the brain exploits statistical regularities within and across the senses for the perception space, time and multisensory integration. In particular, I will show how results from a series of psychophysical experiments can be interpreted in the light of Bayesian Decision Theory, and I will demonstrate how such canonical computations can be implemented into simple and biologically plausible neural circuits. Finally, I will show how such principles of sensory information processing can be leveraged in virtual and augmented reality to overcome display limitations and expand human perception.

A central goal in neuroscience is to understand how orchestrated computations in the brain arise from the properties of single neurons and networks of such neurons. Answering this question requires theoretical advances that shine light into the ‘black box’ of neuronal networks. In this talk, I will demonstrate theoretical approaches that help describe how cognitive and behavioral task implementations emerge from structure in neural populations and from biologically plausible learning rules. First, I will introduce an analytic theory that connects geometric structures that arise from neural responses (i.e., neural manifolds) to the neural population’s efficiency in implementing a task. In particular, this theory describes how easy or hard it is to discriminate between object categories based on the underlying neural manifolds’ structural properties. Next, I will describe how such methods can, in fact, open the ‘black box’ of neuronal networks, by showing how we can understand a) the role of network motifs in task implementation in neural networks and b) the role of neural noise in adversarial robustness in vision and audition. Finally, I will discuss my recent efforts to develop biologically plausible learning rules for neuronal networks, inspired by recent experimental findings in synaptic plasticity. By extending our mathematical toolkit for analyzing representations and learning rules underlying complex neuronal networks, I hope to contribute toward the long-term challenge of understanding the neuronal basis of behaviors.

I am working on color vision in Drosophila, identifying behaviors that involve color vision and understanding the neural circuits supporting them (Longden 2016). I have a long-term interest in understanding how neural computations operate reliably under changing circumstances, be they external changes in the sensory context, or internal changes of state such as hunger and locomotion. On internal state-modulation of sensory processing, I have shown how hunger alters visual motion processing in blowflies (Longden et al. 2014), and identified a role for octopamine in modulating motion vision during locomotion (Longden and Krapp 2009, 2010). On responses to external cues, I have shown how one kind of uncertainty in the motion of the visual scene is resolved by the fly (Saleem, Longden et al. 2012), and I have identified novel cells for processing translation-induced optic flow (Longden et al. 2017). I like working with colleagues who use different model systems, to get at principles of neural operation that might apply in many species (Ding et al. 2016, Dyakova et al. 2015). I like work motivated by computational principles - my background is computational neuroscience, with a PhD on models of memory formation in the hippocampus (Longden and Willshaw, 2007).

The idea that perception in humans relies on some form of probabilistic computations has become very popular over the last decades. It has been extremely difficult however to characterize the extent and the nature of the probabilistic representations and operations that are manipulated by neural populations in the human cortex. Several theoretical works suggest that probabilistic representations are present from low-level sensory areas to high-level areas. According to this view, the neural dynamics implements some forms of probabilistic message passing (i.e. neural sampling, probabilistic population coding, etc.) which solves the problem of perceptual inference. Here I will present recent experimental evidence that human and non-human primate perception implements some form of message passing. I will first review findings showing probabilistic integration of sensory evidence across space and time in primate visual cortex. Second, I will show that the confidence reports in a hierarchical task reveal that uncertainty is represented both at lower and higher levels, in a way that is consistent with probabilistic message passing both from lower to higher and from higher to lower representations. Finally, I will present behavioral and neural evidence that human perception takes into account pairwise correlations in sequences of sensory samples in agreement with the message passing hypothesis, and against standard accounts such as accumulation of sensory evidence or predictive coding.

We use the olfactory system and forebrain of (adult) zebrafish as a model to analyze how relevant information is extracted from sensory inputs, how information is stored in memory circuits, and how sensory inputs inform behavior. A series of recent findings provides evidence that inhibition has not only homeostatic functions in neuronal circuits but makes highly specific, instructive contributions to behaviorally relevant computations in different brain regions. These observations imply that the connectivity among excitatory and inhibitory neurons exhibits essential higher-order structure that cannot be determined without dense network reconstructions. To analyze such connectivity we developed an approach referred to as “dynamical connectomics” that combines 2-photon calcium imaging of neuronal population activity with EM-based dense neuronal circuit reconstruction. In the olfactory bulb, this approach identified specific connectivity among co-tuned cohorts of excitatory and inhibitory neurons that can account for the decorrelation and normalization (“whitening”) of odor representations in this brain region. These results provide a mechanistic explanation for a fundamental neural computation that strictly requires specific network connectivity.

Low-dimensional population dynamics can be observed in neural activity recorded from the prefrontal cortex (PFC) of subjects performing simple cognitive tasks. Many studies have shown that recurrent neural networks (RNNs) trained on the same tasks can reproduce qualitatively these state space trajectories, and have used them as models of how neuronal dynamics implement task computations. The PFC is also viewed as a conductor that organizes the communication between cortical areas and provides contextual information. It is then not clear what is its role in solving simple cognitive tasks. Do the low-dimensional trajectories observed in the PFC really correspond to the computations that it performs? Or do they indirectly reflect the computations occurring within the cortical areas projecting to the PFC? To address these questions, we modelled cortical areas with a modular RNN and equipped it with a PFC-like cognitive system. When trained on cognitive tasks, this multi-system brain model can reproduce the low-dimensional population responses observed in neuronal activity as well as classical RNNs. Qualitatively different mechanisms can emerge from the training process when varying some details of the architecture such as the time constants. In particular, there is one class of models where it is the dynamics of the cognitive system that is implementing the task computations, and another where the cognitive system is only necessary to provide contextual information about the task rule as task performance is not impaired when preventing the system from accessing the task inputs. These constitute two different hypotheses about the causal role of the PFC in solving simple cognitive tasks, which could motivate further experiments on the brain.

Brains must integrate complex sensory information and compare to past events to generate appropriate behavioral responses. The neural circuit basis of these computations is unclear and the underlying structure unknown. Here, we mapped the comprehensive synaptic wiring diagram of the fruit fly larva brain, which contains 3,013 neurons and 544K synaptic sites. It is the most complete insect connectome to date: 1) Both brain hemispheres are reconstructed, allowing investigation of neural pathways that include contralateral axons, which we found in 37% of brain neurons. 2) All sensory neurons and descending neurons are reconstructed, allowing one to follow signals in an uninterrupted chain—from the sensory periphery, through the brain, to motor neurons in the nerve cord. We developed novel computational tools, allowing us to cluster the brain and investigate how information flows through it. We discovered that feedforward pathways from sensory to descending neurons are multilayered and highly multimodal. Robust feedback was observed at almost all levels of the brain, including descending neurons. We investigated how the brain hemispheres communicate with each other and the nerve cord, leading to identification of novel circuit motifs. This work provides the complete blueprint of a brain and a strong foundation to study the structure-function relationship of neural circuits.

Modeling neural responses to naturalistic stimuli has been instrumental in advancing our understanding of the visual system. Dominant computational modeling efforts in this direction have been deeply rooted in preconceived hypotheses. In contrast, hypothesis-neutral computational methodologies with minimal apriorism which bring neuroscience data directly to bear on the model development process are likely to be much more flexible and effective in modeling and understanding tuning properties throughout the visual system. In this study, we develop a hypothesis-neutral approach and characterize response selectivity in the human visual cortex exhaustively and systematically via response-optimized deep neural network models. First, we leverage the unprecedented scale and quality of the recently released Natural Scenes Dataset to constrain parametrized neural models of higher-order visual systems and achieve novel predictive precision, in some cases, significantly outperforming the predictive success of state-of-the-art task-optimized models. Next, we ask what kinds of functional properties emerge spontaneously in these response-optimized models? We examine trained networks through structural ( feature visualizations) as well as functional analysis (feature verbalizations) by running `virtual' fMRI experiments on large-scale probe datasets. Strikingly, despite no category-level supervision, since the models are solely optimized for brain response prediction from scratch, the units in the networks after optimization act as detectors for semantic concepts like `faces' or `words', thereby providing one of the strongest evidences for categorical selectivity in these visual areas. The observed selectivity in model neurons raises another question: are the category-selective units simply functioning as detectors for their preferred category or are they a by-product of a non-category-specific visual processing mechanism? To investigate this, we create selective deprivations in the visual diet of these response-optimized networks and study semantic selectivity in the resulting `deprived' networks, thereby also shedding light on the role of specific visual experiences in shaping neuronal tuning. Together with this new class of data-driven models and novel model interpretability techniques, our study illustrates that DNN models of visual cortex need not be conceived as obscure models with limited explanatory power, rather as powerful, unifying tools for probing the nature of representations and computations in the brain.

Behavior relies on the ability of sensory systems to infer changing properties of the environment from incoming sensory stimuli. However, the demands that detecting and adjusting to changes in the environment place on a sensory system often differ from the demands associated with performing a specific behavioral task. This necessitates neural coding strategies that can dynamically balance these conflicting needs. I will discuss our ongoing theoretical work to understand how this balance can best be achieved. We connect ideas from efficient coding and Bayesian inference to ask how sensory systems should dynamically allocate limited resources when the goal is to optimally infer changing latent states of the environment, rather than reconstruct incoming stimuli. We use these ideas to explore dynamic tradeoffs between the efficiency and speed of sensory adaptation schemes, and the downstream computations that these schemes might support. Finally, we derive families of codes that balance these competing objectives, and we demonstrate their close match to experimentally-observed neural dynamics during sensory adaptation. These results provide a unifying perspective on adaptive neural dynamics across a range of sensory systems, environments, and sensory tasks.

Neuronal computations are matched to optimally encode the sensory information that is available and relevant for the animal. However, the physical distribution of sensory information is often shaped by the animal’s own behavior. One prominent example is the encoding of optic flow fields that are generated during self-motion of the animal and will therefore depend on the type of locomotion. How evolution has matched computational resources to the behavioral constraints of an animal is not known. Here we use in vivo two photon imaging to record from a population of >3.500 local-direction selective cells. Our data show that the local direction-selective T4/T5 neurons in Drosophila form a population code that is matched to represent optic flow fields generated during translational and rotational self-motion of the fly. This coding principle for optic flow is reminiscent to the population code of local direction-selective ganglion cells in the mouse retina, where four direction-selective ganglion cells encode four different axes of self-motion encountered during walking (Sabbah et al., 2017). However, in flies we find six different subtypes of T4 and T5 cells that, at the population level, represent six axes of self-motion of the fly. The four uniformly tuned T4/T5 subtypes described previously represent a local snapshot (Maisak et al. 2013). The encoding of six types of optic flow in the fly as compared to four types of optic flow in mice might be matched to the high degrees of freedom encountered during flight. Thus, a population code for optic flow appears to be a general coding principle of visual systems, resulting from convergent evolution, but matching the individual ethological constraints of the animal.

Cortical circuits process information by rich recurrent interactions between excitatory neurons and inhibitory interneurons. One of the prime functions of interneurons is to stabilize the circuit by feedback inhibition, but the level of specificity on which inhibitory feedback operates is not fully resolved. We hypothesized that inhibitory circuits could enable separate feedback control loops for different synaptic input streams, by means of specific feedback inhibition to different neuronal compartments. To investigate this hypothesis, we adopted an optimization approach. Leveraging recent advances in training spiking network models, we optimized the connectivity and short-term plasticity of interneuron circuits for compartment-specific feedback inhibition onto pyramidal neurons. Over the course of the optimization, the interneurons diversified into two classes that resembled parvalbumin (PV) and somatostatin (SST) expressing interneurons. The resulting circuit can be understood as a neural decoder that inverts the nonlinear biophysical computations performed within the pyramidal cells. Our model provides a proof of concept for studying structure-function relations in cortical circuits by a combination of gradient-based optimization and biologically plausible phenomenological models

Neural responses are variable: even under identical experimental conditions, single neuron and population responses typically differ from trial to trial and across time. Recent work has demonstrated that this variability has predictable structure, can be modulated by sensory input and behaviour, and bears critical signatures of the underlying network dynamics and computations. However, current methods for characterising neural variability are primarily geared towards sensory coding in the laboratory: they require trials with repeatable experimental stimuli and behavioural covariates. In addition, they make strong assumptions about the parametric form of variability, rely on assumption-free but data-inefficient histogram-based approaches, or are altogether ill-suited for capturing variability modulation by covariates. Here we present a universal probabilistic spike count model that eliminates these shortcomings. Our method uses scalable Bayesian machine learning techniques to model arbitrary spike count distributions (SCDs) with flexible dependence on observed as well as latent covariates. Without requiring repeatable trials, it can flexibly capture covariate-dependent joint SCDs, and provide interpretable latent causes underlying the statistical dependencies between neurons. We apply the model to recordings from a canonical non-sensory neural population: head direction cells in the mouse. We find that variability in these cells defies a simple parametric relationship with mean spike count as assumed in standard models, its modulation by external covariates can be comparably strong to that of the mean firing rate, and slow low-dimensional latent factors explain away neural correlations. Our approach paves the way to understanding the mechanisms and computations underlying neural variability under naturalistic conditions, beyond the realm of sensory coding with repeatable stimuli.

Dendrites play a central role in neuronal computation, and many complex mechanisms shape their structure, function, and connectivity. Dendrites can undergo plastic changes during development and learning, as well as during neurodevelopmental and neurodegenerative disease. We will discuss how the molecular and electrophysiological properties of dendrites enable them to perform complex computations important for sensory-motor processing and higher cognitive function, and how these can go awry.

Perception of object motion is fundamentally multisensory, yet little is known about similarities and differences in the computations that give rise to our experience across senses. Insight can be provided by examining auditory motion processing in early blind individuals. In those who become blind early in life, the ‘visual’ motion area hMT+ responds to auditory motion. Meanwhile, the planum temporale, associated with auditory motion in sighted individuals, shows reduced selectivity for auditory motion, suggesting competition between cortical areas for functional role. According to the metamodal hypothesis of cross-modal plasticity developed by Pascual-Leone, the recruitment of hMT+ is driven by it being a metamodal structure containing “operators that execute a given function or computation regardless of sensory input modality”. Thus, the metamodal hypothesis predicts that the computations underlying auditory motion processing in early blind individuals should be analogous to visual motion processing in sighted individuals - relying on non-separable spatiotemporal filters. Inconsistent with the metamodal hypothesis, evidence suggests that the computational algorithms underlying auditory motion processing in early blind individuals fail to undergo a qualitative shift as a result of cross-modal plasticity. Auditory motion filters, in both blind and sighted subjects, are separable in space and time, suggesting that the recruitment of hMT+ to extract motion information from auditory input includes a significant modification of its normal computational operations.

In nature, sensory inputs are often highly structured, and statistical regularities of these signals can be extracted to form expectation about future sensorimotor associations, thereby optimizing behavior. One of the fundamental questions in neuroscience concerns the neural computations that underlie these probabilistic sensorimotor processing. Through a recurrent neural network (RNN) model and human psychophysics and electroencephalography (EEG), the present study investigates circuit mechanisms for processing probabilistic structures of sensory signals to guide behavior. We first constructed and trained a biophysically constrained RNN model to perform a series of probabilistic decision-making tasks similar to paradigms designed for humans. Specifically, the training environment was probabilistic such that one stimulus was more probable than the others. We show that both humans and the RNN model successfully extract information about stimulus probability and integrate this knowledge into their decisions and task strategy in a new environment. Specifically, performance of both humans and the RNN model varied with the degree to which the stimulus probability of the new environment matched the formed expectation. In both cases, this expectation effect was more prominent when the strength of sensory evidence was low, suggesting that like humans, our RNNs placed more emphasis on prior expectation (top-down signals) when the available sensory information (bottom-up signals) was limited, thereby optimizing task performance. Finally, by dissecting the trained RNN model, we demonstrate how competitive inhibition and recurrent excitation form the basis for neural circuitry optimized to perform probabilistic information processing.

Given the complex and dynamic nature of our social relationships, the human brain needs to quickly learn and adapt to new social situations. The breakdown of any of these computations could lead to social deficits, as observed in many psychiatric disorders. In this talk, I will present our recent neurocomputational and intracranial work that attempts to model both 1) how humans dynamically adapt beliefs about other people and 2) how individuals can exert influence over social others through model-based forward thinking. Lastly, I will present our findings of how impaired social computations might manifest in different disorders such as addiction, delusion, and autism. Taken together, these findings reveal the dynamic and proactive nature of human interactions as well as the clinical significance of these high-order social processes.

Not all individuals are equally competent at recognizing the faces they interact with. Revealing how the brains of different individuals support variations in this ability is a crucial step to develop an understanding of real-world human visual behaviour. In this talk, I will present findings from a large high-density EEG dataset (>100k trials of participants processing various stimulus categories) and computational approaches which aimed to characterise the brain representations behind real-world proficiency of “super-recognizers”—individuals at the top of face recognition ability spectrum. Using decoding analysis of time-resolved EEG patterns, we predicted with high precision the trial-by-trial activity of super-recognizers participants, and showed that evidence for face recognition ability variations is disseminated along early, intermediate and late brain processing steps. Computational modeling of the underlying brain activity uncovered two representational signatures supporting higher face recognition ability—i) mid-level visual & ii) semantic computations. Both components were dissociable in brain processing-time (the first around the N170, the last around the P600) and levels of computations (the first emerging from mid-level layers of visual Convolutional Neural Networks, the last from a semantic model characterising sentence descriptions of images). I will conclude by presenting ongoing analyses from a well-known case of acquired prosopagnosia (PS) using similar computational modeling of high-density EEG activity.

Detection of motion is essential for survival, but how the visual system processes moving stimuli is not fully understood. Here, based on a detailed analysis of glutamate release from bipolar cells, we outline the rules that govern the representation of object motion in the early processing stages. Our main findings are as follows: (1) Motion processing begins already at the first retinal synapse. (2) The shape and the amplitude of motion responses cannot be reliably predicted from bipolar cell responses to stationary objects. (3) Enhanced representation of novel objects - particularly in bipolar cells with transient dynamics. (4) Response amplitude in bipolar cells matches visual salience reported in humans: suddenly appearing objects > novel motion > existing motion. These findings can be explained by antagonistic interactions in the center-surround receptive field, demonstrate that despite their simple operational concepts, classical center-surround receptive fields enable sophisticated visual computations.

In human and non-human animals, conceptual knowledge is partially organized according to low-dimensional geometries that rely on brain structures and computations involved in spatial representations. Recently, two separate lines of research have investigated cognitive maps, that are associated with the hippocampal formation and are similar to world-centered representations of the environment, and image spaces, that are associated with the parietal cortex and are similar to self-centered spatial relationships. I will suggest that cognitive maps and image spaces may be two manifestations of a more general propensity of the mind to create low-dimensional internal models, and may play a role in analogical reasoning and metaphorical thinking. Finally, I will show some data suggesting that the metaphorical relationship between colors and emotions can be accounted for by the structural alignment of low-dimensional conceptual spaces.

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We have engineered a suite of technologies to enable easy, robust access to much of the dorsal cortex of mice for optical and electrophysiological recordings. First, I will describe microsurgery robots that can programmed to perform delicate microsurgical procedures such as large bilateral craniotomies across the cortex and skull thinning in a semi-automated fashion. Next, I will describe digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>300 days) optical access. These polymer skulls allow mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. We next engineered a widefield, miniaturized, head-mounted fluorescence microscope that is compatible with transparent polymer skull preparations. With a field of view of 8 × 10 mm2 and weighing less than 4 g, the ‘mini-mScope’ can image most of the mouse dorsal cortex with resolutions ranging from 39 to 56 µm. We used the mini-mScope to record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, social interactions and transitions from wakefulness to sleep.

I am interested in developing a neurally mechanistic understanding of how primate brains represent the world through its visual system and how such representations enable a remarkable set of intelligent behaviors. In this talk, I will primarily highlight aspects of my current research that focuses on dissecting the brain circuits that support core object recognition behavior (primates’ ability to categorize objects within hundreds of milliseconds) in non-human primates. On the one hand, my work empirically examines how well computational models of the primate ventral visual pathways embed knowledge of the visual brain function (e.g., Bashivan*, Kar*, DiCarlo, Science, 2019). On the other hand, my work has led to various functional and architectural insights that help improve such brain models. For instance, we have exposed the necessity of recurrent computations in primate core object recognition (Kar et al., Nature Neuroscience, 2019), one that is strikingly missing from most feedforward artificial neural network models. Specifically, we have observed that the primate ventral stream requires fast recurrent processing via ventrolateral PFC for robust core object recognition (Kar and DiCarlo, Neuron, 2021). In addition, I have been currently developing various chemogenetic strategies to causally target specific bidirectional neural circuits in the macaque brain during multiple object recognition tasks to further probe their relevance during this behavior. I plan to transform these data and insights into tangible progress in neuroscience via my collaboration with various computational groups and building improved brain models of object recognition. I hope to end the talk with a brief glimpse of some of my planned future work!

We see the last cookie in the box and think, can I take that? We reach a hand out. In the 2.1 seconds that this impulse travels through our brain, billions of neurons communicate with one another, sending blips of voltage through our sensory and motor regions. Neuroscientists call these blips “spikes.” Spikes enable us to do everything: talk, eat, run, see, plan, and decide. In The Spike, Mark Humphries takes readers on the epic journey of a spike through a single, brief reaction. In vivid language, Humphries tells the story of what happens in our brain, what we know about spikes, and what we still have left to understand about them. Drawing on decades of research in neuroscience, Humphries explores how spikes are born, how they are transmitted, and how they lead us to action. He dives into previously unanswered mysteries: Why are most neurons silent? What causes neurons to fire spikes spontaneously, without input from other neurons or the outside world? Why do most spikes fail to reach any destination? Humphries presents a new vision of the brain, one where fundamental computations are carried out by spontaneous spikes that predict what will happen in the world, helping us to perceive, decide, and react quickly enough for our survival. Traversing neuroscience’s expansive terrain, The Spike follows a single electrical response to illuminate how our extraordinary brains work.

During natural behavior animals dynamically switch between different behaviors, yet little is known about how the brain performs behavioral-switches. Navigation is a complex dynamic behavior that enables testing these kind of behavioral switches: It requires the animal to know its own allocentric (world-centered) location within the environment, while also paying attention to incoming sudden events such as obstacles or other conspecifics – and therefore the animal may need to rapidly switch from representing its own allocentric position to egocentrically representing ‘things out-there’. Here we used an ethological task where two bats flew together in a very large environment (130 meters), and had to switch between two behaviors: (i) navigation, and (ii) obstacle-avoidance during ‘cross-over’ events with the other bat. Bats increased their echolocation click-rate before a cross-over, indicating spatial attention to the other bat. Hippocampal CA1 neurons represented the bat’s own position when flying alone (allocentric place-coding); surprisingly, when meeting the other bat, neurons switched very rapidly to jointly representing the inter-bat distance × position (egocentric × allocentric coding). This switching to a neuronal representation of the other bat was correlated on a trial-by-trial basis with the attention signal, as indexed by the bat’s echolocation calls – suggesting that sensory attention is controlling these major switches in neural coding. Interestingly, we found that in place-cells, the different place-fields of the same neuron could exhibit very different tuning to inter-bat distance – creating a non-separable coding of allocentric position × egocentric distance. Together, our results suggest that attentional switches during navigation – which in bats can be measured directly based on their echolocation signals – elicit rapid dynamics of hippocampal spatial coding. More broadly, this study demonstrates that during natural behavior, when animals often switch between different behaviors, neural circuits can rapidly and flexibly switch their core computations.