Predictive processing offers a unifying view of neural computation, proposing that brains continuously anticipate sensory input and update internal models based on prediction errors. In this talk, I will present converging evidence for the computational mechanisms underlying this framework across human neuroscience and deep neural networks. I will begin with recent work showing that large-scale distributed prediction-error encoding in the human brain directly predicts how sensory representations reorganize through predictive learning. I will then turn to PredNet, a popular predictive coding inspired deep network that has been widely used to model real-world biological vision systems. Using dynamic stimuli generated with our Spatiotemporal Style Transfer algorithm, we demonstrate that PredNet relies primarily on low-level spatiotemporal structure and remains insensitive to high-level content, revealing limits in its generalization capacity. Finally, I will discuss new recurrent vision models that integrate top-down feedback connections with intrinsic neural variability, uncovering a dual mechanism for robust sensory coding in which neural variability decorrelates unit responses, while top-down feedback stabilizes network dynamics. Together, these results outline how prediction error signaling and top-down feedback pathways shape adaptive sensory processing in biological and artificial systems.

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.

Facial expressions are inherently dynamic, and our visual system is sensitive to subtle changes in their temporal sequence. However, researchers often use dynamic morphs of photographs—simplified, linear representations of motion—to study the neural correlates of dynamic face perception. To explore the brain's sensitivity to natural facial motion, we constructed a novel dynamic face database using generative neural networks, trained on a verified set of video-recorded emotional expressions. The resulting deepfakes, consciously indistinguishable from videos, enabled us to separate biological motion from photorealistic form. Results showed that conventional dynamic morphs elicit distinct responses in the brain compared to videos and photos, suggesting they violate expectations (n400) and have reduced social salience (late positive potential). This suggests that dynamic morphs misrepresent facial dynamism, resulting in misleading insights about the neural and behavioural correlates of face perception. Deepfakes and videos elicited largely similar neural responses, suggesting they could be used as a proxy for real faces in vision research, where video recordings cannot be experimentally manipulated. And yet, despite being consciously undetectable as fake, deepfakes elicited an expectation violation response in the brain. This points to a neural sensitivity to naturalistic facial motion, beyond conscious awareness. Despite some differences in neural responses, the realism and manipulability of deepfakes make them a valuable asset for research where videos are unfeasible. Using these stimuli, we proposed a novel marker for the conscious perception of naturalistic facial motion – Frontal delta activity – which was elevated for videos and deepfakes, but not for photos or dynamic morphs.

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.

Within the last decade, Deep Artificial Neural Networks (DNNs) have emerged as powerful computer vision systems that match or exceed human performance on many benchmark tasks such as image classification. But whether current DNNs are suitable computational models of the human visual system remains an open question: While DNNs have proven to be capable of predicting neural activations in primate visual cortex, psychophysical experiments have shown behavioral differences between DNNs and human subjects, as quantified by error consistency. Error consistency is typically measured by briefly presenting natural or corrupted images to human subjects and asking them to perform an n-way classification task under time pressure. But for how long should stimuli ideally be presented to guarantee a fair comparison with DNNs? Here we investigate the influence of presentation time on error consistency, to test the hypothesis that higher-level processing drives behavioral differences. We systematically vary presentation times of backward-masked stimuli from 8.3ms to 266ms and measure human performance and reaction times on natural, lowpass-filtered and noisy images. Our experiment constitutes a fine-grained analysis of human image classification under both image corruptions and time pressure, showing that even drastically time-constrained humans who are exposed to the stimuli for only two frames, i.e. 16.6ms, can still solve our 8-way classification task with success rates way above chance. We also find that human-to-human error consistency is already stable at 16.6ms.

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.

Neuroimaging has greatly extended our capacity to study the workings of the human brain. Despite the wealth of knowledge this tool has generated however, there are still critical gaps in our understanding. While tremendous progress has been made in mapping areas of the brain that are specialized for particular stimuli, or cognitive processes, we still know very little about how large-scale interactions between different cortical networks facilitate the integration of information and the execution of complex tasks. Yet even the simplest behavioral tasks are complex, requiring integration over multiple cognitive domains. Our knowledge falls short not only in understanding how this integration takes place, but also in what drives the profound variation in behavior that can be observed on almost every task, even within the typically developing (TD) population. The search for the neural underpinnings of individual differences is important not only philosophically, but also in the service of precision medicine. We approach these questions using a three-pronged approach. First, we create a battery of behavioral tasks from which we can calculate objective measures for different aspects of the behaviors of interest, with sufficient variance across the TD population. Second, using these individual differences in behavior, we identify the neural variance which explains the behavioral variance at the network level. Finally, using covert neurofeedback, we perturb the networks hypothesized to correspond to each of these components, thus directly testing their casual contribution. I will discuss our overall approach, as well as a few of the new directions we are currently pursuing.

Filmmakers and editors have empirically developed techniques to ensure the spatiotemporal continuity of a film's narration. In terms of time, editing techniques (e.g., elliptical, overlapping, or cut minimization) allow for the manipulation of the perceived duration of events as they unfold on screen. More specifically, a scene can be edited to be time compressed, expanded, or real-time in terms of its perceived duration. Despite the consistent application of these techniques in filmmaking, their perceptual outcomes have not been experimentally validated. Given that viewing a film is experienced as a precise simulation of the physical world, the use of cinematic material to examine aspects of time perception allows for experimentation with high ecological validity, while filmmakers gain more insight on how empirically developed techniques influence viewers' time percept. Here, we investigated how such time manipulation techniques of an action affect a scene's perceived duration. Specifically, we presented videos depicting different actions (e.g., a woman talking on the phone), edited according to the techniques applied for temporal manipulation and asked participants to make verbal estimations of the presented scenes' perceived durations. Analysis of data revealed that the duration of expanded scenes was significantly overestimated as compared to that of compressed and real-time scenes, as was the duration of real-time scenes as compared to that of compressed scenes. Therefore, our results validate the empirical techniques applied for the modulation of a scene's perceived duration. We also found interactions on time estimates of scene type and editing technique as a function of the characteristics and the action of the scene presented. Thus, these findings add to the discussion that the content and characteristics of a scene, along with the editing technique applied, can also modulate perceived duration. Our findings are discussed by considering current timing frameworks, as well as attentional saliency algorithms measuring the visual saliency of the presented stimuli.

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.

This presentation delves into the necessity for simplified models in the field of psychological sciences to cater to a diverse audience of practitioners. We introduce the #PsychMapping model, evaluate its merits and limitations, and discuss its place in contemporary scientific culture. The #PsychMapping model is the product of an extensive literature review, initially within the realm of sport and exercise psychology and subsequently encompassing a broader spectrum of psychological sciences. This model synthesizes the progress made in psychological sciences by categorizing variables into a framework that distinguishes between traits (e.g., body structure and personality) and states (e.g., heart rate and emotions). Furthermore, it delineates internal traits and states from the externalized self, which encompasses behaviour and performance. All three components—traits, states, and the externalized self—are in a continuous interplay with external physical, social, and circumstantial factors. Two core processes elucidate the interactions among these four primary clusters: external perception, encompassing the mechanism through which external stimuli transition into internal events, and self-regulation, which empowers individuals to become autonomous agents capable of exerting control over themselves and their actions. While the model inherently oversimplifies intricate processes, the central question remains: does its pragmatic utility outweigh its limitations, and can it serve as a valuable tool for comprehending human behaviour?

Perhaps the most impressive aspect of the way the brain enables us to act on the sensory world is its flexibility. We can make a general inference about many sensory features (rating the ripeness of mangoes or avocados) and map a single stimulus onto many choices (slicing or blending mangoes). These can be thought of as flexibly mapping many (features) to one (inference) and one (feature) to many (choices) sensory inputs to actions. Both theoretical and experimental investigations of this sort of flexible sensorimotor mapping tend to treat sensory areas as relatively static. Models typically instantiate flexibility through changing interactions (or weights) between units that encode sensory features and those that plan actions. Experimental investigations often focus on association areas involved in decision-making that show pronounced modulations by cognitive processes. I will present evidence that the flexible formatting of visual information in visual cortex can support both generalized inference and choice mapping. Our results suggest that visual cortex mediates many forms of cognitive flexibility that have traditionally been ascribed to other areas or mechanisms. Further, we find that a primary difference between visual and putative decision areas is not what information they encode, but how that information is formatted in the responses of neural populations, which is related to difference in the impact of causally manipulating different areas on behavior. This scenario allows for flexibility in the mapping between stimuli and behavior while maintaining stability in the information encoded in each area and in the mappings between groups of neurons.

This presentation delves into the necessity for simplified models in the field of psychological sciences to cater to a diverse audience of practitioners. We introduce the #PsychMapping model, evaluate its merits and limitations, and discuss its place in contemporary scientific culture. The #PsychMapping model is the product of an extensive literature review, initially within the realm of sport and exercise psychology and subsequently encompassing a broader spectrum of psychological sciences. This model synthesizes the progress made in psychological sciences by categorizing variables into a framework that distinguishes between traits (e.g., body structure and personality) and states (e.g., heart rate and emotions). Furthermore, it delineates internal traits and states from the externalized self, which encompasses behaviour and performance. All three components—traits, states, and the externalized self—are in a continuous interplay with external physical, social, and circumstantial factors. Two core processes elucidate the interactions among these four primary clusters: external perception, encompassing the mechanism through which external stimuli transition into internal events, and self-regulation, which empowers individuals to become autonomous agents capable of exerting control over themselves and their actions. While the model inherently oversimplifies intricate processes, the central question remains: does its pragmatic utility outweigh its limitations, and can it serve as a valuable tool for comprehending human behaviour?

In the current virtual journal club Dr Di Luca will present findings from a series of psychophysical investigations where he measured sensitivity and bias in the perception of the timing of stimuli. He will present how improved detection with longer sequences and biases in reporting isochrony can be accounted for by optimal statistical predictions. Among his findings was also that the timing of stimuli that occasionally deviate from a regularly paced sequence is perceptually distorted to appear more regular. Such change depends on whether the context these sequences are presented is also regular. Dr Di Luca will present a Bayesian model for the combination of dynamically updated expectations, in the form of a priori probability, with incoming sensory information. These findings contribute to the understanding of how the brain processes temporal information to shape perceptual experiences.

To form a coherent perception of the world around us, we are constantly processing and integrating sensory information from multiple modalities. In fact, when auditory and visual stimuli occur within ~100 ms of each other, individuals tend to perceive the stimuli as a single event, even though they occurred separately. In recent years, our lab, and others, have developed rat models of audiovisual temporal perception using behavioural tasks such as temporal order judgments (TOJs) and synchrony judgments (SJs). While these rodent models demonstrate metrics that are consistent with humans (e.g., perceived simultaneity, temporal acuity), we have sought to confirm whether rodents demonstrate the hallmarks of audiovisual temporal perception, such as predictable shifts in their perception based on experience and sensitivity to alterations in neurochemistry. Ultimately, our findings indicate that rats serve as an excellent model to study the neural mechanisms underlying audiovisual temporal perception, which to date remains relativity unknown. Using our validated translational audiovisual behavioural tasks, in combination with optogenetics, neuropharmacology and in vivo electrophysiology, we aim to uncover the mechanisms by which inhibitory neurotransmission and top-down circuits finely control ones’ perception. This research will significantly advance our understanding of the neuronal circuitry underlying audiovisual temporal perception, and will be the first to establish the role of interneurons in regulating the synchronized neural activity that is thought to contribute to the precise binding of audiovisual stimuli.

The last decade has seen a burgeoning interest in studying the neural and computational mechanisms that underpin social learning (learning from others). Many findings support the view that learning from other people is underpinned by the same, ‘domain-general’, mechanisms underpinning learning from non-social stimuli. Despite this, the idea that humans possess social-specific learning mechanisms - adaptive specializations moulded by natural selection to cope with the pressures of group living - persists. In this talk I explore the persistence of this idea. First, I present dissociations between social and non-social learning - patterns of data which are difficult to explain under the domain-general thesis and which therefore support the idea that we have evolved special mechanisms for social learning. Subsequently, I argue that most studies that have dissociated social and non-social learning have employed paradigms in which social information comprises a secondary, additional, source of information that can be used to supplement learning from non-social stimuli. Thus, in most extant paradigms, social and non-social learning differ both in terms of social nature (social or non-social) and status (primary or secondary). I conclude that status is an important driver of apparent differences between social and non-social learning. When we account for differences in status, we see that social and non-social learning share common (dopamine-mediated) mechanisms.

Advanced noninvasive neuroimaging methods provide valuable information on the brain function, but they have obvious pros and cons in terms of temporal and spatial resolution. Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) effect provides good spatial resolution in the order of millimeters, but has a poor temporal resolution in the order of seconds due to slow hemodynamic responses to neuronal activation, providing indirect information on neuronal activity. In contrast, electroencephalography (EEG) and magnetoencephalography (MEG) provide excellent temporal resolution in the millisecond range, but spatial information is limited to centimeter scales. Therefore, there has been a longstanding demand for noninvasive brain imaging methods capable of detecting neuronal activity at both high temporal and spatial resolution. In this talk, I will introduce a novel approach that enables Direct Imaging of Neuronal Activity (DIANA) using MRI that can dynamically image neuronal spiking activity in milliseconds precision, achieved by data acquisition scheme of rapid 2D line scan synchronized with periodically applied functional stimuli. DIANA was demonstrated through in vivo mouse brain imaging on a 9.4T animal scanner during electrical whisker-pad stimulation. DIANA with milliseconds temporal resolution had high correlations with neuronal spike activities, which could also be applied in capturing the sequential propagation of neuronal activity along the thalamocortical pathway of brain networks. In terms of the contrast mechanism, DIANA was almost unaffected by hemodynamic responses, but was subject to changes in membrane potential-associated tissue relaxation times such as T2 relaxation time. DIANA is expected to break new ground in brain science by providing an in-depth understanding of the hierarchical functional organization of the brain, including the spatiotemporal dynamics of neural networks.

The dominant theoretical framework to account for reinforcement learning in the brain is temporal difference (TD) reinforcement learning. The TD framework predicts that some neuronal elements should represent the reward prediction error (RPE), which means they signal the difference between the expected future rewards and the actual rewards. The prominence of the TD theory arises from the observation that firing properties of dopaminergic neurons in the ventral tegmental area appear similar to those of RPE model-neurons in TD learning. Previous implementations of TD learning assume a fixed temporal basis for each stimulus that might eventually predict a reward. Here we show that such a fixed temporal basis is implausible and that certain predictions of TD learning are inconsistent with experiments. We propose instead an alternative theoretical framework, coined FLEX (Flexibly Learned Errors in Expected Reward). In FLEX, feature specific representations of time are learned, allowing for neural representations of stimuli to adjust their timing and relation to rewards in an online manner. In FLEX dopamine acts as an instructive signal which helps build temporal models of the environment. FLEX is a general theoretical framework that has many possible biophysical implementations. In order to show that FLEX is a feasible approach, we present a specific biophysically plausible model which implements the principles of FLEX. We show that this implementation can account for various reinforcement learning paradigms, and that its results and predictions are consistent with a preponderance of both existing and reanalyzed experimental data.

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

Critical phenomena abound in nature, from forest fires and earthquakes to avalanches in sand and neuronal activity. Since the 2003 publication by Beggs & Plenz on neuronal avalanches, a growing body of work suggests that the brain homeostatically regulates itself to operate near a critical point where information processing is optimal. At this critical point, incoming activity is neither amplified (supercritical) nor damped (subcritical), but approximately preserved as it passes through neural networks. Departures from the critical point have been associated with conditions of poor neurological health like epilepsy, Alzheimer's disease, and depression. One complication that arises from this picture is that the critical point assumes no external input. But, biological neural networks are constantly bombarded by external input. How is then the brain able to homeostatically adapt near the critical point? We’ll see that the theory of quasicriticality, an organizing principle for brain dynamics, can account for this paradoxical situation. As external stimuli drive the cortex, quasicriticality predicts a departure from criticality while maintaining optimal properties for information transmission. We’ll see that simulations and experimental data confirm these predictions and describe new ones that could be tested soon. More importantly, we will see how this organizing principle could help in the search for biomarkers that could soon be tested in clinical studies.

During development, the complex neuronal circuitry of the brain arises from limited information contained in the genome. After the genetic code instructs the birth of neurons, the emergence of brain regions, and the formation of axon tracts, it is believed that neuronal activity plays a critical role in shaping circuits for behavior. Current AI technologies are modeled after the same principle: connections in an initial weight matrix are pruned and strengthened by activity-dependent signals until the network can sufficiently generalize a set of inputs into outputs. Here, we challenge these learning-dominated assumptions by quantifying the contribution of neuronal activity to the development of visually guided swimming behavior in larval zebrafish. Intriguingly, dark-rearing zebrafish revealed that visual experience has no effect on the emergence of the optomotor response (OMR). We then raised animals under conditions where neuronal activity was pharmacologically silenced from organogenesis onward using the sodium-channel blocker tricaine. Strikingly, after washout of the anesthetic, animals performed swim bouts and responded to visual stimuli with 75% accuracy in the OMR paradigm. After shorter periods of silenced activity OMR performance stayed above 90% accuracy, calling into question the importance and impact of classical critical periods for visual development. Detailed quantification of the emergence of functional circuit properties by brain-wide imaging experiments confirmed that neuronal circuits came ‘online’ fully tuned and without the requirement for activity-dependent plasticity. Thus, contrary to what you learned on your mother's knee, complex sensory guided behaviors can be wired up innately by activity-independent developmental mechanisms.

Visual working memory (VWM) is limited in capacity, but memorizing meaningful objects may refine this limitation. However, meaningless and meaningful stimuli usually differ perceptually and an object’s association with meaning is typically already established before the actual experiment. We applied a strict control over these potential confounds by asking observers (N=45) to actively learn associations of (initially) meaningless objects. To this end, a change detection task presented Chinese characters, which were meaningless to our observers. Subsequently, half of the characters were consistently paired with pictures of animals. Then, the initial change detection task was repeated. The results revealed enhanced VWM performance after learning, in particular for meaning-associated characters (though not quite reaching the accuracy level attained by N=20 native Chinese observers). These results thus provide direct experimental evidence that the short-term retention of objects benefits from active learning of an object’s association with meaning in long-term memory.

I describe a well-tested Python module that does automated alignment and warping of faces images, and some advantages over existing solutions. An additional tool I’ve developed does automated extraction of facial features, which can be used in a number of interesting ways. I illustrate the value of wavelet-based features with a brief description of 2 recent studies: perceptual in-painting, and the robustness of the whole-part advantage across a large stimulus set. Finally, I discuss the suitability of various deep learning models for generating stimuli to study perceptual face spaces. I believe those interested in the forensic aspects of face perception may find this talk useful.

Vector-space models are used frequently to compare similarity and dimensionality among entity concepts. What happens when we apply these models to relational concepts? What is the evidence that such models do apply to relational concepts? If we use such a model, then one implication is that maximizing surface feature variation should improve relational concept learning. For example, in STEM instruction, the effectiveness of teaching by analogy is often limited by students’ focus on superficial features of the source and target exemplars. However, in contrast to the prediction of the vector-space computational model, the strategy of progressive alignment (moving from perceptually similar to different targets) has been suggested to address this issue (Gentner & Hoyos, 2017), and human behavioral evidence has shown benefits from progressive alignment. Here I will present some preliminary data that supports the computational approach. Participants were explicitly instructed to match stimuli based on relations while perceptual similarity of stimuli varied parametrically. We found that lower perceptual similarity reduced accurate relational matching. This finding demonstrates that perceptual similarity may interfere with relational judgements, but also hints at why progressive alignment maybe effective. These are preliminary, exploratory data and I to hope receive feedback on the framework and to start a discussion in a group on the utility of vector-space models for relational concepts in general.

A signature feature of cortical circuits is the irregularity of neuronal firing, which manifests itself in the high temporal variability of spiking and the broad distribution of rates. Theoretical works have shown that this feature emerges dynamically in network models if coupling between cells is strong, i.e. if the mean number of synapses per neuron K is large and synaptic efficacy is of order 1/\sqrt{K}. However, the degree to which these models capture the mechanisms underlying neuronal firing in cortical circuits is not fully understood. Results have been derived using neuron models with current-based synapses, i.e. neglecting the dependence of synaptic current on the membrane potential, and an understanding of how irregular firing emerges in models with conductance-based synapses is still lacking. Moreover, at odds with the nonlinear responses to multiple stimuli observed in cortex, network models with strongly coupled cells respond linearly to inputs. In this talk, I will discuss the emergence of irregular firing and nonlinear response in networks of leaky integrate-and-fire neurons. First, I will show that, when synapses are conductance-based, irregular firing emerges if synaptic efficacy is of order 1/\log(K) and, unlike in current-based models, persists even under the large heterogeneity of connections which has been reported experimentally. I will then describe an analysis of neural responses as a function of coupling strength and show that, while a linear input-output relation is ubiquitous at strong coupling, nonlinear responses are prominent at moderate coupling. I will conclude by discussing experimental evidence of moderate coupling and loose balance in the mouse cortex.

Can nonhuman animals perceive the relation-between-relations? This intriguing question has been studied over the last 40 years; nonetheless, the extent to which nonhuman species can do so remains controversial. Here, I review empirical evidence suggesting that pigeons, parrots, crows, and baboons join humans in reliably acquiring and transferring relational matching-to-sample (RMTS). Many theorists consider that RMTS captures the essence of analogy, because basic to analogy is appreciating the ‘relation between relations.’ Factors affecting RMTS performance include: prior training experience, the entropy of the sample stimulus, and whether the items that serve as sample stimuli can also serve as choice stimuli.

Brains can gracefully weed out irrelevant stimuli to guide behavior. This feat is believed to rely on a progressive selection of task-relevant stimuli across the cortical hierarchy, but the specific across-area interactions enabling stimulus selection are still unclear. Here, we propose that population gating, occurring within A1 but controlled by top-down inputs from mPFC, can support across-area stimulus selection. Examining single-unit activity recorded while rats performed an auditory context-dependent task, we found that A1 encoded relevant and irrelevant stimuli along a common dimension of its neural space. Yet, the relevant stimulus encoding was enhanced along an extra dimension. In turn, mPFC encoded only the stimulus relevant to the ongoing context. To identify candidate mechanisms for stimulus selection within A1, we reverse-engineered low-rank RNNs trained on a similar task. Our analyses predicted that two context-modulated neural populations gated their preferred stimulus in opposite contexts, which we confirmed in further analyses of A1. Finally, we show in a two-region RNN how population gating within A1 could be controlled by top-down inputs from PFC, enabling flexible across-area communication despite fixed inter-areal connectivity.

Behavioral studies have demonstrated that certain task features reliably enhance classification performance for challenging visual stimuli. These include extended image presentation time and the valid cueing of attention. Here, I will show how convolutional neural networks can be used as a model of the visual system that connects neural activity changes with such performance changes. Specifically, I will discuss how different anatomical forms of recurrence can account for better classification of noisy and degraded images with extended processing time. I will then show how experimentally-observed neural activity changes associated with feature attention lead to observed performance changes on detection tasks. I will also discuss the implications these results have for how we identify the neural mechanisms and architectures important for behavior.

Cognitive control guides behavior by controlling what, where, and how information is represented in the brain. Perhaps the most well-studied form of cognitive control has been ‘attention’, which controls how external sensory stimuli are represented in the brain. In contrast, the neural mechanisms controlling the selection of representations held ‘in mind’, in working memory, are unknown. In this talk, I will present evidence that the prefrontal cortex controls working memory by selectively enhancing and transforming the contents of working memory. In particular, I will show how the neural representation of the content of working memory changes over time, moving between different ‘subspaces’ of the neural population. These dynamics may play a critical role in controlling what and how neural representations are acted upon.

We recorded and analyzed the population activity of hundreds of neurons in the medial premotor areas (MPC) of rhesus monkeys performing an isochronous tapping task guided by brief flashing stimuli or auditory tones. The animals showed a strong bias towards visual metronomes, with rhythmic tapping that was more precise and accurate than for auditory metronomes. The population dynamics in state space as well as the corresponding neural sequences shared the following properties across modalities: the circular dynamics of the neural trajectories and the neural sequences formed a regenerating loop for every produced interval, producing a relative time representation; the trajectories converged in similar state space at tapping times while the moving bumps restart at this point, resetting the beat-based clock; the tempo of the synchronized tapping was encoded by a combination of amplitude modulation and temporal scaling in the neural trajectories. In addition, the modality induced a displacement in the neural trajectories in auditory and visual subspaces without greatly altering time keeping mechanism. These results suggest that the interaction between the amodal internal representation of pulse within MPC and a modality specific external input generates a neural rhythmic clock whose dynamics define the temporal execution of tapping using auditory and visual metronomes.

Face detection is an initial step of many social interactions involving a comparison between a visual input and a mental representation of faces, built from previous experience. Whilst emotional state was found to affect the way humans attend to faces, little research has explored the effects of emotions on the mental representation of faces. Here, we examined the specific perceptual modulation of geometric properties of the mental representations associated with state anxiety and state depression on face detection, and to compare their emotional expression. To this end, we used an adaptation of the reverse correlation technique inspired by Gosselin and Schyns’, (2003) ‘Superstitious Approach’, to construct visual representations of observers’ mental representations of faces and to relate these to their mental states. In two sessions, on separate days, participants were presented with ‘colourful’ noise stimuli and asked to detect faces, which they were told were present. Based on the noise fragments that were identified as faces, we reconstructed the pictorial mental representation utilised by each participant in each session. We found a significant correlation between the size of the mental representation of faces and participants’ level of depression. Our findings provide a preliminary insight about the way emotions affect appearance expectation of faces. To further understand whether the facial expressions of participants’ mental representations reflect their emotional state, we are conducting a validation study with a group of naïve observers who are asked to classify the reconstructed face images by emotion. Thus, we assess whether the faces communicate participants’ emotional states to others.

The human middle temporal complex (hMT+) has a crucial biological relevance for the processing and detection of direction and speed of motion in visual stimuli. In both humans and monkeys, it has been extensively investigated in terms of its retinotopic properties and selectivity for direction of moving stimuli; however, only in recent years there has been an increasing interest in how neurons in MT encode the speed of motion. In this talk, I will explore the proposed mechanism of speed encoding questioning whether hMT+ neuronal populations encode the stimulus speed directly, or whether they separate motion into its spatial and temporal components. I will characterize how neuronal populations in hMT+ encode the speed of moving visual stimuli using electrocorticography ECoG and 7T fMRI. I will illustrate that the neuronal populations measured in hMT+ are not directly tuned to stimulus speed, but instead encode speed through separate and independent spatial and temporal frequency tuning. Finally, I will suggest that this mechanism may play a role in evaluating multisensory responses for visual, tactile and auditory stimuli in hMT+.

Artificial neural networks simplify complex biological circuits into tractable models for computational exploration and experimentation. However, the simplification of artificial models also undermines their applicability to real brain dynamics. Typical efforts to address this mismatch add complexity to increasingly unwieldy models. Here, we take a different approach; by reducing the complexity of a biological cortical culture, we aim to distil the essential factors of neuronal dynamics and plasticity. We leverage recent advances in growing neurons from human induced pluripotent stem cells (hiPSCs) to analyse ex vivo cortical cultures with only two distinct excitatory and inhibitory neuron populations. Over 6 weeks of development, we record from thousands of neurons using high-density microelectrode arrays (HD-MEAs) that allow access to individual neurons and the broader population dynamics. We compare these dynamics to two-population artificial networks of single-compartment neurons with random sparse connections and show that they produce similar dynamics. Specifically, our model captures the firing and bursting statistics of the cultures. Moreover, tightly integrating models and cultures allows us to evaluate the impact of changing architectures over weeks of development, with and without external stimuli. Broadly, the use of simplified cortical cultures enables us to use the repertoire of theoretical neuroscience techniques established over the past decades on artificial network models. Our approach of deriving neural networks from human cells also allows us, for the first time, to directly compare neural dynamics of disease and control. We found that cultures e.g. from epilepsy patients tended to have increasingly more avalanches of synchronous activity over weeks of development, in contrast to the control cultures. Next, we will test possible interventions, in silico and in vitro, in a drive for personalised approaches to medical care. This work starts bridging an important theoretical-experimental neuroscience gap for advancing our understanding of mammalian neuron dynamics.

Memory consolidation is the process by which recent experiences are assimilated into long-term memory. In animals, this process requires the offline replay of sequences observed during online exploration in the hippocampus. Recent experimental work has found that salient but task-irrelevant stimuli are systematically excluded from these replay epochs, suggesting that replay samples from an abstracted model of the world, rather than verbatim previous experiences. We find that this phenomenon can be explained parsimoniously and biologically plausibly by a Hebbian spike time-dependent plasticity rule at inhibitory synapses. Using spiking networks at three levels of abstraction–leaky integrate-and-fire, biophysically detailed, and abstract binary–we show that this rule enables efficient inference of a model of the structure of the world. While plasticity has previously mainly been studied at excitatory synapses, we find that plasticity at excitatory synapses alone is insufficient to accomplish this type of structural learning. We present theoretical results in a simplified model showing that in the presence of Hebbian excitatory and inhibitory plasticity, the replayed sequences form a statistical estimator of a latent sequence, which converges asymptotically to the ground truth. Our work outlines a direct link between the synaptic and cognitive levels of memory consolidation, and highlights a potential conceptually distinct role for inhibition in computing with SNNs.

Drosophila olfactory sensory hairs ("sensilla") typically house two olfactory receptor neurons (ORNs) which can laterally inhibit each other via electrical ("ephaptic") coupling. ORN pairing is highly stereotyped and genetically determined. Thus, olfactory signals arriving in the Antennal Lobe (AL) have been pre-processed by a fixed and shallow network at the periphery. To uncover the functional significance of this organization, we developed a nonlinear phenomenological model of asymmetrically coupled ORNs responding to odor mixture stimuli. We derived an analytical solution to the ORNs’ dynamics, which shows that the peripheral network can extract the valence of specific odor mixtures via transient amplification. Our model predicts that for efficient read-out of the amplified valence signal there must exist specific patterns of downstream connectivity that reflect the organization at the periphery. Analysis of AL→Lateral Horn (LH) fly connectomic data reveals evidence directly supporting this prediction. We further studied the effect of ephaptic coupling on olfactory processing in the AL→Mushroom Body (MB) pathway. We show that stereotyped ephaptic interactions between ORNs lead to a clustered odor representation of glomerular responses. Such clustering in the AL is an essential assumption of theoretical studies on odor recognition in the MB. Together our work shows that preprocessing of olfactory stimuli by a fixed and shallow network increases sensitivity to specific odor mixtures, and aids in the learning of novel olfactory stimuli. Work led by Palka Puri, in collaboration with Chih-Ying Su and Shiuan-Tze Wu.

Understanding the nature of neural representation is a central challenge of neuroscience. One common approach to this challenge is to compute receptive fields by correlating neural activity with external variables drawn from sensory signals. But these receptive fields are only meaningful to the experimenter, not the organism, because only the experimenter has access to both the neural activity and knowledge of the external variables. To understand neural representation more directly, recent methodological advances have sought to capture the intrinsic geometry of sensory driven neural responses without external reference. To date, this approach has largely been restricted to low-dimensional stimuli as in spatial navigation. In this talk, I will discuss recent work from my lab examining the intrinsic geometry of sensory representations in a model vocal communication system, songbirds. From the assumption that sensory systems capture invariant relationships among stimulus features, we conceptualized the space of natural birdsongs to lie on the surface of an n-dimensional hypersphere. We computed composite receptive field models for large populations of simultaneously recorded single neurons in the auditory forebrain and show that solutions to these models define convex regions of response probability in the spherical stimulus space. We then define a combinatorial code over the set of receptive fields, realized in the moment-to-moment spiking and non-spiking patterns across the population, and show that this code can be used to reconstruct high-fidelity spectrographic representations of natural songs from evoked neural responses. Notably, we find that topological relationships among combinatorial codewords directly mirror acoustic relationships among songs in the spherical stimulus space. That is, the time-varying pattern of co-activity across the neural population expresses an intrinsic representational geometry that mirrors the natural, extrinsic stimulus space.  Combinatorial patterns across this intrinsic space directly represent complex vocal communication signals, do not require computation of receptive fields, and are in a form, spike time coincidences, amenable to biophysical mechanisms of neural information propagation.

It is critical for all animals to make appropriate, but also flexible, foraging decisions, especially when facing starvation. Sensing olfactory information is essential to evaluate food quality before ingestion. Previously, we found that <i>Drosophila</i> larvae switch their response to certain odors from aversion to attraction when food deprived. The neural mechanism underlying this switch in behavior involves serotonergic modulation and reconfiguration of odor processing in the early olfactory sensory system. We now investigate if a change in hunger state also influences other behavioral decisions. Since it had been shown that fly larvae can perform cannibalism, we investigate the effect of food deprivation on feeding on dead conspecifics. We find that fed fly larvae rarely use dead conspecifics as a food source. However, food deprivation largely enhances this behavior. We will now also investigate the underlying neural mechanisms that mediate this enhancement and compare it to the already described mechanism for a switch in olfactory choice behavior. Generally, this flexibility in foraging behavior enables the larva to explore a broader range of stimuli and to expand their feeding choices to overcome starvation.

Engineering designers practice design-by-analogy (DbA) during concept generation to retrieve knowledge from external sources or memory as inspiration to solve design problems. DbA is a tool for innovation that involves retrieving analogies from a source domain and transferring the knowledge to a target domain. While DbA produces innovative results, designers often come up with analogies by themselves or through serendipitous, random encounters. Computational support systems for searching analogies have been developed to facilitate DbA in systematic design practice. However, many systems have focused on a query-based approach, in which a designer inputs a keyword or a query function and is returned a set of algorithmically determined stimuli. In this presentation, a new analogical retrieval process that leverages a visual interaction technique is introduced. It enables designers to explore a space of analogies, rather than be constrained by what’s retrieved by a query-based algorithm. With an exploration-based DbA tool, designers have the potential to uncover more useful and unexpected inspiration for innovative design solutions.

Peripersonal space (PPS) defines the portion of space where interactions between our body and the external environment more likely occur. There is no physical boundary defining the PPS with respect to the extrapersonal space, but PPS is continuously constructed by a dedicated neural system integrating external stimuli and tactile stimuli on the body, as a function of their potential interaction. This mechanism represents a primary interface between the individual and the environment. In this talk, I will present most recent evidence and highlight the current debate about the neural and computational mechanisms of PPS, its main functions and properties. I will discuss novel data showing how PPS dynamically shapes to optimize body-environment interactions. I will describe a novel electrophysiological paradigm to study and measure PPS, and show how this has been used to search for a basic marker of potentials of self-environment interaction in newborns and patients with disorders of consciousness. Finally, I will discuss how PPS is also involved in, and in turn shaped by, social interactions. Under these acceptances, I will discuss how PPS plays a key role in self-consciousness.

Humans, as a social species, have an increased ability to detect and perceive visual elements involved in social exchanges, such as faces and eyes. The gaze, in particular, conveys information crucial for social interactions and social cognition. Researchers have hypothesized that in order to engage in dynamic face-to-face communication in real time, our brains must quickly and automatically process the direction of another person's gaze. There is evidence that direct gaze improves face encoding and attention capture and that direct gaze is perceived and processed more quickly than averted gaze. These results are summarized as the "direct gaze effect". However, in the recent literature, there is evidence to suggest that the mode of visual information processing modulates the direct gaze effect. In this presentation, I argue that top-down processing, and specifically the relevance of eye features to the task, promotes the early preferential processing of direct versus indirect gaze. On the basis of several recent evidences, I propose that low task relevance of eye features will prevent differences in eye direction processing between gaze directions because its encoding will be superficial. Differential processing of direct and indirect gaze will only occur when the eyes are relevant to the task. To assess the implication of task relevance on the temporality of cognitive processing, we will measure event-related potentials (ERPs) in response to facial stimuli. In this project, instead of typical ERP markers such as P1, N170 or P300, we will measure lateralized ERPs (lERPS) such as lateralized N170 and N2pc, which are markers of early face encoding and attentional deployment respectively. I hypothesize that the relevance of the eye feature task is crucial in the direct gaze effect and propose to revisit previous studies, which had questioned the existence of the direct gaze effect. This claim will be illustrate with different past studies and recent preliminary data of my lab. Overall, I propose a systematic evaluation of the role of top-down processing in early direct gaze perception in order to understand the impact of context on gaze perception and, at a larger scope, on social cognition.

In sexually reproducing species, males and females respond to environmental sensory cues and transform the input into sexually dimorphic traits. Yet, how sexually dimorphic behavior is encoded in the nervous system is poorly understood. We characterize the sexually dimorphic nociceptive behavior in C. elegans – hermaphrodites present a lower pain threshold than males in response to aversive stimuli, and study the underlying neuronal circuits, which are composed of the same neurons that are wired differently. By imaging receptor expression, calcium responses and glutamate secretion, we show that sensory transduction is similar in the two sexes, and therefore explore how downstream network topology shapes dimorphic behavior. We generated a computational model that replicates the observed dimorphic behavior, and used this model to predict simple network rewirings that would switch the behavior between the sexes. We then showed experimentally, using genetic manipulations, artificial gap junctions, automated tracking and optogenetics, that these subtle changes to male connectivity result in hermaphrodite-like aversive behavior in-vivo, while hermaphrodite behavior was more robust to perturbations. Strikingly, when presented with aversive cues, rewired males were compromised in finding mating partners, suggesting that the network topology that enables efficient avoidance of noxious cues would have a reproductive "cost". To summarize, we present a deconstruction of a sex-shared neural circuit that affects sexual behavior, and how to reprogram it. More broadly, our results are an example of how common neuronal circuits changed their function during evolution by subtle topological rewirings to account for different environmental and sexual needs.

Magnitude estimation and stimulus discrimination tasks are affected by perceptual biases that cause the stimulus parameter to be perceived as shifted toward the mean of its distribution. These biases have been extensively studied in psychophysics and, more recently and to a lesser extent, with neural activity recordings. New computational techniques allow us to train spiking recurrent neural networks on the tasks used in the experiments. This provides us with another valuable tool with which to investigate the network mechanisms responsible for the biases and how behavior could be modeled. As an example, in this talk I will consider networks trained to discriminate the durations of temporal intervals. The trained networks presented the contraction bias, even though they were trained with a stimulus sequence without temporal correlations. The neural activity during the delay period carried information about the stimuli of the current trial and previous trials, this being one of the mechanisms that originated the contraction bias. The population activity described trajectories in a low-dimensional space and their relative locations depended on the prior distribution. The results can be modeled as an ideal observer that during the delay period sees a combination of the current and the previous stimuli. Finally, I will describe how the neural trajectories in state space encode an estimate of the interval duration. The approach could be applied to other cognitive tasks.

Individuals vary widely in how they categorize novel phenomena. This individual variation has led canonical theories in cognitive and social science to suggest that communication in large social networks leads populations to construct divergent category systems. Yet, anthropological data indicates that large, independent societies consistently arrive at similar categories across a range of topics. How is it possible for diverse populations, consisting of individuals with significant variation in how they view the world, to independently construct similar categories? Through a series of online experiments, I show how large communication networks within cultures can promote the formation of similar categories across cultures. For this investigation, I designed an online “Grouping Game” to observe how people construct categories in both small and large populations when tasked with grouping together the same novel and ambiguous images. I replicated this design for English-speaking subjects in the U.S. and Mandarin-speaking subjects in China. In both cultures, solitary individuals and small social groups produced highly divergent category systems. Yet, large social groups separately and consistently arrived at highly similar categories both within and across cultures. These findings are accurately predicted by a simple mathematical model of critical mass dynamics. Altogether, I show how large communication networks can filter lexical diversity among individuals to produce replicable society-level patterns, yielding unexpected implications for cultural evolution. In particular, I discuss how participants in both cultures readily harnessed analogies when categorizing novel stimuli, and I examine the role of communication networks in promoting cross-cultural similarities in analogy-making as the key engine of category formation.

The taste system detects 5 major categories of ethologically relevant stimuli (sweet, bitter, umami, sour and salt) and accordingly elicits acceptance or avoidance responses. While these taste responses are innate, the taste system retains a remarkable flexibility in response to changing external and internal contexts. Taste chemicals are first recognized by dedicated taste receptor cells (TRCs) and then transmitted to the cortex via a multi-station relay. I reasoned that if I could identify taste neural substrates along this pathway, it would provide an entry to decipher how taste signals are encoded to drive innate response and modulated to facilitate adaptive response. Given the innate nature of taste responses, these neural substrates should be genetically identifiable. I therefore exploited single-cell RNA sequencing to isolate molecular markers defining taste qualities in the taste ganglion and the nucleus of the solitary tract (NST) in the brainstem, the two stations transmitting taste signals from TRCs to the brain. How taste information propagates from the ganglion to the brain is highly debated (i.e., does taste information travel in labeled-lines?). Leveraging these genetic handles, I demonstrated one-to-one correspondence between ganglion and NST neurons coding for the same taste. Importantly, inactivating one ‘line’ did not affect responses to any other taste stimuli. These results clearly showed that taste information is transmitted to the brain via labeled lines. But are these labeled lines aptly adapted to the internal state and external environment? I studied the modulation of taste signals by conflicting taste qualities in the concurrence of sweet and bitter to understand how adaptive taste responses emerge from hardwired taste circuits. Using functional imaging, anatomical tracing and circuit mapping, I found that bitter signals suppress sweet signals in the NST via top-down modulation by taste cortex and amygdala of NST taste signals. While the bitter cortical field provides direct feedback onto the NST to amplify incoming bitter signals, it exerts negative feedback via amygdala onto the incoming sweet signal in the NST. By manipulating this feedback circuit, I showed that this top-down control is functionally required for bitter evoked suppression of sweet taste. These results illustrate how the taste system uses dedicated feedback lines to finely regulate innate behavioral responses and may have implications for the context-dependent modulation of hardwired circuits in general.

The visual system of the brain is highly parallel in its architecture. This is clearly evident in the outputs of the retina, which arise from neurons called ganglion cells. Work in our lab has shown that mammalian retinas contain more than a dozen distinct types of ganglion cells. Each type appears to filter the retinal image in a unique way and to relay this processed signal to a specific set of targets in the brain. My students and I are working to understand the meaning of this parallel organization through electrophysiological and anatomical studies. We record from light-responsive ganglion cells in vitro using the whole-cell patch method. This allows us to correlate directly the visual response properties, intrinsic electrical behavior, synaptic pharmacology, dendritic morphology and axonal projections of single neurons. Other methods used in the lab include neuroanatomical tracing techniques, single-unit recording and immunohistochemistry. We seek to specify the total number of ganglion cell types, the distinguishing characteristics of each type, and the intraretinal mechanisms (structural, electrical, and synaptic) that shape their stimulus selectivities. Recent work in the lab has identified a bizarre new ganglion cell type that is also a photoreceptor, capable of responding to light even when it is synaptically uncoupled from conventional (rod and cone) photoreceptors. These ganglion cells appear to play a key role in resetting the biological clock. It is just this sort of link, between a specific cell type and a well-defined behavioral or perceptual function, that we seek to establish for the full range of ganglion cell types. My research concerns the structural and functional organization of retinal ganglion cells, the output cells of the retina whose axons make up the optic nerve. Ganglion cells exhibit great diversity both in their morphology and in their responses to light stimuli. On this basis, they are divisible into a large number of types (>15). Each ganglion-cell type appears to send its outputs to a specific set of central visual nuclei. This suggests that ganglion cell heterogeneity has evolved to provide each visual center in the brain with pre-processed representations of the visual scene tailored to its specific functional requirements. Though the outline of this story has been appreciated for some time, it has received little systematic exploration. My laboratory is addressing in parallel three sets of related questions: 1) How many types of ganglion cells are there in a typical mammalian retina and what are their structural and functional characteristics? 2) What combination of synaptic networks and intrinsic membrane properties are responsible for the characteristic light responses of individual types? 3) What do the functional specializations of individual classes contribute to perceptual function or to visually mediated behavior? To pursue these questions, we label retinal ganglion cells by retrograde transport from the brain; analyze in vitro their light responses, intrinsic membrane properties and synaptic pharmacology using the whole-cell patch clamp method; and reveal their morphology with intracellular dyes. Recently, we have discovered a novel ganglion cell in rat retina that is intrinsically photosensitive. These ganglion cells exhibit robust light responses even when all influences from classical photoreceptors (rods and cones) are blocked, either by applying pharmacological agents or by dissociating the ganglion cell from the retina. These photosensitive ganglion cells seem likely to serve as photoreceptors for the photic synchronization of circadian rhythms, the mechanism that allows us to overcome jet lag. They project to the circadian pacemaker of the brain, the suprachiasmatic nucleus of the hypothalamus. Their temporal kinetics, threshold, dynamic range, and spectral tuning all match known properties of the synchronization or "entrainment" mechanism. These photosensitive ganglion cells innervate various other brain targets, such as the midbrain pupillary control center, and apparently contribute to a host of behavioral responses to ambient lighting conditions. These findings help to explain why circadian and pupillary light responses persist in mammals, including humans, with profound disruption of rod and cone function. Ongoing experiments are designed to elucidate the phototransduction mechanism, including the identity of the photopigment and the nature of downstream signaling pathways. In other studies, we seek to provide a more detailed characterization of the photic responsiveness and both morphological and functional evidence concerning possible interactions with conventional rod- and cone-driven retinal circuits. These studies are of potential value in understanding and designing appropriate therapies for jet lag, the negative consequences of shift work, and seasonal affective disorder.

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.

Neural representations of time are central to our understanding of the world around us. I review cognitive, neurophysiological and theoretical work that converges on three simple ideas. First, the time of past events is remembered via populations of neurons with a continuum of functional time constants. Second, these time constants evenly tile the log time axis. This results in a neural Weber-Fechner scale for time which can support behavioral Weber-Fechner laws and characteristic behavioral effects in memory experiments. Third, these populations appear as dual pairs---one type of population contains cells that change firing rate monotonically over time and a second type of population that has circumscribed temporal receptive fields. These ideas can be used to build artificial neural networks that have novel properties. Of particular interest, a convolutional neural network built using these principles can generalize to arbitrary rescaling of its inputs. That is, after learning to perform a classification task on a time series presented at one speed, it successfully classifies stimuli presented slowed down or sped up. This result illustrates the point that this confluence of ideas originating in cognitive psychology and measured in the mammalian brain could have wide-reaching impacts on AI research.

The human middle temporal complex (hMT+) has a crucial biological relevance for the processing and detection of direction and speed of motion in visual stimuli. In both humans and monkeys, it has been extensively investigated in terms of its retinotopic properties and selectivity for direction of moving stimuli; however, only in recent years there has been an increasing interest in how neurons in MT encode the speed of motion. In this talk, I will explore the proposed mechanism of speed encoding questioning whether hMT+ neuronal populations encode the stimulus speed directly, or whether they separate motion into its spatial and temporal components. I will characterize how neuronal populations in hMT+ encode the speed of moving visual stimuli using electrocorticography ECoG and 7T fMRI. I will illustrate that the neuronal populations measured in hMT+ are not directly tuned to stimulus speed, but instead encode speed through separate and independent spatial and temporal frequency tuning. Finally, I will show that this mechanism plays a role in evaluating multisensory responses for visual, tactile and auditory motion stimuli in hMT+.

Discriminating distinct objects and concepts from sensory stimuli is essential for survival. Our brains accomplish this feat by forming meaningful internal representations in deep sensory networks with plastic synaptic connections. Experience-dependent plasticity presumably exploits temporal contingencies between sensory inputs to build these internal representations. However, the precise mechanisms underlying plasticity remain elusive. We derive a local synaptic plasticity model inspired by self-supervised machine learning techniques that shares a deep conceptual connection to Bienenstock-Cooper-Munro (BCM) theory and is consistent with experimentally observed plasticity rules. We show that our plasticity model yields disentangled object representations in deep neural networks without the need for supervision and implausible negative examples. In response to altered visual experience, our model qualitatively captures neuronal selectivity changes observed in the monkey inferotemporal cortex in-vivo. Our work suggests a plausible learning rule to drive learning in sensory networks while making concrete testable predictions.

Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes, but it is not known whether these subtypes have correspondingly diverse activity patterns in the living brain. We show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We classified inhibitory neurons imaged in layers 1-3 into a three-level hierarchy of 5 Subclasses, 11 Types, and 35 Subtypes using previously-defined transcriptomic clusters. Responses to visual stimuli differed significantly only across Subclasses, suppressing cells in the Sncg Subclass while driving cells in the other Subclasses. Modulation by brain state differed at all hierarchical levels but could be largely predicted from the first transcriptomic principal component, which also predicted correlations with simultaneously recorded cells. Inhibitory Subtypes that fired more in resting, oscillatory brain states have less axon in layer 1, narrower spikes, lower input resistance and weaker adaptation as determined in vitro and express more inhibitory cholinergic receptors. Subtypes firing more during arousal had the opposite properties. Thus, a simple principle may largely explain how diverse inhibitory V1 Subtypes shape state-dependent cortical processing.

Excitatory and inhibitory (E & I) inputs to cortical neurons remain balanced across different conditions. The balanced network model provides a self-consistent account of this observation: population rates dynamically adjust to yield a state in which all neurons are active at biological levels, with their E & I inputs tightly balanced. But global tight E/I balance predicts population responses with linear stimulus-dependence and does not account for systematic cortical response nonlinearities such as divisive normalization, a canonical brain computation. However, when necessary connectivity conditions for global balance fail, states arise in which only a localized subset of neurons are active and have balanced inputs. We analytically show that in networks of neurons with different stimulus selectivities, the emergence of such localized balance states robustly leads to normalization, including sublinear integration and winner-take-all behavior. An alternative model that exhibits normalization is the Stabilized Supralinear Network (SSN), which predicts a regime of loose, rather than tight, E/I balance. However, an understanding of the causal relationship between E/I balance and normalization in SSN and conditions under which SSN yields significant sublinear integration are lacking. For weak inputs, SSN integrates inputs supralinearly, while for very strong inputs it approaches a regime of tight balance. We show that when this latter regime is globally balanced, SSN cannot exhibit strong normalization for any input strength; thus, in SSN too, significant normalization requires localized balance. In summary, we causally and quantitatively connect a fundamental feature of cortical dynamics with a canonical brain computation. Time allowing I will also cover our work extending a normative theoretical account of normalization which explains it as an example of efficient coding of natural stimuli. We show that when biological noise is accounted for, this theory makes the same prediction as the SSN: a transition to supralinear integration for weak stimuli.

Animals traversing different environments encounter both stable background stimuli and novel cues, which are generally thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Sensory adaptation is a neural mechanism that filters background by minimizing responses to stable sensory stimuli, and a fundamental feature of sensory systems. Adaptation over relatively fast timescales (milliseconds to minutes) have been reported in many sensory systems. However, adaptation to persistent environmental stimuli over longer timescales (hours to days) have been largely unexplored, even though those timescales are ethologically important since animals typically stay in one environment for hours. I showed that each of the ~1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of many genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional mechanism whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.

Natural language is strongly context-dependent and can be perceived through different sensory modalities. For example, humans can easily comprehend the meaning of complex narratives presented through auditory speech, written text, or visual images. To understand how complex language-related information is represented in the human brain there is a necessity to map the different linguistic and non-linguistic information perceived under different modalities across the cerebral cortex. To map this information to the brain, I suggest following a naturalistic approach and observing the human brain performing tasks in its naturalistic setting, designing quantitative models that transform real-world stimuli into specific hypothesis-related features, and building predictive models that can relate these features to brain responses. In my talk, I will present models of brain responses collected using functional magnetic resonance imaging while human participants listened to or read natural narrative stories. Using natural text and vector representations derived from natural language processing tools I will present how we can study language processing in the human brain across modalities, in different levels of temporal granularity, and across different languages.

A great deal of understanding can be gleaned from direct observation of organismal growth, development, and behavior. However, direct observation can be time consuming and influence the organism through unintentional stimuli. Additionally, video capturing equipment can often be prohibitively expensive, difficult to modify to one’s specific needs, and may come with unnecessary features. Here, we describe the PiSpy, a low-cost, automated video acquisition platform that uses a Raspberry Pi computer and camera to record video or images at specified time intervals or when externally triggered. All settings and controls, such as programmable light cycling, are accessible to users with no programming experience through an easy-to-use graphical user interface. Importantly, the entire PiSpy system can be assembled for less than $100 using laser-cut and 3D-printed components. We demonstrate the broad applications and flexibility of the PiSpy across a range of model and non-model organisms. Designs, instructions, and code can be accessed through an online repository, where a global community of PiSpy users can also contribute their own unique customizations and help grow the community of open-source research solutions.

Perception and action are biased by our recent experiences. Even when a sequence of stimuli are randomly presented, responses are sometimes attracted toward the past. The mechanism of such bias, recently termed serial dependence, is still under investigation. Currently, there is mixed evidence indicating that such bias could be either from a sensory and perceptual origin or occurring only at decisional stages. In this talk, I will present recent findings from our group showing that biases are decreased when disrupting the memory trace in a premotor region in a simple visuomotor task. In addition, we have shown that this bias is stable over periods of up to 8 s. At the end, I will show ongoing analysis of a recent experiment and argue that serial dependence may rely on distributed memory representations of stimuli and task relevant features.

Modeling brain mechanisms is often confined to a given scale, such as single-cell models, network models or whole-brain models, and it is often difficult to relate these models. Here, we show an approach to build models across scales, starting from the level of circuits to the whole brain. The key is the design of accurate population models derived from biophysical models of networks of excitatory and inhibitory neurons, using mean-field techniques. Such population models can be later integrated as units in large-scale networks defining entire brain areas or the whole brain. We illustrate this approach by the simulation of asynchronous and slow-wave states, from circuits to the whole brain. At the mesoscale (millimeters), these models account for travelling activity waves in cortex, and at the macroscale (centimeters), the models reproduce the synchrony of slow waves and their responsiveness to external stimuli. This approach can also be used to evaluate the impact of sub-cellular parameters, such as receptor types or membrane conductances, on the emergent behavior at the whole-brain level. This is illustrated with simulations of the effect of anesthetics. The program codes are open source and run in open-access platforms (such as EBRAINS).

The view of human brain function has drastically shifted over the last decade, owing to the observation that the majority of brain activity is intrinsic rather than driven by external stimuli or cognitive demands. Specifically, all brain regions continuously communicate in spatiotemporally organized patterns that constitute the functional connectome, with consequences for cognition and behavior. In this talk, I will argue that another shift is underway, driven by new insights from synergistic interrogation of the functional connectome using different acquisition methods. The human functional connectome is typically investigated with functional magnetic resonance imaging (fMRI) that relies on the indirect hemodynamic signal, thereby emphasizing very slow connectivity across brain regions. Conversely, more recent methodological advances demonstrate that fast connectivity within the whole-brain connectome can be studied with real-time methods such as electroencephalography (EEG). Our findings show that combining fMRI with scalp or intracranial EEG in humans, especially when recorded concurrently, paints a rich picture of neural communication across the connectome. Specifically, the connectome comprises both fast, oscillation-based connectivity observable with EEG, as well as extremely slow processes best captured by fMRI. While the fast and slow processes share an important degree of spatial organization, these processes unfold in a temporally independent manner. Our observations suggest that fMRI and EEG may be envisaged as capturing distinct aspects of functional connectivity, rather than intermodal measurements of the same phenomenon. Infraslow fluctuation-based and rapid oscillation-based connectivity of various frequency bands constitute multiple dynamic trajectories through a shared state space of discrete connectome configurations. The multitude of flexible trajectories may concurrently enable functional connectivity across multiple independent sets of distributed brain regions.