Seminars

The ventral visual pathway extends from the occipital to the anterior temporal regions, and is specialized in giving meaning to objects and people that are perceived through vision. Numerous studies in functional magnetic resonance imaging have focused on the cerebral basis of visual recognition. However, this technique is susceptible to magnetic artefacts in ventral anterior temporal regions and it has led to an underestimation of the role of these regions within the ventral visual stream, especially with respect to face recognition and semantic representations. Moreover, there is an increasing need for implicit methods assessing these functions as explicit tasks lack specificity. In this talk, I will present three studies using fast periodic visual stimulation (FPVS) in combination with scalp and/or intracerebral EEG to overcome these limitations and provide high SNR in temporal regions. I will show that, beyond face recognition, FPVS can be extended to investigate semantic representations using a face-name association paradigm and a semantic categorisation paradigm with written words. These results shed new light on the role of temporal regions and demonstrate the high potential of the FPVS approach as a powerful electrophysiological tool to assess various cognitive functions in neurotypical and clinical populations.

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 correlates of visual working memory have been found in early visual, parietal, and prefrontal regions. These findings have spurred fruitful debate over how and where in the brain memories might be represented. Here, I will present data from multiple experiments to demonstrate how a focus on behavioral requirements can unveil a more comprehensive understanding of the visual working memory system. Specifically, items in working memory must be maintained in a highly robust manner, resilient to interference. At the same time, storage mechanisms must preserve a high degree of flexibility in case of changing behavioral goals. Several examples will be explored in which visual memory representations are shown to undergo transformations, and even shift their cortical locus alongside their coding format based on specifics of the task.

I will offer a broad-brush account of what explains the emergence of agents from a physics perspective, what sorts of conditions have to be in place for them to arise, and the essential features of agents when they are viewed through the lenses of physics. One implication will be a tight link to informational asymmetries associated with the thermodynamic gradient. Another will be a reversal of the direction of explanation from the one that is usually assumed in physical discussions. In in an evolved system, while it is true in some sense that the macroscopic behavior is the way it is because of the low-level dynamics, there is another sense in which the low-level dynamics is the way that it is because of the high-level behavior it supports. (More precisely and accurately, the constraints on the configuration of its components that define system as the kind of system it is are the way they are to exploit the low-level dynamics to produce the emergent behavior.) Another will be some insight into what might make human agency special.

Individual bacteria transported in viscous flows, show complex interactions with flows and bounding surfaces resulting from their complex shape as well as their activity. Understanding these transport dynamics is crucial, as they impact soil contamination, transport in biological conducts or catheters, and constitute thus a serious health threat. Here we investigate the trajectories of individual E-coli bacteria in confined geometries under flow, using microfluidic model systems in bulk flows as well as close to surfaces using a novel Langrangian 3D tracking method. Combining experimental observations and modelling we elucidate the origin of upstream swimming, lateral drift or persistent transport along corners. [1] Junot et al, EPL, 126 (2019) 44003 [2] Mathijssen et al. 10:3 (2019) Nature Comm. [3] Figueroa-Morales et al., Soft Matter, 2015,11, 6284-6293 [4] Darnige et al. Review of Scientific Instruments 88, 055106 (2017) [5] Jing et al, Science Advances, 2020; 6 : eabb2012 [6] Figueroa-Morales et al, Sci. Adv. 2020; 6 : eaay0155, 2020, 10.1126/sciadv.aay0155

Monetary incentive delay task (MID) is a well-validated human functional MRI task widely used in probing affective-motivational processes in psychiatric disorders. We are developing a mouse version of the MID task in order to facilitate translations of findings from the wealth of human imaging studies. This talk presents our task design and behavioural data from the ongoing work.

Threshold-linear networks (TLNs) are popular firing rate models of recurrent networks. They have been used to model associative memory, decision-making, and position coding in cortical and hippocampal networks. Unlike rate models with other choices of nonlinearity, TLNs are piecewise linear, making them more amenable to mathematical analysis. In this talk I will present ten theorems about TLNs from the past five years. Many of these theorems connect the fixed points of a network to the structure of an underlying connectivity graph. These results have enabled us to develop graph rules to predict both static and dynamic attractors from network motifs. The theorems will be complemented with examples that illustrate how the mathematical results can be used to analyze and design recurrent networks that support a rich variety of computations and dynamics. Examples include internally-generated sequences, neural integrators, and central pattern generator circuits. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2021-06-23. Recording duration: 00:53:51.

Human participant research is somehow both antithetical and complementary to science. On the one hand, working with human participants provides incredibly rich and complex data with ‘real-world’ ecological validity. On the other, this richness is due to the incredible number of variables which uncontrollably become intertwined with your research interest, potentially limiting the conclusions you can draw from your work. Historical over-representation of white men as research participants, coupled with often overly-stringent exclusion criteria has led to a diversity crisis in human participant research. For our research to be truly inclusive, representative and generalisable to the rest of the population, our data must be collected from diverse individuals. This session will explore common barriers to diversity in studies with human participants, and will provide guidance on how to make sure your own research is accessible and inclusive.

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.

Visual working memory (VWM) allows us to maintain a small amount of task-relevant information in mind so that we can use them to guide our behavior. Although past studies have successfully characterized its capacity limit and representational quality during maintenance, the consequence of its usage for task-relevant behaviors has been largely unknown. In this talk, I will demonstrate that VWM representations get distorted when they are used for perceptual comparisons with new visual inputs, especially when the inputs are subjectively similar to the VWM representations. Furthermore, I will show that this similarity-induced memory bias (SIMB) occurs for both simple (e.g. , color, shape) and complex stimuli (e.g., real world objects, faces) that are perceptually encoded and retrieved from long-term memory. Given the observed versatility of the SIMB, its implication for other memory distortion phenomena (e.g., distractor-induced distortion, misinformation effect) will be discussed.

My laboratory studies how the retina processes visual scenes and transmits this information to the brain. We use multi-electrode arrays to record the activity of hundreds of retina neurons simultaneously in conjunction with transgenic mouse lines and chemogenetics to manipulate neural circuit function. We are interested in three major areas. First, we work to understand how neurons in the retina are functionally connected. Second we are studying how light-adaptation and circadian rhythms alter visual processing in the retina. Finally, we are working to understand the mechanisms of retinal degenerative conditions and we are investigating potential treatments in animal models.

In this lecture, Dr Stevens will discuss recent work that implicates brain immune cells, called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders. Her recent work revealed a key role for microglia and a group of immune related molecules called complement in normal developmental synaptic pruning, a normal process required to establish precise brain wiring. Emerging evidence suggests aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders, including schizophrenia. Recent research has revealed that a person’s risk of schizophrenia is increased if they inherit specific variants in complement C4, gene plays a well-known role in the immune system but also helps sculpt developing synapses in the mouse visual system (Sekar et al., 2016). Together these findings may help explain known features of schizophrenia, including reduced numbers of synapses in key cortical regions and an adolescent age of onset that corresponds with developmentally timed waves of synaptic pruning in these regions. Stevens will discuss this and ongoing work to understand the mechanisms by which complement and microglia prune specific synapses in the brain. A deeper understanding of how these immune mechanisms mediate synaptic pruning may provide novel insight into how to protect synapses in autism and other brain disorders, including Alzheimer’s and Huntington’s Disease.

While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Direct visualization enables us to reveal a new mode of motility exhibited by individual cells, in stark contrast to the paradigm of run-and-tumble motility, in which cells are intermittently and transiently trapped as they navigate the pore space; further, analysis of these dynamics enables prediction of single-cell transport over large length and time scales. Moreover, we show that concentrated populations of E. coli can collectively migrate through a porous medium—despite being strongly confined—by chemotactically “surfing” a self-generated nutrient gradient. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter.

A central issue in reinforcement learning (RL) is the ‘curse-of-dimensionality’, arising when the degrees-of-freedom are much larger than the number of training samples. In such circumstances, the learning process becomes too slow to be plausible. In the brain, higher cognitive functions (such as abstraction or metacognition) may be part of the solution by generating low dimensional representations on which RL can operate. In this talk I will discuss a series of studies in which we used functional magnetic resonance imaging (fMRI) and computational modeling to investigate the neuro-computational basis of efficient RL. We found that people can learn remarkably complex task structures non-consciously, but also that - intriguingly - metacognition appears tightly coupled to this learning ability. Furthermore, when people use an explicit (conscious) policy to select relevant information, learning is accelerated by abstractions. At the neural level, prefrontal cortex subregions are differentially involved in separate aspects of learning: dorsolateral prefrontal cortex pairs with metacognitive processes, while ventromedial prefrontal cortex with valuation and abstraction. I will discuss the implications of these findings, in particular new questions on the function of metacognition in adaptive behavior and the link with abstraction.

Recent years have seen a considerable surge of research on interest-based engagement, examining how and why people are engaged in activities without relying on extrinsic rewards. However, the field of inquiry has been somewhat segregated into three different research traditions which have been developed relatively independently --- research on curiosity, interest, and trait curiosity/interest. The current talk sets out an integrative perspective; the reward-learning framework of knowledge acquisition. This conceptual framework takes on the basic premise of existing reward-learning models of information seeking: that knowledge acquisition serves as an inherent reward, which reinforces people’s information-seeking behavior through a reward-learning process. However, the framework reveals how the knowledge-acquisition process is sustained and boosted over a long period of time in real-life settings, allowing us to integrate the different research traditions within reward-learning models. The framework also characterizes the knowledge-acquisition process with four distinct features that are not present in the reward-learning process with extrinsic rewards --- (1) cumulativeness, (2) selectivity, (3) vulnerability, and (4) under-appreciation. The talk describes some evidence from our lab supporting these claims.