Seminars

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.

There is a fundamental tension between storing discrete traces of individual experiences, which allows recall of particular moments in our past without interference, and extracting regularities across these experiences, which supports generalization and prediction in similar situations in the future. One influential proposal for how the brain resolves this tension is that it separates the processes anatomically into Complementary Learning Systems, with the hippocampus rapidly encoding individual episodes and the neocortex slowly extracting regularities over days, months, and years. But this does not explain our ability to learn and generalize from new regularities in our environment quickly, often within minutes. We have put forward a neural network model of the hippocampus that suggests that the hippocampus itself may contain complementary learning systems, with one pathway specializing in the rapid learning of regularities and a separate pathway handling the region’s classic episodic memory functions. This proposal has broad implications for how we learn and represent novel information of specific and generalized types, which we test across statistical learning, inference, and category learning paradigms. We also explore how this system interacts with slower-learning neocortical memory systems, with empirical and modeling investigations into how the hippocampus shapes neocortical representations during sleep. Together, the work helps us understand how structured information in our environment is initially encoded and how it then transforms over time.

Humans and other animals can estimate rapidly the number of items in a scene, flashes or tones in a sequence and motor actions. Adaptation techniques provide clear evidence in humans for the existence of specialized numerosity mechanisms that make up the numbersense. This sense of number is truly general, encoding the numerosity of both spatial arrays and sequential sets, in vision and audition, and interacting strongly with action. The adaptation (cross-sensory and cross-format) acts on sensory mechanisms rather than decisional processes, pointing to a truly general sense.

In this talk I will present our recent behavioural and neuroscience research on how the brain motivates itself to form particular beliefs and why it does so. I will propose that the utility of a belief is derived from the potential outcomes associated with holding it. Outcomes can be internal (e.g., positive/negative feelings) or external (e.g., material gain/loss), and only some are dependent on belief accuracy. We show that belief change occurs when the potential outcomes of holding it alters, for example when moving from a safe environment to a threatening environment. Our findings yield predictions about how belief formation alters as a function of mental health. We test these predictions using a linguistic analysis of participants’ web searches ‘in the wild’ to quantify the affective properties of information they consume and relate those to reported psychiatric symptoms. Finally, I will present a study in which we used our framework to alter the incentive structure of social media platforms to reduce the spread of misinformation and improve belief accuracy.

The predictive map hypothesis provides a promising framework to model representations in the hippocampal formation. I will introduce a tractable implementation of a predictive map called the successor representation (SR), before presenting data showing that rats and humans display SR-like navigational choices on a novel open-field maze. Next, I will show how such a predictive map could be implemented using spatial representations found in the hippocampal formation, before finally presenting how such learning might be well approximated by phenomena that exist in the spatial memory system - namely spike-timing dependent plasticity and theta phase precession.

Executive control processes and flexible behaviors rely on the integrity of, and dynamic interactions between, large-scale functional brain networks. The right insular cortex is a critical component of a salience/midcingulo-insular network that is thought to mediate interactions between brain networks involved in externally oriented (central executive/lateral frontoparietal network) and internally oriented (default mode/medial frontoparietal network) processes. How these brain systems reconfigure with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. I will describe studies examining how brain network dynamics support flexible behaviors in typical and atypical development, presenting evidence suggesting a unique role for the dorsal anterior insular from studies of meta-analytic connectivity modeling, dynamic functional connectivity, and structural connectivity. These findings from adults, typically developing children, and children with autism suggest that structural and functional maturation of insular pathways is a critical component of the process by which human brain networks mature to support complex, flexible cognitive processes throughout the lifespan.

The gradual accumulation of hyperphosphorylated forms of the Tau protein (pTau) in the human brain correlate with cognitive dysfunction and neurodegeneration. I will present our recent findings on the consequences of human pTau aggregation in the hippocampal formation of a mouse tauopathy model. We show that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to their neurodegeneration. In aged but not younger mice, pTau spreads to oligodendrocytes. During ‘goal-directed’ navigation, we detect fewer high-firing pyramidal cells, but coupling to network oscillations is maintained in the remaining cells. The firing patterns of individually recorded and labelled pyramidal and GABAergic neurons are similar in transgenic and non-transgenic mice, as are network oscillations, suggesting intact neuronal coordination. This is consistent with a lack of pTau in subcortical brain areas that provide rhythmic input to the cortex. Spatial memory tests reveal a reduction in short-term familiarity of spatial cues but unimpaired spatial working and reference memory. These results suggest that preserved subcortical network mechanisms compensate for the widespread pTau aggregation in the hippocampal formation. I will also briefly discuss ideas on the subcortical origins of spatial memory and the concept of the cortex as a monitoring device.

Affectively charged analogies are commonly used in literature and art, but also in politics and argumentation. There are reasons to think we may process these analogies differently. Notably, analogical reasoning is a complex process that requires the use of cognitive resources, which are limited. In the presence of affectively charged content, some of these resources might be directed towards affective processing and away from analogical reasoning. To investigate this idea, I investigated effects of affective charge on differences in brain activity evoked by sound versus unsound analogies. The presentation will detail the methods and results for two such experiments, one in which participants saw analogies formed of neutral and negative words and one in which they were created by combining conditioned symbols. I will also briefly discuss future research aiming to investigate the effects of analogical reasoning on brain activity related to affective processing.

Environmental boundaries anchor cognitive maps that support memory. However, trapezoidal boundary geometry distorts the regular firing patterns of entorhinal grid cells proposedly providing a metric for cognitive maps. Here, we test the impact of trapezoidal boundary geometry on human spatial memory using immersive virtual reality. Consistent with reduced regularity of grid patterns in rodents and a grid-cell model based on the eigenvectors of the successor representation, human positional memory was degraded in a trapezoid compared to a square environment; an effect particularly pronounced in the trapezoid’s narrow part. Congruent with spatial frequency changes of eigenvector grid patterns, distance estimates between remembered positions were persistently biased; revealing distorted memory maps that explained behavior better than the objective maps. Our findings demonstrate that environmental geometry affects human spatial memory similarly to rodent grid cell activity — thus strengthening the putative link between grid cells and behavior along with their cognitive functions beyond navigation.

Working memory is the sketchpad of consciousness, the fundamental mechanism the brain uses to gain volitional control over its thoughts and actions. For the past 50 years, working memory has been thought to rely on cortical neurons that fire continuous impulses that keep thoughts “online”. However, new work from our lab has revealed more complex dynamics. The impulses fire sparsely and interact with brain rhythms of different frequencies. Higher frequency gamma (>35 Hz) rhythms help carry the contents of working memory while lower frequency alpha/beta (~8-30 Hz) rhythms act as control signals that gate access to and clear out working memory. In other words, a rhythmic dance between brain rhythms may underlie your ability to control your own thoughts.

Episodic memory performance decreases with advancing age. According to theoretical models, such memory decline might be a consequence of age-related reductions in the ability to form distinct neural representations of our past. In this talk, I want to present our new age-comparative fMRI study investigating age-related neural dedifferentiation across different representational levels. By combining univariate analyses and searchlight pattern similarity analyses, we found that older adults show reduced category selective processing in higher visual areas, less specific item representations in occipital regions and less stable item representations. Dedifferentiation on all these representational levels was related to memory performance, with item specificity being the strongest contributor. Overall, our results emphasize that age-related dedifferentiation can be observed across the entire cortical hierarchy which may selectively impair memory performance depending on the memory task.

Natural soundscapes such as from a forest, a busy restaurant, or a busy intersection are generally composed of a cacophony of sounds that the brain needs to interpret either independently or collectively. In certain instances sounds - such as from moving cars, sirens, and people talking - are perceived in unison and are recognized collectively as single sound (e.g., city noise). In other instances, such as for the cocktail party problem, multiple sounds compete for attention so that the surrounding background noise (e.g., speech babble) interferes with the perception of a single sound source (e.g., a single talker). I will describe results from my lab on the perception and neural representation of auditory textures. Textures, such as a from a babbling brook, restaurant noise, or speech babble are stationary sounds consisting of multiple independent sound sources that can be quantitatively defined by summary statistics of an auditory model (McDermott & Simoncelli 2011). How and where in the auditory system are summary statistics represented and the neural codes that potentially contribute towards their perception, however, are largely unknown. Using high-density multi-channel recordings from the auditory midbrain of unanesthetized rabbits and complementary perceptual studies on human listeners, I will first describe neural and perceptual strategies for encoding and perceiving auditory textures. I will demonstrate how distinct statistics of sounds, including the sound spectrum and high-order statistics related to the temporal and spectral correlation structure of sounds, contribute to texture perception and are reflected in neural activity. Using decoding methods I will then demonstrate how various low and high-order neural response statistics can differentially contribute towards a variety of auditory tasks including texture recognition, discrimination, and categorization. Finally, I will show examples from our recent studies on how high-order sound statistics and accompanying neural activity underlie difficulties for recognizing speech in background noise.

Did we eat spaghetti for lunch because we saw our colleague eat spaghetti? What drives a risk decision? How can our breakfast impact our decisions throughout the day? Research from different disciplines such as economics, psychology and neuroscience have attempted to investigate the motives and modulators of human decision making. Human decisions can be flexibly modulated by the different experiences we have in our daily lives, at the same time, bodily processes, such as metabolism can also impact economic behavior. These modulations can occur through our social networks, through the impact of our own behavior on the social environment, but also simply by the food we have eaten. Here, I will present a series of recent studies from my lab in which we shed light on the psychological, neural and metabolic motives and modulators of human decision making.

As Socrates said that "I know that I know nothing," our mind's function to be aware of our ignorance is essential for abstract and conceptual reasoning. However, the biological mechanism to enable such a hierarchical thought, or meta-cognition, remained unknown. In the first part of the talk, I will demonstrate our studies on the neural mechanism for metacognition on memory in macaque monkeys. In reality, awareness of ignorance is essential not only for the retrospection of the past but also for the exploration of novel unfamiliar environments for the future. However, this proactive feature of metacognition has been understated in neuroscience. In the second part of the talk, I will demonstrate our studies on the neural mechanism for prospective metacognitive matching among uncertain options prior to perceptual decision making in humans and monkeys. These studies converge to suggest that higher-order processes to self-evaluate mental state either retrospectively or prospectively are implemented in the primate neural networks.

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

The brain is a prediction machine. Yet the world is never entirely predictable, for any animal. Unexpected events are surprising and this typically evokes prediction error signatures in animal brains. In humans such mismatched expectations are often associated with an emotional response as well. Appropriate emotional responses are understood to be important for memory consolidation, suggesting that valence cues more generally constitute an ancient mechanism designed to potently refine and generalize internal models of the world and thereby minimize prediction errors. On the other hand, abolishing error detection and surprise entirely is probably also maladaptive, as this might undermine the very mechanism that brains use to become better prediction machines. This paradoxical view of brain functions as an ongoing tug-of-war between prediction and surprise suggests a compelling new way to study and understand the evolution of consciousness in animals. I will present approaches to studying attention and prediction in the tiny brain of the fruit fly, Drosophila melanogaster. I will discuss how an ‘active’ sleep stage (termed rapid eye movement – REM – sleep in mammals) may have evolved in the first animal brains as a mechanism for optimizing prediction in motile creatures confronted with constantly changing environments. A role for REM sleep in emotional regulation could thus be better understood as an ancient sleep function that evolved alongside selective attention to maintain an adaptive balance between prediction and surprise. This view of active sleep has some interesting implications for the evolution of subjective awareness and consciousness.

Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans – which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.

I will begin by describing recent research taking a new, model-based approach to perceptual development. This approach uncovers fundamental changes in information processing underlying the protracted development of perception, action, and decision-making in childhood. For example, integration of multiple sensory estimates via reliability-weighted averaging – widely used by adults to improve perception – is often not seen until surprisingly late into childhood, as assessed by both behaviour and neural representations. This approach forms the basis for a newer question: the scope for the nervous system to deploy useful computations (e.g. reliability-weighted averaging) to optimise perception and action using newly-learned sensory signals provided by technology. Our initial model system is augmenting visual depth perception with devices translating distance into auditory or vibro-tactile signals. This problem has immediate applications to people with partial vision loss, but the broader question concerns our scope to use technology to tune in to any signal not available to our native biological receptors. I will describe initial progress on this problem, and our approach to operationalising what it might mean to adopt a new signal comparably to a native sense. This will include testing for its integration (weighted averaging) alongside the native senses, assessing the level at which this integration happens in the brain, and measuring the degree of ‘automaticity’ with which new signals are used, compared with native perception.