Spring 2024

Translational Models for Psychosis Research

April 18, 2024

Rapaporte Treasure Hall, Goldfarb Library, 12:20pm

Phil Corlett, Yale University School of Medicine


Computational approaches to explaining the symptoms of psychiatric illnesses are undergoing a renaissance. This chapter will describe the development of computational approaches to psychotic symptoms  through a series of phases: from conceptual, to empirical, and quantitative. The strengths of the approach include the ability to connect levels of explanation – from epidemiological data down to circuit neuroscience. The work suggests that delusions are aberrant beliefs driven by inappropriate prediction errors and hallucinations are errant percepts driven by overweighted prior beliefs. In order to unite these two symptom categories theorists and empiricists have begun to examine volatility processing. When the world is perceived to be changing unpredictably an organism is faced with two possibilities – learn quickly to pre-empt the changes or ignore that signals that change is afoot. These two strategies may underwrite delusions and hallucinations respectively and each may be implemented in independent neural circuits, each responding to aberrant signals of volatility. Furthermore, the social content of delusions and hallucinations demands explanation. Computational psychiatrists appeal either to a domain specific problem with social cognition or a domain general issue with inference. Future work in computational psychiatry, building upon the progress already made, will continue to refine the hypothesis space, ideally leading to a deeper understanding and better treatments for psychosis.


Lumping and Splitting: Insights into Executive Functions from Individual Differences Analyses

Naomi Friedman, University of Colorado Boulder

AbstractExecutive functions are general purpose, high-level cognitive processes that enable individuals to regulate their thoughts and actions during goal-directed behavior.  Individual differences in executive function abilities are associated with academic achievement and everyday self-regulation, and executive function deficits are implicated in a number of psychiatric disorders. Across different sub-areas of psychology, executive functions are often lumped with conceptually similar constructs, such as self-reported impulse control and general cognitive ability. In this talk, I will discuss some of my recent work probing the relations of executive functions to these constructs at multiple levels of analysis. This work suggests that executive functions are phenotypically and genetically separable from these constructs, and, importantly, predict independent variance in psychopathology. Thus, measures of executive functions, general cognitive ability, and impulse control are not interchangeable, and considering what distinguishes them at the psychological, neural, and genetic levels can increase insights into associated mental health disorders.

Neurocognitive models of sustained attention and their clinical application

Michael Esterman, Boston University, School of Medicine

Abtract:  Sustaining a moderate level of attention over time is critical to the performance of many everyday activities, such as driving, reading, or listening to a lecture. Remaining focused is challenging, however, and, in reality, our attention waxes and wanes.  At times our attention is focused on task goals, while at others our focus is lost through distraction, fatigue, or lack of motivation. Although such fluctuations in attention are commonplace, only recently has research been dedicated to better understanding their occurrence, their clinical relevance, and their relationship to ongoing brain activity. I will introduce our neurocognitive approach to characterizing intra- and interindividual differences sustained attention. I will next demonstrate, using an information processing perspective, how sustained attention is linked to coordinated activity in multiple brain networks. Using this framework, I will illustrate that attention can be impacted negatively across a range of pathologies, with a particular focus traumatic stress. Finally, I will highlight how sustained attention and the underlying neural circuits can serve as targets for interventions aimed at enhancing cognitive and mental health. 

Neural Dynamics of Music

Ed Large, University of Connecticut

Abstract: A great deal of research in the neuroscience of music focuses on expectation. Violations of
musical expectancies are thought to lead to affective responses, such as chills, and embodied responses,
such as groove, which form the basis of rewarding musical experiences. Neural resonance theory
(NRT) holds that the neural oscillations synchronize with musical stimuli, and expectation is a
consequence of synchronization. But it is not the only one. The theory also predicts statistically
universal structures such as pitch, interval, tonality, and meter, to arise from physical resonance,
corresponding to (meta) stable states of complex, pattern-forming dynamical systems. In other words,
the interaction of certain kinds of sounds with ongoing pattern-forming dynamics results in structured
patterns of perception, action, and coordination that we collectively experience as music. The theory is
based on simple dynamical principles such as resonance, stability, attunement (adaptation), and time
delay. Musical structures depend on intrinsic dynamics, tuned by previous experience, and coupled to
the environment. I will contrast NRT with other approaches to expectation such as predictive coding. I
argue that people anticipate events not through brain-bound predictive processes, but because neural
and ecological dynamics physically embody musical structure.

Previous Colloquiums

Dynamic Visual Attention and Perception

Julie Golomb, Ohio State University

Abstract: How does our visual system make sense of the world around us? Our brains construct incredibly rich visual experiences from the rawest of visual inputs: patterns oflight on our retinas. In a fraction of a second, we integrate this information to recognize objects, deduce their locations and trajectories, and encode relevant information into memory. Visual attention plays a critical role in all of these processes. But in the real world, visual attention is rarely stable. How do attention, perception, and memory interact under dynamic conditions? Recent work from my lab has revealed widespread perceptual and neural consequences of dynamic attention, including findings that the costs of spatial distraction can ripple across various cognitive processes, resulting in altered visual feature perception and disruption of neural filters gating category­ tuned object processing and visual working memory access. I'll end by discussing some of our ongoing efforts to use - and improve -- model-based £MRI and EEG approaches to reconstruct the internal contents of attention under both static and dynamic scenarios.

Language as a life experience: How using two languages shapes the bilingual mind and brain

Judith F. Kroll, University of California, Irvine 

In the last two decades there has been an upsurge of research on the bilingual mind and brain. Although the world is multilingual, only recently have cognitive and language scientists come to see that the use of two or more languages provides a unique lens to examine the neural plasticity engaged by language experience. How does bilingualism change the mind? It is now uncontroversial to claim that the bilingual's two languages are continually active, creating a dynamic interplay across them. But there continues to be controversy about the consequences of that cross-language exchange for how cognitive and neural resources are recruited when a second language is learned and used actively and whether native speakers of a language retain privilege in their first acquired language. In the earliest months of life, minds and brains are tuned differently when exposed to more than one language from birth. That tuning has been hypothesized to open the speech system to new learning. For the oldest bilingual adults, there is evidence that a life of being bilingual confers protections against cognitive decline. In this talk, I illustrate the ways that recent studies have shown that the minds and brains of bilinguals are inherently complex and social, taking into account the variation in contexts in which the two languages are learned and used, and shaping the dynamics of cross-language exchange across the lifespan.

Uncertainty and the Social Brain

 Anna C. Jenkins, PhD University of Pennsylvania

To make social decisions, people often rely on information about the hidden contents of other minds, including what other people think or feel, how they might react, or what they might do. Does the person asking for money actually need to take a bus, or is she trying to deceive you? Are your friends adventurous enough to enjoy the new restaurant you want to try? Although information about the minds of others is sometimes provided explicitly in the environment, more often it must be inferred or predicted under conditions of uncertainty. In this talk, I will discuss recent behavioral and fMRI evidence from my lab for elevated uncertainty in social (compared to non-social) contexts and its consequences for social thought and behavior. 


The Effects of Spaceflight on the Human Brain and Behavior

 Rachael Seidler , PhD University of Florida

Emerging plans for travel to Mars and other deep space destinations make it critical for us to understand how spaceflight affects the human brain and behavior. Moreover, studying adaptation to the microgravity environment provides insight into how the central nervous system responds to an environment for which it has not evolved. I will share findings from my work indicating that the spaceflight environment induces adverse effects on the brain, including intracranial fluid shifts, gray matter changes, and white matter declines. I will also present evidence that adaptive processes co-occur with these brain position and intracranial fluid shifts. I will close with recommendations for future research.

Heroic Bodies and their Burdens: Taking Homeric 'Psychology' Seriously

 Joel Christensen, PhD Brandeis University

This talk will survey 20th century psychological approaches to ancient Epic in order to frame the place of my recent book, The Many Minded Man, in classical scholarship. I will provide a summary of how I have used principles and insights from modern clinical and cognitive psychology to help us understand challenging structural and interpretive features of the Odyssey, focusing in particular on the Homeric depiction of Telemachus and the end of the Poem. I will close by talking about how some of these approaches apply to the Iliad and why reframing Greek epic as therapeutic rather than literary is important.

Embedding of early adversity: evidence that early experience shapes risk for health and wellbeing through shaping neural structure and function.

 Margaret Sheridan, PhD University of North Carolina

Dr. Sheridan will present her work investigating if and how early adversity impacts brain and behavioral development. In particular, she investigates the way in which experiences in early childhood shape risk for psychopathology across the lifespan. Dr. Sheridan's work includes some of the only causal longitudinal evidence in humans documenting the impact of adversity on brain and behavioral development long-term. In addition, Dr. Sheridan focuses on how early experiences shape brain development delineating associations between dimensions of experience, measurable across a variety of exposures, and cognitive and neural processes in early childhood and adolescence.

Dynamic Representations For Behavioral Flexibility

 Matt Nassar, PhD Brown University

People flexibly adjust their use of information according to context. The same piece of information, for example the unexpected outcome of an action, might be highly influential on future behavior in one situation -- but utterly ignored in another one. Bayesian models have provided insight into why people display this sort of behavior, and even identified potential neural mechanisms that link to behavior in specific tasks and environments, but to date have fallen short of providing broader mechanistic insights that generalize across tasks or statistical environments. Here I'll examine the possibility that such broader insights might be gained through careful consideration of task structure. I'll show that we can think about a large number of sequential tasks as requiring the same inference problem -- that is to infer the latent states of the world and the parameters of those latent states -- with the primary distinctions within the class defined by transition structure. Then I'll talk about how a neural network that updates latent states according to a known transition structure and learns "parameters" of the world for each latent state can explain adaptive learning behavior across environments and provide the first insights into neural correlates of adaptive learning across environments. This model generates internal signals that identify the need for latent state updating, which maps onto previous observations made in pupil dilations and P300 responses across different task environments. I will also discuss an experiment that we are currently setting up to test the idea that these signals might reflect a latent state update signal, with a focus on relationships to learning and perception. Finally, I discuss how deviations from normative structure learning might give rise to aberrant belief updating in mental illness.

Cognitive and Neural Representations of Time

 Marc Howard, PhD Boston University

Time is central to our experience.   As events unfold we remember the past and anticipate the future. Recent years have seen progress in our understanding of how the brain represents the time of past events.  After a stimulus is experienced, so-called "time cells" activate in a reliable sequence.  Because the sequence is reliable, at any moment we can decode how far in the past the stimulus was presented.  Because different stimuli trigger different sequences we can use the activity of time cells in the present to decode what happened when in the past.   These findings from neuroscience have been paralleled, and in many cases anticipated, by empirical results and computational models from cognitive psychology.   Findings using response times from short-term memory experiments suggest that people can "scan" a timeline of the recent past to find a target in much the same way that they can scan a visual display.  We review recent evidence (Tiganj, Singh, et al., 2022; JEP:G) showing that people can also scan a timeline of the proximate future.  This suggests that the brain manages somehow to construct an ordered timeline of the future that mirrors the representation of the time of past events.

New Insights into Aging through the Lens of Network Neuroscience

Dr. Anne Krendl, Indiana University

Healthy aging has been widely shown to have deleterious impacts on older adults’ (individuals over the age of 60) cognitive function, including their memory, executive function, and social cognition. Although the mechanisms associated with these declines have been widely studied, numerous questions remain. We thus used a network neuroscience approach to provide new insights into the effects of aging on the structure and function of brain networks. We focus specifically on the networks that support theory of mind (inferring others’ mental states), a core social cognitive function. There are two goals of this work: 1) to characterize how older adults’ brain networks differ from young adults’ (individuals between the ages of 18-30) at rest and during task; and 2) to characterize how these differences might affect older adults’ theory of mind. Together, these data will reveal more specific mechanisms of how aging impacts social cognitive function.

Motivations to Learn: Regulation of Distinct Neural Contexts for Adaptive Memory Systems

 Dr. Alison Adcock, Duke University

Motivation guides and animates behavior based on predictions from memory representations. The role of motivation in reinforcement learning has long been studied in animal paradigms that require extrinsic incentives. Ironically, however, neuroscience is only recently coming to study how motivation guides memory to assemble complex models of the world and the pursuit of knowledge – motives that guide science itself. Now, a fortuitous explosion of tools for understanding the biology of human cognition allows linking such questions to the long and rich experimental traditions in animals. Specifically, the ability to characterize brain configurations associated with distinct motivational states offers exciting new insights into neuromodulatory systems associated with motivation and the neural foundations of adaptive memory formation. These biological findings, in turn, point to new behavioral predictions and questions about learning and memory. The work of the Adcock laboratory is to understand how motivation shapes memory formation and to help leverage that understanding to improve education, learning-based therapies, and biological targets for well-being. In this talk, I review our work to selectively use behavior to change the brain and to understand how motivational regulation may support specialized memories for successful human adaptation.

Influences of Age and Culture on Memory

 Dr. Angela Gutchess, Department of Psychology, Brandeis University

In my talk, I will discuss research my lab has conducted investigating the influences of aging and culture on memory. Although many losses and changes occur in traditional memory systems with age, declines may be more pronounced in some domains than others, some strategies may help to mitigate changes in memory, and the effectiveness of strategies could vary across individuals. I will discuss two lines of work, the first examining how self-referencing, relating information to the self, impacts memory and neural engagement. The second will focus on cross-cultural differences in memory, exploring how culture can act as a lens to shape information processing in terms of memory for specific visual details, the ways in which cultures differ in the engagement of underlying neural regions, and how these cultural differences could be impacted by aging.

Taste Quality Representations in Human EEG Predict Taste-Related Behavior

  Dr. Kathrin Ohla, Cognitive Neuroscience, Forschungszentrum Jülich, Germany

 The taste system provides important information about the edibility and makro-nutrient content of a food via differentiation between taste qualities. Specific receptors on the tongue are activated by chemicals signifying a taste quality before the signal is conveyed to the brain. How this peripheral signal is used by the central nervous system to encode taste quality is largely unknown. Cortical activation patterns change rapidly, within milliseconds, rendering temporal information a candidate variable for taste quality coding. Using non-invasive electrophysiological recordings, which provide a window into taste-neuronal processing with millisecond resolution, I will illustrate that large-scale neuronal response patterns carry information about taste quality and bear significance to taste-related behavior. I will demonstrate that these neuronal response patterns carry information about which taste participants tasted and that their onset predicts the timing of perceptual decisions. Furthermore, I will present novel data that suggest that taste perception and neuronal responses are susceptible to information. Together, I aim to show that the information encoded in taste-related neural response patterns is also the foundation for gustatory decision-making and that the timing aligns with task-specific goals.

The role of vicarious neural activations in experience sharing – Pitfalls and promise for cross-group empathy

 Dr. Jennifer Gutsell, Department of Psychology, Brandeis University

With increasing diversity in society and organizations, intergroup interactions will become a much more integral part of every American's day to day experience, requiring empathy, perspective-taking, and cooperation that can transcend across group boundaries. My and others' work shows that neural resonance, a basic neural process involved in these critical social functions, might be reduced or even absent during intergroup interactions. Usually, people show similar neural activation during experience and observation of similar experiences in others, and such neural resonance is thought to provide a basic, embodied understanding of the other's state potentially contributing to empathy. Often neural resonance has been thought of as a bottom-up process, but we now understand that it is affected by top-down cognitive and motivational factors including those based on social perception, biases, and the broader interaction context. In this talk, I will first review studies that suggest an ingroup bias in neural resonance: People show neural resonance in response to the actions and emotions of ingroup members, but not in response to the actions and emotions of outgroup members. I will then highlight biased empathy as a potential consequence of neural resonance biases by looking at to what extent neural resonance is associated with the tendency to empathize and with how accurately people infer others affective states. Finally, I will present a series of studies that explore facilitating and hampering conditions for cross-group neural resonance. I will end with an outlook on the methodological challenges and potential solutions to study neural processing involved in cross-group empathy within naturalistic interaction settings that take place in a broader cultural context.

Banishing Ghosts of Process from the Neural Machinery of Human Memory: A Representational Account of Cognition

 Dr. Rosie Cowell, University of Massachusetts, Amherst

Abstract:  Accounts of cognition often assume that the brain is organized along lines of cognitive process, for example, with recollection mediated by one neural substrate and familiarity by another. We argue that cognitive processes – introspectively-identifiable mental events like recollection – are inadequate labels for characterizing neural mechanisms, because they conflate lower-level components of the mechanisms we seek to identify. Recollection involves both a neurocomputational operation (pattern completion) and a neural representation (high-dimensional, associative content). To uncover memory's mechanisms, we must decompose cognitive processes into their operations and representations, asking how each separately, and their interaction, gives rise to neural and behavioral phenomena. I will present theoretical and empirical work ‒ including connectionist simulations and fMRI data ̶ that implies we can replace process-based accounts of memory with a representational account. In other words, rather than explaining what different brain regions do by appeal to cognitive processes (e.g., recollection happens in hippocampus and familiarity in neocortex), we should appeal to representational content (high-dimensional representations are supported by hippocampus and lower-dimensional representations by neocortex).

"Measuring and overcoming cognitive challenge in speech comprehension"

 Dr. Jonathan Peelle, Washington University in St. Louis

Abstract: How does acoustic clarity affect the way our brains process speech, and how might this change with adult aging? I will review data from behavioral and brain imaging studies that speak to the added cognitive demands associated with acoustic challenge. Findings support a shared resource framework of speech comprehension in which domain-general cognitive processes are required for both auditory and linguistic processing. The specific patterns of neural activity depend on the difficulty of the speech being heard, as well as the hearing and cognitive ability of each individual listener. I will also talk about some preliminary work looking at how we might be able to help listeners compensate for cognitive challenges and improve their understanding of what they are hearing.

"Memory networks in the human brain"

 Dr. Mike Kahana, UPenn

Abstract: Human memory function is highly variable, fluctuating between periods of high and low performance even within a given person. Neurosurgical patients with indwelling electrodes present a unique opportunity to study the neural correlates of this variability and to define both the features of neural activity at a given brain location and the functional connections between brain regions that predict variability in memory encoding and retrieval. Here, I will describe our recent efforts to characterize brain networks that support memory via correlative (passive neural recording) and causal (direct electrical stimulation) approaches. Throughout the brain, we find that low-frequency networks exhibit reduced local power but stronger functional connectivity during successful episodic encoding and retrieval. Furthermore, many canonical memory regions emerge as hubs of such low-frequency connections, including the lateral frontotemporal cortices, the parahippocampal gyrus – and within it – the entorhinal cortex. High-frequency bands (i.e. gamma, 30+ Hz) almost exclusively exhibit desynchronization during successful memory operations. We recently extended these correlative studies and used intracranial stimulation to ask whether functional connections imply causality. We confirmed that electrical stimulation evokes increases in theta power at remote regions, as predicted by the strength of low-frequency functional connections. This relation was strongest when stimulation occurred in or near white matter. These findings demonstrate the importance of low-frequency connectivity to episodic memory, integrating these findings over spatial scales and through causal and correlative approaches.

Developmental tuning of action selection

 Dr. Catherine Hartley, NYU

Abstract:  Computational reinforcement learning models provide a framework for understanding how individuals can evaluate which actions are beneficial and which are best avoided. To date, these models have primarily been leveraged to understand learning and decision-making in adults. In this talk, I will present studies characterizing developmental changes, from childhood to adulthood, in the cognitive representations and computations engaged to evaluate and select actions. I will discuss how these changes may optimize behavior for an individual’s developmental stage and unique life experiences.