3 April 2024: Ecological drivers of emotion and their links to individual differences in depression

Aaron Heller
Department of Psychology
University of Miami

The specific way emotions ebb and flow in life differentiate someone who has depression from someone who do not. Given such a central role for emotion in well-being and psychopathology, it is critical that we understand what causes emotion in everyday life and whether these emotional causes tell us anything about mental health. It is especially important to understand what causes real-world emotion because to be able change emotion we need to understand what drives it in the first place. Using a combination of mobile tracking, experience sampling, and functional neuroimaging methods, I will present studies addressing the role that deviations from expectations play in driving naturalistic emotion, that deviations from expectations drive emotion differently in people who are depressed from those who are not, and that deviations from expectations are learning signals that help explain how individuals may develop mental health difficulties. This work suggests that how we form, update, and respond to real-world expectations play a key role in promoting well-being as well as preventing psychopathology.  

View a recording of this session here.

20 March 2024: Translation, Treatment and Technology: An Integrative Approach to Pediatric Psychopathology

Melissa Brotman
Neuroscience and Novel Therapeutics Unit
National Institute of Health

The goal of the Neuroscience and Novel Therapeutics Unit (NNT) is to develop and test psychological treatments for anxiety and irritability, two of the most common and impairing pediatric mental health problems. Despite their prevalence and public health impact, advances in treatment have stalled. To capitalize on this opportunity, NNT deploys an experimental medicine approach. First, we identify and probe mechanistically relevant behaviors and corresponding brain-based dysfunction. Second, we develop interventions modifying putative behavioral and neural targets integrating in vivo, mobile metrics. Our work implicates two psychological processes in both anxiety and irritability: (1) aberrant threat processing, and (2) impaired inhibitory control. Exposure therapy, a behavioral technique, engages both threat (e.g., salience network) and inhibition (e.g., executive control networks). Exposure therapy is a first line treatment for anxiety disorders. However, the neural mechanisms mediating improvement remain unknown. Critically, the clinical application beyond fear-based disorders has only recently been considered. Both clinically impairing irritability and anxiety are stimulus-evoked, high arousal, negative valence states, with differential downstream behavioral manifestations.

In this presentation, I will present two studies. First, in a large, unmedicated sample of youth with anxiety disorders and healthy controls, we identified specific brain-based regions associated with clinical improvement in anxiety (e.g., fronto-parietal regions), as well as subcortical circuitry (e.g., amygdala) showing sustained dysfunction following exposure therapy. Second, because like fear, anger is an acute stimulus driven emotional state, we conceptualized, tested, and demonstrated efficacy for a novel application of exposure therapy for youth with impairing irritability and anger. I will also share some early work where we are augmenting our work on brain-based behavioral therapeutics by developing, assessing, and validating digital mobile health applications.

View a recording of this session here.

6 March 2024: Circuit Mechanisms Determining Dopamine’s Role In Learning Versus Moving

Christine Constantinople
NYU Center for Neural Science
New York University

Midbrain dopamine (DA) neurons are thought to be critical for reinforcement learning as well as motor control. A major outstanding question for the field is understanding how dopamine can satisfy these dual functions within the striatum, the input structure of the basal ganglia. I will describe our ongoing efforts to reconcile these dual functions of dopamine using rats performing a value-based decision-making task that includes reward- and movement-related events at distinct time points. Fiber photometry measurement of DA release in dorsomedial striatum revealed that only some event-aligned phasic DA signals were accompanied by movement, the amplitude of which predicted the vigor of upcoming contralateral movements. Phasic DA in the absence of movement signaled reward prediction errors (RPEs) and modulated rats’ behavior on subsequent trials. Electrophysiological recordings in the dorsomedial striatum showed trial-by-trial changes in firing rates at RPE-associated events, but not at movement-associated events. These data demonstrate DA-dependent plasticity and behavioral change following RPE on a trial-by-trial basis. To explain the dual role of DA in supporting movement and learning at distinct time points within a single trial, we hypothesized that acetylcholine’s (ACh) effect on striatal cell excitability may act as a gating mechanism. Fiber photometry measurement of ACh release in DMS revealed a unique pre-burst rise in ACh at movement initiation, and dips at RPE events, and optogenetic activation of ACh cells reliably initiated movements and impaired learning. These data suggest that the neuromodulator acetylcholine dynamically gates whether dopamine in the striatum is used for learning or moving on a moment-by-moment basis.

View a recording of this session here.

21 February 2024: How can we do better? Identifying mechanisms of action as a path to precision psychotherapies for depression

Nili Solomonov
Department of Psychiatry
Weil Cornell Medical College

Psychotherapy is effective in reducing depression. Yet, 40-60% of patients remain symptomatic at treatment end. Identifying brain‐based and clinical mechanisms of action that underlie symptomatic improvement can guide the development of neuroscience‐informed, scalable and effective interventions. Dr. Solomonov will present studies conducted using imaging and computational approaches to detect mechanisms of action and improve psychotherapies. Studies will focus on understudied populations, including middle‐aged and older adults, mothers with postpartum depression and healthcare workers suffering from depression and anxiety.ffort and critical dynamics in EEG data while participants perform various levels of the N-back working memory task.

View a recording of this session here.

7 February 2024: Dopamine kinetics and brain function: insights from simultaneous PET-fMRI

Peter Manza
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Health

The addictiveness of stimulant drugs such as methylphenidate (MP) depends crucially on how fast they raise dopamine in the brain. Yet the brain circuits underlying the rate dependency to drug reward have not been resolved. We used simultaneous PET-fMRI to link dynamic changes in brain dopamine signaling, functional brain activity/connectivity, and the self-reported experience of ‘high’ in 20 healthy adults receiving MP at different speeds: slow (oral 60mg) and fast (intravenous-IV 0.25mg/kg) doses in a double-blind, counterbalanced, placebo-controlled study. We estimated speed of striatal dopamine increases to oral and IV MP and then tested where brain activity/connectivity was associated with slow and fast dopamine kinetics. The two administrations produced dramatically different effects on brain functional activation and connectivity despite a comparable overall magnitude of dopamine increases. These data demonstrate how fast dopamine increases generate unique effects on brain function that have relevance for the addictive potential of drugs.

View a recording of this session here.

13 December 2023: Cognitive and neural markers of foraging during memory search for understanding thought and speech organization in psychosis

Nancy Lundin
Department of Psychiatry and Behavioral Health
The Ohio State University

Thought disorder is a cardinal feature of psychotic disorders, described as disorganized, tangential, illogical, and/or impoverished thought observed through speech. Higher levels of thought disorder relate to poorer functioning and long-term outcomes among individuals with psychotic disorders, yet the cognitive and neural underpinnings of this set of symptoms remain poorly understood. “Semantic foraging” is a new theoretical framework for examining potential processes underlying thought disorder with bases in behavioral ecology and cognitive science. Just as non-human animals search for food and mates by exploiting local patches of the environment and leaving to explore new patches when resources are depleted, humans may search for related concepts in memory using similar explore-exploit trade-offs. This has been studied using the verbal fluency test, in which individuals name items from a particular category or beginning with a particular letter in a limited time and often “cluster” (exploit) and “switch” (explore) between related groupings of items to optimize performance. In this seminar, I will discuss research examining search strategies during verbal fluency word retrieval tasks among individuals with psychotic disorders indicating preliminary evidence of alterations in semantic foraging, such as lower semantic similarity and longer interitem response times during search for related items than comparison groups. I will also discuss findings of neural signatures of semantic foraging processes from a study in which participants without a psychiatric diagnosis performed verbal fluency tests during functional magnetic resonance imaging (fMRI). We found that switching to new patches of related items was associated with activation in the hippocampus or posterior cerebellum depending on the way switching was operationalized (i.e., switches designated post hoc by participants versus computational metrics of similarity). Moreover, these regions exhibited activity which linearly increased during within-cluster search and re-set once a participant switched to a new patch, suggesting potential cognitive monitoring processes guiding the search. I will close with discussion of several future directions of this work. These include the need for replication of findings and consolidation of methodologies, with a particular focus on addressing the challenges to defining patch boundaries for when someone has stopped exploiting and started exploring, given the multifaceted ways in which concepts are related. Additional future directions include investigating the neural correlates of altered semantic foraging patterns among individuals with psychotic disorders and, most importantly, testing whether these explore-exploit patterns serve as a reliable marker of the production of cohesive speech to identify treatment targets for thought disorder.

View a recording of this session here.

29 November 2023: Using Virtual Hallucinations to understand the Sense of Reality

Roy Salomon
Department of Cognitive Science
University of Haifa

We all rely on our senses to convey veridical information about the world around us, which we call “Reality”. However, distortions of reality in the form of hallucinations or illusions originating from neurological, psychiatric, pharmacological or psychological origins are prevalent. Thus, the sense of reality, the capacity to discriminate between true and false perceptions of the world, is a central criterion for neurological and psychiatric health. Despite the critical role of the sense of reality in our daily life, little is known about how this is formed in the mind and brain. The UnReal project explores the phenomenological, computational and neural processes underlying the Sense of Reality (SoR). We employ a specialized immersive virtual reality environment along with psychophysical paradigms to construct personalized “virtual hallucinations”. These “virtual hallucinations” are then used to modify the sense of reality while recording behavioral, ocular and neurophysiological responses to these perturbations of reality. Our results show differential behavioral and physiological responses to virtual hallucinations across different domains indicating divergent underlying models of reality. Developmental experiments along with computational modeling allowed us insight into the evolution of the sense of reality. This work may help to define a neurocognitive model of reality across healthy and clinical populations, and shed new light upon the fundamental philosophical question of “how do we know what is real?”.

View a recording of this session here.

15 November 2023: Mathematical and Computational Modeling of Suicidal Thoughts and Behaviors

Shirley Wang
Department of Psychology
Yale University

Suicide is a leading cause of death worldwide, claiming over 800,000 lives each year. Unfortunately, whereas scientific advances have led to declines in other leading causes of death over time, the current suicide rate is nearly identical to what it was 100 years ago. In order to make meaningful progress, new methods and approaches are needed that can capture and model the immense complexity of suicide and other forms of self-harm. In the first half of this talk, I will present a series of studies harnessing machine learning and real-time monitoring to predict who is at risk for suicide and when risk is highest. In the second half of this talk, I will take a complementary theory-driven computational approach to investigate why and how suicide and self-harm arise by building formal mathematical models of these phenomena as complex dynamical systems. Together, this work may help us advance the understanding, prediction, and prevention of suicide and self-harm.

View a recording of this session here.

8 November 2023: Neuromodulation and cognitive effort

Andrew Westbrook
Robert Wood Johnson Medical School
Rutgers University

Cognitive control is effortful, causing people to avoid demanding tasks, and undermining their goal-directed behavior. Yet the nature of effort costs, and the systems biasing decisions to exert or withhold effort are largely unknown. Striatal dopamine promotes physical effort for reward, by increasing sensitivity to reward benefits and decreasing sensitivity to effort costs. In the first part of my talk, I will discuss evidence that, as with physical action, striatal dopamine boosts motivation for cognitive effort as well. In a study combining [18F]-DOPA PET imaging of dopamine synthesis capacity with dopamine transport blocker methylphenidate, the D2 agent sulpiride, and placebo, we find that greater striatal dopamine signaling biases participants to choose harder working memory tasks to earn more money over easier tasks for less money. Moreover, gaze-informed drift diffusion modeling supports the inference that dopamine signaling increases willingness to exert effort by making people more sensitive to the benefits, and less sensitive to the costs of cognitive work.

In the second part of this talk, I consider a novel hypothesis about the nature of effort costs. Namely, that subjective cognitive effort is a phenomenological readout of divergence from criticality in the brain. Brains at rest exhibit emergent properties indicative of a dynamical system near a critical point – regulated by the balance of cortical excitation to inhibition. These properties are monotonically suppressed with increasing cognitive load, reflecting increasing divergence from criticality. Importantly, because criticality maximizes functional flexibility and information processing capacity, divergence implies computational costs. In my talk, I will discuss the rationale for the hypothesis linking subjective effort and criticality. I will also discuss a first study examining subjective cognitive effort and critical dynamics in EEG data while participants perform various levels of the N-back working memory task.

View a recording of this session here.

25 October 2023: Modeling Decision-Making in Schizophrenia: Associations Between Computationally Derived Risk Propensity and Self-Reported Risk Perception

Emma Herms
Department of Psychological & Brain Sciences
Indiana University

Risk-taking is an integral part of decision-making. We take small risks throughout our daily life, from not feeding a parking meter to asking someone on a date. Taking risks in moderation can be advantageous – nothing ventured, nothing gained – and is an important part of learning. In contrast, taking too much or even too little risk may be disadvantageous. Thus, we are interested in the extent to which individuals with psychosis pursue risky rewards. A major limitation of task-based risky decision-making in psychosis-spectrum samples is that cognitive impairments are not typically controlled for, or explicitly examined (Purcell et al., 2021). In the current talk, I will present evidence from the Balloon Analogue Risk Task (BART), an uncertain-risk task where participants integrate information across trials to learn and weigh relative outcome probabilities. In this case, the likelihood that a balloon will explode. The BART is particularly interesting to examine because there is consistent evidence that individuals with psychosis pursue risky rewards less. However, given the complexities of the BART and confounds in psychosis samples, specific processes that contribute to this disadvantageous behavior remain poorly understood. Utilizing computational modeling, uncertain-risk decision-making behavior was parsed into subprocesses and examined for relationships with cognition, self-reported risk-specific processes, and non-risk specific personality traits to determine which of these external measures best explained group and individual differences in risk-taking.

View a recording of this session here.