Presenters

“The Burden of Wake and the Reasons for Sleep”

Sleep is universal, tightly regulated, and many cognitive functions are impaired if we do not sleep, including learning and memory, inhibitory control and emotion regulation. But why? I will discuss a comprehensive hypothesis about the core function of sleep – The Synaptic Homeostasis Hypothesis (SHY) – according to which sleep is the price we pay for brain plasticity. During wakefulness the excitatory synapses that allow neurons to communicate with each other undergo net potentiation as a result of learning, an ongoing process that happens all the time while we are awake, constantly adapting to an ever-changing environment. The plasticity of the brain is essential for survival but is also a costly process because stronger synapses increase the demand for energy and cellular supplies, lead to decreases in signal-to-noise ratios, and saturate the ability to learn. According to SHY, while our brain is offline during sleep, neural circuits are reactivated in a neuromodulatory milieu that promotes the renormalization of synaptic strength. This renormalization favors memory consolidation and the integration of new with old memories, and weakens the synapses that contribute more to the “noise” than to the “signal.” Just as crucially, synaptic renormalization during sleep restores the homeostasis of energy and cellular supplies, including many proteins and lipids that are part of the synapses, with beneficial effects at both the systems and cellular level. I will discuss the rationale underlying this hypothesis, summarize studies in flies, rodents and humans that confirmed SHY’s main predictions, and discuss open questions and future challenges.

Chiara Cirelli received her medical degree and Ph.D. in Neuroscience from the University of Pisa, Italy, where she investigated the role of the noradrenergic system in sleep regulation. She continued this work as Fellow in experimental neuroscience at the Neuroscience Institute in San Diego, California, and since 2001 at the University of Wisconsin – Madison, where she is currently Professor at the Department of Psychiatry. Her laboratory aims at understanding the function of sleep and clarifying the functional consequences of sleep loss. Her team identified neuronal and glial genes whose expression changes due to sleep and sleep loss, suggesting specific cellular processes that are favored by sleep and impaired by sleep deprivation. Using large-scale mutagenesis screening in Drosophila, they also identified the first extreme short sleeper fly mutant. With Dr. Giulio Tononi, Dr. Cirelli has developed the synaptic homeostasis hypothesis, according to which sleep is needed for synaptic renormalization, to counterbalance the net increase of synaptic strength due to wake plasticity. Dr. Cirelli has published over 150 papers on sleep and received many awards for her original and sustained contribution to sleep research, including the 2017 Farrell Prize in Sleep Medicine from Harvard Medical School, the 2022 Pisa Sleep Award from Pisa University, and the 2023 Distinguished Scientist Award from the Sleep Research Society.

Reading List:

• Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration
• Sleep and Synaptic Homeostasis: Causal Evidence in Drosophila
• Ultrastructural Evidence for Synaptic Scaling Across the Wake/sleep Cycle
• Net decrease in spine-surface GluA1-containing AMPA receptors after post-learning sleep in the adult mouse cortex
• The why and how of sleep-dependent synaptic down-selection

“Imagining worlds anew: social neuroscience, master narratives, and the cultural evolution of morality”

Dr. Molly Crockett is an Associate Professor in Psychology at the University Center for Human Values at Princeton University. Crockett’s lab investigates social cognition: how people decide whether to help or harm, punish or forgive, trust or condemn. Their research integrates theory and methods from psychology, neuroscience, economics, philosophy, and data science. Crockett’s recent work has explored moral outrage in the digital age and trust in leaders during a pandemic.

Reading List: 

• Prosocial correlates of transformative experience at secular multi-day mass gatherings
• Moral dilemmas and trust in leaders during a global health crisis
• How social learning amplifies moral outrage expression in online social networks
• The relational logic of moral inference
• Narrating the “what” and “why” of our moral actions

“Synergistic, Bio-behavioral Interventions to Leverage Neuroplasticity Windows and Improve Emotional Disorders”

Neural and cognitive processing patterns have been found to distinguish groups of individuals with emotional disorders (e.g., anxiety, depression) from healthy samples, but translating such findings into true advances in clinical care remains a challenge. Research in psychiatry increasingly emphasizes cross-cutting biopsychosocial factors that are heterogeneous within, and across, discrete psychiatric diagnoses. The promise of this work is that it will generate a process-based framework to improve psychiatric assessment and treatment. In this talk, I will discuss neurocognitive factors that may contribute to anxiety and depression across diagnoses, with a focus on impairments in cognitive flexibility and neuroplasticity. I will discuss ongoing attempts to translate such findings into mechanistic treatment strategies and personalized treatment prescriptions capable of remediating neurocognitive disruptions and alleviating symptoms. Specific areas of focus within this work include: 1) characterizing neurocognitive processing patterns in anxiety and depression through behavioral information processing tasks and fMRI; 2) the targeted modification of cognitive processing mechanisms through computer-based training; and 3) leveraging biological treatments (neuromodulation, intravenous ketamine) to acutely enhance neuroplasticity and promote the uptake of adaptive learning.

Rebecca B. Price, PhD is an Associate Professor in the Departments of Psychiatry and Psychology at the University of Pittsburgh. She completed undergraduate studies in cognitive science at Stanford University and a PhD in Clinical Psychology at Rutgers University. She has been the recipient of several awards including an NIMH Biobehavioral Research Award for Innovative New Scientists (NIMH BRAINS) R01, a “Rising Star” award by the Association for Psychological Science, and the University of Pittsburgh Chancellor’s Distinguished Research Award. Dr. Price’s research interests center on the role of neurocognitive factors and neuroplasticity in the etiology, course, and treatment of depression, anxiety, compulsive behaviors, and suicidality. She has recently focused on developing novel synergistic treatment strategies to target these features by coupling computer-based interventions with biological interventions (e.g., non-invasive neuromodulation; intravenous ketamine). Dr. Price is particularly grateful for her three greatest gifts—her husband Andy and their two daughters.

Reading List: 

• A novel, brief, fully automated intervention to extend the antidepressant effect of a single ketamine infusion: A randomized clinical trial
• International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators
• Experimental manipulation of the orbitofrontal cortex impacts short-term markers of human compulsive behavior: A Theta Burst Stimulation study
• Neuroplasticity in cognitive and psychological mechanisms of depression: An integrative model
• Neural connectivity subtypes predict discrete attentional bias profiles among heterogeneous anxiety patients

“Stress, Resilience, and Mental Health: A Neurovisceral Integration Perspective”

The intimate connection between the brain and the heart via the vagus nerve was enunciated by Claude Bernard over 150 years ago. Darwin in his classic book on the expression of emotion in man and animals also stressed the importance of the vagus nerve. In our neurovisceral integration model we have tried to build on this pioneering work and revive interest in the vagus. We have proposed that vagally-mediated heart rate variability (HRV) is a transdiagnostic marker for psychopathology. Both cross-sectional and longitudinal studies suggest an important role for HRV in the identification of those at risk for psychopathology as well as being a potential marker for treatment outcome. In the present talk I further elaborate our model and update it with recent results. Supportive evidence from recent studies of neuroimaging, fear conditioning, attention, and executive function show that low HRV predicts hypervigilance, poor safety learning, and inefficient allocation of attentional and cognitive resources. In addition, the role of vagal afferents in emotion and fear extinction will be discussed. Importantly, evidence will be presented on the potential role of HRV in resilience to poor outcomes. HRV may provide a transdiagnostic target for the understanding of the etiology as well as the diagnosis and treatment of stress-related mental disorders.

Dr. Julian F. Thayer received his Ph.D. from New York University in psychophysiology with a minor in quantitative methods. Dr. Thayer has held faculty positions at Penn State University and the University of Missouri. Before moving to the Ohio State University in 2006 as the Ohio Eminent Scholar Professor in Health Psychology. Dr. Thayer was Chief of the Emotions and Quantitative Psychophysiology Section in the Laboratory of Personality and Cognition at the National Institute on Aging. Dr. Thayer is currently Distinguished University Professor of Psychological Sciences at the University of California, Irvine and the Ohio Eminent Scholar Professor in Health Psychology Emeritus and Academy Professor at The Ohio State University. He has also been a visiting professor at Sapienza University in Rome, the University of Bergen in Norway and the Free University of Amsterdam and a Research Fellow in Residence at the STUDIO for Creative Inquiry at Carnegie Mellon University. He has published over 400 research papers and book chapters covering a wide range of topics including behavioral medicine, cardiology, emotion, psychopathology, bioengineering, research design and multivariate statistical techniques.

Dr. Thayer has received numerous research awards including the Sigma Xi Research Recognition Award, the Early Career Award for Contributions to Psychosomatic Medicine from the American Psychosomatic Society, and distinguished scientist awards from the Association for Applied Psychophysiology and Biofeedback, The Society for Psychophysiological Research, the Society of Behavioral Medicine, the Academy of Behavioral Medicine Research, and the American Psychosomatic Society. From 2020 to 2022 he was identified by the Web of Science as a “Highly Cited Researcher”, a designation given to the top 0.1% of researchers. He is a Fellow of the Association for Psychological Sciences, the Society of Behavioral Medicine, and the Academy of Behavioral Medicine Research. He has also received a Fulbright Fellowship to conduct research on emotion in Norway and an Alexander von Humboldt Research Award to conduct research in Germany.

Dr. Thayer is an Associate Editor of Psychosomatic Medicine, former Associate Editor of Psychophysiology, and Bio-Psycho-Social Medicine, is on the editorial board of  Music and Medicine. He has also served as the program chair for the Society for Behavioral Medicine, the American Psychosomatic Society, and the Rocky Mountain Bioengineering Symposium. He is the Past-President of the Rocky Mountain Bioengineering Symposium and Past-President of the Academy of Behavioral Medicine Research. Dr. Thayer is also a critically acclaimed musician with numerous recordings and international performances including with Charlie Mariano, Geri Allen, Scott Robinson, and Pheeroan ak Laff.

Reading List: 

• A model of neurovisceral integration in emotion regulation and dysregulation
• Cardiac sympathetic-vagal activity initiates a functional brain–body response to emotional arousal
• Emotion Downregulation Targets Interoceptive Brain Regions While Emotion Upregulation Targets Other Affective Brain Regions
• The hierarchical basis of neurovisceral integration
• How heart rate variability affects emotion regulation brain networks

“Directed ACC signaling patterns as MDD biomarker”

Major Depressive Disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet prior resting state fMRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to conduct the first investigation of the relationship between directed rs-fMRI activity, MDD, and treatment response to a novel FDA-approved neurostimulation paradigm termed Stanford Neuromodulation Therapy (SNT). We find that SNT over left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pre-treatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response. Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD.

Dr. Williams is an Assistant Professor within the Department of Psychiatry and Behavioral Sciences and the Director of the Stanford Brain Stimulation Lab. Dr. Williams has a broad background in neuropsychiatry and is double board-certified in both neurology and psychiatry. In addition, he has specific training and clinical expertise in the development of brain stimulation methodologies under Mark George, MD. Themes of his work include (a) examining the use of spaced learning theory in the application of neurostimulation techniques, (b) development and mechanistic understanding of rapid-acting antidepressants, and (c) identifying objective biomarkers that predict neuromodulation responses in treatment-resistant neuropsychiatric conditions. He has published papers in high impact peer-reviewed journals including Brain, American Journal of Psychiatry, and the Proceedings of the National Academy of Science. He has also contributed to two reviews related to novel therapeutics for neuropsychiatric conditions that have been published in the journal of Clinical Investigation and Current Opinion in Neurobiology, which are both highly cited. Results from his studies have gained widespread attention in journals such as Science and New England Journal of Medicine Journal Watch as well as in the popular press and have been featured in various news sources including Time, Smithsonian, and Newsweek. Dr. Williams received two NARSAD Young Investigator Awards in 2016 and 2018 along with the 2019 Gerald R. Klerman Award. Dr. Williams received the National Institute of Mental Health Biobehavioral Research Award for Innovative New Scientists in 2020.

Reading List: 

• Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression
• Stanford Neuromodulation Therapy (SNT): A double-blind randomized controlled trial
• Five-year follow-up of bilateral epidural prefrontal cortical stimulation fortreatment-resistant depression
• High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression
• Accelerated neuromodulation therapy for obsessive-compulsive disorder

Richard J. Davidson received his Ph.D. from Harvard University in Psychology and has been at Wisconsin since 1984.  He has published more than 400 articles, numerous chapters and reviews and edited 14 books. He is the author (with Sharon Begley) of “The Emotional Life of Your Brain” published by Penguin in 2012. He is co-author with Daniel Goleman of “Altered Traits: Science Reveals How Meditation Changes Your Mind, Brain, and Body”, published by Penguin Books in 2017.

He is the recipient of numerous awards for his research including a National Institute of Mental Health Research Scientist Award, a MERIT Award from NIMH, an Established Investigator Award from the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), a Distinguished Investigator Award from NARSAD, the William James Fellow Award from the American Psychological Society, and the Hilldale Award from the University of Wisconsin-Madison. He was the year 2000 recipient of the most distinguished award for science given by the American Psychological Association –the Distinguished Scientific Contribution Award. He was the Founding Co-Editor of the new American Psychological Association journal EMOTION and is Past-President of the Society for Research in Psychopathology and of the Society for Psychophysiological Research.

In 2003 he was elected to the American Academy of Arts and Sciences and in 2004 elected to the Wisconsin Academy of Sciences, Arts and Letters. Named one of the 100 most influential people in the world by Time Magazine in 2006.  In 2006 awarded the first Mani Bhaumik Award by UCLA for advancing the understanding of the brain and conscious mind in healing. Madison Magazine named him Person of the Year in 2007. In 2008, he founded the Center for Healthy Minds, a research center dedicated to the study of positive qualities, such as kindness and compassion. In 2011 given the Paul D. MacLean Award for Outstanding Neuroscience Research in Psychosomatic Medicine. Serves on the Scientific Advisory Board at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig from 2011-2020 and was Chair of the Psychology section of the American Association for the Advancement of Science from 2011-2013. In 2013 received the NYU College of Arts and Science Alumni Achievement Award. He is a current member of the World Economic Forum’s Global Agenda Council on Mental Health. From 1992-2017, he was a member of the Mind and Life Institute’s Board of Directors.  In 2017 elected to the National Academy of Medicine, the premier authority dedicated to the health and medical sciences. In 2018, appointed to the Governing Board of UNESCO’s Mahatma Gandhi Institute of Education for Peace and Sustainable Development (MGIEP).

His research is broadly focused on the neural bases of emotion and emotional style and methods to promote human flourishing including meditation and related contemplative practices.  His studies have included persons of all ages from birth though old age and have also included individuals with disorders of emotion such as mood and anxiety disorders and autism, as well as expert meditation practitioners with tens of thousands of hours of experience.  His research uses a wide range of methods including different varieties of MRI, positron emission tomography, electroencephalography and modern genetic and epigenetic methods.

Ned H. Kalin, MD, is Hedberg Professor and Chairman of the Department of Psychiatry at the University of Wisconsin School of Medicine and Public Health. He is the Editor in Chief of the American Journal of Psychiatry, the premier scientific journal of the American Psychiatric Association. Dr. Kalin is the Director of the HealthEmotions Research Institute and the Lane Neuroimaging Laboratory, a Professor in the Department of Psychology at the University of Wisconsin, and an affiliate scientist at the Wisconsin Regional Primate Center and the Harlow Primate Laboratory. He serves as the principal investigator for several ongoing NIH funded research projects and has published over 200 peer-reviewed journal articles related to the adaptive and maladaptive expression of emotion and anxiety. His research focuses on uncovering basic mechanisms that relate stress to the development of psychopathology and to understanding the mechanisms that cause some children to be vulnerable for the development of anxiety and depression. In addition to his research activities, he treats patients who suffer from anxiety and depression who are refractory to standard treatment.

Dr. Kalin earned his medical degree from Jefferson Medical School in Philadelphia, Pennsylvania, did his residency in the Department of Psychiatry at the University of Wisconsin, and a fellowship in Neuropsychopharmacology at the National Institute of Mental Health. Dr. Kalin is board certified by the American Board of Psychiatry and Neurology. He is a Fellow Emeritus of the American College of Neuropsychopharmacology and a Fellow of the American College of Psychiatry. He has been recognized for numerous awards including the 1985 A.E. Bennett Award for basic science research in biological psychiatry, 2005 Edward A. Strecker Award, 2007 American College of Psychiatrists Award for research in mood disorders, 2007 Gerald Klerman Senior Investigator Award, 2015 Anna-Monika Prize of the European College of Neuropsychopharmacology, Institute of Living/Hartford Hospital 2020 C. Charles Burlingame Award for compelling contributions to the field of psychiatry throughout his career , and most recently the International Society of Psychoneuroendocrinology Bruce McEwen Lifetime Achievement Award.. In 2013 he was inducted as a Fellow in the American Association for the Advancement of Science, and in 2015 he was elected as a member of the National Academy of Medicine. In 2017, Dr. Kalin was inducted as a Distinguished Life Fellow of the American Psychiatric Association. He has served as President of the International Society of Psychoneuroendocrinology and President of the Society of Biological Psychiatry, as a member of the National Advisory Mental Health Council and as Co-Editor for the international journal, Psychoneuroendocrinology. In 2019, Dr. Kalin was appointed as the Editor-in-Chief of the American Journal of Psychiatry and continues to serve as the editor today.