Virtual Frontiers Spring Series 2021

Mid-Life Activities are Important for Late-Life Cognition

Dr. Rik Henson will discuss three studies addressing the factors that contribute to “cognitive reserve”, meaning how some people retain cognitive abilities in late life despite the brain changes associated with normal aging. The first study used retrospective reports from elders in the Lothian Birth Cohort, and showed that mid-life activities make a unique contribution to late-life cognition, over and above childhood cognitive scores; the second study from the CamCAN cohort, replicates this effect and goes further to show that mid-life activities, outside the workplace, moderate (weaken) the relationship between brain structural health and cognitive health in late life, ie a defining feature of cognitive reserve; the third study, from The University of Texas at Dallas, provides some clues that functional segregation of brain networks may be a neural correlate of such cognitive reserve. He will also briefly discuss whether such mid-life activities should be physical, social or intellectual, but there is not sufficient evidence yet for claims about which of these lifestyle activities is critical

Dr. Henson is from University of Cambridge and his primary interest concerns are the recollection of people's memories –  specifically, using the techniques of functional magnetic resonance imaging (fMRI) and electro- and magneto- encephalography (EEG/MEG) to examine brain activity. Even more specifically, in the neural bases of both explicit (conscious) memory and implicit (unconscious) memory, particularly the relationship between recollection, familiarity and priming. A deeper knowledge of these different expressions of memory is important for understanding the memory impairments associated with neurological damage or disease, or with healthy aging and rehabilitation.

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Unwinding Anxiety: Brain Mechanisms That Empower Us to Break Free from Anxiety and Stress

Dr. Jud is passionate about understanding how our brains work, and how to use that knowledge to help people make deep, permanent change in their lives — with the goal of reducing suffering in the world.

As an addiction psychiatrist and internationally known expert in mindfulness training for treating addictions, Dr. Jud has developed and tested novel mindfulness programs for habit change, including both in-person and app-based treatments for smoking, emotional eating, and anxiety. He is the Director of Research and Innovation at the Mindfulness Center and associate professor in psychiatry at the School of Medicine at Brown University, as well as a research affiliate at MIT.

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Brain-Based Biomarkers: A Focus on the Heterogeneous by Enhancing Sensitivity to Brain Disorders and Change

Background: The use of neuroimaging to study mental and neurological disorder has shown to be a powerful tool to capture information on the underlying brain changes. However diagnostic heterogeneity is a major issue as the field struggles to learn from the brain imaging data. One important aspect which has not been well explored is the use of rich, high-dimensional brain data to guide us through this complex territory. We show that by focusing on more similar subsets of data, identified via advanced algorithmic strategies, we can facilitate an apples-to-apples comparison, enhance sensitivity to mental illness, and provide a framework for improved stratification.

Methods: We focus on several examples using multiple large N data sets. Our first approach highlights a novel approach which identified ‘statelets’ or homogeneous temporal primitives of transient connectivity patterns in fMRI data. The second approach captures homogeneous subsets of individuals within data driven subspaces in multimodal brain imaging data. We also show that we can leverage this information to refine grouping of individuals, essentially showing where the biological data is pushing against a pre-defined category. And finally, we present some results based on visualization of deep learning approaches that provide insight into possible biological subclusters within existing clinical categories.

Results: Results show that leveraging advanced ‘clustering’ like approaches to identify subsets of data which are more homogeneous within and between subjects groupings enhances our ability to capture neural data which is linked to unique patterns of symptoms. We can also capture new information about how brain disorders impact brain dynamics, for example showing that patients with schizophrenia show much shorter statelet behavior than do controls. And finally, we show that such strategies, perhaps counter-intuitively, enhance our sensitivity to uncover changes in brain that may inform our approach to nosology as well as prove useful targets for future treatment studies.

Conclusions: The brain imaging field has largely focused on group studies, or more recently on individual subject classification using existing categories. We show that a focus on identifying unique subsets of data and subjects which exhibit homogeneity can leverage the benefits of both approaches, increase sensitivity to unique clusters of symptoms, and potentially help refine our understanding of diagnostic categories.

Dr. Vince Calhoun is a recognized expert in developing algorithms to strengthen understanding of brain function, structure and genomics, and how each is affected during various tasks or by mental or neurological illness. He also works to develop neuroinformatics tools that enable experts to use larger data sets and improve efficiency in data capture, management, analysis and sharing.

Dr. Calhoun is the founding director of the Center for Translational Research in Neuroimaging and Data Science, a joint effort between Georgia State, Georgia Tech, and Emory University, which is focused on improving our understanding of the human brain using advanced analytic approaches with an emphasis on translational research such as the development of predictive biomarkers for mental and neurological disorders.

New Strategies for Promoting 'Organic' Brain Health

Our growing understanding of the physical and functional brain provides us with growing insights into the organic bases of brain performance and health, and informs us about strategies for managing it to keep us safe and neurologically effective all across the span of our lives.  Brain health, like physical health, is substantially a product of brain engagement.  The brain is unique in our ability to assay its operational abilities by (in a sense) simply "asking it how it's doing".  The gift of brain plasticity provides us with an always-available strategy for addressing emergent weaknesses, and for growing and sustaining our brain health and brainpower.  Because brain health is an under-valued contributor to body health, managing brain health across our lifespan holds the promise of having better, safer--and longer--lives.  Here, we'll review our efforts to apply these strategies in everyday medicine--to improve and strengthen everyday lives.

Dr. Merzenich is the brain behind BrainHQ and the author of Soft-Wired: How the New Science of Brain Plasticity Can Change Your Life. For nearly five decades, he has been a leading pioneer in brain plasticity research. As co-founder and Chief Scientific Officer of Posit Science, Michael Merzenich heads the company’s science team. Dr. Merzenich has published more than 150 articles in leading peer-reviewed journals (such as Science and Nature), and received numerous awards and prizes (including the Russ Prize, Ipsen Prize, Zülch Prize, Thomas Alva Edison Patent Award and Purkinje Medal). He has been granted nearly 100 patents, and he and his work have been highlighted in hundreds of books about the brain, learning, rehabilitation, and plasticity. In 2016, Dr. Merzenich was awarded one of the world’s top neuroscience prizes, the Kavli Prize, for his achievements in the field of brain plasticity.

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Drug addiction can be viewed as a stable form of drug-induced neural plasticity, whereby long-lasting changes in gene expression mediate some of the stable behavioral abnormalities that define an addicted state. Our laboratory has focused on transcriptional pathways in addiction, deduced from large RNA-sequencing datasets of RNAs that show altered expression in brain reward regions of mice as a consequence of drug self-administration, withdrawal, and relapse. Activation or induction of certain transcription factors represent homeostatic adaptations that oppose drug action and mediate aspects of drug tolerance and dependence. In contrast, induction of other transcription factors exerts the opposite effect and contributes to sensitized responses to drug exposure.

Studies are underway to explore the detailed molecular mechanisms by which these various transcription factors regulate target genes and thereby contribute to the complex state of addiction. We are approaching this question by studying a range of chromatin mechanisms genome-wide, including post-translational modifications of histones, DNA methylation, nucleosome positioning, and the 3-dimensional structure of chromatin. These studies are identifying many of the molecular targets of drug self-administration in brain reward regions and the biochemical pathways most prominently affected. Among these targets are those that regulate synaptic function and plasticity as well as the morphology of drug-regulated neurons and other cell types, thus linking transcriptional and chromatin regulation to neural and behavioral plasticity. Parallel work has focused on homologous regions in the brains of addicted humans examined postmortem.

This work establishes transcriptional and chromatin regulation as important mechanisms underlying the ways in which a history of drug use causes lasting changes in targeted brain reward neurons, and the circuits in which they operate, to result in addiction-related behavioral abnormalities. These advances can now be mined to develop improved diagnostic tests and treatments for addictive disorders.

Dr. Nestler is the Nash Family Professor of Neuroscience, Director of the Friedman Brain Institute and Dean for Academic and Scientific Affairs. His laboratory studies the molecular mechanisms of drug addiction and depression in animal models.

Professor Ed Boyden completed his undergraduate degrees in Physics and Electrical Engineering and Computer Sciences and a Master of Engineering at MIT. He completed PhD studies as a fellow in the Neurosciences Program at Stanford University. Prof. Boyden joined MIT as an Assistant Professor in 2007, and is now a Professor in the Departments of Brain and Cognitive Sciences, Media Arts and Sciences, and Biological Engineering, and an HHMI investigator.

Your brain mediates everything that you sense, feel, think, and do. The brain is incredibly complex - each cubic millimeter of your brain contains perhaps a hundred thousand cells, connected by a billion synapses, each operating with millisecond precision. We develop tools that enable the mapping of the molecules and wiring of the brain, the recording and control of its neural dynamics, and the repair of its dysfunction. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision; optogenetic tools, which enable the activation and silencing of neural activity with light; robotic methods for directed evolution that are yielding new synthetic biology reagents for dynamic imaging of physiological signals; novel methods of noninvasive focal brain stimulation; and new methods of nanofabrication using shrinking of patterned materials to create nanostructures with ordinary lab equipment. We distribute our tools as freely as possible to the scientific community, and also apply them to the systematic analysis of brain computations, aiming to reveal the fundamental mechanisms of brain function, and yielding new, ground-truth therapeutic strategies for neurological and psychiatric disorders.