Awarded studies
Effect of Age on Brain Vascular Permeability
Principal Investigator: Issam A. Awad, MD PhD (Surgery)
Summary: The aging brain involves chronic vascular pathology, causing ischemic and hemorrhagic changes, and cognitive decline.
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These have been associated with vascular leak in pre-clinical studies. Our group has optimized assessment of brain vascular permeability, using magnetic resonance (MR) dynamic contrast-enhanced quantitative perfusion (DCEQP) of gadolinium (Gd) contrast agent, in studying effects of haploinsufficiency of cerebral cavernous malformation (CCM) genes causing premature hemorrhagic stroke. In this project, we propose to study brain vascular permeability in the aging human brain. In a second aim, we will correlate brain vascular permeability with blood biomarkers implicated in brain vascular senescence. We will use the pilot data from this project to support feasibility arguments for two proposed external funding applications. We ultimately aim to correlate the brain vascular permeability with ischemic and hemorrhagic cerebrovascular disease burden, and cognitive change in the aging brain, and with plasma biomarkers implicated in the vascular biology of aging. Results from these studies will define prognostic and monitoring biomarkers in the aging brain, and potential predictive biomarkers and targets for calibrating putative therapies to mitigate ischemic and hemorrhagic cerebrovascular disease, and cognitive changes with aging.
Effort-Reward Decision-Making in Math Anxious Individuals
Principal Investigator: Sian Beilock, PhD (Psychology)
Summary: Many individuals report strong feelings of tension, apprehension, and fear of math. This emotional reaction, termed math anxiety, has long been associated with avoidance of math and poor math performance.
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To stop adverse effects of math anxiety on math learning and performance, reducing math avoidance behavior in math anxious individuals is critical. Yet, little research has directly investigated the relationship between math anxiety and math avoidance, hindering the development of effective interventions. By adopting a neuroeconomic approach, i.e., effort-reward decision-making, we have devised a novel behavioral paradigm that can capture math avoidance behavior of math anxious individuals in the lab; we found that math anxious individuals are less willing to exert effort in math, even when there are high rewards for doing so. We hypothesize that math anxiety interacts with the neural systems underlying value computation, steeply discounting the reward associated with math-related effort and thus resulting in the math avoidance behavior. Using fMRI, we will investigate why math anxious individuals avoid math and, more importantly, how some math anxious individuals can overcome math anxiety and approach math. Our research will lead to the better understanding of math anxiety and the development of effective preventions and interventions.
Drug Effects on Neural Responses to Stimuli
Principal Investigator: Harriet de Wit, PhD (Psychiatry and Behavioral Neuroscience)
Summary: The goal of this study is to examine the effects of a stimulant drug on brain activity while participants view images of varying sensory complexity.
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Recent findings from our laboratory suggest that the effects of amphetamine on brain activity elicited by visual stimuli may depend on the complexity of the stimuli. Here we will investigate the effects of a low dose of methamphetamine (MA; 20 mg oral) on brain activation while subjects view relatively simple versus more complex visual stimuli. We hypothesize that MA enhances brain activity to a greater extent during more complex images, compared to more simple images. Healthy volunteers (N=20) will participate in two scanning sessions, one with MA pretreatment and one with placebo. On each session they will view the stimuli used in our previous study, i.e., the more complex mountain image and the simpler ocean image. In addition, we will determine the effects of MA with several other variants of sensory or motor activity, including the addition of sound with the images, the addition of a simple motor task superimposed on the images, and novel images varying in complexity. The study will help us understand our recent findings, and perhaps more importantly, they will provide novel data about how stimulant drugs alter brain function during sensory stimulation.
Aesthetic Sensitivity, Art Education, and Empathy
Principal Investigator: Jean Decety, PhD (Psychology)
Summary: This project employs fMRI to characterize the neurocognitive mechanisms underpinning aesthetic evaluation.
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Understanding the significance of human experience relies on the
ability to feel emotions including love, compassion, hate, grief, and shame. The capacity for empathy, in particular, represents a powerful means of identifying with others and plays a critical role in aesthetic sensitivity. A competing theoretical perspective, however, postulates that emotional distancing is central to aesthetic evaluation. Imaging data will be integrated with dispositional and behavioral data to determine whether empathy or distancing is necessary for the aesthetic appreciation of paintings, as well as the role of art education in facilitating the relation between empathy and aesthetic judgments. Although aesthetic experiences are frequent in modern life, there is as of yet no comprehensive theory that explains what constitutes such experiences. The proposed research cuts across disciplinary boundaries between psychology, aesthetic sensitivity and art education, thereby moving beyond current academic knowledge relating to this unique aspect of human nature. Pilot data will be used to support a full proposal to The National Endowment for the Arts.
ability to feel emotions including love, compassion, hate, grief, and shame. The capacity for empathy, in particular, represents a powerful means of identifying with others and plays a critical role in aesthetic sensitivity. A competing theoretical perspective, however, postulates that emotional distancing is central to aesthetic evaluation. Imaging data will be integrated with dispositional and behavioral data to determine whether empathy or distancing is necessary for the aesthetic appreciation of paintings, as well as the role of art education in facilitating the relation between empathy and aesthetic judgments. Although aesthetic experiences are frequent in modern life, there is as of yet no comprehensive theory that explains what constitutes such experiences. The proposed research cuts across disciplinary boundaries between psychology, aesthetic sensitivity and art education, thereby moving beyond current academic knowledge relating to this unique aspect of human nature. Pilot data will be used to support a full proposal to The National Endowment for the Arts.
The Effect of Nitrous Oxide on Front-Limbic Circuits in Aggressive Individuals
Principal Investigator: Sarah Keedy, PhD (Psychiatry & Behavioral Neuroscience)
Summary: This is a pilot study to determine if inhalation of Nitrous Oxide (N2O; AKA “Laughing Gas”) will reduce fMRI Bold responses to exposure to angry emotional faces and/or increase fMRI Bold responses to viewing socially ambiguous videos in cortico-limbic circuits.
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The parent protocol that this imaging study will be coupled with is a pilot clinical trial to see if N2O can reduce aggressive behavior (IRB 18-1307 approved on January 18, 2019). Based on work in depression, sub-anesthetic doses of agents such a ketamine (Krystal et al., 2013) and N2O (Nagele et al., 2015) are reported to reduce depressive symptoms in 24 hours of administration with effects lasting up to one week. We seek to determine if similar treatment will have an anti-aggressive effect in aggressive individuals.
Mental Imagery in a Foreign Language
Principal Investigator: Marc Berman, PhD (Psychology)
Summary: Mental imagery is a fundamental cognitive process often elicited via language.
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When someone describes a scene such as a sunset, our minds construct a visual representation from our prior memories. Our ability to visualize what we read or hear can impact how we feel, think, and make decisions about what is being described. It can also have negative downstream effects on basic cognitive functions which rely on clear, accurate visualizations. Recent work testing whether the use of a foreign language affects visualization found that scenes presented in a foreign versus native language were judged as less vivid. This project seeks to build on this behavioral finding by examining neural responses when bilinguals read highly imaginable words in a native versus foreign language. Specifically, we predict that when participants read highly imaginable words in their native language, they will rate these words as more vivid and will exhibit neural activations consistent with clearer, and potentially less effortful, visualization. The goal of this project is to identify the mechanism of this language-dependent visualization effect, and provide insight into why bilinguals often think and make decisions differently in a foreign tongue.
Effect of Electrical Stimulation on Brain Activity During Recollection Attempts
Principal Investigator: David Gallo, PhD (Psychology)
Summary: Electrical brain stimulation with transcranial direct current stimulation (tDCS) has the potential to significantly advance our understanding of human cognition, but the technique’s validity has been questioned.
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Recently, my lab demonstrated that tDCS to dorsolateral prefrontal cortex (dlPFC) immediately prior to memory retrieval can
improve episodic memory, or the ability to accurately recollect past events (Gray et al., 2015, Cortex). Since then, we have replicated this tDCS effect twice, discovering that AM testing is key to finding reproducible tDCS effects in younger adults. Using this same task in several fMRI studies, we also have found robust modulation of dlPFC activity as a function of recollection difficulty (for review, see Gallo, 2013, Current Directions in Psychology). Here, we propose the first study combining tDCS and fMRI to investigate episodic memory retrieval, testing the hypothesis that dlPFC is causally involved in retrieval processes that regulate recollection accuracy.
improve episodic memory, or the ability to accurately recollect past events (Gray et al., 2015, Cortex). Since then, we have replicated this tDCS effect twice, discovering that AM testing is key to finding reproducible tDCS effects in younger adults. Using this same task in several fMRI studies, we also have found robust modulation of dlPFC activity as a function of recollection difficulty (for review, see Gallo, 2013, Current Directions in Psychology). Here, we propose the first study combining tDCS and fMRI to investigate episodic memory retrieval, testing the hypothesis that dlPFC is causally involved in retrieval processes that regulate recollection accuracy.
Neural Alterations Associated with Hallucination Propensity in Borderline Personality Disorder
Principal Investigator: Sarah Keedy, PhD (Psychiatry & Behavioral Neuroscience)
Summary: This study aims to map this potential neurophysiological overlap of BOR with the major psychotic disorders schizophrenia, schizoaffective, and bipolar disorder.
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The scanning protocol will include an auditory processing task, resting state, and two structural sequences to facilitate testing the hypothesis of altered auditory system integrity in BOR+H relative to BOR-H. This would be parallel to findings for other disorders (primarily schizophrenia) where hallucinations may or may not be present. For this, a direct comparison of BOR and those three psychotic disorders will be conducted using data from the PI’s ongoing, funded study with parallel scan sequences to those proposed. Findings could support expansion of the construct of a psychotic disorder spectrum, usually anchored by schizophrenia and bipolar disorder, to include BOR. Findings would also support an approach to subgrouping within the psychosis spectrum on the basis of altered biology associated with cross-diagnostic symptoms, an approach in line with current federal funding priorities (RDoC).
The Neural Correlates of Learning Through Gesture
Principal Investigator: Susan Golding-Meadow, PhD (Psychiatry & Behavioral Neuroscience)
Summary: This project investigates the neural processes that underlie learning with gesture.
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Previous studies suggest that learning through gesture-observation and gesture-production promotes mathematical learning more than learning without gesture. However, the mechanisms that underlie this learning process are unknown. Based on the behavioral literature we propose two
neural mechanisms by which gesture may promote learning and test the predictions of these mechanisms in two sets of studies. The first study (Aim 1) uses fMRI to measure the neural processes that underlie learning in a gesture-observation paradigm. We use these whole-brain data to fully explore the predictions of these mechanisms and establish which regions are involved during this learning process. To investigate the neural processing that underlies learning via gesture-production and spontaneous gesture-production, we turn to fNIRS, which permits movement during neural recordings (Aim 2). We use the fMRI results of Aim 1 to identify regions of interest for the fNIRS recordings. We also conduct a parallel gesture-observation study using fNIRS, which allows for a direct comparison of gesture-observation and gesture-production. Broadly, the results of these studies will inform questions about the mechanisms that underlie learning, the mechanisms by which gesture facilitates learning, and the neural correlates that underlie spontaneous gesture production.
neural mechanisms by which gesture may promote learning and test the predictions of these mechanisms in two sets of studies. The first study (Aim 1) uses fMRI to measure the neural processes that underlie learning in a gesture-observation paradigm. We use these whole-brain data to fully explore the predictions of these mechanisms and establish which regions are involved during this learning process. To investigate the neural processing that underlies learning via gesture-production and spontaneous gesture-production, we turn to fNIRS, which permits movement during neural recordings (Aim 2). We use the fMRI results of Aim 1 to identify regions of interest for the fNIRS recordings. We also conduct a parallel gesture-observation study using fNIRS, which allows for a direct comparison of gesture-observation and gesture-production. Broadly, the results of these studies will inform questions about the mechanisms that underlie learning, the mechanisms by which gesture facilitates learning, and the neural correlates that underlie spontaneous gesture production.
Functional Mechanisms Underlying Abnormalities of Fidgety Movements in Three Month Old Infants Following Perinatal Brain Hypoxia-Ischemia
Principal Investigator: Jeremy Marks, PhD MD (Pediatrics)
Summary: Perinatal brain hypoxia-ischemia in newborns results in a spectrum of neurodevelopmental outcomes, from no disability to intellectual disability and cerebral palsy.
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While brain MR structural imaging delineates the extent and progression of anatomic abnormalities, the relationship between imaging and the extent of subsequent neurodevelopmental impairment is poor. However, we1 and others2-4 have found that the presence or absence of spontaneous movements exhibited by calm, alert infants at 12-15 weeks, termed Fidgety Movements (FM), provides early, accurate prediction of subsequent cerebral palsy. The brain regions mediating these stereotypical movements are unknown. Our goal is to identify regional brain activation during FM generation. While fMRI in three month old infants has been performed during natural sleep5, fMRI during wakefulness has not. Our goals are to 1) develop techniques to obtain fMR images in restrained, awake, and alert infants; 2) obtain preliminary fMRI data in infants with normal and abnormal FM to delineate the cortical regions mediating FM. Term infants who were treated for perinatal brain hypoxia-ischemia will be studied at 12-15 weeks of age. FM will be assessed and classified as normal or absent. Infants will be scanned and BOLD responses during sleeping and wakefulness will be recorded and analyzed, and activation maps in the two groups compared.