Brain Imaging Lab

The Brain Imaging Lab is housed in the Molecular Imaging and Neuropathology Division at the New York State Psychiatric Institute and the Department of Psychiatry at Columbia University Irvine Medical Center. The lab conducts studies that increase our understanding of the neurobiology of mood disorders and suicide and the mechanisms of medication and psychotherapeutic interventions with a goal to develop more effective treatments. The lab also focuses on the development and application of a wide range of computational tools and statistical methods to address these topics using multimodal neuroimaging (functional, structural and molecular in vivo neuroimaging) and genomics data in healthy humans and patients with mood disorders.

Lab Members

Directors

  • Jeffrey Miller, MD

    • Associate Professor of Clinical Psychiatry

    Dr. Miller is an Associate Professor of Clinical Psychiatry at Columbia University and conducts multimodal brain imaging research investigating biological correlates of depression and suicide risk using Positron Emission Tomography (PET) and magnetic resonance imaging (MRI).  In addition, he uses brain imaging to predict treatment outcome, with a long term goal of contributing to personalized medicine in psychiatry.  He codirects a brain imaging laboratory devoted to these goals.

    Research focus

    Dr. Miller has investigated pathophysiology in major depressive disorder using PET imaging to quantify relevant neurochemical systems, including the serotonin and kappa opioid neurotransmitter systems. He has conducted studies related to the pathophysiology of major depressive disorder, using PET imaging to focus on the serotonin and kappa opioid neurotransmitter systems. With colleagues, he has found consistent and replicated evidence of trait abnormalities of elevated 5-HT1A receptor binding in major depressive disorder, that are present both during active illness as well as during periods of sustained remission. He conducted the first study quantifying the kappa opioid receptor in major depressive disorder, identifying a trend-level relationship between kappa opioid receptor binding and activation of the hypothalamic-pituitary-adrenal axis. In currently funded work, he is investigating markers of neuroinflammation and of neurotransmitter catabolism in the pathophysiology of depression and suicide risk. 

     

    Identifying predictors of treatment outcome in psychiatry is an urgent clinical issue given the inadequate response and remission rates to existing treatments, the limited ability that clinicians have presently to predict treatment outcome, and the high morbidity that results from ineffectively treated illness. Dr. Miller’s work has used PET imaging to identify serotonergic abnormalities that predict better response to serotonergic antidepressants. He has also identified predictors of outcome to medication-based and psychotherapeutic treatment for depression using functional MRI and diffusion tensor imaging.

     

  • Francesca Zanderigo, PhD

    • Associate Professor of Clinical Neurobiology (in Psychiatry)

    Dr. Francesca Zanderigo, PhD, is a Bioengineer, Associate Professor of Clinical Neurobiology (in Psychiatry) at Columbia University, and the Director of the Laboratory of Image Analysis within Brain Imaging in the Molecular Imaging and Neuropathology (MIND) Area at the New York State Psychiatric Institute (NYSPI). She has worked for over 15 years now in the field of medical imaging research, performing extensive quantification, mathematical modeling and analysis of brain images and data from both Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) for the investigation of cerebral hemodynamics and neuroreceptor systems. Dr. Zanderigo's research focuses on the extraction of accurate quantitative information from medical data and images, for the purpose of improving disease diagnosis and treatment. This includes the development of sophisticated methods for data quantification that simplify the acquisition of Positron Emission Tomography (PET) images, while maintaining accuracy and precision of the information extracted from such images, with the aim of promoting the translation of PET technique into clinical practice. These advanced methods allow investigators to reduce, and in some cases, eliminate the need for arterial blood sampling during imaging with PET, and have been applied to PET radiotracers used to image, for example, the translocator protein, monoamine oxidase A, the incorporation of arachidonic acid, the serotonin 1A receptor and transporter, and glucose metabolism. Further contributions from Dr. Zanderigo include creating approaches that overcome the problem posed by many targets of PET imaging, the absence of a valid reference region, to provide measurements of PET binding that are specific only to the target of interest. As well, her work includes developing other advanced methodologies in the field of in vivo brain imaging, ranging in scope from the generation of quantitative parametric images at the voxel level, to data-adaptive robust fitting approaches to improve statistical power and sensitivity of imaging studies, to model-free quantification for PET images. Dr. Zanderigo is currently Principal Investigator of an R01 funded by the National Institute of Biomedical Imaging and Bioengineering that aims at developing noninvasive quantification methods for data acquired with next-generation portable PET cameras. A complete list of Dr. Zanderigo’s publications can be found at the following link: https://scholar.google.com/citations?user=L3uS04cAAAAJ&hl=en

Principal Investigators and Faculty

  • Todd Ogden, PhD

    • Professor, Biostatistics (in Psychiatry)

    I am interested in statistical modeling of imaging data and, more broadly, in modeling of functional data and other high dimensional data sources.  A major focus of my recent work is on development of modeling solutions to various problems that arise in PET imaging applications. Recent contributions in that area have involved simultaneous (across regions and/or across subjects) modeling, methods for relaxing modeling assumptions, and non-parametric alternatives to the popular kinetic modeling approaches.

  • Spiro P. Pantazatos, PhD

    • Assistant Professor of Clinical Neurobiology (in Psychiatry)

    I have interests and experience in translational neuroinformatics, computational neuroimaging and psychiatric genomics. My work includes development and application of computational tools to accelerate mental health research. A primary research track applies data mining to brain imaging, molecular neuroanatomy and genomics data to identify and understand the etiology of anxiety, mood disorders and suicide in order to help guide treatment development for these disorders. I am also spearheading development of My Brain and Me, a web interface to crowdsource brain imaging and behavioral data while allowing participants to explore their own brain. The goal is to create a scalable approach that speeds up neuroimaging and mental health research and also increases public awareness and engagement with neuroscience. Other ongoing interests include birth season and neurobehavioral traits, political psychology and cognitive neuroscience, intuition and psychoinformatics. My publications can be accessed on Researchgate.

  • Dongrong Xu, PhD

    • Associate Professor of Clinical Neurobiology (in Psychiatry)

    Dongrong Xu's research interests are developing novel algorithms and methods for  neuroimaging data analysis, and their applications to various neuroscience, psychiatric and neurological  studies. Dr. Xu also develops virtual reality paradigms for neuroimaging studies. Please see the following link for more details and his recent publications: http://www.columbia.edu/~dx2103/

  • Zhengchao Dong, PhD

    • Associate Professor of Clinical Neurobiology (in Psychiatry)

    Research Interest

    MR physics and MRI methodology

    •  MRI image reconstruction and processing   
    •   MR spectroscopic imaging techniques

    Applications of MRI in

    • Mental disorders
    • Metabolism and physiology

     

    Current Work

    Collaborating with colleagues on projects involving magnetic resonance spectroscopy (MRS). The MRS work includes:

    • Quantification of dynamic changes of metabolites during drug infusion/administration in patients with depression or bipolar disorders
    •  Quantification of change of metabolite levels in response to treatment in patients with depression or bipolar disorders.

    MRI methodology development

    • Dynamic or functional MRS
    • 1H MRS-based thermometry
    • 1H MRS imaging without water suppression
    • Magnetic resonance fingerprinting and MR spectroscopic fingerprinting

  • M. Elizabeth Sublette, MD, PhD

    • Associate Professor of Clinical Psychiatry

    Dr. Sublette has a longstanding interest in brain mechanisms underlying mood disorders and suicide risk. She is particularly focused on the mechanisms of action of polyunsaturated fatty acids (PUFAs) on the brain. Her research in these areas encompasses a broad variety of translational approaches, including not only neuroimaging but clinical, biochemical, , genetic and epigenetic methodologies. Dr. Sublette is the Director of the Molecular Imaging and Neuropathology Division (MIND) Research Clinic and Core Leader for the Clinical Evaluation Core of the MIND Silvio O. Conte Center for Basic or Translational Mental Health Research (MH090964). In studying brain mechanisms related to PUFAs, depression and suicide risk, Dr. Sublette’s work has utilized multiple neuroimaging modalities, including structural magnetic resonance imaging (MRI), positron emission tomography (PET) and diffusion tensor imaging (DTI):

     

    Gopaldas, M., Zanderigo, F., Zhan, S., Ogden, R.T., Miller, J.M., Rubin-Falcone, H., Cooper, T.B., Oquendo M.A., Sullivan, G., Mann, J.J., Sublette, M.E., “Brain serotonin transporter binding, plasma arachidonic acid and depression severity: A positron emission tomography study of major depression.” Journal of Affective Disorders, in press.

    Zanderigo, F., Kang, Y., Kumar, D., Nikolopoulou, A., Mozley, P.D., Kothari, P., He, B., Schlyer, D., Rapoport, S., Oquendo, M., Vallabhajosula, S., Mann, J.J., Sublette, M.E.,  “[11C]arachidonic acid incorporation measurement in human brain: optimization for clinical use." Synapse (2018) 72(2). doi: 10.1002/syn.22018. Epub 2017 Nov 27. PubMed PMID: 29144569; PubMed Central PMCID: PMC6075823.

    Chhetry B.T., Hezghia A., Miller J.M., Lee S., Rubin-Falcone H., Cooper T.B., Oquendo M.A., Mann J.J., Sublette M.E., “Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression.” Journal of psychiatric research (2016) 75:65-74. PMCID:PMC4948754

    Sublette, M.E., Milak, M.S., Galfalvy, H.C., Oquendo, M.A., Malone, K.M., Mann, J.J., “Regional brain glucose uptake distinguishes suicide attempters from non-attempters in Major Depression.” Archives of Suicide Research (2013) 17(4):434-447. PMCID: PMC3831169

    Sublette, M.E., Milak, M.S., Hibbeln, J.R., Freed, P.J., Oquendo, M.A., Malone, K.M., Parsey, R.V., John Mann, J., “Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression.” Prostaglandins Leukotrienes & Essential Fatty Acids (2009) 80(1):57-64. PMCID: PMC2712826

  • Martin J. Lan, MD, PhD

    • Assistant Professor of Psychiatry

    My research utilizes neuroimaging with both PET and MRI to better understand the biological underpinnings of mood disorders.  I have a particular interest in the depressed phase of bipolar disorder.  One track of my research aims to identify and characterize biomarkers related to treatment response to medications.  Those studies aim to work out the mechanism of the medications, to elucidate the underlying pathophysiology that the medications reverse, and to move us towards developing a test that can identify which patients will respond to which medications.  Another track of my research uses PET and MRI to characterize clinically important aspects of mood disorders.  For example, past studies have focused on markers to distinguish bipolar and unipolar depression, or markers that are associated with suicidal ideation.

  • Noam Schneck, PhD

    • Assistant Professor of Clinical Medical Psychology (in Psychiatry)

    Dr. Schneck studies the way that people adapt to the suicide loss of a loved one. Specifically, his research aims to identify unconscious processes of coping with the loss that help people grow and adapt while also allowing them to remain engaged in current life demands. These unconscious processes are identified using a machine learning based approach to functional magnetic resonance brain imaging called neural decoding. The goal of this research is to ultimately develop a treatment technique that would entrain greater unconscious processing of the loss.

Fellows and Assistant Research Scientists

  • Mina Rizk, M.B.B.Ch., MS

    • Paul Janssen Translational Neuroscience Postdoctoral Research Fellow

    Mina Rizk completed his medical degree and psychiatry residency at Minia University, Egypt. He is currently doing his postdoctoral research training on a prospective NIH-funded study investigating the neurobiological underpinnings of suicidal subgroups. For the past three years, Dr. Rizk’s research has been focusing on understanding the brain and neuroendocrinological correlates of different clinical and cognitive aspects of depression and suicidality. He has received the Paul Janssen postdoctoral fellowship in translational neuroscience research and will start collaborating with the Division on Substance Abuse on a project examining the functional brain mechanisms underlying the anti-suicidal effects of buprenorphine in opioid use disorder patients at high-risk for suicidal behavior. This may help refine the use of buprenorphine or other opioid-active compounds in treatment of suicidality. A complete list of Dr. Rizk’s publications can be found at the following link: https://scholar.google.com/citations?user=iSuWTScAAAAJ&hl=en

  • Mike Schmidt, PhD

    • Postdoctoral Research Scientist

    Mike Schmidt has spent most of his life wondering how the brain makes us who we are. He started out academically in computer science, then moved to exercise physiology. After working in banking and video game development for several years, he spent nearly a decade child-rearing and watching neuro-developmental milestones happen in front of him. He then earned his PhD in neuroscience by investigating how the hippocampus changes in aging and cognitive decline with the wonderful people at The University of Mississippi Medical Center. In addition to helping Dr. Pantazatos with My Brain and Me, he is currently working with Dr. Pantazatos to figure out which genes are most important for supporting connectivity in peoples' brains. He thinks a stronger background in philosophy and mathematics would give him a deeper understanding of everything.

  • Louisa Steinberg, MD, PhD

    • Research Fellow

    Dr. Steinberg completed her residency training in psychiatry at Columbia University & the New York State Psychiatric Institute. She is currently a T32 funded research fellow in mood and anxiety disorders. Dr. Steinberg's research focuses on studying the underlying neural dysfunction in depression and how to improve treatment outcomes for patients using brain imaging. Currently, she is examining how BOLD responses in primary auditory cortex and cortical GABA levels are altered in major depressive disorder and whether these measures can be used to predict treatment response to SSRIs.

     

  • Katie Surrence, MS

    • Assistant Research Scientist

    Katie Surrence received her MS in psychology from UW-Madison where she worked in a lab devoted to understanding the effects of child abuse and neglect.  Since then she has worked in New York City as a researcher, therapist, software developer, and professor.  Her research collaborators have included Regina Miranda, in work on how thought patterns can predict later suicidal ideation, and currently Andrew Gerber, as data analyst on an fMRI study of transference -- the experience of importing your expectations from previous relationships onto someone new.  She has worked as a therapist in Depression Evaluation Services at New York State Psychiatric Institute and currently in NYSPI's Gambling Disorders clinic.  She taught Abnormal Psychology at John Jay College of Criminal Justice, and she worked as a software developer at Spring Health, a company that provides a tele-mental health platform.  Right now in the lab she is collaborating with Spiro Pantazatos and Mike Schmidt on building My Brain and Me.  When she isn't working on any of that she likes drawing comics, studying voice, and going to -- and occasionally teaching -- yoga. She understands all of the above as an investigation of how the mind interacts with the world outside it.

  • Elizabeth Bartlett, PhD

    • Postdoctoral Research Scientist

    Elizabeth (Betsy) Bartlett, PhD completed her doctoral work at Stony Brook University in Biomedical Engineering. Her postdoctoral work focuses on development and validation of quantification techniques for in vivo human positron emission tomography (PET) brain imaging, mentored by Dr. Francesca Zanderigo, PhD. These less-invasive and non-invasive techniques will simplify PET acquisition, minimize patient burden, and reduce cost, thereby reducing the barrier to entry for PET imaging, while preserving quantification accuracy. Current work on these non-invasive techniques includes optimization for use with standard PET scanners using the most popular PET radiotracer, [18F]FDG, which quantifies cerebral glucose metabolism. However, ongoing work will extend the quantification techniques to novel PET radiotracers and to next-generation portable PET scanners. In addition to PET methods development, Dr. Bartlett is also interested in using multimodal PET/magnetic resonance imaging (MRI) to discover and develop biomarkers for the onset, pathophysiology, and treatment of psychiatric disorders, utilizing modalities including structural MRI (to derive brain volume and thickness), diffusion tensor imaging (DTI; to derive metrics of white matter health and integrity), and arterial spin labeling (ASL; to derive cerebral blood flow). Specifically, she is interested in using multimodal neuroimaging approaches to better understand the depressogenic effects of stress. A list of Betsy’s publications can be found at: https://scholar.google.com/citations?hl=en&user=uoAjzqgAAAAJ&view_op=list_works&gmla=AJsN-F6kLvCmjnM2unHNssKwyazIsszKRSeQ1SB0cDCCNEuVj_eA3Tlq6I9O9yuPwSHzIu130b9eabWWIm-nK49bzMjo4J9Jsg

     

  • Ashley Yttredahl, PhD

    • Postdoctoral Research Fellow

    Ashley Yttredahl, PhD, is a T32-funded postdoctoral research fellow in Translational Neuroscience. Dr. Yttredahl received her PhD in Integrative Neuroscience from Stony Brook University’s Psychology Department. There, she investigated the behavioral and neurometabolic effects of a novel unpredictable threat paradigm in rats, with the goal of better understanding the development of affective psychopathologies that arise from chronic stress. During the final 3 years of her PhD, Dr. Yttredahl shifted her focus to neuroimaging and psychiatry, using functional magnetic resonance imaging (fMRI) and positron-emission tomography (PET) in humans to study the neural correlates of emotion dysregulation in mood disorders. Dr. Yttredahl was able to mechanistically probe downstream BOLD signal changes in the neural circuits involved in emotion-regulation by using transcranial direct current stimulation (tDCS), a noninvasive form of neuromodulation. Due to its low cost and small side-effect profile, tDCS has also shown promise as a treatment for several psychiatric conditions. However, wide variability in the experimental designs of research using tDCS has made it difficult to appropriately quantify its clinical efficacy. More research is needed to better understand how to properly dose and effectively direct the intervention for a given neural target, for example. Currently, Dr. Yttredahl is interested in implicit emotion regulation and in using neuroimaging to optimize tDCS application as a treatment for maladaptive emotion regulation strategies in psychiatric illness. Dr. Yttredahl’s current work includes using fMRI and Ecological Momentary Assessment (EMA) to evaluate target engagement by tDCS as a treatment intervention for non-suicidal self-injury.

Select Publications

  • Brain serotonin transporter binding, plasma arachidonic acid and depression severity: A positron emission tomography study of major depression Gopaldas M, Zanderigo F, Zhan S, Ogden RT, Miller JM, Rubin-Falcone H, Cooper TB, Oquendo MA, Sullivan G, Mann JJ, Sublette ME J Affect Disord 2019; 257: 495-503

  • Variability in Suicidal Ideation is Associated with Affective Instability in Suicide Attempters with Borderline Personality Disorder Rizk MM, Choo TH, Galfalvy H, Biggs E, Brodsky BS, Oquendo MA, Mann JJ, Stanley B Psychiatry 2019; 82(2): 173-178

  • Quantifying Brain [18F]FDG Uptake Noninvasively by Combining Medical Health Records and Dynamic PET Imaging Data Roccia E, Mikhno A, Ogden T, Mann JJ, Laine A, Angelini E, Zanderigo F IEEE J Biomed Health Inform 2019 doi: 10.1109/JBHI.2018.2890459

  • 5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression Steinberg LJ, Underwood MD, Bakalian MJ, Kassir SA, Mann JJ, Arango V J Psychiatry Neurosci 2019; 44(4): 1-8

  • Gray matter volumetric study of major depression and suicidal behavior Rizk MM, Rubin-Falcone H, Lin X, Keilp JG, Miller JM, Milak MS, Sublette ME, Oquendo MA, Ogden RT, Abdelfadeel NA, Abdelhameed MA, Mann JJ Psychiatry Res Neuroimaging 2019; 283: 16-23

  • Nonlinear Mixed-Effects Models for PET Data Chen Y, Goldsmith J, Ogden RT IEEE Trans Biomed Eng 2019; 66(3): 881-891

  • Cortisol Stress Response and in Vivo PET Imaging of Human Brain Serotonin 1A Receptor Binding Steinberg LJ, Rubin-Falcone H, Galfalvy HC, Kaufman J, Miller JM, Sublette ME, Cooper TB, Min E, Keilp JG, Stanley BH, Oquendo MA, Ogden RT, Mann JJ Int J Neuropsychopharmacol 2019; 22(5): 329-338

  • Kappa opioid receptor binding in major depression: A pilot study Miller JM, Zanderigo F, Purushothaman PD, DeLorenzo C, Rubin-Falcone H, Ogden RT, Keilp J, Oquendo MA, Nabulsi N, Huang YH, Parsey RV, Carson RE, Mann JJ Synapse 2018; 72(9): e22042

  • Longitudinal effects of cognitive behavioral therapy for depression on the neural correlates of emotion regulation Rubin-Falcone H, Weber J, Kishon R, Ochsner K, Delaparte L, Doré B, Zanderigo F, Oquendo MA, Mann JJ, Miller JM Psychiatry Res Neuroimaging 2018; 271: 82-90

  • In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder Zanderigo F, Pantazatos S, Rubin-Falcone H, Ogden RT, Chhetry BT, Sullivan G, Oquendo M, Miller JM, Mann JJ Brain Struct Funct 2018; 223(6): 2609-2625

  • [11C]arachidonic acid incorporation measurement in human brain: Optimization for clinical use Zanderigo F, Kang Y, Kumar D, Nikolopoulou A, Mozley PD, Kothari PJ, He B, Schlyer D, Rapoport SI, Oquendo MA, Vallabhajosula S, Mann JJ, Sublette ME Synapse 2018; 72(2)  

  • Statistical evaluation of test-retest studies in PET brain imaging Baumgartner R, Joshi A, Feng D, Zanderigo F, Ogden RT EJNMMI Res 2018; 8(1): 13

  • Altered effective connectivity in the default network of the brains of first-episode, drug-naïve schizophrenia patients with auditory verbal hallucinations Zhao Z, Li X, Feng G, Shen Z, Li S, Xu Y, Huang M, Xu D Frontiers 2018; 12:456

  • A Platform of Digital Brain Using Crowd Power Xu D, Dai F, Lu Y Frontiers of Information Technology and Electronic Engineering 2018; 19(1): 78-90

  • Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies Bartlett EA, Ananth M, Rossano S, Zhang M, Yang J, Lin SF, Nabulsi N, Huang Y, Zanderigo F, Parsey RV, DeLorenzo C Mol Imaging Biol 2018; doi: 10.1007/s11307-018-1300-1

  • A hybrid deconvolution approach for estimation of in vivo non-displaceable binding for brain PET targets without a reference region Zanderigo F, Mann JJ, Ogden RT PLoS One 2017; 12(5): e0176636

  • Methods for scalar-on-function regression Reiss PT, Goldsmith J, Shang HL, Ogden RT Int Stat Rev 2017; 85(2): 228-249

  • Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity Pantazatos SP, Huang YY, Rosoklija GB, Dwork AJ, Arango V, Mann JJ Mol Psychiatry 2017; 22(5): 760-773

  • Altered Microstructure of Brain White Matter in Females with Anorexia Nervosa: a Diffusion Tensor Imaging Study Hu S, Feng H, Xu T, Zhang H, Zhao Z, Hu J, Qi H, Hu C, Zhang P, Lai J, Lu Q, Huang M, Xu W, Wei N, Mou T, Lu S, Lu J, Zhou W, Xu Y, Xu D (Nature) Scientific Reports, 2017

  • White matter correlates of impaired attention control in major depressive disorder and healthy volunteers Rizk MM, Rubin-Falcone H, Keilp J, Miller JM, Sublette ME, Burke A, Oquendo MA, Kamal AM, Abdelhameed MA, Mann JJ J Affect Disord 2017; 222: 103-111

  • Relationship of recent stress to amygdala volume in depressed and healthy adults Sublette ME, Galfalvy HC, Oquendo MA, Bart CP, Schneck N, Arango V, Mann JJ J Affect Disord 2016; 203: 136-142

  • Isoform-level brain expression profiling of the spermidine/spermine N1 Acetyltransferase1 (SAT1) gene in major depression and suicide Pantazatos SP, Andrews SJ, Dunning-Broadbent J, Pang J, Huang YY, Arango V, Nagy PL, Mann JJ Neurobiol Dis 2015; 79: 123-34

  • Proton MRS and MRSI of the brain without water suppression Dong Z Prog Nucl Magn Reson Spectrosc 2015; 86-87: 65-79. Review.

  • Prediction of individual season of birth using MRI Pantazatos SP Neuroimage 2014; 88: 61-8

  • Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder Miller JM, Hesselgrave N, Ogden RT, Zanderigo F, Oquendo MA, Mann JJ, Parsey RV Biol Psychiatry 2013; 74(10): 760-7