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Linda Chang, MD, MS

Academic Title:

Professor

Primary Appointment:

Diagnostic Radiology and Nuclear Medicine

Secondary Appointment(s):

Neurology

Additional Title:

Vice Chair for Faculty Development

Location:

Baltimore, MD 21201

Phone (Primary):

(410) 706-1036

Education and Training

After completing her B.S. in Biochemistry at the University of Maryland College Park, Linda Chang obtained her M.S. in Physiology and Biophysics, and her M.D. from Georgetown University School of Medicine. She then completed her internship at Los Angeles County/USC, and her Neurology Residency, as well as her Neurophysiology and Neuroimaging Research Fellowships at the University of California, Los Angeles (UCLA) Medical Center.  

Biosketch

Other Academic Positions:

1992-1999        Assistant Professor of Neurology (tenure-track), UCLA School of Medicine, Los Angeles, CA

1999-2000        Associate Professor of Neurology (In-Residence, Tenured), UCLA School of Medicine. Los Angeles, CA

2000-2004        Scientist, Medical Department, Brookhaven National Laboratory, Upton, NY

2004-2017        Professor of Medicine (Tenured), John A. Burns School of Medicine, UH Manoa, Honolulu, HI

2017–2020        Adjunct Clinical Professor, John A. Burns School of Medicine, the University of Hawai'i at Manoa, Honolulu, HI

2017–Present    Adjunct Professor, Dept. of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD

Prior Administrative Positions:

2000 – 2004     Chair, Medical Department, Brookhaven National Laboratory, Upton, NY. Directed and managed all biomedical research conducted at BNL, including the Clinical Research Center and the Animal Facility.

2004 – 2017     Co-Director, the University of Hawaii (UH) MR Research Center, The Queen’s Medical Center

2007 – 2012     Program Director, Specialized Neuroscience Research Program (SNRP) and Neuroscience Research, John A. Burns School of Medicine, UH Manoa

Services to the Scientific Community (National and International):

2006-present   Section Editor for Journal of NeuroImmune Pharmacology

2007-2017      Editorial Board, Psychiatry Research: Neuroimaging

2007-2016      Editorial Board, Journal of Magnetic Resonance in Imaging

2008-2011      Editorial Board, Magnetic Resonance in Medicine

2008-2012      Board Member, Scientific Council for the Intramural Research Program, NIDA/NIH

2017-Present   Associate Editor, Frontiers in Neurology; Neuroinfection Section

2017-2020   Council Member, National Advisory Council on Drug Abuse, NIDA/NIH

2019-present (until 2024)  Council Member, Council of Councils, NIH

Research/Clinical Keywords

The ongoing research in Linda Chang's laboratory focuses on the application of several advanced neuroimaging techniques (including morphometry, diffusion tensor imaging, blood oxygenation-level-dependent (BOLD)-functional MRI, cerebrovascular reactivity, and MR spectroscopy) to study elderly individuals with brain disorders (including people with HIV, Alzheimer’s disease, or substance use disorders) and in adolescent brain development. She also applied multiple MRI techniques to evaluate brain injury associated with long-COVID symptoms. Her new research direction focuses on using animal models to evaluate MRI-guided-focused ultrasound (FUS)-mediated blood brain barrier opening for improve delivery of gene therapy and ultralong-acting antiretroviral medications to eradicate the CNS HIV reservoirs, as well as the delivery of monoclonal antibodies to treat Alzheimer’s disease. Furthermore, she is using MRI-guided FUS to modulate brain function associated with drug-seeking behaviors for substance use disorders.

Highlighted Publications

Selected Publications (from >250):

  1. Isaiah A, Ernst T, Cloak CC, Clark DB, Chang L. Structural alterations in the frontal lobe mediate the impact of snoring and associated symptoms on childhood behavior. Nature Communication 2021 Apr 13;12(1):2205 PMCID: PMC8044120 [Open Access]
  2. Kevadiya BD, Machhi J, Herskovitz J, Oleynikov MD, Blomberg WR, Bajwa N, Soni D, Das S, Hasan M, Patel M, Senan AM, Gorantla S, McMillan J, Edagwa B, Eisenberg R, Gurumurthy CB, Reid SPM, Punyadeera C, Chang L and Gendelman HE. Diagnostics of SARS-CoV-2 Infections. Nature Materials 2021 May;20(5):593-605.

  3. Isaiah A, Ernst T, Cloak CC, Clark DB, Chang L. Association Between Habitual Snoring and Cognitive Performance Among a Large Sample of Preadolescent Children. JAMA Otolaryngology Head and Neck Surgery 2021 May 1;147(5):426-433 PMCID: PMC7907984.

  4. Chang L, Lohaugen G, Andres T, Jiang C, Douet V, Tanizaki N, Walker C, Castillo D, Lim A, Skranes J, Miller E, Ernst T. Improved Brain Function after Working Memory Training in HIV Patients. Annals of Neurology 2017 Jan; 81(1):17-34. Epub 2016 Dec 28. PMID:27761943; PMC5299494 [Open Access]

  5. Chang L, Oishi K, Skranes J, Buchthal S, Cunningham E, Yamakawa R, Hayama S,Jiang CS, Alicata D, Hernandez A, Cloak C, Wright T, Ernst T. Sex-Specific Alterations of White Matter Developmental Trajectories in Infants with Prenatal Methamphetamine and Tobacco-Exposure.  JAMA Psychiatry. 2016 Dec 1;73(12):1217-1227. PMID: 27829078; [PMC in process]

  6. Chang L, Douet V, Bloss C, Lee K, Pritchett A, Jernigan TL, Akshoomoff N, Murray SS, Frazier J, Kennedy DN, Amaral DG,  Gruen J, Kaufmann WE, Casey BJ, Sowell E and Ernst T,for the Pediatric Imaging, Neurocognition, and Genetics (PING) Study Consortium. Gray Matter Maturation in Children with Different APOE-epsilon Genotypes.  Neurology 2016 Aug 9;87(6):585-94. Epub 2016 Jul 13. PMID: 27412137; PMC4977368.

  7. Noble KG, Houston SM, Bartsch H, Kan E, Kuperman JM, Akshoomoff N, Bloss CS, Casey BJ, Chang L, Ernst TM, Frazier JA, Gruen JR, Kennedy DN, Murray SS, Schork N, Dale AM, Jernigan TL and Sowell ER, for the Pediatric Imaging, Neurocognition, and Genetics Study. Family income, parental dducation and brain development in children and adolescents. Nature Neuroscience 2015 May;18(5):773-8. Epub 2015 Mar 30. PMID:25821911; PMC4414816

  8. Panee J, Pang X, Munsaka S, Berry MJ, Chang L.Association of depressive symptoms and CSF oxidative stress markers in independent or co-morbid HIV and methamphetamine use disorders. Journal of Neuroimmune Pharmacology 2015 Mar;10(1):111-21. Epub 2015 Jan 10. PMID:25575491; PMC4900457.

  9. Holland D, Chang L, Kuperman KM, Ernst TM, Curran M, Buchthal SD,Alicata D, Skranes J, Johansen H, Hernandez A, Yamakawa R, Dale AM. The first three months: A longitudinal analysis of early postnatal brain development. JAMA Neurology 2014 Oct 1;71(10):1266-74. PMID:25111045; PMC4940157.

  10. Chang L, Jiang CS, Cunningham E, Buchthal S, Douet V, Andres M, Ernst T.  Effects of APOE-e4, age and HIV on glial metabolites and cognitive deficits.  Neurology 2014 Jun 17;82(24):2213-22. Epub 2014 May 21. PMID:24850492; PMC4113464.

  11. Chang L, Munsaka SM, Kraft-Terry S, Ernst T.  Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain.  Journal of NeuroImmune Pharmacology 2013 Jun;8(3):576-593. Epub 2013 May 12. NIHMSID#478852; PMID:23666436; PMC3698315

  12. Chang L, Yakupov R, Jiang C, Holt J, Ernst T.  Lower cognitive reserve in the aging human immunodeficiency virus-infected brain.  Neurobiology of Aging 2013; 34(4):1240-1253. Epub 2012 Nov 15. PMID: 23158761; PMC3984923.

  13. Chang L, Andres M, Sadino J, Jiang CS, Nakama H, Miller E, Ernst T. Impact of APOEε4 Allelle, age and HIV on cognitive function and brain atrophy: Antagonistic pleiotropy and premature brain aging. Neuroimage 2011 Oct 15;58(4):1017-27. Epub 2011 Jul 21. PMID: 21803164; PMC3171637

  14. Chang L, Yakupov R, Cloak C, Ernst T.  Marijuana use is associated with a reorganized visual attention network and cerebellar hypoactivity.  Brain 2006 May;129(Pt 5):1096-112. Epub 2006 Apr 3.PMID: 16585053 (Free article).

  15. Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, Watters M, Ricardo-Dukelow M, Chang L. Declined neural efficiency in cognitively stable HIV patients. Annals of Neurology 2009 Mar;65(3):316-325. PMID:19334060; PMC2734503.

  16. Chang L, Wang GJ, Volkow N, Ernst T, Telang F, Logan J, Fowler J. Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse.  Neuroimage 2008 Aug 15;42(2):869-78. Epub 2008 May 20. PMID:18579413; PMC2730417

  17. Volkow N, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN.  Association of Dopamine Transporter Reduction with Psychomotor Impairment in Methamphetamine Abusers.  American Journal of Psychiatry 2001;158:377-382.

  18. Chang L, Tomasi D, Yakupov R, Lozar C, Arnold S, Caparelli EC, Ernst T.  Adaptation of the Attention Network in Human Immunodeficiency Virus Brain Injury.  Annals of Neurology 2004 August;56:259-272.

  19. Chang L, Miller BL, McBride D, Cornford M, Oropilla G, Buchthal S, Chiang F, Aronow H, Beck K, Ernst T. Brain Lesions in Patients with AIDS: H-1 MR spectroscopy. Radiology 1995; 197:525-531 [erratum to add “Beck K” as a co-author: Radiology 1996;198(2):586].

  20. Chang L, Anderson T, Migneco OA, Boone K, Mehringer CM, Villanueva-Meyer J, Berman N, Mena I.  Cerebral Abnormalities in Myotonic Dystrophy: Cerebral Blood Flow, MRI and Neuropsychological Tests. Archives of Neurology (JAMA Neurology) 1993;50:917-923.

Additional Publication Citations

Selected additional publications (from >250 papers, 350 abstracts and 30 Book Chapter):

  1. Hernes SS, Flak MM, Løhaugen GCC, Skranes J, Hol HR, Madsen BO, Knapskog AB, Engvig A, Pripp A, Ulstein I, Lona T, Zhang X, Chang L.  Working memory training in amnestic and non-amnestic MCI: genotype variants and training effects. Frontiers in Aging Neurosciences 2021 Feb 15; 13:624253. doi: 10.3389/fnagi.2021.624253
  2. Douet V and Chang L. Fornix As An imaging marker for memory deficits in healthy aging and in neurological disorders.  Frontiers in Aging Neuroscience 2015 Jan 14;6:343. fnagi.2014.00343. eCollection 2014.

  3. Panee J, Pang X, Liu XQ, Berry MJ, Chang SL, Chang L. Regional variation of antioxidant capacity and oxidative stress responses in HIV-1 transgenic rats with and without methamphetamine administration. Journal of NeuroImmune Pharmacology 2013 Jun;8(3):691-704. doi: 10.1007/s11481-013-9454-8. Epub 2013 Apr 2. PMID:23546885; PMC#3773562

  4. Nakama H, Chang L, Fein G, Shimotsu R, Jiang C, Ernst T. Metheamphetamine users show greater than normal age-related cortical gray matter loss.  Addiction 2011 Aug;106(8):1474-83. doi: 10.1111/j.1360-0443.2011.03433.x. Epub 2011 May 12. PMID:21438934; PMC3135731.

  5. Oishi K, Mori S, Donahue P, Ernst T, Anderson L, Buchthal S, Faria A, Jiang H, Li X, Miller MI, van Zijl P, and Chang L.Multi-contrast human neonatal brain atlas: Application to normal neonate development analysis. Neuroimage 2011 May 1;56(1):8-20. Epub 2011 Jan 26. PMID:21276861; PMC3066278.

  6. Andres M, Feger U, Nath A, Munsaka S, Chang L. APOE ε4 allele and CSF APOE on cognition in HIV-infected subjects. Journal of NeuroImmune Pharmacology 2011 Sep;6(3):389-98. Epub 2010 Dec 24. PMID:21184197; PMC4899041.

  7. Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L.  Lower Brain Glutamate Is Associated With Cognitive Deficits in HIV Patients: A New Mechanism for HIV-Associated Neurocognitive Disorder. Journal of Magnetic Resonance Imaging 2010 Nov;32(5):1045-53. PMID:21031507; PMC2967445.

  8. Chang L, Cloak C, Jiang CS, Farnham S, Tokeshi B, Hedemark B, Smith L, and Ernst T.  Altered neurometabolites and motor integration in the brains of children exposed to methamphetamine prenatally. Neuroimage 2009; 48: 391-397. Epub Jul 5. PMID: 19576287; PMC3142567.

  9. Chang L, Wong V, Nakama H, Watters M, Ramones D, Cloak C, Ernst T.  Greater than age-related changes in brain diffusion of HIV patients after one-year. Journal of NeuroImmune Pharmacology 2008 Dec;3(4):265-74. Epub 2008 Aug 15. PMID:18709469; PMC2693362.

  10. Chang L, Jiang CS, Ernst T.  Effects of age and sex on brain glutamate and other metabolites.  Magnetic Resonance Imaging 2009 Jan;27(1):142-5. Epub 2008 Aug 6. PMC3164853.

  11. Chang L, Friedman J, Ernst T, Zhong K, Tsopelas N, Davis K. Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction. Biological Psychiatry 2007 Dec 15;62(12):1396-404. Epub 2007 Aug 13

  12. Chang L, Cloak C, Yakupov R, and Ernst T.  Combined and independent effects of chronic marijuana use and HIV on brain metabolites.  Journal of NeuroImmune Pharmacology 2006 Mar;1:65-76.

  13. Keller MA; Venkotraman TN, Thomas A, Deveikis A, Hayes J, Berman N, Walot I, Ernst T, Chang L.  Cerebral Metabolites in HIV-infected Children Followed for Ten Months with 1H-MRS.  Neurology 2006 Mar;66:874-879.

  14. Chang L, Ernst T, Speck O, Grob C.  Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities.  American Journal of Psychiatry 2005;162(2)Feb 2005:1-9.

  15. Tomasi D, Ernst T, Arnold S, Caparelli EC, Chang L.  The Effect of Practice in Visual Attention Processing: A functional MRI study at 4 Tesla. Neuroimage December 2004;23(4):1414-1421.

  16. Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, Fowler J.  Decreased brain dopamine transporters in patients with HIV-associated dementia. Brain 2004 Nov;127(Pt 11):2452-8. Epub 2004 Aug 19.

  17. Chang L, Ernst T, Witt M, Ames N, Gaiefsky M, Miller E.  Relationships Among Cerebral Metabolites, Cognitive Function and Viral Loads in Antiretroviral-Naïve HIV Patients. NeuroImage 2002;17(3):1638-1648.

  18. Volkow ND, Chang L, Wang G-J, Fowler JS, Franceschi, D, Sedler M, Gatley SJ, Miller E., Hitzemann R, Ding Y-S, Logan J. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.  Journal of Neuroscience 2001 Dec 1;21(23):9414-8.

  19. Chang L, Speck O, Miller E, Braun A, Jovicich J, Itti L, Ernst T.  Neural Correlates Of Attention And Working Memory Deficits In Patients With HIV-1. Neurology 2001; 57:1001-1007.

  20. Smith L, Chang L, Yonekura ML, Osborne D, Grob C, Ernst T.  Brain proton magnetic resonance spectroscopy and imaging in children exposed to methamphetamine in utero.  Neurology 2001;57(2):255-260.

  21. Chang L, Grob C, Ernst T, Itti L, Mishkin F, Jose-Melchor R, Poland R.  Effect of Ecstasy [3,4-Methylenedioxymethamphetamine (MDMA)] on Cerebral Blood Flow: A Co-registered SPECT and MRI study. Psychiatry Research: Neuroimaging 2000;98:15-28.

  22. Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller EN.  Highly Active Antiretroviral Therapy Reverses Brain Metabolite Abnormalities in Mild HIV-1 Dementia.  Neurology 1999;53(4):782-789.

  23. Chang L, Ernst T, Grob CS, Poland RE.  Cerebral 1H MRS Alterations in Recreational 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) Users. Journal of Magnetic Resonance Imaging 1999;10(4):521-526.

  24. Chang L, Ernst T, Strickland T, Mehringer CM.  Gender Effects on Persistent Cerebral Metabolite Changes in the Frontal Lobes of Abstinent Cocaine Users. American Journal of Psychiatry 1999;156:716-722.

  25. Chang L, Ernst T, Osborn D, Seltzer W. Leonido-Yee M, Poland RE.  Proton Spectroscopy in Myotonic Dystrophy: Correlation with CTG Repeats.  Archives of Neurology (JAMA Neurology) 1998;55(3):305-311.

  26. Galasko D, Chang L, Motter R, Clark CM, Kaye J, Knopman D, Thomas R, Kholodenko D, Schenk D, Lieberburg I, Miller B, Green R, Basherad R, Kertiles L, Boss MA, Seubert P.  High Cerebrospinal Fluid Tau and Low Amyloid b42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype.  Archives of Neurology (JAMA Neurology) 1998;55:937-945.

  27. Chang L, Mehringer CM, Ernst T, Melchor R, Myers H, Forney D, Satz P.  Neurochemical Alterations in Asymptomatic Abstinent Cocaine Users: A Proton Magnetic Resonance Spectroscopy Study.  Biological Psychiatry 1997;42(12):1105-1114.

  28. Chang L, Ernst T, Tornatore C, Aronow H, Melchor R, Walot I, Singer E, Cornford M.  Metabolite Abnormalities in Progressive Multifocal Leukoencephalopathy by Proton Magnetic Resonance Spectroscopy.  Neurology 1997;48(4):836-845.

  29. Chang L, Ernst T, Poland RE, Jenden DJ.  In Vivo Proton Magnetic Resonance Spectroscopy of the Normal Aging Human Brain.  Life Sciences 1996;58(22):2049-2056.

  30. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clarke C, Green R, Olson D, Southwick P, Wolfert R, Munroe B, Lieberburg I, Seubert P, Schenk D.  Reduction of Amyloid Beta Peptide42 and Elevation of Tau in the CSF of Alzheimer Patients. Annals of Neurology 1995;38:643-648.

  31. Vigo-Pelfrey C, Seubert P, Barbour R, Blomquist C, Lee M, Lee D, Coria FBA, Chang L, Miller B, Lieberburg I, Schenk D.  Elevation of Microtubule-Associated Protein Tau in the Cerebrospinal Fluid of Alzheimer's Patients.  Neurology 1995;45:788-793

  32. Small G, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, LaRue A, Adamson CA, Chang L, Guze BH, Corder EH, Saunders AM, Haines JL, Pericak-Vance MA, Roses AD.  The Effect of Apolipoprotein E Type 4 Allele on Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease. JAMA 1995;273:942-947.

Clinical Specialty Details

Board Certifications

Neurology, American Board of Psychiatry and Neurology (since 1994)

Electrophysiology/EMG, American Board of Electrodiagnostic Medicine (1997-2007) 

    

Awards and Affiliations

Honors And Awards

2021     Avant-Garde Award for HIV/AIDS and Substance Use Disorder Research, a Director’s Pioneer award (DP1), NIDA, NIH 

2020     Reuben S. Mezrich Research Prize, an annual award for a Faculty with significant contributions in the radiological sciences, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD   

2015, 2016  Best Doctors of Hawaii

2009-2012   Best Doctors of Hawaii every year

2010      Joseph Wybran Research Award, from the Society of NeuroImmune Pharmacology (SNIP)

2003-2014    Midcareer Investigator Award in Patient-Oriented Research (K24 x 2), NIDA, NIH

2002      Woman in Science of Year, Town of Brookhaven, New York

2001      Bristol-Meyers Visiting Professor at University of Kentucky, Dept of Neurology, Lexington, KY

1999      Patient Care Leader Award, Harbor-UCLA Medical Center

1998      Richard E. Weitzman Award in Biomedical Research – An annual Young Investigator Award

1995-2001  Clinician Scientist Development Award (K-20), NIDA, NIH

1993-1995  Clinical Associate Physician (CAP) Award, GCRC/NCRR, NIH

1992-1994  Augustus Rose Fellowship from The French Foundation for Alzheimer’s Research

1985          Rock Sleyster Memorial Scholarship Award from the AMA – for special promise in Psychiatry

1981         Research Award-Department of Chemistry, Honors Program, University of Maryland

Current Society Memberships:

American Academy of Neurology (AAN), Member 1989-2017, Fellow Member since 2003

International Society of Magnetic Resonance in Medicine (ISMRM), Member since 1993, Elected Fellow Member since 2008

College of Problems in Drug Dependence (CPDD), Member since 1999

American Neurological Association (ANA), Elected Member since 2003, Fellow Member since 2012

Organization of Human Brain Mapping (OHBM), Member since 2004

American College of Neuropsychopharmacology (ACNP), Elected Member since 2005

Society of Neuro-Immune Pharmacology (SNIP), Founding member since 2001 

Grants and Contracts

Active Grants as PI or MPI:

NIH/NIDA 1DP1DA053719-01 (PI: Chang) - MR-guided focused ultrasound to maximize eradication of the viral reservoir and to promote neurogenesis in the HIV-infected brain”  06/01/21 – 04/30/26; Annual Total Costs / Grant Total Costs:    $1,081,500 / $5,407,500

NIH / NINDS 1R21NS121615-01 (PI: Chang (contact) / Wilson) “Neuroimaging and Behavioral Studies to Assess For neuroinflammation in COVID-19 During Convalescence” 04/01/21-9/30/22; Direct / Total Costs (18 months): $275,000 / $424,875

NIH/NIDA/NINDS/NIAAA, 2U01 DA041117-06 (MPI: Linda Chang and Thomas Ernst) Adolescent Brain Cognitive Development (ABCD) Study- UMB Site”  Total project period: 09/30/15 – 03/31/27; Annual Total Costs:  $1,887,992; Years 6-10 Total Costs:  $13,098,562 

In the News

https://www.medschool.umaryland.edu/news/2021/UM-School-of-Medicine-Researchers-Receive-NIH-Avant-Garde-Award-for-Out-Of-Box-Concept-to-Cure-HIV-and-Treat-Co-Existing-Addiction.html

NIH Avant Garde Award for out-of-box, innovative concept to cure HIV and treat addiction - Multi-disciplinary approach to eradicate all traces of HIV from body, and treat co-existing substance use disorders/addiction - UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE https://www.eurekalert.org/pub_releases/2021-07/uoms-nag070221.php

“Chronic Marijuana Use Unlikely to Further Harm the Brain in HIV” – by Marilyn Larkin, Reuters Health, August 27, 2020 https://www.medscape.com/viewarticle/936376

"University of Maryland explores how actions affect brain development in kids" - by Meredith Cohn, February 23, 2018 https://www.baltimoresun.com/science/bs-hs-md-brain-study-20180219-story.html