Brain Imaging and Behavior

, Volume 11, Issue 5, pp 1302–1315 | Cite as

Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity

  • Edith V. SullivanEmail author
  • Barton Lane
  • Dongjin Kwon
  • M. J. Meloy
  • Susan F. Tapert
  • Sandra A. Brown
  • Ian M. Colrain
  • Fiona C. Baker
  • Michael D. De Bellis
  • Duncan B. Clark
  • Bonnie J. Nagel
  • Kilian M. Pohl
  • Adolf Pfefferbaum
Original Research


Structural MRI of volunteers deemed “normal” following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as “incidental findings.” Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as “normal variants” to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.


Brain anomaly Dysmorphology Development, adolescence Incidental findings 


Compliance with ethical standard


This work was supported by the U.S. National Institute on Alcohol Abuse and Alcoholism with co-funding from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Child Health and Human Development [NCANDA grant numbers: AA021697 (A.P. + K.M.P.), AA021695 (S.A.B. + S.F.T.), AA021692 (S.A.B. + S.F.T.), AA021696 (I.M.C. + F.C.B.), AA021681 (M.D.D.B.), AA021690 (D.B.C.), AA021691 (B.N.)]. Additional funding supported E.V.S. (AA017168).

Conflict of interest

The authors declare that they have no conflict of interest with the work reported herein.

Informed consent

Informed consent was obtained from all individual participants, parents, or legal guardians who were majority, and assent from minors included in the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

11682_2016_9634_MOESM1_ESM.docx (243 kb)
ESM 1 ESM (DOCX 242 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Edith V. Sullivan
    • 1
    Email author
  • Barton Lane
    • 2
  • Dongjin Kwon
    • 1
    • 3
  • M. J. Meloy
    • 4
  • Susan F. Tapert
    • 4
  • Sandra A. Brown
    • 4
  • Ian M. Colrain
    • 3
  • Fiona C. Baker
    • 3
  • Michael D. De Bellis
    • 5
  • Duncan B. Clark
    • 6
  • Bonnie J. Nagel
    • 7
  • Kilian M. Pohl
    • 1
    • 3
  • Adolf Pfefferbaum
    • 1
    • 3
  1. 1.Department of Psychiatry & Behavioral SciencesStanford University School of MedicineStanfordUSA
  2. 2.Department of RadiologyStanford University School of MedicineStanfordUSA
  3. 3.Center for Health SciencesMenlo ParkUSA
  4. 4.Department of PsychiatryUniversity of CaliforniaLa JollaUSA
  5. 5.Department of Psychiatry & Behavioral SciencesDuke University School of MedicineDurhamUSA
  6. 6.Department of PsychiatryUniversity of PittsburghPittsburghUSA
  7. 7.Departments of Psychiatry and Behavioral NeuroscienceOregon Health & Sciences UniversityPortlandUSA

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