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Imaging the “At-Risk” Brain: Future Directions

  • Maki S. Koyama (a1) (a2), Adriana Di Martino (a3), Francisco X. Castellanos (a2) (a3), Erica J. Ho (a1), Enitan Marcelle (a1), Bennett Leventhal (a4) and Michael P. Milham (a1) (a2)...


Objectives: Clinical neuroscience is increasingly turning to imaging the human brain for answers to a range of questions and challenges. To date, the majority of studies have focused on the neural basis of current psychiatric symptoms, which can facilitate the identification of neurobiological markers for diagnosis. However, the increasing availability and feasibility of using imaging modalities, such as diffusion imaging and resting-state fMRI, enable longitudinal mapping of brain development. This shift in the field is opening the possibility of identifying predictive markers of risk or prognosis, and also represents a critical missing element for efforts to promote personalized or individualized medicine in psychiatry (i.e., stratified psychiatry). Methods: The present work provides a selective review of potentially high-yield populations for longitudinal examination with MRI, based upon our understanding of risk from epidemiologic studies and initial MRI findings. Results: Our discussion is organized into three topic areas: (1) practical considerations for establishing temporal precedence in psychiatric research; (2) readiness of the field for conducting longitudinal MRI, particularly for neurodevelopmental questions; and (3) illustrations of high-yield populations and time windows for examination that can be used to rapidly generate meaningful and useful data. Particular emphasis is placed on the implementation of time-appropriate, developmentally informed longitudinal designs, capable of facilitating the identification of biomarkers predictive of risk and prognosis. Conclusions: Strategic longitudinal examination of the brain at-risk has the potential to bring the concepts of early intervention and prevention to psychiatry. (JINS, 2016, 22, 164–179)


Corresponding author

Correspondence and reprint requests to: Michale P. Milham, Child Mind Institute, Nathan S. Kline Institute for Psychiatric Research, 455 Park Avenue, New York, New York 10022. E-mail:


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