title: Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?
abstract: BACKGROUND
  High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points.
  
  
  METHODS
  A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels.
  
  
  RESULTS
  Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas.
  
  
  CONCLUSIONS
  The combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.
authors.affiliation: Department of Computer Science, Centre for Computational Statistics and Machine Learning, University College London, London, United Kingdom.|Department of Physiology and Pharmacology, Federal Fluminense University, Niteroi, Brazil.
authors.forename: Liana C L
authors.initials: LC
authors.lastname: Portugal
authors.affiliation: Department of Computer Science, Centre for Computational Statistics and Machine Learning, University College London, London, United Kingdom.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Rosa
authors.affiliation: Department of Computer Science, Centre for Computational Statistics and Machine Learning, University College London, London, United Kingdom.
authors.forename: Anil
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Hinze
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Perlman
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Claudiu
authors.initials: C
authors.lastname: Schirda
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Travis
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Demeter
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, United States of America.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Ciuffetelli
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Erika E
authors.initials: EE
authors.lastname: Forbes
authors.affiliation: University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, United States of America.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Sunshine
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, United States of America.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Holland
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kowatch
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Department of Child Psychiatry, New York University School of Medicine, New York, United States of America.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, United States of America.
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, Ohio State University, Columbus, United States of America.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Fristad
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.affiliation: University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, United States of America.|Department of Psychiatry, Johns Hopkins University, Baltimore, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Department of Physiology and Pharmacology, Federal Fluminense University, Niteroi, Brazil.
authors.forename: Mirtes
authors.initials: M
authors.lastname: Pereira
authors.affiliation: Department of Physiology and Pharmacology, Federal Fluminense University, Niteroi, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: Oliveira
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, United States of America.|Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
authors.affiliation: Department of Computer Science, Centre for Computational Statistics and Machine Learning, University College London, London, United Kingdom.
authors.forename: Janaina
authors.initials: J
authors.lastname: Mourao-Miranda
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D000342:Affective Symptoms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000067290:Behavior Rating Scale; D001714:Bipolar Disorder / Q000523:psychology; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005500:Follow-Up Studies; D005717:Games, Experimental; D006801:Humans; D008032:Limbic System / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010363:Pattern Recognition, Automated; D000297:Psychology, Adolescent; D011619:Psychotropic Drugs / Q000494:pharmacology / Q000627:therapeutic use; D012201:Reward; D063189:Symptom Assessment
chemical_list: D011619:Psychotropic Drugs