title: Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.
abstract: OBJECTIVE
  Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm.
  
  
  METHODS
  A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words.
  
  
  RESULTS
  The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017).
  
  
  CONCLUSIONS
  Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.
authors.affiliation: University of São Paulo Medical School (FMUSP), São Paulo, Brazil. Electronic address: marcelobatistuzzo@gmail.com.
authors.forename: Marcelo Camargo
authors.initials: MC
authors.lastname: Batistuzzo
authors.affiliation: University of São Paulo Medical School (FMUSP), São Paulo, Brazil.
authors.forename: Joana Bisol
authors.initials: JB
authors.lastname: Balardin
authors.affiliation: Departamento de Radiologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo.
authors.forename: Maria da Graça Morais
authors.initials: Mda G
authors.lastname: Martin
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Marcelo Queiroz
authors.initials: MQ
authors.lastname: Hoexter
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Elisa Teixeira
authors.initials: ET
authors.lastname: Bernardes
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Sonia
authors.initials: S
authors.lastname: Borcato
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Marina de Marco E
authors.initials: Mde M
authors.lastname: Souza
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Cicero Nardini
authors.initials: CN
authors.lastname: Querido
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Rosa Magaly
authors.initials: RM
authors.lastname: Morais
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Pedro Gomes
authors.initials: PG
authors.lastname: de Alvarenga
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Lopes
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Roseli Gedanke
authors.initials: RG
authors.lastname: Shavitt
authors.affiliation: Center for Health Behavior Neuroscience, Kansas University Medical Center, Kansas City, KA.
authors.forename: Cary R
authors.initials: CR
authors.lastname: Savage
authors.affiliation: Departamento de Radiologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo.
authors.forename: Edson
authors.initials: E
authors.lastname: Amaro
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Euripedes C
authors.initials: EC
authors.lastname: Miguel
authors.affiliation: National Institute of Developmental Psychiatry for Children and Adolescents, Obsessive-Compulsive Spectrum Disorders Program (PROTOC) at FMUSP.
authors.forename: Guilherme V
authors.initials: GV
authors.lastname: Polanczyk
authors.affiliation: University of São Paulo Medical School (FMUSP), São Paulo, Brazil.
authors.forename: Eliane C
authors.initials: EC
authors.lastname: Miotto
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D001938:Brazil; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012660:Semantics
keywords: functional magnetic resonance imaging; obsessive-compulsive disorder; semantic clustering; verbal episodic memory