title: Measuring the construct of executive control in schizophrenia: defining and validating translational animal paradigms for discovery research.
abstract: Executive control is an aspect of cognitive function known to be impaired in schizophrenia. Previous meetings of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group have more precisely defined executive control in terms of two constructs: "rule generation and selection", and "dynamic adjustments of control". Next, human cognitive tasks that may effectively measure performance with regard to these constructs were identified to be developed into practical and reliable measures for use in treatment development. The aim of this round of CNTRICS meetings was to define animal paradigms that have sufficient promise to warrant further investigation for their utility in measuring these constructs. Accordingly, "reversal learning" and the "attentional set-shifting task" were nominated to assess the construct of rule generation and selection, and the "stop signal task" for the construct of dynamic adjustments of control. These tasks are described in more detail here, with a particular focus on their utility for drug discovery efforts. Presently, each assay has strengths and weaknesses with regard to this point and increased emphasis on improving practical aspects of testing, understanding predictive validity, and defining biomarkers of performance represent important objectives in attaining confidence in translational validity here.
authors.affiliation: Eli Lilly & Co. Ltd., Lilly Research Centre, Sunninghill Road, Windlesham, Surrey, GU20 6PH, UK. Electronic address: gilmour_gary@lilly.com.
authors.forename: Gary
authors.initials: G
authors.lastname: Gilmour
authors.forename: Alexander
authors.initials: A
authors.lastname: Arguello
authors.forename: Andrea
authors.initials: A
authors.lastname: Bari
authors.forename: Verity J
authors.initials: VJ
authors.lastname: Brown
authors.forename: Cameron
authors.initials: C
authors.lastname: Carter
authors.forename: Stan B
authors.initials: SB
authors.lastname: Floresco
authors.forename: David J
authors.initials: DJ
authors.lastname: Jentsch
authors.forename: David S
authors.initials: DS
authors.lastname: Tait
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D004195:Disease Models, Animal; D056344:Executive Function / Q000502:physiology*; D006801:Humans; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000150:complications*; D057170:Translational Research, Biomedical