title: A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients.
abstract: BACKGROUND
  Intellectual Disability (ID) is characterized by deficits in intellectual functions such as reasoning, problem-solving, planning, abstract thinking, judgment, and learning. As new avenues are emerging for treatment of genetically determined ID (such as Down's syndrome or Fragile X syndrome), it is necessary to identify objective reliable and sensitive outcome measures for use in clinical trials.
  
  
  OBJECTIVE
  We developed a novel visual analogical reasoning paradigm, inspired by the Progressive Raven's Matrices, but appropriate for Intellectually Disabled patients. This new paradigm assesses reasoning and inhibition abilities in ID patients.
  
  
  METHODS
  We performed behavioural analyses for this task (with a reaction time and error rate analysis, Study 1) in 96 healthy controls (adults and typically developed children older than 4) and 41 genetically determined ID patients (Fragile X syndrome, Down syndrome and ARX mutated patients). In order to establish and quantify the cognitive strategies used to solve the task, we also performed an eye-tracking analysis (Study 2).
  
  
  RESULTS
  Down syndrome, ARX and Fragile X patients were significantly slower and made significantly more errors than chronological age-matched healthy controls. The effect of inhibition on error rate was greater than the matrix complexity effect in ID patients, opposite to findings in adult healthy controls. Interestingly, ID patients were more impaired by inhibition than mental age-matched healthy controls, but not by the matrix complexity. Eye-tracking analysis made it possible to identify the strategy used by the participants to solve the task. Adult healthy controls used a matrix-based strategy, whereas ID patients used a response-based strategy. Furthermore, etiologic-specific reasoning differences were evidenced between ID patients groups.
  
  
  CONCLUSIONS
  We suggest that this paradigm, appropriate for ID patients and developmental populations as well as adult healthy controls, provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition, enabling testing for the effect of pharmacological or behavioural intervention in these specific populations.
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.|CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.|Université de Lyon, Faculté de médecine Lyon Sud-Charles Mérieux, Lyon, France.|Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States of America.|EPICIME-CIC 1407/Inserm, UMR5558, LBBE, Université de Lyon, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Curie
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.|CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Brun
authors.affiliation: CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cheylus
authors.affiliation: CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Reboul
authors.affiliation: CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nazir
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.|CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Bussy
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.|CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Delange
authors.affiliation: CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Paulignan
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Mercier
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Marignier
authors.affiliation: Centre de Recherche en Neurosciences de Lyon, INSERM U1028, CNRS UMR5292, CH le Vinatier, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Merle
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Saint-Etienne, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: de Fréminville
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Saint-Etienne, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Prieur
authors.affiliation: Médecine interne, Hôpital Saint Luc Saint Joseph, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Till
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Tours, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mortemousque
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.affiliation: Génétique, Centre Hospitalier Universitaire, Saint-Etienne, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.affiliation: Service de génétique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, CRNL, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon I, Lyon, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: IGBMC, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France.
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ott
authors.affiliation: EPICIME-CIC 1407/Inserm, UMR5558, LBBE, Université de Lyon, France.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Kassai
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States of America.|Gillberg Neuropsychiatric Center, Gothenburg, Sweden.
authors.forename: Nouchine
authors.initials: N
authors.lastname: Hadjikhani
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States of America.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.affiliation: Centre de Référence, Déficiences Intellectuelles de Causes Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.|CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, Bron, France.|Université de Lyon, Faculté de médecine Lyon Sud-Charles Mérieux, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003071:Cognition; D004314:Down Syndrome / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005600:Fragile X Syndrome / Q000503:physiopathology / Q000523:psychology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013850:Thinking; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors