A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients

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. Conclusion 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.

[1]  S. Greenspan,et al.  Intellectual disability as a disorder of reasoning and judgement: the gradual move away from intelligence quotient-ceilings , 2014, Current opinion in psychiatry.

[2]  M. Gligorović,et al.  Inhibitory control and adaptive behaviour in children with mild intellectual disability. , 2014, Journal of intellectual disability research : JIDR.

[3]  Alice C. Roy,et al.  The c.429_452 duplication of the ARX gene: a unique developmental-model of limb kinetic apraxia , 2014, Orphanet Journal of Rare Diseases.

[4]  Tiina K. Urv,et al.  Outcome Measures for Clinical Trials in Fragile X Syndrome , 2013, Journal of developmental and behavioral pediatrics : JDBP.

[5]  C. Walsh,et al.  New innovations: Therapeutic opportunities for intellectual disabilities , 2013, Annals of neurology.

[6]  E. Vakil,et al.  Solving the Raven Progressive Matrices by adults with intellectual disability with/without Down syndrome: different cognitive patterns as indicated by eye-movements. , 2012, Research in developmental disabilities.

[7]  D. Messer,et al.  Strengths and weaknesses in executive functioning in children with intellectual disability. , 2012, Research in developmental disabilities.

[8]  Janice Branson,et al.  Epigenetic Modification of the FMR1 Gene in Fragile X Syndrome Is Associated with Differential Response to the mGluR5 Antagonist AFQ056 , 2011, Science Translational Medicine.

[9]  L. Nilsson,et al.  Executive functions in individuals with intellectual disability. , 2010, Research in developmental disabilities.

[10]  Mara Dierssen,et al.  Cognitive deficits and associated neurological complications in individuals with Down's syndrome , 2010, The Lancet Neurology.

[11]  S. Lanfranchi,et al.  Executive function in adolescents with Down Syndrome. , 2010, Journal of intellectual disability research : JIDR.

[12]  P. Willner,et al.  Evaluation of executive functioning in people with intellectual disabilities. , 2010, Journal of intellectual disability research : JIDR.

[13]  K. R. Ridderinkhof,et al.  Profiling Fragile X Syndrome in males: strengths and weaknesses in cognitive abilities. , 2010, Research in developmental disabilities.

[14]  Robert L. Schalock,et al.  Intellectual Disability: Definition, Classification, and Systems of Supports , 2009 .

[15]  Daniel Ansari,et al.  Using developmental trajectories to understand developmental disorders. , 2009, Journal of speech, language, and hearing research : JSLHR.

[16]  G. Humphreys,et al.  Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader–Willi syndrome chromosome 15 q11–q13 deletion and boys with Fragile X syndrome , 2009, Cognitive neuropsychology.

[17]  B. Bourdin,et al.  Verbal, visual, and spatio-sequential short-term memory: assessment of the storage capacities of children and teenagers with Down's syndrome. , 2009, Journal of intellectual disability research : JIDR.

[18]  Alan D. Baddeley,et al.  Long-Term Memory for Verbal and Visual Information in Down Syndrome and Williams Syndrome: Performance on the Doors and People Test , 2007, Cortex.

[19]  Canan Karatekin,et al.  Eye tracking studies of normative and atypical development , 2007 .

[20]  P. Ornstein,et al.  Sustained attention and response inhibition in boys with fragile X syndrome: Measures of continuous performance , 2007, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[21]  Rafat Hussain,et al.  The four ages of Down syndrome. , 2007, European journal of public health.

[22]  D. Bors,et al.  Eye-movement analysis demonstrates strategic influences on intelligence , 2006 .

[23]  Stefano Vicari,et al.  Motor Development and Neuropsychological Patterns in Persons with Down Syndrome , 2006, Behavior genetics.

[24]  T. Paus Mapping brain maturation and cognitive development during adolescence , 2005, Trends in Cognitive Sciences.

[25]  B. J. Casey,et al.  Differential patterns of striatal activation in young children with and without ADHD , 2003, Biological Psychiatry.

[26]  V. Menon,et al.  Maturation of brain function associated with response inhibition. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[27]  Gary H. Glover,et al.  A Developmental fMRI Study of the Stroop Color-Word Task , 2002, NeuroImage.

[28]  J. Fryns,et al.  ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. , 2002, Human molecular genetics.

[29]  J. Wilding,et al.  A neuropsychological profile of attention deficits in young males with fragile X syndrome , 2000, Neuropsychologia.

[30]  M. J. Emerson,et al.  The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis , 2000, Cognitive Psychology.

[31]  F. Munir,et al.  Spatial Cognition in Males With Fragile-X Syndrome: Evidence for a Neuropsychological Phenotype , 1999, Cortex.

[32]  P. Boeck,et al.  Generation speed in Raven's progressive matrices test , 1999 .

[33]  J. Mandel,et al.  Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome , 1991, Science.

[34]  C. E. Bethell-Fox,et al.  Adaptive reasoning: Componential and eye movement analysis of geometric analogy performance ☆ , 1984 .

[35]  M A Just,et al.  From the SelectedWorks of Marcel Adam Just 1990 What one intelligence test measures : A theoretical account of the processing in the Raven Progressive Matrices Test , 2016 .

[36]  Developmental Disabilities,et al.  Intellectual disability : definition, classification, and systems of supports , 2010 .

[37]  Annette Karmiloff-Smith,et al.  Nativism versus neuroconstructivism: rethinking the study of developmental disorders. , 2009, Developmental psychology.

[38]  Deborah D. Hatton,et al.  Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study. , 2008, Neuropsychology.

[39]  I. Scheffer,et al.  Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy , 2002, Nature Genetics.

[40]  S. Vicari Implicit versus explicit memory function in children with Down and Williams syndrome. , 2001, Down's syndrome, research and practice : the journal of the Sarah Duffen Centre.

[41]  A. Jensen,et al.  Individual differences in the Hick paradigm. , 1987 .

[42]  Edward Zigler,et al.  Mental Retardation : The Developmental-difference Controversy , 1982 .