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.

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.

Fig 1. Example of the 5 different conditions included in the task (1a: Identical matrix (Id), 1b: One-relation matrix with neutral response (1R_Neu), 1c: One-relation matrix with “to be inhibited” false response (1R_Inhib), Two-relation matrix with neutral response (2R_Neu), Two-relation matrix with “to be inhibited” false response (2R_Inhib)).

Fig 2. AOI (Area of Interest) defined for each stimuli of the eye-tracking task (the Matrix with its four elements and the two responses).

Fig 3. Result of the ER in 34 adult healthy controls (*:p<0.05, ***:p<0.005, ****:p<0.001, NS: Non Significant).

Fig 4. Non-linear regression analysis of ER with chronological age in healthy controls, children older than 4 and adults.

Fig 5. Group effect between DS, ARX, FraX, MA HC and CA HC on ER (MA HC: Mental Age-matched Healthy Controls, CA HC: Chronological Age-matched Healthy Controls, *:p<0.05, ***: p<0.005, ****: p<0.001).

Fig 6. ER for each of the five conditions for each group of patients (DS, FraX, ARX) and for both CA HC and MA HC.

(For display purposes and because the different chronological age-matched and mental age-matched control groups did not respectively differ significantly one from the other, the results of only one chronological age-matched control group and one mental age-matched control group are displayed).

Fig 7. Correlation between ER and the Raven’s Coloured Progressive Matrices in ID patients (Pearson's product-moment correlation = -0.62, p<0.0001).

Fig 8. ER for each run in Adult healthy controls, DS and FraX patients.

Fig 9. Analysis of the latency (ms) of the first transition between the matrix and the responses in DS, Fra X, and for both CA HC and MA HC.

(For display purposes and because the different chronological age-matched and mental age-matched control groups did not respectively differ significantly one from the other, the results of only one chronological age-matched control group and one mental age-matched control group are displayed).

Fig 10. Analysis of the number of transitions between the matrix and the responses for the DS, FraX, and for both CA HC and MA HC.

(For display purposes and because the different chronological age-matched and mental age-matched control groups did not respectively differ significantly one from the other, the results of only one chronological age-matched control group and one mental age-matched control group are displayed).

Fig 11. Analysis of the latency (ms) of the first transition between the matrix and the responses for each of the 5 conditions in DS, Fra X, and for both CA HC and MA HC.

(For display purposes and because the different chronological age-matched and mental age-matched control groups did not respectively differ significantly one from the other, the results of only one chronological age-matched control group and one mental age-matched control group are displayed).

Fig 12. Analysis of the proportion of time on each AOI in DS, FraX, and for both CA HC and MA HC.

(For display purposes and because the different chronological age-matched and mental age-matched control groups did not respectively differ significantly one from the other, the results of only one chronological age-matched control group and one mental age-matched control group are displayed).