Abstract
Duchenne Muscular Dystrophy has emerged as a model to assess cognitive domains. The DMD gene variant location and its association with variable degrees of cognitive impairment necessitate identification of a common denominator. Computer architectures provide a framework to delineate the mechanisms involved in the cognitive functioning of the human brain. Copy number variations in the 79 exons of DMD gene were screened in 84 DMD subjects by Multiplex Ligation-dependent Probe Amplification (MLPA). DMD subjects were categorized based on the presence or absence of DP140 isoform. The cognitive and neuropsychological assessments were carried out as per inclusion criteria using standard scales. Instance-based learning theory (IBLT) based on the partial matching process was developed to mimic Stroop Color and Word Task (SCWT) performance on Adaptive Control of Thought-Rational (ACT-R) cognitive architecture based on IBLT. Genotype–phenotype correlation was conducted based on the mutation location in DMD gene. Assessment of specific cognitive domains in DP140 − ve group corresponded to the involvement of multiple brain lobes including temporal (verbal and visual learning and memory), parietal (visuo-conceptual and visuo-constructive abilities) and frontal (sustained and focused attention, verbal fluency, cognitive control). Working memory axis was found to be the central domain through tasks including RAVLT trial 1, recency effect, digit span backward, working memory index, arithmetic subtests in the Dp140 − ve group. IBLT validated the non-reliance of DMD subjects on recency indicating affected working memory domain. Modeling strategy revealed altered working memory processes in DMD cases with affected Dp140 isoform. DMD brain was observed to rely on primacy than the recency suggesting alterations in working memory capacity. Modeling revealed lowered activation of DMD brain with Dp140 − ve in order to retrieve the instances.
Highlights
Duchenne Muscular Dystrophy has emerged as a model to assess cognitive domains
The lesser known cognitive impairment develops in Duchenne Muscular Dystrophy (DMD) in one third of cases due to which DMD has emerged as a model to understand processes and functioning of crucial cognitive d omains[4]
We have reported a nonprogressive deterioration of neuropsychological domains[16]
Summary
Duchenne Muscular Dystrophy has emerged as a model to assess cognitive domains. The DMD gene variant location and its association with variable degrees of cognitive impairment necessitate identification of a common denominator. IBLT validated the non-reliance of DMD subjects on recency indicating affected working memory domain. Modeling strategy revealed altered working memory processes in DMD cases with affected Dp140 isoform. A case study reported manifestation of intellectual disability without usual muscular dystrophy phenotype due to deletion of three base pairs (c.9711_9713del) in the distal region of DMD gene[22], providing substantial evidence regarding DMD distal region’s association with human cognition. IBLT is explained by three slots in an instance i.e. Situation (S), Decision (D) and Utility (U) to term it as S DUs23,24 It contributes in gaining insight about decision making processes in a dynamic neuropsychological task[24] and may be proven beneficial for determining association between dystrophin isoforms and cognitive deficits. SCWT provides an opportunity to understand the phenomenon of cognitive inhibition as well as association to working memory process through cognitive control mechanism
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