Random number generation deficits in patients with multiple sclerosis: Characteristics and neural correlates

Abstract

Human subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinico-anatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of MS, while the imaging results suggest an association between this loss and cortical pathology. AbstractHuman subjects typically deviate systematically from randomness when attempting to produce a sequence of random numbers. Despite an increasing number of behavioral and functional neuroimaging studies on random number generation (RNG), its structural correlates have never been investigated. We set out to fill this gap in 44 patients with multiple sclerosis (MS), a disease whose impact on RNG has never been studied. The RNG task required the paced (1 Hz) generation of the numbers from 1 to 6 in a sequence as random as possible. The same task was administered in 39 matched healthy controls. To assess neuroanatomical correlates such as cortical thickness, lesion load and third ventricle width, all subjects underwent high-resolution structural MRI. Compared to controls, MS patients exhibited an enhanced tendency to arrange consecutive numbers in an ascending order ("forward counting"). Furthermore, patients showed a higher susceptibility to rule breaks (producing out-of-category digits like 7) and to skip beats of the metronome. Clinicoanatomical correlation analyses revealed two main findings: First, increased counting in MS patients was associated with higher cortical lesion load. Second, increased number of skipped beats was related to widespread cortical thinning. In conclusion, our test results illustrate a loss of behavioral complexity in the course of multiple sclerosis, while the imaging results suggest an association between this loss and cortical pathology. KeywordsRandom number generation; mental dice task; multiple sclerosis, neural correlates

Human behavioral complexity peaks at age 25

“…Neuropsychological investigations could use the tasks and measures employed here with selected patient groups to perform lesion-symptom mappings, as has been done recently [57], but preferably in patients with focal vascular lesions. In parallel with such investigations, Internet-based work such as the project presented here may still play a powerful role.…”

Quantitative Limbic System Mapping of Main Cognitive Domains in Multiple Sclerosis

“…Damage to white matter structures from demyelination or axonal loss leading to disconnection between the cortical and subcortical regions responsible for cognition, underlies the cognitive symptomatology in MS ( 3 , 4 ). Although MS was originally thought to be mainly a white matter disease, gray matter structures are also known to be involved in the disease pathogenesis and shown to correlate with impairment ( 5 , 6 ).…”

Performance of Children and Adolescents on Random Number Generation as a measure of Executive Functions

“…An RNG task employs inhibitory control (Inhibition) and the ability to update verbal production (i.e., Updating), while keeping in working memory previous answers; these abilities tap different sets of randomness indices (Miyake et al, 2000). Despite RNG's easy administration and usefulness (Brugger, 1997;Geisseler et al, 2016) a recent scoping review demonstrates that this task is not frequently used in order to investigate EF in adolescent populations (Nyongesa et al, 2019). performance, school-aged children did not.…”

“…Thus, R scores of 10% or 20% signify a more random sequence than an R score of 70% (For a mathematical approach of R score you can see Towse & Neil, 1998). Turning Point Index (TPI) measures the change between ascending and descending series (Geisseler et al, 2016). For example, in the sequence "2,3,5,1,4,2" there are two turning points: one at the digit "5" and one at the digit "4".…”