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

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.