title: 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.
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Department of Psychology, University of Zurich, Switzerland. Electronic address: olivia.geisseler@usz.ch.
authors.forename: Olivia
authors.initials: O
authors.lastname: Geisseler
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Department of Internal Medicine, Neurology and Neurorehabilitation Center, State Hospital/Kantonsspital Lucerne, Switzerland. Electronic address: tobias.pflugshaupt@luks.ch.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pflugshaupt
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: andreas.Buchmann@bli.uzh.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buchmann
authors.affiliation: URPP Dynamics of Healthy Aging, University of Zurich, Switzerland. Electronic address: l.bezzola@psychologie.uzh.ch.
authors.forename: Ladina
authors.initials: L
authors.lastname: Bezzola
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: katja.reuter@usz.ch.
authors.forename: Katja
authors.initials: K
authors.lastname: Reuter
authors.affiliation: Medical Radiological Institute, Zurich, Switzerland. Electronic address: image-solution@ggaweb.ch.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schuknecht
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: david.weller@usz.ch.
authors.forename: David
authors.initials: D
authors.lastname: Weller
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: michael.linnebank@helios-kliniken.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland. Electronic address: peter.brugger@usz.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Brugger
mesh_terms: D000328:Adult; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology*; D009483:Neuropsychological Tests
keywords: Mental dice task; Multiple sclerosis; Neural correlates; Random number generation