title: Cortical thinning in the anterior cingulate cortex predicts multiple sclerosis patients' fluency performance in a lateralised manner.
abstract: Cognitive impairment is as an important feature of Multiple Sclerosis (MS), and might be even more relevant to patients than mobility restrictions. Compared to the multitude of studies investigating memory deficits or basic cognitive slowing, executive dysfunction is a rarely studied cognitive domain in MS, and its neural correlates remain largely unexplored. Even rarer are topological studies on specific cognitive functions in MS. Here we used several structural MRI parameters - including cortical thinning and T2 lesion load - to investigate neural correlates of executive dysfunction, both on a global and a regional level by means of voxel- and vertex-wise analyses. Forty-eight patients with relapsing-remitting MS and 48 healthy controls participated in the study. Five executive functions were assessed, i.e. verbal and figural fluency, working memory, interference control and set shifting. Patients scored lower than controls in verbal and figural fluency only, and displayed widespread cortical thinning. On a global level, cortical thickness independently predicted verbal fluency performance, when controlling for lesion volume and central brain atrophy estimates. On a regional level, cortical thinning in the anterior cingulate region correlated with deficits in verbal and figural fluency and did so in a lateralised manner: Left-sided thinning was related to reduced verbal - but not figural - fluency, whereas the opposite pattern was observed for right-sided thinning. We conclude that executive dysfunction in MS patients can specifically affect verbal and figural fluency. The observed lateralised clinico-anatomical correlation has previously been described in brain-damaged patients with large focal lesions only, for example after stroke. Based on focal grey matter atrophy, we here show for the first time comparable lateralised findings in a white matter disease with widespread pathology.
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland; Department of Psychology, University of Zurich, Binzmühlestrasse 14/1, 8050 Zürich, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Geisseler
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland; Neurology and Neurorehabilitation Center, Luzerner Kantonsspital, 6016 Luzern, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pflugshaupt
authors.affiliation: URPP Dynamics of Healthy Aging, University of Zurich, Andreasstrasse 15/Box 2, 8050 Zurich, Switzerland.
authors.forename: Ladina
authors.initials: L
authors.lastname: Bezzola
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Reuter
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Weller
authors.affiliation: Medizinisch Radiologisches Institut, Bahnhofplatz 3, 8001 Zurich, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schuknecht
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Brugger
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland; Department of Neurology, Helios-Klinik Hagen-Ambrock, Ambrocker Weg 60, 58091 Hagen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
mesh_terms: D000328:Adult; D001284:Atrophy; D002540:Cerebral Cortex / Q000473:pathology; D056344:Executive Function; D005260:Female; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D009483:Neuropsychological Tests; D013064:Speech Disorders / Q000150:complications
keywords: Atrophy; Cortical thinning; EDSS, Expanded Disability Status Scale; Executive function; FDR, false discovery rate; FLAIR, fluid attenuated inversion recovery; Fluency; MPRAGE, magnetization prepared rapid gradient-echo imaging; MS, multiple sclerosis; Multiple sclerosis; TVW, third ventricle width; VLSM, voxel-lesion symptom mapping