title: Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study.
abstract: The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing-remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293-2304, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Neuroimaging Research Unit, Vita-Salute San Raffaele University, Milan, Italy.|Ospedale di Gallarate, Multiple Sclerosis Center, Gallarate, Italy.|Traumatic Brain Injury Research, Kessler Foundation, West Orange, New Jersey.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dobryakova
authors.affiliation: Neuroimaging Research Unit, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: Neuroimaging Research Unit, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.affiliation: Ospedale di Gallarate, Multiple Sclerosis Center, Gallarate, Italy.|Traumatic Brain Injury Research, Kessler Foundation, West Orange, New Jersey.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Colombo
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Ospedale di Gallarate, Multiple Sclerosis Center, Gallarate, Italy.|Traumatic Brain Injury Research, Kessler Foundation, West Orange, New Jersey.|Department of Physical Medicine and Rehabilitation, Rutgers, New Jersey Medical School, Newark, New Jersey.
authors.forename: John
authors.initials: J
authors.lastname: DeLuca
authors.affiliation: Neuroimaging Research Unit, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001499:Bayes Theorem; D001931:Brain Mapping / Q000379:methods; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D010641:Phenotype; D011930:Reaction Time; D057190:Stroop Test
keywords: Bayes networks; Stroop; effective connectivity; executive control; fMRI; interference; multiple sclerosis; phenotypes