title: Brain function during cognitive flexibility and white matter integrity in alcohol-dependent patients, problematic drinkers and healthy controls.
abstract: Cognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol-dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task-related functional connectivity between these areas was assessed. There were no significant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence.
authors.affiliation: Academic Medical Centre, Department of Psychiatry, Amsterdam Institute for Addiction Research, The Netherlands.
authors.forename: Jochem M
authors.initials: JM
authors.lastname: Jansen
authors.affiliation: Academic Medical Centre, Department of Psychiatry, Amsterdam Institute for Addiction Research, The Netherlands.|Donders Institute for Cognition, Brain and Behaviour, Radboud University, The Netherlands.|Department of Neurology, Radboud University Medical Centre, The Netherlands.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: van Holst
authors.affiliation: Academic Medical Centre, Department of Psychiatry, Amsterdam Institute for Addiction Research, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Academic Medical Centre, Department of Psychiatry, Amsterdam Institute for Addiction Research, The Netherlands.|VU University Medical Center, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Academic Medical Centre, Department of Radiology, University of Amsterdam, The Netherlands.
authors.forename: Matthan W A
authors.initials: MW
authors.lastname: Caan
authors.affiliation: Academic Medical Centre, Department of Psychiatry, Amsterdam Institute for Addiction Research, The Netherlands.|Arkin Mental Health, The Netherlands.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Goudriaan
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015203:Reproducibility of Results; D066127:White Matter / Q000187:drug effects / Q000503:physiopathology
keywords: Alcohol dependence; cognitive flexibility; fMRI; fiber tracking