Differences in cerebral activation patterns in idiopathic inflammatory demyelination using the paced visual serial addition task: An fMRI study Dagmar Rachbauer a, * , Martin Kronbichler c,d , Stefan Ropele a,b , Christian Enzinger a , Franz Fazekas a,b a Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria b Division of Neuroradiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria c Department of Psychology and Center for Neurocognitive Research, University of Salzburg, Hellbrunnerstrasse 32, A-5020 Salzburg, Austria d Christian Doppler Clinic, Paracelsus Private Medical University, Ignaz Harrerstr.79 A-5020 Salzburg, Austria Received 15 June 2005; received in revised form 28 October 2005; accepted 4 November 2005 Available online 9 February 2006 Abstract We performed a functional MRI (fMRI) study during the execution of the Paced Visual Serial Addition Task (PVSAT) in 9 patients with a clinically isolated syndrome suggestive of multiple sclerosis (CIS), 9 patients with clinically definite multiple sclerosis (CDMS), and 18 matched healthy control subjects. In controls, the PVSAT elicited a fronto-parietal network with cerebellar activation which we expected for this kind of working memory test and which indicates that this PVSAT version is an appropriate tool for measuring functional changes during a cognitive task. Although there were no significant differences in the actual test results of patients vs. controls, CDMS and CIS patients activated distinct cerebral networks in their attempt to solve the fMRI-PVSAT. Compared to CIS patients, CDMS patients showed increased hippocampal and parahippocampal activation, suggesting the need to additionally support their working memory. In contrast, compared to CDMS patients and healthy controls, CIS patients demonstrated stronger activation of the anterior cingulate cortex, which might indicate focused involvement of executive processes. On the PASAT (Paced Auditory Serial Addition Task) patients also performed similarly to controls but they showed decreased scores on most of the sub-tests of the Wechsler Memory Scale. Based on our observations using the fMRI-PVSAT, we hypothesize that distinct differences in cognitive processing occur with the evolution of MS and that, at these early stages of the disease, they cannot be detected with sufficient sensitivity using only the PASAT. D 2005 Elsevier B.V. All rights reserved. Keywords: fMRI; Clinically definite multiple sclerosis; Clinically isolated syndrome; PVSAT; Neuropsychological tests; Anterior cingulate cortex 1. Introduction Several studies indicate that multiple sclerosis (MS) patients frequently suffer from cognitive deficits. Cognitive disturbances may be quite subtle at first, but can cause substantial burden over the course of the disease [1]. Therefore full assessment of MS patients should include a cognitive evaluation. The PASAT (Paced Auditory Serial Addition Task) has been the most consistently used clinical tool for testing cognitive abilities of MS patients in the past years and has therefore become part of the so-called Multiple Sclerosis Functional Composite (MSFC) [2]. More recently, it has also become apparent that MS-related accumulation of deficits might partly be counterbalanced by brain plasticity and cerebral reorganization [3,4]. This notion has been nurtured predominantly by fMRI (functional Magnetic Resonance Imaging). In this context, several fMRI studies have already investigated changes of cerebral activation in MS patients using the PASAT or related stimulation paradigms. All studies consistently showed that MS patients activate different or additional brain regions compared to controls, but the studies varied in their results and conclusions [5–7]. This may partly be explained by differences in methodology 0022-510X/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2005.11.035 * Corresponding author. E-mail address: drachbauer@gmx.at (D. Rachbauer). Journal of the Neurological Sciences 244 (2006) 11 – 16 www.elsevier.com/locate/jns