Progressive decline of decision-making performances during multiple sclerosis

The purpose of this study was to evaluate longitudinally, using the Iowa Gambling Task (IGT), the dynamics of decision-making capacity at a two-year interval (median: 2.1 years) in a group of patients with multiple sclerosis (MS) (n = 70) and minor neurological disability [Expanded Disability Status Scale (EDSS) ≤ 2.5 at baseline]. Cognition (memory, executive functions, attention), behavior, handicap, and perceived health status were also investigated. Standardized change scores [(score at retest-score at baseline)/standard deviation of baseline score] were computed. Results showed that IGT performances decreased from baseline to retest (from 0.3, SD = 0.4 to 0.1, SD = 0.3, p = .005). MS patients who worsened in the IGT were more likely to show a decreased perceived health status and emotional well-being (SEP-59; p = .05 for both). Relapsing rate, disability progression, cognitive, and behavioral changes were not associated with decreased IGT performances. In conclusion, decline in decision making can appear as an isolated deficit in MS. (JINS, 2009, 15, 291-295.

Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis

Epstein-Barr virus (EBV) has been associated with multiple sclerosis (MS), however, most studies examining the relationship between the virus and the disease have been based on serologies, and if EBV is linked to MS, CD8+ T cells are likely to be involved as they are important both in MS pathogenesis and in controlling viruses. We hypothesized that valuable information on the link between MS and EBV would be ascertained from the study of frequency and activation levels of EBV-specific CD8+ T cells in different categories of MS patients and control subjects. We investigated EBV-specific cellular immune responses using proliferation and enzyme linked immunospot assays, and humoral immune responses by analysis of anti-EBV antibodies, in a cohort of 164 subjects, including 108 patients with different stages of MS, 35 with other neurological diseases and 21 healthy control subjects. Additionally, the cohort were all tested against cytomegalovirus (CMV), another neurotropic herpes virus not convincingly associated with MS, nor thought to be deleterious to the disease. We corrected all data for age using linear regression analysis over the total cohorts of EBV- and CMV-infected subjects. In the whole cohort, the rate of EBV and CMV infections were 99% and 51%, respectively. The frequency of IFN-γ secreting EBV-specific CD8+ T cells in patients with clinically isolated syndrome (CIS) was significantly higher than that found in patients with relapsing-remitting MS (RR-MS), secondary-progressive MS, primary-progressive MS, patients with other neurological diseases and healthy controls. The shorter the interval between MS onset and our assays, the more intense was the EBV-specific CD8+ T-cell response. Confirming the above results, we found that EBV-specific CD8+ T-cell responses decreased in 12/13 patients with CIS followed prospectively for 1.0 ± 0.2 years. In contrast, there was no difference between categories for EBV-specific CD4+ T cell, or for CMV-specific CD4+ and CD8+ T-cell responses. Anti-EBV-encoded nuclear antigen-1 (EBNA-1)-specific antibodies correlated with EBV-specific CD8+ T cells in patients with CIS and RR-MS. However, whereas EBV-specific CD8+ T cells were increased the most in early MS, EBNA-1-specific antibodies were increased in early as well as in progressive forms of MS. Our data show high levels of CD8+ T-cell activation against EBV—but not CMV—early in the course of MS, which support the hypothesis that EBV might be associated with the onset of this diseas

Multiple Sclerosis Decreases Explicit Counterfactual Processing and Risk Taking in Decision Making

Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished.Methods: We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded.Results: In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (p <0.005) and greater risk aversion (p <0.001). They reported less negative affect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains).Conclusions: The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients

Comparisons in terms of choice behavior and betting behavior between MS patients and controls in the CGT.

<p>Msec = milliseconds. Values are means ± standard deviation (SD). P-values reflect non parametric comparisons.</p>*<p>reflects significant difference. After correction for type 1 error, alpha was set at.025 for choice behavior (2 Items) and for betting behavior (idem).</p

Description of the two gambling tasks.

<p>A) Wheel of Fortune (WOF): the subject (with SCR recorded) has to choose between two possible lotteries with different risk and earning possibilities. The subject was asked to choose one of the two wheels by pressing a left or a right button (choice period). A spinning arrow then appeared at the center of the wheel, spins for a variable duration (wait period), and stopped revealing the outcome(s) (feedback period). In the partial feedback condition (30 trials) the subject does not know the outcome of the other lottery; in the complete feedback condition (30 trials) both outcomes are presented. At the end of each trial, subjects had to indicate their affective state using a rating scale. B) Cambridge gambling task (CGT): the subject has to bet points on a choice associated with a given level of risk. Trials are run in blocks (two sets of four blocks), each containing nine trials. A row of ten boxes (red or blue, with a ratio varying across trials) is presented at the top of the screen. Participants are told that a yellow token was hidden in one of the boxes. They then have to guess whether it is in a red or blue box (color). Then they decide how many of their points they wanted to gamble on their choice (point choice) by pressing when they choose: available bets (5, 25, 75, 95 and total) are presented on the right of the screen in a ascending or descending sequence. Then feedback is given about gain or loss and total ongoing fortune (left).</p

Emotional processing in the WOF task.

<p>A. Diminished negative emotional ratings in RRMS patients. Mean emotional ratings were plotted for <i>disappointment</i> (comparison of an obtained outcome with a more favorable unobtained outcome in partial feedback condition), <i>regret</i> (comparison of an obtained outcome with a more favorable unobtained outcome in complete feedback condition), <i>rejoy</i> (comparison of an obtained outcome with a less favorable unobtained outcome in partial feedback condition) and <i>relief</i> (comparison of an obtained outcome with a less favorable unobtained outcome in complete feedback condition). Wilcoxon signed rank tests between groups for disappointment and regret: disappointment (z = −2.45, p = 0.01) and regret (z = −2.38, p = 0.02). B. Comparable emotional arousal in SCRs for RRMS patients and controls. Mean SCRs during feedback plotted for disappointment, regret, rejoy and relief. No statistical differences between groups.</p

Quality of DM in the Cambridge Gambling Task.

<p>Comparisons in terms of choice behavior between MS patients and controls in the CGT (% of best choices).</p

Choice behavior in the Wheels of Fortune task for MS patients and healthy controls (regression analyses, panel logit with individual random effect).

<p>A. Model of choice integrating the effects of anticipating disappointment (d) and regret (r) in addition to the maximization of expected values (EV). Both MS patients and controls chose anticipating r and maximizing EV. MS patients did not choose anticipating d.</p><p>B. Model of choice integrating the effects of risk in addition to the maximization of expected values (e). Healthy controls were risk neutral while MS patients were risk averse.</p

Demographics, clinical neuropsychological characteristics of MS patients and controls.

<p>Values are mean ± standard deviation (SD), excepted for ¹where values are n. ²Brief Repeatable Battery of Neuropsychological tests (BRB-N): Selective Reminding Test (SRT), 10/36 Spatial Recall Test (10/36), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), Word List Generation (WLG). SOC: Stockings of Cambridge; HAD: Hospital Anxiety and Depression scale.</p

Model of choice integrating the effects of disappointment and risk in addition to the maximization of expected values.

<p>Negative coefficients reflect minimization of disappointment or risk. Model A integrates the effects of anticipating disappointment (d) in addition to the maximization of expected values (EV). MS patients did not minimize d. Model B integrates the effects of risk in addition to the maximization of expected values (e). Healthy controls were risk neutral while MS patients were risk averse.</p