Thursday, April 19, 2018

Risky decision making in juvenile myoclonic epilepsy

Unterberger I, Zamarian L, Prieschl M, Bergmann M, Walser G, Luef G, Javor A, Ransmayr G, Delazer M. Risky Decision Making in Juvenile Myoclonic Epilepsy. Front Neurol. 2018 Mar 26;9:195.

It is not known whether patients with juvenile myoclonic epilepsy (JME) differ from healthy people in decision making under risk, i.e., when the decision-making context offers explicit information about options, probabilities, and consequences already from the beginning. In this study, we adopted the Game of Dice Task-Double to investigate decision making under risk in a group of 36 patients with JME (mean age 25.25/SD 5.29 years) and a group of 38 healthy controls (mean age 26.03/SD 4.84 years). Participants also underwent a comprehensive neuropsychological assessment focused on frontal executive functions. Significant group differences were found in tests of psychomotor speed and divided attention, with the patients scoring lower than the controls. Importantly, patients made risky decisions more frequently than controls. In the patient group, poor decision making was associated with poor executive control, poor response inhibition, and a short interval since the last seizure episode. Executive control and response inhibition could predict 42% of variance in the frequency of risky decisions. This study indicates that patients with JME with poorer executive functions are more likely to make risky decisions than healthy controls. Decision making under risk is of major importance in every-day life, especially with regard to treatment decisions and adherence to long-term medical therapy. Since even a single disadvantageous decision may have long-lasting consequences, this finding is of high relevance.

From the manuscript

Our findings add to previous studies on decision making in patients with JME. While this study investigated decision making under risk with explicit information on task contingencies, previous studies on JME have focused on decision making under initial ambiguity adopting the Iowa Gambling Task (IGT). When the decision situation is ambiguous, probabilities and outcomes are, at least at the beginning of a task, unknown. However, feedback on previous decisions can be used to choose the most advantageous options. Conversely, in decisions under risk, the situation is exactly defined from the beginning. Also, options, probabilities, and consequences are explicitly given or can be estimated. Recent research has provided evidence that the neural signals vary between decision situations reflecting different degrees of uncertainty and that different brain circuits are involved in decisions under risk and in decisions under ambiguity. In both studies adopting the IGT, patients with JME showed difficulties in learning to choose advantageous options. Both studies also reported a correlation between executive functions and decision making. Poor performance on the IGT was associated with an increased activation in the dorsolateral prefrontal cortex during a functional magnetic resonance working memory task, emphasizing frontal lobe dysfunction in patients with. Our study adds to these findings suggesting that low executive control and response inhibition also predict disadvantageous decisions under exactly defined conditions.

In this study, the direct comparison of seizure-free patients and non-seizure-free patients did not yield any significant results. However, we found that poor decision making was associated with a short interval since the last seizure episode. These results add to previous investigations suggesting that problems in decision making are more pronounced in patients with ongoing seizures. The fact that we did not find any significant differences between seizure-free patients and non-seizure-free patients when directly compared to each other might be due to the small sizes of the two subgroups. Future studies should investigate the impact of disease-related variables in larger groups of patients with JME.

Another limitation of our study regards the lack of an additional group of patients taking the same medications but having a different type of epilepsy. Although cognitive side effects of AEDs are very often subtle, they may have an impact on complex cognitive mechanisms such as decision making. Indeed, previous investigations have shown that AEDs compared to nondrug conditions may impair performance in executive functions tasks. In this study, all but four patients (88.9%) were under AED therapy, and we cannot disentangle the possible influence of AED treatment from other disease-related conditions. As in other investigations, decision-making deficits were observed under current antiepileptic medication. However, a recent study on TLE and decision-making  indicates that AED are unlikely to be the major cause of risky decision making. In the study by Delazer et al., two groups of patients (one with structural abnormalities in the mesial temporal lobe, the other with abnormalities in the lateral, basal, or polar parts of the temporal lobe) received standard AED therapy, but only the group with mesial temporal lobe epilepsy showed decision-making deficits. It should be noted, however, that Delazer et al.  used a different decision-making task (IGT) as the one adopted here (GDT-D). In our study, specific AED effects on cognition could not be explored due to the small sample sizes of different medications. Future studies might investigate the impact of AED therapy on decision making and risky behavior in more detail.

In conclusion, our findings show that the number of optimal decisions did not differ between patients and healthy controls. However, patients with JME made more risky decisions. High levels of executive control and response inhibition seem to be essential for making less risky decisions. Several cognitive models have been proposed where reflective processing, including executive control, guides decision making. Apart from reflective processing, heuristics, intuition, and emotions are crucial in the process of decision making. Recent studies propose that reflective processing and intuitive processing interact and inform each other and that advantageous decision-making relies on both, intuitions and reflections. While healthy people switch between resources without any effort and may safely follow their intuitions without hesitation, patients with low cognitive control may be attracted by risky, disadvantageous alternatives. Providing full and exact information (e.g., about treatment options and consequences) and encouraging deliberate and slow reasoning may lead to safe and advantageous decisions also in patients with JME. This may be of particular importance when discussing possible treatment options with patients.


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