فرکانس یکپارچه و اطلاعات دامنه در تصمیم گیری در اسکیزوفرنی: حساب عملکرد بیمار در آزمون قمار آیوا

Background The Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994) has frequently been used to assess risky decision making in clinical populations, including patients with schizophrenia (SZ). Poor performance on the IGT is often attributed to reduced sensitivity to punishment, which contrasts with recent findings from reinforcement learning studies in schizophrenia. Methods In order to investigate possible sources of IGT performance deficits in SZ patients, we combined data from the IGT from 59 SZ patients and 43 demographically-matched controls with data from the Balloon Analog Risk Task (BART) in the same participants. Our analyses sought to specifically uncover the role of punishment sensitivity and delineate the capacity to integrate frequency and magnitude information in decision-making under risk. Results Although SZ patients, on average, made more choices from disadvantageous decks than controls did on the IGT, they avoided decks with frequent punishments at a rate similar to controls. Patients also exhibited excessive loss-avoidance behavior on the BART. Conclusions We argue that, rather than stemming from reduced sensitivity to negative consequences, performance deficits on the IGT in SZ patients are more likely the result of a reinforcement learning deficit, specifically involving the integration of frequencies and magnitudes of rewards and punishments in the trial-by-trial estimation of expected value.

Optimal decision-making often requires the ability to learn from the outcomes of previous choices, both rewards and punishments, and to adjust future choices accordingly. The study of the neural substrates of these types of decision processes was pioneered by Bechara and Damasio (Bechara et al. 1994, 1997), who developed the Iowa Gambling Task (IGT). In this task, subjects can choose gambles from four different decks. Two of the decks offer $100 rewards, on average, and two offer $50 rewards, on average. However, the decks offering the higher rewards also involve large punishments and choosing from these higher paying decks is ultimately disadvantageous, and choices from the decks with smaller rewards turn out to be more advantageous. Learning these contingencies typically requires an extended period of sampling across decks, as the frequencies and magnitudes of the punishments vary across decks. Rather remarkably, the initial sample of patients, with lesions encompassing orbitofrontal cortex (OFC), showed a robust preference for the higher-paying but ultimately disadvantageous decks, and appeared to be almost totally indifferent to punishment (Bechara, et al., 1994). Thus, it appeared that their behavior was driven by reward seeking alone, as if the punishments simply failed to occur. There are multiple lines of evidence suggesting OFC dysfunction in patients with schizophrenia (SZ), including evidence of reduced volumes (Davatzikos et al. 2005), task-evoked hypoactivity (Quintana et al. 2003), and impairments in reversal learning (Waltz & Gold, 2007; Waltz et al., 2013), considered a key cognitive process mediated by OFC. In light of these findings, it would be reasonable to expect that patients with SZ would show robust impairments on the IGT. Surprisingly, the literature is somewhat mixed; most, but not all studies suggest a reduced preference for the advantageous decks relative to the disadvantageous decks, perhaps suggesting a reduced sensitivity to punishments in SZ patients. In an effort to better understand the accumulated literature, we performed a small meta-analysis (weighted by sample size) of the eight studies (Wilder et al. 1998; Ritter et al. 2004; Shurman et al. 2005; Kester et al. 2006; Lee et al. 2007; Sevy et al. 2007; Kim et al. 2009, 2012), in SZ patients, that reported the number of choices from each of the four IGT decks (see Supplementary Table s1 for a list of the studies used in the meta-analysis). As shown in Figure 1, patients, relative to controls, show an increase in the number of selections from the disadvantageous decks (A and B), and a reduction in the number of selections from the advantageous decks (C and D). While the results from individual published studies vary, the summary figure suggests a relatively robust pattern of group differences. Also seen in Figure 1 is the fact that controls show a clear preference for Deck B relative to A (among the disadvantageous decks) and for Deck D relative to C (among the advantageous decks). Interestingly, Deck A delivers more frequent punishments whereas Deck B delivers larger, but less frequent, punishments. Similarly, Deck C delivers smaller, but more frequent punishments, relative to Deck D. Thus the choice or avoidance of Decks A and C can be primarily attributed to the frequency of punishments. In contrast, Decks B and D require a more complex calculation of expected value over an extended number of selections and experienced outcomes. Patients maximally deviate from controls on Decks B and D (the mean effect-sizes for those differences are the farthest from zero), and show near normal sensitivity to the frequency of punishments. This raises the possibility that the IGT deficit in schizophrenia arises from a problem in calculating expected value rather than a reduced sensitivity to punishment. Full-size image (17 K) Figure 1. Weighted averages of individual deck choices on the Iowa Gambling Task (IGT) by patients and controls across 8 previous studies reporting individual deck choices. Error bars reflect one standard error. Relative to controls, patients show an increase in the number of selections from both disadvantageous decks (for Deck A, mean Cohen’s d = 0.421; 95% CI of Cohen’s d: [0.23, 0.61]; for Deck B (mean d = 0.670; 95% CI of d: [0.48, 0.86]). Relative to controls, patients show a decrease in the number of selections from both advantageous decks (for Deck C, d = -0.202; 95% CI of d: [-0.39, -0.01]; for Deck D, d = -0.703; 95% CI of d: [-0.90, -0.51]). Figure options To examine this issue, we also administered the Balloon Analog Risk Task (BART; Lejuez et al. 2003), another experiment paradigm designed to examine decision making under risk. In this task, subjects “inflate” a balloon using the space bar on the computer. As the balloon gets bigger, the potential reward gets bigger. However, every trial will end with the balloon popping if the subject continues to press, resulting in a loss of earnings. The only sure way to retain earnings is to decide to stop pressing. Note: the balloon pops randomly somewhere between the first and the 128th potential press, such that the optimal strategy to maximize gains would be to press 64 times each time, thereby ensuring the fewest pops coupled with the maximal retained gains. Thus, unlike the IGT, eventual loss is certain in the BART, and the question is how much risk subjects are willing to take to increase the magnitude of their reward. Prior studies with the BART have found that several clinical populations with impulse control deficits show abnormal risk seeking, whereby individuals make larger than optimal numbers of pumps, on average, seemingly less deterred by impending punishment. By contrast: three previous studies have used the BART in studies of SZ patients, and in all three studies, SZs showed risk aversion (fewer pumps) relative to controls ( Cheng et al. 2012; Reddy et al. 2014; Fischer et al. 2015). That is, they appeared to be abnormally sensitive to the prospect of a punishment and settled for lesser gains. This is not the pattern of results that would be expected based on findings from IGT studies in SZ patients, which appear to show reduced sensitivity to punishments. The results, however, can be reconciled as follows: if patients with SZ have relatively intact sensitivity to the frequency of punishments in guiding choice, and impaired ability to simultaneously consider magnitude and frequency of aversive outcomes, one would expect to find risk aversion on the BART (where punishment will occur on every trial – a pure case of learning based on punishment frequency), and risk seeking on the IGT (resulting in a preference for the disadvantageous decks, coupled with a reduced preference for Deck D). That is, one would expect SZ patients to prefer the advantageous deck with smaller, more frequent punishments (Deck C) to the advantageous deck with larger, but less frequent punishments (Deck D), as estimating the expected value of Deck D requires a more subtle calculation of expected value than Deck C (where more frequent punishments occur).