Prior studies have reported deficits in decision-making, as assessed by the IGT, among HIV+ individuals with and without substance use disorders (Hardy et al., 2006
; Martin et al., 2004
). However, HIV+ individuals in these samples show ample variability in their performance on the IGT; therefore, it is possible that deficits in abilities other than decision-making may be affecting their performance on this task. The IGT is a complex task that likely requires various component neurocognitive processes for adequate performance. The current investigation was prompted by evidence of deficits on the IGT among HIV+ individuals, coupled with a lack of knowledge on the role of other neurocognitive abilities accounting for such deficits. Furthermore, nondeclarative processes have been implicated in IGT performance and the IGT shares many features with measures of PL, but there is a dearth of studies examining their relationship. In this manuscript, we set out to examine if performance on the IGT among HIV+ individuals with substance dependence was influenced by PL. Contrary to our hypotheses, we found no significant associations between three different measures of PL and performance on the IGT. Indeed, the absence of significant relationships persisted across various sets of analyses, including those that examined initial and absolute levels of performance and those that only examined performance on the earlier trials of the IGT, when participants are thought to rely more on nondeclarative processes. Moreover, measures of PL did not predict impairment classification on the IGT. Thus, we found no evidence to suggest that PL is important for performing the IGT in this sample. In contrast, we did find significant correlations among the three measures of PL, suggesting that they do indeed measure a similar construct. The absence of significant correlations between PL tasks and the IGT were not likely the result of differences in motor demands among these tasks, as we found significant correlations between two measures of PL that vary significantly in their motor demands (i.e., the rotary pursuit and WPT); whereas the WPT and the IGT, which have very similar motor demands, were not correlated.
There are several possible reasons why we found no significant associations between PL and IGT performance in our sample. First, it is possible that differences in the sensitivity of the IGT and PL tasks to HIV-associated cognitive impairment may have affected our findings. It is important to consider that our sample consisted of HIV+ individuals in relatively good health, as indexed by measures of immune function. Specifically, almost half the sample had undetectable HIV viral load in plasma and only a fairly small number met an immunological AIDS diagnosis. If deficits in decision-making or PL manifest at differing stages of HIV disease, with one being affected sooner than the other, then it is possible that correlations that would become evident with more advanced disease would be obfuscated in this relatively healthy sample. We do note, however, that participants in our sample showed a broad range of performance across all tasks, with no evident floor or ceiling effects. However, future studies should explore correlations between PL tasks and the IGT across varying disease stages.
Another very important consideration is that the present study examined PL and IGT performance only in a sample of HIV+ individuals with a history of substance dependence. Results may be different in other populations, such as HIV+ individuals without substance dependence or among healthy controls. This is likely given findings from other studies that examined both PL and IGT performance in different patient groups and healthy controls (Beninger et al., 2003
; Perretta et al., 2005
). Deficits in decision-making among substance users have been well established, with numerous studies reporting poor performance on the IGT compared with controls (e.g., Bechara & Damasio, 2002
; Bechara et al., 2002
; Gonzalez et al., 2007
; Grant et al., 2000
). However, our knowledge of PL among samples of individuals with substance dependence and HIV remains very limited. Similarly, little is known about PL among those with substance dependence (cf. van Gorp et al., 1999
). Although we hypothesized that PL performance would account for variance on the IGT in this sample, clearly more work remains to be conducted to better understand the interplay between these constructs. Because we examined only a group of HIV+ individuals with a history of substance dependence, we are unable to dissociate any specific impact of HIV or substance use on the observed correlations. It is worth noting that inferences on independent effects of substance use and HIV in prior studies were also somewhat limited. Of the two studies published to date examining the effects of HIV on IGT performance, one also included only individuals with a history of substance use disorders (both HIV+ and HIV−; Martin et al., 2004
), whereas the other had many individuals with a history of substance use disorders among their HIV+ participants, but covaried for the effects of substance dependence in their analyses (Hardy et al., 2006
). At this time, it is prudent to limit our conclusions only to HIV+ substance users. Future studies should examine PL and IGT performance across a variety of clinical and healthy samples to determine if these results generalize to other populations.
Although current evidence suggests overlap in brain systems affected by HIV and substance use disorders, correlations between PL tasks and the IGT may be affected to the extent that substance use and HIV preferentially affect different structures within basal ganglia and the respective importance of such structures for PL and decision-making. Despite having unique pharmacological properties, substances of abuse have been shown to affect the mesocorticolimbic dopaminergic system (Rogers & Robbins, 2001
) and a similar network of brain structures including prefrontal cortex, anterior cingulate, hippocampus, amygdala, nucleus accumbens, and ventral tegmental area (Goldstein & Volkow, 2002
). These brain systems overlap in part with those affected by HIV and studies examining combined effects of HIV and substance use suggest that they compound neurocognitive impairments (e.g., reviewed in Gonzalez & Cherner, 2008
). Although basal ganglia structures are affected by both of these disorders, there is some evidence to suggest that dorsal striatal structures (e.g., caudate) may be more readily affected by HIV, whereas substance use disorders preferentially affect more ventral striatal structures (e.g., nucleus accumbens). We also note that there are substantial differences between the neuroanatomical substrates implicated in IGT performance and those thought important in PL (including the WPT). Specifically, the caudate and putamen have been consistently reported as vital for PL (Packard & Knowlton, 2002
; Salmon & Butters, 1995
; Squire & Zola, 1996
) as well as a distributed network including prefrontal, occipital, parietal cortex, and cerebellum (Grafton et al., 1992
; Poldrack et al., 2001
). In contrast, investigations important in the development of the somatic marker hypothesis and those examining performance on the IGT identify a system that includes ventromedial prefrontal cortex, amygdala, insula, supplementary motor cortex, and brainstem (Bechara & Damasio, 2005
). On the basis of recent findings one could speculate that mid-temporal lobe structures are also critical for IGT performance. Thus, differences in specific neural systems subserving PL and decision-making, as well as those affected by HIV and substance use disorders may also explain the lack of correlations observed in the current study.
Of studies that have more broadly examined the role of nondeclarative processes in IGT performance, perhaps the most relevant to the current study's findings are those that have examined individuals with dense anterograde amnesia. There is extensive scientific literature demonstrating that individuals with anterograde amnesia due to mid-temporal lobe damage demonstrate intact nondeclarative memory, including adequate performance on tasks of PL (Heindel et al., 1988
; Knowlton, Mangels, & Squire, 1996
; Knowlton et al., 1994
; Squire, 1987
). As such, one could reason that if intact PL was sufficient for performing well on the IGT, such patients should demonstrate adequate performance. Evidence in support of this hypothesis was presented in an initial case study by Turnbull and Evans (2006)
that reported on S.L., an 85-year-old subject with profound amnesia secondary to posterior cerebral artery infarction. SL performed at a level comparable to healthy controls on the IGT despite severe impairments on measures of episodic memory. Moreover, he demonstrated evidence of persisting “knowledge” of the IGT structure over weeks. In contrast, Gutbrod and colleagues (2006)
examined 11 patients with amnesia from varied etiologies (e.g., ruptured anterior communication artery aneurysms, herpes encephalitis, hypoxia, thalamic infarct) and found that only three of the amnestic patients showed evidence of reaching the hunch stage of the IGT and only one reached the conceptual stage. Thus, contrary to the findings of Turnbull and Evans, they concluded that explicit memory was necessary for adequate performance on the IGT. However, they also pointed out that their study employed a 6-s delay between subjects' card selection and feedback (in order to collect skin conductance data), whereas Turnbull and Evans provided SM with immediate feedback. This difference in methodology was speculated to possibly account for the disparate findings. Gupta and colleagues (2009)
addressed this issue in a recent manuscript by administering the IGT to five amnestic patients using a 6-s delay or immediate feedback during separate administrations. Regardless of the delay condition, amnestic patients performed poorly on the IGT by not making more advantageous choices across trial blocks. All of these investigations focused on examining episodic memory and did not specifically measure PL or other aspects of nondeclarative memory in their sample. Nonetheless, when taken together with the findings of the current study, most of the evidence to date suggests that PL is neither necessary nor sufficient for performing adequately on the IGT.
Despite their similarities, the IGT and the measures of PL employed in this investigation differ in important ways that may explain the lack of correlations observed in this study. As noted in the Introduction, the IGT is closely associated with the somatic marker hypothesis, thus performance on the IGT is thought to be influenced by bioregulatory mechanisms and the brain's representation of body states, which do not require conscious awareness to influence behavior. The IGT requires participants to make a choice between obtaining large immediate rewards (at the expense of longer-term losses) or choosing smaller immediate rewards that yield better long-term outcomes and it provides subjects with simulated rewards and punishments after choices are made. The PL tasks employed in this manuscript (and typically examined in the literature) lack a reward/punishment structure. Thus, the IGT is likely to engage the limbic system and prefrontal cortex to a larger extent than PL tasks. As has been suggested by others (e.g., Beninger, 2006
), we think that the “incentive learning” or “emotion-based knowledge” that takes place when performing the IGT represents a different subtype of nondeclarative memory than that assessed by PL tasks such as the WPT. The absence of incentive or emotion-based learning and simulated rewards or punishments in the PL tasks used in this study suggests that somatic markers play a less important role (or none at all) in guiding behavior on PL tasks. The current study only examined one aspect of nondeclarative memory (i.e., PL) and did not administer other emotion-based learning tasks. We cannot rule out the possibility that other nondeclarative processes play some role in performance of the IGT.
In summary, the findings of the current study do not lend support to the hypothesis that PL may be an important component of the IGT, as we found that PL does not contribute to the variability that has been observed on the IGT among HIV+ individuals. Taken together with prior research findings, it appears that decision-making deficits among HIV persons are influenced in part by response inhibition and declarative memory (Hardy et al., 2006
), but not working memory or PL (Martin et al., 2004
). However, none of these other cognitive constructs appear to account for most of the variance in IGT performance observed among HIV+ groups, suggesting that such deficits may indeed be the result of problems with decision-making. This is an important distinction, as deficits in decision-making may have different ramifications for other risky behaviors, such as risky sexual or drug use practices that would serve for vectors of HIV transmission or re-infection. Further research is still needed to understand if the neuropathology associated with HIV directly results in decision-making deficits, or if such deficits are mediated primarily through impairments in other cognitive abilities that have yet to be examined. It is also possible that some deficits in decision-making may precede HIV infection in this population. More broadly, when interpreted in the context of emerging research, the findings of the current study suggest that PL may not be important to the performance of the IGT.