بعد انگیزش و لذت علائم منفی: بسترهای عصبی و خروجی رفتاری

A range of emotional and motivation impairments have long been clinically documented in people with schizophrenia, and there has been a resurgence of interest in understanding the psychological and neural mechanisms of the so-called “negative symptoms” in schizophrenia, given their lack of treatment responsiveness and their role in constraining function and life satisfaction in this illness. Negative symptoms comprise two domains, with the first covering diminished motivation and pleasure across a range of life domains and the second covering diminished verbal and non-verbal expression and communicative output. In this review, we focus on four aspects of the motivation/pleasure domain, providing a brief review of the behavioral and neural underpinnings of this domain. First, we cover liking or in-the-moment pleasure: immediate responses to pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which involves prediction of a forthcoming enjoyable outcome (reward) and feeling pleasure in anticipation of that outcome. Third, we address motivation, which comprises effort computation, which involves figuring out how much effort is needed to achieve a desired outcome, planning, and behavioral response. Finally, we cover the maintenance emotional states and behavioral responses. Throughout, we consider the behavioral manifestations and brain representations of these four aspects of motivation/pleasure deficits in schizophrenia. We conclude with directions for future research as well as implications for treatment.

A range of emotional and motivation impairments have long been clinically documented in people with schizophrenia, and there has been a resurgence of interest in understanding the psychological and neural mechanisms of the negative symptoms in schizophrenia, given their lack of treatment responsiveness and their role in constraining function and life satisfaction in this illness. Negative symptoms comprise five consensus-based domains: anhedonia, asociality, avolition, alogia, and blunted affect (Kirkpatrick et al., 2006). However, conceptual and empirical reviews of newer (e.g., CAINS; (Kring et al., 2013) or BNSS (Strauss et al., 2012)) and older (e.g., SANS; (Andreasen, 1982)) interview-based measures of negative symptoms indicate that a two-factor model more parsimoniously describes the negative symptoms (Blanchard and Cohen, 2006, Kimhy et al., 2006 and Messinger et al., 2011). The first factor reflects diminished motivation and pleasure across a range of life domains; the second factor reflects diminished verbal and non-verbal expression and communicative output. Newer measurement techniques for these two domains—motivation/pleasure and expression—may better capture the underlying mechanisms giving rise to negative symptoms (Blanchard and Cohen, 2006 and Kring et al., 2013) and help in developing more effective treatments. In this review, we focus on the motivation/pleasure domain, providing a brief review of the behavioral and neural underpinnings of this domain. We have argued elsewhere that adopting a translational approach to research on negative symptoms has and will continue to give us the greatest purchase toward more clearly identifying mechanisms of negative symptoms and developing more effective and targeted treatments (Barch and Dowd, 2010 and Kring and Elis, 2013). Indeed, adopting the methods, theories, and measures of affective science, as well as translating from the animal and human affective and cognitive neuroscience, has propelled us ever closer to identifying core deficits that give rise to motivation/pleasure deficits in schizophrenia and other disorders. Independently, we have developed theoretical frameworks to guide our research on the emotional and motivational underpinnings of negative symptoms, highlighting how these deficits necessarily also involve behavior and brain regions that are crucial for cognitive control. Both of us have translated animal and human cognitive and affective neuroscience research to our models of motivation/pleasure deficits in schizophrenia. Kring and colleagues have argued for the importance of characterizing the time course of emotion to distinguish among anticipatory, consummatory (“in-the-moment”), and maintenance of emotion responding (see Fig. 1). Relatedly, Barch and colleagues have argued for the importance of representations about motivationally salient incentives necessary to develop and actively maintain behavioral plans that are necessary to achieve desired pleasurable outcomes (see Fig. 2). Full-size image (24 K) Fig. 1. Temporal experience of emotion. Figure options Full-size image (53 K) Fig. 2. Reward to outcome translation. Figure options In this review, we integrate our approaches to highlight the latest advances in our understanding of behavioral and brain systems that contribute to diminished motivation and pleasure in schizophrenia (see Fig. 3). Specifically, we focus on four common aspects of our models. First, we cover liking or in-the-moment pleasure, which involves immediate responses to pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which involves a prediction about a future enjoyable outcome (reward) and/or a feeling of pleasure in anticipation of that outcome. Third, we address motivation, which includes a calculation of how much effort is needed to achieve a desired outcome (reward), a plan of how to obtain that outcome, and the actual behavioral response to get the reward. Finally, we cover the maintenance of emotional states and behavioral responses. Throughout, we consider the behavioral manifestations and brain representations of these four aspects of motivation/pleasure deficits in schizophrenia. Full-size image (54 K) Fig. 3. Integrating the temporal experience of emotion with reward to outcome translation (Kring & Barch).

Taken together, results from our review are consistent with the notion that “in-the-moment” experience of pleasure is relatively intact in schizophrenia. That is, people with schizophrenia report experiencing as much pleasure as do people without schizophrenia in the presence of putatively positive stimuli, and they show comparable brain activation, at least in response to expected positive stimuli or outcomes. Nevertheless, people with schizophrenia also report experiencing more negative emotion in response to positive stimuli and they also show different versus activation in response to unexpected outcomes suggesting that all is not completely intact when it comes to in-the moment responding or the liking aspect of our model. In addition, there is evidence that value computation is impaired in schizophrenia. Further, there is growing and consistent evidence that people with schizophrenia have deficits in both behavior and neural responses associated with the anticipation of future rewarding or pleasurable experiences, as well as with responses to unexpected rewards. In addition, they have impairments in value and effort computation and goal-directed behavior that are related to functioning in the world. There is suggestive evidence that the active maintenance of emotional information and the ability to use prior emotional experience to guide current behavior is also impaired, though the linkages between this and other cognitive deficits (i.e., working memory) have yet to be worked out. To illustrate the ways in which breakdowns in the interplay among generation and anticipation of goals, value and effort computations, and maintenance may contribute to impairments in goal-directed behavior in schizophrenia, consider the following scenario. A person with schizophrenia may report enjoying brownies and show both behavioral and neural evidence of consummatory pleasure while eating brownies. However, she may not be able to engage in the behaviors necessary to obtain or make more brownies (Barch and Dowd, 2010 and Kring and Moran, 2008). Planning, purchasing, preparing or baking the brownies requires ongoing maintenance or retrieval of the prior emotional experience of pleasure while consuming a brownie, as well as maintenance of contextual or cue information that should trigger associations about the food's rewarding properties. Such anticipation and maintenance of emotional information should guide the volitional pursuits and actions over time that may lead to such a reward (in this case intake of delicious food). An intact reward valuation and prediction system is necessary for this set of behaviors to take place, and deficits in these functions in schizophrenia may reduce the ability of appetitive or pleasure cues to drive behavior. However, these functions also depend on the intact ability to maintain pleasure cues, experiences or context over time—a process that may be reliant on working memory and cognitive control, which are compromised in schizophrenia (Barch and Dowd, 2010 and Ursu et al., 2011). Thus, deficits in reward prediction may be made worse by deficits in the ability actively maintain information about rewards or pleasure, which may extend beyond simple appetitive stimuli to more abstract rewards. What is needed next is research that directly tests the ability to use and maintain internal representations of emotional experience and reward information to modulate behavior and brain function in schizophrenia, along with work that characterizes links between deficits in these abilities and everyday function in this illness. Further, more work is needed to understand the role that effort computations may also play in motivation impairments in schizophrenia. It may be that even when people with schizophrenia are able to generate or maintain representations of emotion or motivation, alternations in computing effort to reward valuation may inhibit the development of goal directed action plans that people need in order to pursue and obtain desired outcomes. Of course, these mechanisms may interact—difficulties in the anticipation of pleasurable outcomes may reduce the “reward” part of the value or effort computation, skewing such computations towards less willingness to exert effort if there is less perception of rewards due to representation and maintenance impairment. Further, much work is still needed to understand how these various deficits interact with medications and the course of illness. There is good evidence that negative symptoms are present in currently unmedicated people and in people who have never taken medication. However, it has been more difficult to conduct the experimental studies parsing mechanisms in unmedicated people, and thus future research is needed to disentangle the effects of the disease versus the effects of medication on these different mechanisms. Another direction for future research is to examine how the components of the model we articulate here are or are not deficient in depression. The temporal course of reward processing impairments in schizophrenia and depression may be different, with more evidence that abnormal reward processing may be more trait-like in schizophrenia and more state-like in depression (Blanchard et al., 2001). Further, there is a growing evidence that the nature of reward processing abnormalities in depression may be different that those found in schizophrenia. For example, there is much more evidence for abnormal responses to the receipts of rewards in depression (Epstein et al., 2006, Eshel and Roiser, 2010, Forbes and Dahl, 2012, Forbes et al., 2009a and Pizzagalli et al., 2008). However, there is also evidence for some similar abnormalities, such as reduced effort computation (Treadway et al., 2012). Unfortunately, very few studies have directly compared different aspects of reward processing in schizophrenia and depression (though see Gradin et al. (2011)), and this will be a critical path for future research that will help us understand the structure of motivational impairments in relationship to varying manifestations of psychopathology. Nonetheless, the intriguing research coming from the work on the mechanisms driving negative symptoms in schizophrenia is beginning to point towards specific processing and neural systems that could be ripe targets for interventions, both at a pharmacological and a psychological level. It is interesting to speculate as to possible interventions that may help to remediate such impairments in reward prediction, effort allocation, and maintenance of information about emotional and/or reward information, with the hope of potentially improving quality of life and work and community function. There may be a range of pharmacological interventions that could manipulate the dopamine system in ways that could enhance reward processing, though the challenge is to ensure that such pharmacological approaches do not also increase positive symptoms, given the role of dopamine in the pathophysiology of the disorder. Further, there may be behavioral interventions that could be effective as well. Indeed, Grant et al. (2012) modified cognitive therapy for schizophrenia to emphasize goals, including changing beliefs that are associated with negative symptoms (Grant and Beck, 2009) and interfere with goal attainment as well as practice in action planning to achieve long- and short-term goals. Results from a randomized trial indicated that people with schizophrenia who received cognitive therapy had lower avolition at the end of treatment as well as better overall functioning. Other behavioral interventions have shown promise in increasing anticipatory pleasure (Favrod et al., 2010) and maintenance (Johnson et al., 2011), but these studies were very small, open trials that are in need of replication with larger samples and in randomized trials. Additional treatment development work is needed, however, to more fully translate the findings we have reviewed here into behavioral interventions. For example, as described above, the work of Kring and colleagues suggests that emotional responses in schizophrenia may not be sustained when stimuli are not present in the immediate environment (Kring et al., 2011 and Ursu et al., 2011) and other work suggests that people with schizophrenia have difficulties understanding which cues predict future rewards when stimuli. In other words, people with schizophrenia seem to have problems bridging the gap between the occurrence of stimuli that predict reward and the future obtainment that reward through the use of internal representations that can support temporally extended goal directed activities, suggesting a common mechanism that may be contributing to a range of impairments in motivation in this disorder. If so, then environmental supports or cues that remind people with this illness about rewarding outcomes over time may increase the likelihood of increased effort allocation to engage in the behaviors necessary to eventually achieve such goals. While speculative, such hypotheses help translate these experimental findings into interventions for motivational impairments in schizophrenia.