Deficits in goal-directed behavior are well-documented in schizophrenia (SZ; Kerns et al, 2008
; Pantelis et al, 1997
), with some authors (Foussias and Remington, 2008
) identifying avolition as the core negative symptom of SZ. Factor analyses of negative symptom scales (Blanchard and Cohen, 2006
; Sayers et al, 1996
) predominantly point to a close association between clinical ratings of avolition and those of anhedonia, suggesting that motivational deficits may be related to a reduced experience
of pleasure in SZ. However, accumulated experimental findings (Cohen and Minor, 2010
) have cast doubt on the idea that SZ patients actually demonstrate
a reduced capacity to experience pleasure.
The fact that SZ patients often report normal experiences of pleasure suggests that motivational deficits in SZ have other sources. One possibility, based on support for a five-factor model of negative symptoms (Andreasen, 1989
; Peralta and Cuesta, 1995
), is that avolition emerges independently of hedonic experience in SZ. Alternately, aspects of hedonics aside from the experience of rewards (consummatory pleasure) may contribute to motivational deficits in SZ. For example, several groups (Gard et al, 2007
; Kring and Neale, 1996
) have suggested that the hedonic deficit in SZ involves an inability to anticipate
pleasure, rather than a reduced ability to feel pleasure upon reward receipt. A second possibility is that there is a dissociation between reward-related neural activity and the reported subjective experience of reinforcement, leading patients to report
an experience of pleasure similar to that of controls, despite aberrant physiological response to rewards. A third possibility is that, even though the majority of studies find that patients and controls do not differ in their self-reports of pleasure experienced when presented with positive stimuli (Cohen and Minor, 2010
), a reduced ability to feel pleasure may contribute to motivational deficits in a subset of patients—particularly in those with severe negative symptoms.
Supportive, but inconclusive, evidence exists to support each of these accounts. The hypothesis that reward anticipation in SZ may be abnormal receives its greatest support from behavioral studies (Gard et al, 2007
; Heerey and Gold, 2007
), whereas neuroimaging results from studies using paradigms similar to the one used in the current study (Juckel et al, 2006b
; Schlagenhauf et al, 2008
) suggest that treatment with second-generation antipsychotics (SGAs) may actually ‘normalize' neural activity in brain regions associated with reward anticipation. The idea that self-reports of normal hedonic experience may not reflect a normal physiological response to rewards has received indirect support from neuroimaging studies showing that neural activity associated with the experience
of rewards, and other pleasant stimuli, is abnormal
in SZ patients (Paradiso et al, 2003
; Walter et al, 2009
), even when the psychological experience of evocative stimuli (Takahashi et al, 2004
) or reinforcers (Waltz et al, 2009
) is reported by patients as normal. Finally, multiple recent studies (Polgar et al, 2008
; Waltz et al, 2007
) have, in fact, found that deficits on reward-driven learning tasks are most characteristic of SZ patients with severe negative symptoms. These results support the idea that reward-processing abnormalities may be characteristic of a subset of SZ patients, possibly leading to avolition in those patients.
In order to investigate brain activity associated with both outcome anticipation and receipt, we used an adaptation of the monetary incentive delay (MID) task. Using this task, Knutson et al (2001
) produced evidence of a possible dissociation between the brain regions involved in reward anticipation (especially ventral striatum, VS) and consumption (especially medial prefrontal cortex, PFC).
The current study had three specific objectives. First, we wanted to determine whether patients with SZ show abnormal brain responses to monetary outcomes that varied in their valence and magnitude. Second, we sought to determine whether our patients, medicated almost exclusively with SGAs, would show abnormal neural activity associated with reward anticipation. Finally, we wanted to investigate relationships between negative symptoms in SZ and measures of neural responses to outcomes in PFC and outcome-predicting cues in the neostriatum.
Based on the results of previous neuroimaging studies of hedonic experience (Crespo-Facorro et al, 2001
; Waltz et al, 2009
), we hypothesized that neural responses in patients would show reduced differentiation according to the valence and magnitude of monetary outcomes, particularly in PFC regions. Based on behavioral results from our group (Heerey and Gold, 2007
), we hypothesized that patients would show reduced differentiation according to the valence and magnitude of cues predicting monetary outcomes, especially in the VS. Finally, based on previous evidence of relationships between clinical ratings of negative symptoms and reward-related neural responses (Waltz et al, 2009
), we hypothesized negative correlations between ratings of negative symptoms and gain-evoked responses in PFC, as well as cue-evoked responses in the striatum.