Anhedonia, a lack of interest or pleasure in normally rewarding experiences, is a defining symptom of Major Depressive Disorder (MDD; American Psychiatric Association, 1994). Anhedonia is also a central feature of a number of theories of MDD, particularly neurobiologic perspectives stating that deficits in emotional and motivational responses to affective stimuli are key to the disorder (e.g., Tomarken and Keener, 1998). Despite the centrality of anhedonia to MDD, the capacity of depressed individuals to experience anticipation of pleasurable events and enjoyment of pleasure during reward presentation has received little empirical attention, and the neurobiology of anhedonia in depression remains to be delineated.
Two non mutually-exclusive neurobiological mechanisms may contribute to anhedonia in MDD: hyporesponsivity of structures within mesolimbic dopamine system related to processing rewards; and hyperresponsivity in cortical regions associated with conflict monitoring. In support of the former hypothesis, lower activation in mesolimbic regions in response to positive stimuli in MDD (Schaefer et al., 2006; Epstein et al., 2006; Keedwell et al., 2005). However, these studies exclusively examined responses to reward presentation, and thus the contributions of mesolimbic/striatal hyporesponsivity during anticipation of rewards were unclear. In support of the cortical hyperresponsivity hypothesis, dorsal anterior cingulate cortex (dACC) activation has been implicated under conditions of uncertainty and affective conflict during the anticipation of potential positive outcomes (Botvinick et al., 1999; Carter et al., 1998). To the extent that individuals with MDD are less confident of potential positive outcomes (Beck and Clark, 1988), heightened dACC activation may be expected during reward anticipation. Knutson and colleagues (2008) employed a Monetary Incentive Delay (MID) task to differentiate brain responses during reward anticipation and positive reward feedback. They reported that activation of the striatum, including the nucleus accumbens (NAc), did not differentiate MDD and control samples during monetary anticipation or during receipt of monetary rewards. Depressed participants did, however, exhibit dorsal anterior cingulate cortex (dACC) hyperactivation during anticipation of monetary rewards. The authors concluded that MDD may not be characterized by hypoactive anticipatory pleasure states during reward anticipation, but rather by increased affective conflict during anticipation of gains.
This key investigation by Knutson and colleagues (2008) warrants replication and further examination for at least two reasons: First, in the MID task, reward anticipation and preparation to engage in a behavior with potential reward (i.e., a speeded button press) occur simultaneously. Thus, brain functioning in MDD to a reward anticipation phase devoid of behavioral preparation has not been examined. Second, the MID task does not incorporate decision-making based on risk/reward trade-offs. Thus, it is unknown if MDD hyperactivity in regions associated with conflict monitoring extends to decision-making processes related to risk/reward behaviors, or, conversely, is purely linked to reward anticipation. Given the direct relevance of behavioral initiation/avoidance to the clinical presentation of MDD (Jacobson et al., 2001), a greater understanding of reward system activity while selecting a response option is of strong interest.
In the present investigation we employed a Wheel of Fortune (WoF) task to assess the functional neural correlates of reward selection, reward anticipation, and reward feedback in adults with MDD and in a matched adult control sample. The WoF has been shown to elicit activation in both striatum and ACC during reward anticipation (Ernst et al., 2004). Based on the existing literature showing relatively lower levels of response in mesolimbic dopamine regions to positive stimuli in MDD (Schaefer et al., 2006; Epstein et al., 2006; Keedwell et al., 2005), we hypothesized hyporesponsivity in striatal regions across all three phases of the task, but most critically during reward anticipation because of preclinical evidence that reward-seeking behaviors are mediated by striatal structures (Salamone et al., 1994; Swerdlow and Koob, 1987). As highlighted earlier, Knutson and colleagues (2008) did not find striatal hypoactivation during reward anticipation, but we hypothesized that the an anticipatory phase devoid of a motor preparatory components may be more sensitive to anticipatory hedonic deficits in MDD. In addition, consistent with the findings of Knutson and colleagues (2008), we hypothesized hyperresponsivity of conflict monitoring regions, including dorsal ACC, during both the reward selection and reward anticipation phases.