Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia.
Amotivation represents problems in the subjective and behavioral aspects of goal-directed activities in schizophrenia (Foussias and Remington, 2010). In real life situations, goal-directed activities are pursued by sustaining anticipation of the rewarding value of an action towards the uncertain future. However, patients with schizophrenia are often amotivational due to a deficit in sustaining a representation of the reward value (Gold et al., 2008). Amotivation involves a deficit in the interrelated neurobehavioral components of the dopaminergic reward system such as reinforcement learning and incentive motivation (Wise, 2004).
Reinforcement learning occurs as the midbrain dopaminergic neurons, responding to unexpected and repeated rewards, begin to respond to the preceding stimuli that predict these rewards (Berridge and Robinson, 2003). Likewise, risk prediction is also incorporated in the reinforcement learning process in which the trade-off between expected reward and risk determines behavior (Preuschoff and Bossaerts, 2007). Behaviorally, the drive-like effect of motivation, called “incentive motivation”, strengthens goal-directed behavior. It involves the stamping-in of motivational importance to neutral stimuli through prior association with a primary reward, via the dopamine system, which results in acceleration of the operant response (Wise, 2004).
The mesolimbic and nigrostriatal dopaminergic systems have been consistently implicated in various aspects of reward and motivation (Koob, 1992, Robbins and Everitt, 1996 and Wise, 2009). Phasic dopaminergic activity projects to the ventral striatum and dorsal striatum that are involved in reward prediction and in modulation of stimulus–response association, respectively (Pagnoni et al., 2002, O'Doherty et al., 2004 and Tricomi et al., 2004). Midbrain dopaminergic firing occurs when risky decisions are made with highly anticipated reward (Fiorillo et al., 2005). The anterior insula and ventral striatum also play an important role in risk avoidance and prediction (Kuhnen and Knutson, 2005 and Preuschoff et al., 2008). Reinforcement learning is controlled by the anterior cingulate cortex (ACC), which decides voluntary behavior by integrating prediction error as well as risk and reward signals (Kennerley et al., 2006 and Holroyd and Coles, 2008). In addition, the cingulo-striatal pathway is involved in self-conscious motivational behaviors (Takahashi et al., 2009).
In a series of behavioral studies, Gold et al. (2008) suggest that early learning may be particularly affected by poor representation of value in schizophrenia. Previous functional imaging studies which examined the feedback-related processing using the probabilistic learning and classical conditioning paradigms have shown that putamen activity is attenuated in response to both expected and unexpected reward and that the striatum and cingulate cortex are hypoactive or hypo-responsive to the reward prediction error signals in patients with schizophrenia (Murray et al., 2008b, Waltz et al., 2009 and Koch et al., 2010), suggesting that the dysfunctional error signals between expectancy and feedback may account for diminished reward anticipation in schizophrenia. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia.
Therefore, we developed a deterministic reinforcement learning task with variable intervals of contingency reversals for a new fMRI study examining the neural processing of response valuation and initiation during incentive motivation. In the present study, we examined the neural basis of reward drive in relation to response value representation and response engagement using this task in patients with schizophrenia and healthy controls. We hypothesized that abnormal neural processing of response valuation and engagement would contribute to deficient incentive motivation in patients with schizophrenia.
In the fMRI study for examining how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we found that patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Our findings emphasize the role of the ACC in transferring the incentive value to a behavior and suggest that reward drive deficits in schizophrenia may be associated with dysfunctional ACC. This may explain how residual negative symptoms persist after the normalization of striatal function by antipsychotic treatment. Future prospective studies, including first episode or at-risk individuals, need to clarify whether reward drive deficits in schizophrenia are triggered by ventral striatum or ACC dysfunction.
