The largest portion of the SBEI efforts has involved fMRI studies of motivation. These involve examination of how the brain responds during the anticipation of working to gain reward or to avoid punishment as well as examination of how the brain responds to notification of the results of an attempt to gain reward or avoid punishment. We have used different versions of a monetary incentive delay (MID) task to study motivation. The SBEI developed this task 11 years ago and since then it has been widely used in the functional neuroimaging imaging community to study reward processing. In the basic version of the task subjects see a cue indicating that on the current trial they are working for money (e.g., $5.00, $1.00, or $.20) or for no money;next they wait for a variable delay, and then press a button in response to presentation of a target. If they respond before the target disappears, they win the money indicated at the start of the trial. If they are too slow they win nothing. The interval between appearance of the initial cue and the target cue signaling the need to make a response is considered to manifest the brain state underlying the motivation for the specific action and involves both elements of motor preparation as well as anticipation of gaining reward. Finally the subjects get visual feedback indicating if they successfully responded, how much they won or lost, and their total earnings. Brain response to this notification can be considered a measure of the significance of the outcome and is similar to the dopaminergic learning signal referred to as a prediction error signal. Multiple studies have shown that MID type tasks reliably activate the ventral striatum (VS) in response to cues that signal an imminent opportunity to respond for monetary rewards. The brain response is proportional to the amount of money at stake. Conversely, the VS is not as robustly recruited by cues for reward deliveries that require no behavioral response. In addition, the VS as well as ventral mesofrontal cortex (mFC) are activated by notification of reward, typically when contrasted with notification that there will be no reward. Thus, the MID task can provide measurements of an individuals sensitivity to anticipation of working for reward as well as sensitivity to notification that the reward has been won or lost. An individuals sensitivity to reward plays a major role in each of the two competing hypotheses about how alterations in brain function motivation lead to the acquisition and maintenance of alcoholism. One of these ideas, the reward deficiency syndrome (RDS) hypothesis, suggests that individuals predisposed to alcoholism (or substance use disorders in general) have a dysfunctional reward circuit which nondrug rewards fail to activate but which can be activated by the more powerful effect provided by addictive substances. In contrast, the competing idea, which we can call the impulsivity hypothesis, suggests that at risk individuals (as well as those currently addicted) have an increased sensitivity to reward in general combined with a failure of effective inhibition of approach behavior. For a detailed discussion of the evidence in favor and against these two hypotheses see the recent review by members of the SBEI on reward sensitivity. In order to directly examine reward sensitivity in alcoholism we compared inpatient alcoholics with healthy controls on a modified MID task that also allowed us to look at the effects of frustrating non-reward on brain oxygenation level dependent (BOLD) signal .We found no significant difference between alcoholics and controls during anticipation of responding for reward, and thus failed to find support for the RDS hypothesis. However, we did find evidence for increased sensitivity to notification of outcome in several brain regions of the alcoholics. These regions included the VS region that is usually activated by rewardinng outcome as well as a greater sensitivity to notification of loss in the anterior insular cortex. Perhaps most striking was a deactivation of the VS when alcoholics were notified that their response to win money was frustrated and they would have to repeat their response again. This effect scaled with the amount of money at stake. These results show that the VS of alcoholics is more sensitive to the mismatch between expectations and outcome than the VS of non-alcoholics. In addition, our findings are consistent with the idea that striatum and dopamine neurons play a critical role in prediction error. During the past few years we have published three studies on motivation among adolescents using the MID task. These studies showed a significant relationship between BOLD activation in striatum and sensation seeking and externalizing disorders. In addition they replicated our initial study of 2004 that showed a blunted activation in the VS of healthy adolescents compared to healthy young adults while they anticipated responding for reward. Recently, we again addressed the differences in brain response during the MID task between alcoholics and controls we first reported in 2008 using the improved methods described above as well as a modification of the task which allows us to more completely separate motor preparation from reward anticipation. We did this because there have been two reports that alcoholics have decreased anticipatory BOLD activation in VS compared to non-alcoholics while they prepare to respond to cues indicating the possibility of reward. As with our earlier report and it contrast to the reports of Beck and Wrase we found no difference in BOLD activation between alcoholics and controls while they prepared to respond to win money. In addition, when we compared anticipation of being notified of outcome following motor response we found less activation in VS among the alcoholics but this did not reach the threshold for statistical significance when compared with the response of the controls. Surprisingly we did not replicate the greater activation in response to outcome notification between alcoholics and controls we had reported previously. However we did find a significant correlation between impulsiveness measured by the NEO personality inventory and VS BOLD in response to successful outcome notification. Considered in their entirety we believe our recent work on imaging of motivation as related to the risk for alcoholism supports two conclusions: 1. The RDS hypothesis is less strongly supported than an alternative model involving greater sensitivity to reward receipt among alcoholics and individuals at risk for alcoholism. 2. This greater sensitivity does not directly map onto alcoholism as a diagnosis but rather is related to a set of personality traits comprising impulsiveness, sensation seeking and uninhibited externalizing behavior. It is possible that later in the course of alcoholism a kind of motivational blunting like that postulated in the RDS does develop. The we have continued to study the effects of intravenously on brain activation measured by fMRI. Intravenously administered ethanol is associated with a significant increase in BOLD signal in the ventral forebrain, including extended amygdala nucleus accumbens and ventral striatum. We are also beginning to explore how administration of alcohol affects risky decision-making in the brain. It appears that alcohol increases striatal activation during anticipation of responding for reward but blunts response to notification of the outcome of the motivated response. This is consistent with alcohol's ability to increase approach behavior while decreasing judgment and other higher cognitive functions. We have also examined BOLD response to alcohol in the VS of heavy and social drinkers. Heavy drinkers have a significantly blunted response in VS suggesting tolerance.
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