1 Department of Psychology, New York University, New York, NY 10003, USA, 2 Department of Radiology, University of Pittsburgh & Center for the Neural Basis of Cognition, Pittsburgh, PA 15260, USA, 3 Department of Neuroscience, University of Pittsburgh & Center for the Neural Basis of Cognition, Pittsburgh, PA 15260, USA, 4 Department of Psychology, University of Pittsburgh & Center for the Neural Basis of Cognition, Pittsburgh, PA 15260, USA
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Abstract |
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Key Words: basal ganglia, emotion, feedback, incentive, learning, punishment, reward, striatum, valence
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Introduction |
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Recently, neuroimaging data have supported a role for the striatum, the input unit of the basal ganglia, in detecting the properties of a reward-related stimulus, such as valence and magnitude. Activity in the human striatum has been shown to respond to the expectation of a possible incentive (Breiter et al., 2001; Knutson et al., 2001a
), further showing differential responses according to the incentives valence (Delgado et al., 2000
) and magnitude (Breiter et al., 2001
; Delgado et al., 2003
), where the delivery of a monetary reward yields a larger signal than the presentation of a lesser monetary reward or punishment. Thus, research suggests that the striatum is capable of responding to reward-related stimuli and that it can differentiate between positive and negative incentives. Most of the human work, however, has highlighted the contributions of the ventral striatum to reward processing. There has been less focus on the responses of the human dorsal striatum to stimuli of positive and negative connotation. If the human dorsal striatum is involved in the brains response to motivational changes in the environment, then the activity of a key striatum structure, such as the caudate nucleus, during performance of a behavioral task should be influenced by changes in the motivational context.
One investigation of how changes in motivation may affect activity in the dorsal striatum was reported by Kawagoe et al. (1998). In an elegant study, the authors recorded from neurons in the caudate nucleus of monkeys while they performed a memory-guided-saccade task in which motivational context was manipulated. Monkeys were trained to make a saccade to the location of a previously presented cue, but only one of four possible locations yielded a reward. The response of caudate neurons was dependent on the expectation of a possible reward, irrespective of location, thus showing that activity in the non-human primate dorsal striatum can be influenced by motivation.
The goal of the current study was to examine how changes in the motivational context of a task would affect activity in the caudate nucleus in humans. In a previous study, we found that during performance of a simple gambling paradigm the caudate nucleus showed a different pattern of activation for reward and punishment trials (Delgado et al., 2000). We adapted the paradigm to include alternating periods of high and low motivational context, in which we varied the incentive to perform the task. Monetary rewards and punishments served as feedback during task periods of increased motivational context (high incentive condition), while non-monetary positive and negative feedback were given during task periods of low motivational context (low incentive condition). To assess the response of the caudate nucleus to variations in motivational context, we kept the motor and cognitive requirements of the task constant, but changed the motivational levels via the incentive value of the outcome. Predictions were made according to our previous experience with this task (Delgado et al., 2000
), where we observed an initial rise in hemodynamic response in the caudate nucleus at the onset of a trial, followed by a differential response to the actual incentive that was higher for positive than negative outcomes. Specifically, we predicted that the anticipation of the desired incentive (in this instance, the positive outcome) would be reflected by the initial rise in activity at the onset of a trial, and such activity would be higher during periods of high incentive. Further, we expected that the difference between the hemodynamic response to positive and negative outcomes should be larger during periods of high incentive versus periods of low incentive.
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Methods |
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The paradigm involved a series of 180 interleaved trials, divided into 12 runs of 15 trials each. Each trial began with the presentation of a visually displayed card projected onto a screen (Fig. 1a). The card had an unknown value ranging from 1 to 9, and the participant was instructed to make a guess about the value of the card. A question mark appeared in the center of the card indicating that the participant had 2.5 s to guess if the card value was higher or lower than the number 5. Participants pressed the left or right button of a response unit to indicate their selection. After the choice-making period, a number appeared in the center of the card for 500 ms, followed by an arrow that was also displayed for another 500 ms. Each correct guess led to the presentation of a positive feedback. An incorrect guess was followed by negative feedback. The trials were blocked into alternating runs of monetary and non-monetary feedback trials (referred to as periods of high and low incentive). Prior to the onset of each run, participants were cued with the words money block indicating that the trials in the upcoming run were all worth money (high incentive trials), or no-money block indicating the trials in the upcoming run were not worth any money (low incentive trials). During the monetary runs, or periods of high incentive, a green positive feedback arrow pointing upwards indicated that the participant correctly guessed the card value and would receive a monetary gain of $4.00 or a reward. A red negative feedback arrow pointing down indicated a monetary loss of $2.00, or a punishment. If the outcome was a 5' then the participant was presented with neutral feedback (), representing neither a loss nor a gain of money. During the non-monetary runs, or periods of low incentive, participants received positive or negative feedback after a response, but no money. The arrows in the low incentive trials pointed upward when the response was correct, and downward following an incorrect response. Both the upward and downward arrows were blue. Neutral feedback () represented neither a correct or incorrect response.
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A conventional 1.5-T GE Signa whole-body scanner and standard RF coil were used to obtain 20 contiguous oblique-axial slices (3.75 x 3.75 x 3.8 mm voxels) parallel to the ACPC line. Structural images were acquired in the same location as the functional images, using a standard T1-weighted pulse sequence. Functional images were acquired using a 2-interleave spiral pulse sequence [TR = 1500 ms, TE = 34 ms, FOV = 24 cm, flip angle = 70° (Noll et al., 1995)]. This T2*-weighted pulse sequence allowed 20 slices to be acquired every 3 s. Images were reconstructed and corrected for motion with AIR (Woods et al., 1992
), smoothed using a three-dimensional Gaussian filter (4 mm FWHM) to account for small variations in signal due to movement and vascular effects, adjusted for scanner drift between runs with an additive baseline correction applied to each voxel-wise time course independently, and detrended with a simple linear regression to adjust for drift within runs. Structural images of each participant were co-registered to a common reference brain (Woods et al., 1993
). Both the statistical maps created in analysis and the reference brain were transformed to standard Talairach stereotaxic space (Talairach and Tournoux, 1988
) using AFNI software (Cox, 1996
). Functional images were then globally mean-normalized to minimize differences in image intensity within a session and between participants, and smoothed using a three-dimensional Gaussian filter (4 mm FWHM) to account for between-subject anatomic differences.
A repeated-measures three-way ANOVA was performed on the entire set of co-registered data, with participants as a random factor. Within-subjects factors included type of trial (high and low incentive), type of feedback (positive and negative) and time (the five sequential 3 s scans in a trial of 15 s, referred to as T1T5). Neutral trials were removed from analysis due to variability in both imaging data and participants responses to such trials observed in our prior study (Delgado et al., 2000). Our analyses were motivated by our experience with this task. Based upon prior findings (Delgado et al., 2000
), we began by examining overall task activation using voxelwise ANOVAs that examined the main effect of time (T1T5). Regions of interest (ROIs) consisting of five or more contiguous voxels were selected, as a precaution against type 1 errors (Forman et al., 1995
). Inferences were made on regions defined by strength of effect (P < 0.00001) and size (five or more voxels). Further evaluation was done by analysis of event-related time-series data for each region of interest, which represent functional magnetic resonance imaging (fMRI) mean intensity value for each condition for time periods T1T5.
Our primary, and a priori focus, was upon the pattern of response in the caudate. Thus, the results from the voxel-wise ANOVAs were used to isolate a left caudate ROI (peak at x, y, z = 8, 8, 5) and a right caudate ROI (peak at x, y, z = 11, 7, 7). We then looked at two phases of the hemodynamic response in these regions: (i) activation during the choice phase, as reflected in the initial rise from the onset of the trial (T1T2) and (ii) activation during the outcome phase, particularly the time point where we have previously observed differential responses to feedback (T4). To examine the choice phase, activity in the caudate ROIs was assessed with a three-way ANOVA, with time (T1 or T2), period (high incentive or low incentive), and hemisphere (left or right) as factors. If changing the motivational context of the task influences activity in the caudate nucleus, we should observe an interaction between time and period, reflected by a higher initial rise at the onset of high incentive trials. The second comparison addressed whether differential responses to positive and negative feedback were affected by the motivational state. Activity in the caudate ROIs was examined at time period T4, the time at which we have previously observed the greatest differences between positive and negative feedback. We used a three-way ANOVA with feedback (positive or negative), period (high incentive or low incentive), and hemisphere (left or right) as factors. If changing the motivational context of a task affects the degree to which the feedback are differentiated at T4, then we should observe an interaction between feedback and period, reflected by clearer positive and negative feedback differences during high incentive trials. For our target area of interest, the caudate nucleus, the alpha level for the a priori contrasts was P < 0.05. Additionally, uncorrected planned contrasts (two paired t-tests, two-tailed) or post hoc tests (two paired t-tests, two-tailed) used a stricter alpha level of P < 0.01. All other regions identified in the task were also subjected to post hoc ANOVAs, although a stricter alpha level of P < 0.01 was used since these regions were not specified a priori.
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Results |
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Participants were asked to make a response for each trial during the fMRI session, during both periods of high and low incentive. One tailed, paired t-tests suggested that participants missed more trials (e.g. failed to respond in time) during periods of low incentive [t(8) = 4.37, P < 0.01]. There was no evidence of a continued cognitive strategy as the distribution of high and low choices was random during both periods of high incentive [choices: high, mean ± SD = 44.89 ± 10.8; low, 45 ± 10.82; t(8) = 0.15, P = 0.49] and low incentive [choices: high, 43.11 ± 7.64; low, 46.44 ± 7.62; t(8) = 0.66, P = 0.27]. Participants reaction times were collected for all trials and were variable across different periods [high incentive 658.29 ± 175.34; low incentive 646.34 ± 125.14; t(8) = 0.38, P = 0.36], although seven out of nine participants showed faster responses during periods of high incentive trials, as opposed to trials of low incentive, based on a Spearman rank correlation (R = 0.82, P < 0.02).
Neuroimaging Results
Regions activated during performance of the task (main effect of time, T1T5) are listed in Table 1 [F(4,32) = 11.00, P < 0.00001]. They included brain areas that contribute to both sensory (i.e. visual cortex, somatosensory cortex) and affective (i.e. striatum) processes. The a priori ROI was the dorsal striatum, and as expected, a left (Fig. 2) and right (Fig. 3) caudate nucleus ROIs were identified in this contrast. The hemodynamic response showed two patterns that were further investigated: an initial rise at the onset of the trial and a differential response to positive and negative feedback.
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Besides the striatal focus of interest, other brain regions were activated during performance of the task (main effect of time, T1T5 Table 1). Although our a priori region of interest was the striatum, we performed exploratory analysis on these other regions. Specifically we applied post hoc ANOVAs that used the same factors as those employed in our analysis of the striatum with the exception that hemisphere was not included when the ROI was unilateral. We report significant results for our two a priori interactions of interest (time x period in the choice phase, and feedback x period in the outcome phase) using a more strict alpha of P < 0.01; however, due to the post hoc nature of these exploratory analyses, these results should be considered preliminary. No regions showed an interaction between time and period in the choice phase. One region showed a significant interaction between feedback and period during the outcome phase, observed in the cingulate cortex [F(8,1) = 19.9, P < 0.01]. Higher signals were observed for the negative feedback in the low incentive periods, perhaps in accordance with a role for the cingulate cortex in error processing (Ullsperger and van Cramon, 2003).
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Discussion |
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It is important to be mindful, however, of the many physiological and psychological processes that can be altered when discussing motivational changes. Arousal, uncertainty and expectation are examples of motivational processes and it is difficult to disengage one from the other; thus, when we refer to changes in the motivational context of a task, it includes potential modulation related to all the aforementioned processes. Motivation itself can be broadly defined as a modulating influence on the direction of behavior (Shizgal, 1999). Both internal (i.e. hormonal changes) and external (i.e. environmental changes) factors can impact motivation, and thus, shape behavior. The addition of an incentive to an action, for example, will lead to an anticipation for the desired incentive and undoubtedly motivate someone to perform such action. Thus, a brain structure such as the caudate nucleus that typically responds to a task where feedback is received (Elliott et al., 1998b
), may respond even more if the motivational context of the task is changed and a more valuable feedback or incentive is presented.
The striatum has been implicated not only in processing task-related feedback but also in processing reward-related information by a variety of studies and is therefore a strong candidate to also process and monitor motivational information. Neurons in both dorsal and ventral striatum have been found to respond to the expectation and delivery of a primary reward (Hikosaka et al., 1989; Apicella et al., 1991
, 1992; Schultz et al., 1992
), to conditioned stimuli that predict a reward (Hollerman and Schultz, 1998
; Hollerman et al., 2000
), and to different types of reward, showing a preference ranking system (Hassani et al., 2001
). Similarly, activation in the striatum has been reported in neuroimaging paradigms during delivery of rewards (Delgado et al., 2000
; Breiter et al., 2001
; Delgado et al., 2003
), conditioned stimuli that predict a reward (Berns et al., 2001
; Pagnoni et al., 2002
; McClure et al., 2003
; O'Doherty et al., 2003
) and even during the anticipation of primary (O'Doherty et al., 2002
) and secondary rewards (Elliott et al., 2000
; Knutson et al., 2000
, 2001a,b; Breiter et al., 2001
). However, few neuroimaging studies have focused specifically on the role of the human caudate nucleus in motivation and reward, despite the various neurophysiological evidence suggesting a link between the non-human primate caudate nucleus and motivated, goal directed behavior (Hikosaka et al., 1989
; Apicella et al., 1991
; Kawagoe et al., 1998
; Hollerman et al., 2000
; Hassani et al., 2001
; Lauwereyns et al., 2002
). The card-guessing paradigm used in this experiment has previously been shown to activate the caudate nucleus during task performance, showing differential responses according to feedback valence (Delgado et al., 2000
) and magnitude (Delgado et al., 2003
).
A variety of neuroimaging tasks have indirectly targeted motivation by inducing manipulations of feedback, where the amount or valence was varied. For example, in one study, striatal activation was found for trials in which a cue indicated if a reward or non-reward should be anticipated (Knutson et al., 2000). Although it is clear from such designs that motivation is influencing striatal activity, the results are blurred since the cues served as predictors of reward. The paradigm used in the current study involved the same cue across trials to indicate that an outcome was following, but not the valence of the outcome. Participants were aware only that an impending feedback was to be presented upon response during all trials, and that the incentive to correctly respond to the trial was higher during periods of high incentive (to gain a monetary reward or avoid a monetary punishment). Therefore, any observed differences in the rise of activity should reflect differences in motivational properties rather than the valence or magnitude of the stimuli. The initial rise in activity at the onset was significantly higher in trials presented during the periods of high incentive rather than those trials presented in the periods of low incentive. This finding indicates that changing the motivational context of the task influenced activity in the caudate nucleus. Although the initial rise is significantly larger during periods of high incentive, it is worth noting that a rise in activity was still observed during periods of low incentive. This is in accordance with studies by Elliott et al. (1998b
) that found activity in the caudate nucleus during blocks of a cognitive task where participants received non-monetary feedback, compared with blocks where feedback was absent. Since the rise is present in both high and low incentive periods, it might be reflecting an array of motivational processes. For example, the initial rise might reflect anticipatory feelings caused by the uncertainty of the outcome. This possibility is supported by observed neuronal response in the striatum in response to stimuli that predict a reward (Schultz et al., 1998
; Hollerman et al., 2000
; Schultz, 2000
). In the case of our paradigm, the question mark at the onset of the trial may serve as a predictor of a possible reward, leading to more activity when the potential feedback is more desirable. Indeed, a recent study found that dopamine neurons, which project to the striatum, respond to uncertainty in accordance with the probability of an eventual outcome (Fiorillo et al., 2003
). The initial rise may also be reflecting some preparatory motor response, as participants were asked to make right-handed responses promptly after presentation of the cue, although this is less likely since the initial rise was observed in both left and right caudate nucleus.
A second component of the observed response of the caudate nucleus is the activation pattern that follows the delivery of positive and negative feedback. Previously, we demonstrated that activity in the caudate nucleus shows a differential response between reward and punishment trials 69 s after delivery of the feedback (Delgado et al., 2000
, 2003). During this same time window, we evaluated the relative difference between correct and incorrect trials for both periods of high and low incentive. As expected, the difference between feedback trials was higher during periods of high incentive (though the interaction between feedback and period was only significant at trend levels). These findings suggest that the affective salience of a feedback (monetary versus non-monetary) can influence the blood-flow response, although, due to statistical significance, further studies are necessary to support this claim.
One difficulty in interpreting the differences between high and low incentive periods after the delivery of the feedback is that we cannot distinguish between the effects of motivational state and the magnitude of the feedback received. We have shown that the caudate nucleus is sensitive to the magnitude of monetary feedback, with larger differences between reward and punishment observed with $4 rewards and $2 punishments than $0.40 rewards and $0.20 punishments (Delgado et al., 2003). Thus, the insignificant difference between correct and incorrect trials during periods of low incentive may represent an extension of these prior results, since at some point feedback of very low magnitude (such as non-monetary feedback) may produce such small responses to the feedback that significant differences between reward and punishment trials can no longer be observed.
Alternatively, it is possible that the response to a particular reward or punishment is influenced by the context in which it is received. For instance, if a few trials with monetary feedback were embedded in a period of low incentive, insignificant differences between these monetary reward and punishment trials might now be found (although the confound between motivation and reward magnitude would now be replaced with a confound between expectancy and reward value). Along similar lines, it is possible that positive and negative feedback differences in low incentive periods might be more prominent if these trials occurred in a scanning session that did not include high incentive, monetary reward and punishment trials. However, the results of other studies, which have also failed to find differences between positive and negative non-monetary feedback in overall activation of the caudate nucleus (Elliott et al., 1998a,b), argue against this interpretation.
Finally, it is important to discuss the lack of ventral striatum activation in this study. Activation in other neuroimaging studies have highlighted the contributions of the ventral striatum to reward processing (Breiter et al., 1997; Elliott et al., 2000
; Berns et al., 2001
; Breiter et al., 2001
; Knutson et al., 2001a
; Montague and Berns, 2002
; O'Doherty et al., 2002
, 2003), concurrent with animal literature (Apicella et al., 1991
; Koob, 1992
; Robbins and Everitt, 1992
, 1996; Koob, 1996
; Berridge and Robinson, 1998
; Shidara et al., 1998
; Di Chiara et al., 1999
; Rolls, 1999
; Cardinal et al., 2002
). This study primarily focuses on the dorsal striatum, which as previously discussed is also involved in reward-related processing, for a variety of reasons. First, it seems to be the region where the most robust activity is seen when using the current paradigm (Delgado et al., 2000
, 2003). Perhaps features of this paradigm are more successful in recruiting dorsal than ventral activation, such as feedback presentation or the fact that the outcome is contingent on an action (making a choice at the presentation of the cue). Second, perhaps technical issues regarding either signal dropout in more ventral areas of the brain (maybe amplified by the oblique-axial acquisition of functional slices, which may have attenuated signals from basal forebrain regions), in conjunction with the low number of samples per participants (and conservative ANOVA threshold) may have obscured that region. Although, activation in the ventral striatum was observed in our first study (Delgado et al., 2000
), twice the number of trials per participant were present and the mean intensity signal was higher for more dorsal than ventral areas of the brain, suggesting some signal drop out. Third, a growing number of studies are finding that the dorsal striatum is important in motivational processes as previously discussed. One recent positron emission tomography (PET) study, for example, looked at dopamine binding in food-deprived participants following food stimulation (i.e. when hungry participants were exposed to food items) and found increases in extracellular dopamine associated with dorsal, but not ventral striatum, and these increases were further correlated with self-reports of desire for the food item (Volkow et al., 2002
).
Overall, our results support the idea that the dorsal striatum, and in particular the caudate nucleus, has an important role in processing reward-related information. The response of the caudate nucleus can be fractionated into pre- and post-outcome effects. An initial rise in activation is present pre-outcome during both periods of high and low incentive, but post-outcome differences between feedback valence were only detected during periods of high incentive associated with the delivery of monetary rewards and punishments. The results and ideas put forth in this study further implicate the caudate nucleus as a structure integral in mediating motivated or goal-directed behaviors.
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Notes |
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Address correspondence to Mauricio Delgado, New York University, Department of Psychology, 6 Washington Place, Room 873, New York, NY 10003, USA. Email: m.delgado{at}nyu.edu.
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