Neuroscience Letters 399 (2006) 39–44 Activation of insular cortex and subcortical regions related to feedback stimuli in a time estimation task: An fMRI study Tetsuji Tsukamoto a,∗ , Yasunori Kotani b , Yoshimi Ohgami b , Kazufumi Omura c , Yusuke Inoue c , Yasutsugu Aihara a a Department of Kinesiology, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachioji, Tokyo 192-0397, Japan b Department of Human System Science, Tokyo Institute of Technology, Tokyo, Japan c Department of Radiology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan Received 9 November 2005; received in revised form 14 January 2006; accepted 17 January 2006 Abstract We used functional magnetic resonance imaging to investigate brain activity related to motivational function of informative feedback stimuli in a time estimation task. In that task, subjects pressed a button as a response 3 s after a cue stimulus; a visual feedback stimulus was presented 2 s after the response. In a true feedback condition, subjects received true information (informative feedback) about their time-estimation performance. In the false feedback condition, the same visual signs were used, but they were presented randomly. Therefore, they were not related to actual performance. In the 20 subjects examined, higher hemodynamic responses were identified in the insular cortex, the thalamus, and the striatum by comparing the true feedback condition to the false feedback condition. The time estimation performance and subjective score on motivation were also markedly higher in the true feedback condition. The anterior insular cortex and striatal regions are known to be involved in motivational and reward processing. Therefore, the hemodynamic responses observed in this study suggest that the motivational function of the feedback information is a crucial factor for behavioral learning; it is considered that the informative feedback might serve as an implicit reward for humans. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Feedback information; Motivation; Insula; Striatum; fMRI; Stimulus-preceding negativity Reward facilitates behavioral learning in humans. Effects of rewards have been investigated in relation to associative learn- ing in animals [25] and humans [8,9]. In daily life, however, humans can learn appropriate behavior without monetary or other explicit rewards like food, using feedback information alone. Schmidt et al. reported significantly improved perfor- mance during a motor task when feedback information was given [24]. Informative feedback provides knowledge of desired actions that should be taken by the subject and it motivates subjects to learn behavior. Therefore, feedback information is considered to have motivational functions by which subjects are engaged to the task [24]. Motivational effects of feedback information have been investigated using electroencephalography (EEG). Event- related slow potential has been identified before feedback stimuli and it is referred to as stimulus-preceding negativity ∗ Corresponding author. Tel.: +81 42 585 5402; fax: +81 42 585 5725. E-mail address: tetsuji.tsukamoto@ge.com (T. Tsukamoto). (SPN) [3,6,7]. The SPN might reflect a motivational effect. For instance, Chwilla and Brunia [6] compared effects of true, false and no feedback stimuli using a time-estimation task. A sig- nificant SPN was found only when the true feedback stimuli were delivered. Furthermore, Kotani et al. [15] applied a mone- tary reward to examine, directly, the effect of motivation on the SPN. They observed that the SPN was larger in a reward con- dition than in a no-reward condition. In another study, they also manipulated the informational valence of the feedback stimuli in addition to the reward manipulation. They revealed that the SPN was increased by a reward when subjects received precise feed- back information. On the other hand, the SPN was not affected by a monetary reward when the feedback information was less informative [16]. From those results, they suggested that the SPN amplitude is influenced by motivation that is enhanced by information values and reward. Although such studies strongly implied involvement of motivational processing and anticipatory attention to the feedback stimuli, few studies have addressed neurophysiological sources by which we might obtain further insight into the motivational function of informative feedback. A 0304-3940/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2006.01.061