Proefschrift_Holstein

Chapter 7

loops with functionally similar cortical regions, when moving from the reward circuit to the cognitive and subsequently action circuit (Haber, 2003; Haber et al., 2006; Haber and Knutson, 2010; Choi et al., 2012; Oh et al., 2014). We provide functional evidence that this gradient in the striatum is indeed associated with task-related processing, where signaling in the anterior caudate nucleus was associated with reward processing and increasingly posterior and lateral portions of the striatum were involved in cognitive and motor processes. Our observation that stimulation of the aPFC can modulate processing in distinct regions of the striatum in a task-specific way provides evidence for the hypothesis that integration of task-related information can occur across circuits, rather than being restricted within parallel loops (Haber et al., 2000). Tracing work in non-human primates has revealed that the dlPFC projects primarily to the dorsal caudate nucleus, but that its projection field extends to other regions in the striatum, primarily the anterior and medial putamen. A similar pattern was observed for cortical regions involved in reward processing: these projections terminated primarily in the ventral striatum, but extent to more dorsal regions of the striatum, including the caudate nucleus (Haber et al., 2006). Although this tracing work did not include the anterior PFC, this work does suggest that these connections could underlie the currently observed interaction between reward, task switching and response switching; a functional, task-related gradient has been shown previously in the frontal cortex (for reviews see: Koechlin and Summerfield, 2007; Botvinick, 2008; Badre and D’Esposito, 2009), where increasingly anterior portions of the frontal cortex are involved in increasingly abstract goals. In addition, using a computational modeling approach, Badre and Frank (2012) recently suggested that a dopaminergic corticostriatal mechanism may underlie the integration across rules when participants need to learn about task structure. We provide, for the first time, functional evidence that integration across corticostriatal circuits takes place when integrating information across functionally dissociable goals by showing that stimulation of the aPFC can have functionally specific effects in distinct regions in the striatum depending on the level of interaction (i.e. evidenced by a reward-related effect of aPFC stimulation in the caudate nucleus, but in the putamen during the integration of reward, task switching and response switching ( figure 7.5 ). However, the mechanisms underlying this integration across circuits are poorly understood. We put forward three ways by which information about rewards can influence cognitive- and action goals. The first involves direct cortico-cortical projections (Fuster, 2001; Wood and Grafman, 2003; Badre and D’Esposito, 2009), while the second and third way assign also a role to the striatum in the integration across corticostriatal circuits: via direct cortico- striatal connections or via spiraling dopaminergic connections between the striatum and the midbrain, i.e. striatal-nigral-striatal (SNS) connections (Haber et al., 2000; Haber, 2003; Haber and Knutson, 2010). Future work should directly test these hypotheses, but here we highlight in particular, based on recent convergent evidence from studies using the same experimental paradigm, a role for the dopaminergic midbrain SNS projections in conveying information about rewards to cognitive and action circuits. Specifically, the SNS account is

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