Reward-based associative learning is mediated by a distributed network of brain regions that are dependent on the dopaminergic system. Age-related changes in key regions of this system, the striatum and the prefrontal cortex, may adversely affect the ability to use reward information for the guidance of behavior. The present study investigated the effects of healthy aging on different components of reward learning, such as acquisition, reversal, effects of reward magnitude, and transfer of learning. A group of 30 young (mean age = 24.2 yr) and a group of 30 older subjects (mean age = 64.1 yr) completed two probabilistic reward-based stimulus association learning tasks. Older subjects showed poorer overall acquisition and impaired reversal learning, as well as deficits in transfer learning. When only those subjects who showed evidence of significant learning were considered, younger subjects showed equivalently fast learning irrespective of reward magnitude, while learning curves in older subjects were steeper for high compared to low reward magnitudes. Acquired equivalence learning, which requires generalization across stimuli and transfer of learned contingencies to new stimuli, was mildly impaired in older subjects.

Episodic memory and episodic future thinking are known to share a set of brain regions. Potential differences in activation patterns associated with the two conditions are as yet inconclusive, in particular with respect to hippocampal involvement. Hippocampal activation is modulated by a range of phenomenal qualities during the imagination of both past and future events (Addis et al. (2004) Hippocampus 14:752-762; Addis and Schacter (2008) Hippocampus 18:227-237). A relevant variable in this regard is the occurrence probability of an episode, which varies for future but not past events and thus cannot be equated across conditions. Using parametric modulation analysis, we investigated the effect of occurrence probability of imagined future events on brain activation patterns, while effects of temporal distance, amount of details, and emotionality were controlled for. Activation of right anterior hippocampus increased with decreasing occurrence probability, presumably reflecting higher processing demands during binding of more disparate details for unlikely events. This finding may contribute to the understanding of previously reported inconsistent results concerning hippocampal involvement during the imagination of past and future events.

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Recent models assume that some symptoms of schizophrenia originate from defective reward processing mechanisms. Understanding the precise nature of reward-based learning impairments might thus make an important contribution to the understanding of schizophrenia and the development of treatment strategies. The present study investigated several features of probabilistic reward-based stimulus association learning, namely the acquisition of initial contingencies, reversal learning, generalization abilities, and the effects of reward magnitude. Compared to healthy controls, individuals with schizophrenia exhibited attenuated overall performance during acquisition, whereas learning rates across blocks were similar to the rates of controls. On the group level, persons with schizophrenia were, however, unable to learn the reversal of the initial reward contingencies. Exploratory analysis of only the subgroup of individuals with schizophrenia who showed significant learning during acquisition yielded deficits in reversal learning with low reward magnitudes only. There was further evidence of a mild generalization impairment of the persons with schizophrenia in an acquired equivalence task. In summary, although there was evidence of intact basic processing of reward magnitudes, individuals with schizophrenia were impaired at using this feedback for the adaptive guidance of behavior.

Vividly remembering the past and imagining the future (mental time travel) seem to rely on common neural substrates and mental time travel impairments in patients with brain lesions seem to encompass both temporal domains. However, because future thinking-or more generally imagining novel events-involves the recombination of stored elements into a new event, it requires additional resources that are not shared by episodic memory. We aimed to demonstrate this asymmetry in an event generation task administered to two patients with lesions in the medial dorsal thalamus. Because of the dense connection with pFC, this nucleus of the thalamus is implicated in executive aspects of memory (strategic retrieval), which are presumably more important for future thinking than for episodic memory. Compared with groups of healthy matched control participants, both patients could only produce novel events with extensive help of the experimenter (prompting) in the absence of episodic memory problems. Impairments were most pronounced for imagining personal fictitious and impersonal events. More precisely, the patients' descriptions of novel events lacked content and spatio-temporal relations. The observed impairment is unlikely to trace back to disturbances in self-projection, scene construction, or time concept and could be explained by a recombination deficit. Thus, although memory and the imagination of novel events are tightly linked, they also partly rely on different processes.