Corollary discharge signals play an important role in monitoring self-generated movements to guarantee spatial constancy. Recent work in macaques suggests that the thalamus conveys corollary discharge information of upcoming saccades passing from the superior colliculus to the frontal eye field. The present study aimed to investigate the involvement of the thalamus in humans by assessing the effect of thalamic lesions on the processing of corollary discharge information. Thirteen patients with selective thalamic lesions and 13 healthy age-matched control subjects performed a saccadic double-step task in which retino-spatial dissonance was induced, i.e. the retinal vector of the second target and the movement vector of the second saccade were different. Thus, the subjects could not rely on retinal information alone, but had to use corollary discharge information to correctly perform the second saccade. The amplitudes of first and second saccades were significantly smaller in patients than in controls. Five thalamic lesion patients showed unilateral deficits in using corollary discharge information, as revealed by asymmetries compared with the other patients and controls. Three patients with lateral thalamic lesions including the ventrolateral nucleus (VL) were impaired contralaterally to the side of damage and one patient with a lesion in the mediodorsal thalamus (MD) was impaired ipsilaterally to the lesion. The largest asymmetry was found in a patient with a bilateral thalamic lesion. The results provide evidence for a thalamic involvement in the processing of corollary discharge information in humans, with a potential role of both the VL and MD nuclei.

The basal ganglia (BG) are thought to play a key role in learning from feedback, with mesencephalic dopamine neurons coding errors in reward prediction, thereby mediating information processing in the BG and the prefrontal cortex. In the present study, reward-based learning was assessed in patients with focal BG lesions, by studying outcome-based acquisition and reversal of stimulus-stimulus associations with different reward magnitudes in two probabilistic learning tasks. Eleven patients with selective BG lesions (three females) and 18 healthy control subjects (six females) participated in this study. Two cognitive transfer tasks provided a measure of declarative learning strategy application. On the group level, BG patients showed deficits in reversal learning, with dorsal striatum lesion patients being most severely affected. While basic mechanisms of learning from feedback such as the processing of different reward magnitudes appeared to be intact, patients needed more trials than controls to learn a second reward-based task, suggesting reduced carry-over effects in learning. A patient with a bilateral BG lesion showed better performance than controls on most learning tasks, applying a compensatory declarative learning strategy. The results are discussed in terms of the implication of different BG subregions in different aspects of learning from feedback.

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The cerebellum has recently been discussed in terms of a possible involvement in reward-based associative learning. To clarify the cerebellar contribution, eight patients with focal vascular lesions of the cerebellum and a group of 24 healthy subjects matched for age and IQ were compared on a range of different probabilistic outcome-based associative learning tasks, assessing acquisition, reversal, cognitive transfer, and generalization as well as the effect of reward magnitude. Cerebellar patients showed intact acquisition of stimulus contingencies, while reward-based reversal learning was significantly impaired. In addition, the patients showed slower acquisition of new stimulus contingencies in a second reward-based learning task, which might reflect reduced carry-over effects. Reward magnitude affected learning only during initial acquisition, with better learning on trials with high rewards in patients and control subjects. Overall, the findings suggest that the cerebellum is implicated in reversal learning as a dissociable component of reward-based learning.

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Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response – the error-related negativity (ERN) - as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

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.