The role of the cerebellum for feedback processing and behavioral switching in a reversal-learning task.

Previous studies have reported cerebellar activations during error and reward processing. The present study investigated if the cerebellum differentially processes feedback depending on changes in response strategy during reversal learning, as is conceivable given its internal models for movement and thought. Negative relative to positive feedback in an fMRI-based reversal learning task was hypothesized to be associated with increased cerebellar activations. Moreover, increased activations were expected for negative feedback followed by a change in response strategy compared to negative feedback not followed by such a change, and for first positive feedback after compared to final negative feedback before a change, due to updating of internal models. As predicted, activation in lobules VI and VIIa/Crus I was increased for negative relative to positive feedback, and for final negative feedback before a change in response strategy relative to negative feedback not associated with a change. Moreover, activation was increased for first positive feedback after relative to final negative feedback before a change. These findings are consistent with updating of cerebellar internal models to accommodate new behavioral strategies. Recruitment of posterior regions in reversal learning is in line with the cerebellar functional topography, with posterior regions involved in complex motor and cognitive functions.

Parametric modulation of reward sequences during a reversal task in ACC and VMPFC but not amygdala and striatum.

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE.

A single-trial estimation of the feedback-related negativity and its relation to BOLD responses in a time-estimation task.

An event-related potential (ERP) component reliably associated with feedback processing and well studied in humans is the feedback-related negativity (FRN), which is assumed to indicate activation of midcingulate cortex (MCC) neurons. However, recent approaches have conceptualized this frontocentral ERP component as reflecting at least partially a reward positivity associated with activation in reward-related brain regions, in line with fMRI studies investigating feedback processing in the context of reward evaluation. To discover convergence of electrophysiological and BOLD responses elicited by performance feedback, we concurrently recorded EEG and fMRI during a time-estimation task. The ERP showed relatively more negative amplitudes to negative than to positive feedback. Conventional analyses of fMRI data revealed activation of a number of areas, including ventral striatum, anterior cingulate cortex, and medial prefrontal cortex to positive versus negative feedback. Most importantly, when using single-trial amplitudes of electrophysiological feedback signals to estimate hemodynamic responses, we found feedback-related BOLD-responses in ventral striatum, midcingulate, and midfrontal cortices to positive but not to negative feedback associated with feedback signals in the time range of the FRN. Specifically, activation in these areas increased as amplitudes became more positive. These findings suggest that, in the time-estimation task, a positivity elicited by reward is associated with brain activation in several reward-related brain regions and is driving differential ERP responses in the time range of the FRN.

Altered emotional and BOLD responses to negative, positive and ambiguous performance feedback in OCD.

While abnormal processing of performance feedback has been associated with obsessive-compulsive disorder (OCD), neural responses to different kinds of feedback information, especially to ambiguous feedback are widely unknown. Using fMRI and a performance adaptive time-estimation task, we acquired blood oxygenation level-dependant responses and emotional ratings to positive, negative and ambiguous performance feedback in patients and healthy controls. Negative and ambiguous feedback led to increased levels of anxiety, guilt and shame in patients. Both negative and ambiguous feedback, as compared to positive feedback, induced increased activation of the insular cortex in patients. Furthermore, patients showed no differential activation to negative feedback in the putamen and to ambiguous feedback in the ventromedial prefrontal cortex (VMPFC). Finally, negative feedback induced increased activation in the midcingulate cortex in patients compared to controls. Findings indicate that both negative and ambiguous performance feedbacks are associated with abnormal negative emotions and altered brain activation, in particular increased insula activation, while activation in the putamen and VMPFC does not differentiate between feedback types in OCD patients. This suggests a parallel pattern of increased and decreased neural sensitivity to different kinds of feedback information and a general emotional hyperresponsivity to negative and ambiguous performance feedback in OCD.

Impaired Representation of Time in Schizophrenia Is Linked to Positive Symptoms and Cognitive Demand.

Time processing critically relies on the mesencephalic dopamine system and striato-prefrontal projections and has thus been suggested to play a key role in schizophrenia. Previous studies have provided evidence for an acceleration of the internal clock in schizophrenia that may be linked to dopaminergic pathology. The present study aimed to assess the relationship between altered time processing in schizophrenia and symptom manifestation in 22 patients and 22 controls. Subjects were required to estimate the time needed for a visual stimulus to complete a horizontal movement towards a target position on trials of varying cognitive demand. It was hypothesized that patients - compared to controls - would be less accurate at estimating the movement time, and that this effect would be modulated by symptom manifestation and task difficulty. In line with the notion of an accelerated internal clock due to dopaminergic dysregulation, particularly patients with severe positive symptoms were expected to underestimate movement time. However, if altered time perception in schizophrenia was better explained in terms of cognitive deficits, patients with severe negative symptoms should be specifically impaired, while generally, task performance should correlate with measures of processing speed and cognitive flexibility. Patients underestimated movement time on more demanding trials, although there was no link to disease-related cognitive dysfunction. Task performance was modulated by symptom manifestation. Impaired estimation of movement time was significantly correlated with PANSS positive symptom scores, with higher positive symptom scores associated with stronger underestimation of movement time. The present data thus support the notion of a deficit in anticipatory and predictive mechanisms in schizophrenia that is modulated both by symptom manifestation and by cognitive demand.