Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia

Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer’s disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population

Threat perception: Fear and the retrorubal field.

A new study has found that neurons within a structure of the rat midbrain known as the retrorubral field show diverse responses to stimuli that signal different levels of threat, as well as a separate pattern of diverse responses to differentially predicted aversive outcomes

Adaptive behaviour under conflict: Deconstructing extinction, reversal, and active avoidance learning.

In complex environments, organisms must respond adaptively to situations despite conflicting information. Under natural (i.e. non-laboratory) circumstances, it is rare that cues or responses are consistently paired with a single outcome. Inconsistent pairings are more common, as are situations where cues and responses are associated with multiple outcomes. Such inconsistency creates conflict, and a response that is adaptive in one scenario may not be adaptive in another. Learning to adjust responses accordingly is important for species to survive and prosper. Here we review the behavioural and brain mechanisms of responding under conflict by focusing on three popular behavioural procedures: extinction, reversal learning, and active avoidance. Extinction involves adapting from reinforcement to non-reinforcement, reversal learning involves swapping the reinforcement of cues or responses, and active avoidance involves performing a response to avoid an aversive outcome, which may conflict with other defensive strategies. We note that each of these phenomena relies on somewhat overlapping neural circuits, suggesting that such circuits may be critical for the general ability to respond appropriately under conflict

Configural integration of temporal and contextual information in rats: Automated measurement in appetitive and aversive preparations

Two experiments investigated the capacity of rats to learn configural discriminations requiring integration of contextual (where) with temporal (when) information. In Experiment 1, during morning training sessions, food was delivered in context A and not in context B, whereas during afternoon sessions food was delivered in context B and not in context A. Rats acquired this discrimination over the course of 20 days. Experiment 2 employed a directly analogous aversive conditioning procedure in which footshock served in place of food. This procedure allowed the acquisition of the discrimination to be assessed through changes in activity to the contextual + temporal configurations (i.e., inactivity or freezing) and modulation of the immediate impact of footshock presentations (i.e., post-shock activity bursts). Both measures provided evidence of configural learning over the course of 12 days, with a final test showing that the presentation of footshock resulted in more post-shock activity in the nonreinforced than reinforced configurations. These behavioral effects reveal important parallels between (i) configural discrimination learning involving components allied to episodic memory and (ii) simple conditioning

The neuroscience of memory: implications for the courtroom

Although memory can be hazy at times, it is often assumed that memories of violent or otherwise stressful events are so well-encoded that they are largely indelible and that confidently retrieved memories are likely to be accurate. However, findings from basic psychological research and neuroscience studies indicate that memory is a reconstructive process that is susceptible to distortion. In the courtroom, even minor memory distortions can have severe consequences that are in part driven by common misunderstandings about memory, e.g. expecting memory to be more veridical than it may actually be