Human Processing of Behaviorally Relevant and Irrelevant Absence of Expected Rewards: A High-Resolution ERP Study

Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of reality confusion marked by confabulation, disorientation, and currently inappropriate actions. This clinical state is strongly associated with an inability to abandon previously valid anticipations, that is, extinction capacity. In healthy subjects, the filtering of memories according to their relation with ongoing reality is associated with activity in posterior medial OFC (area 13) and electrophysiologically expressed at 220–300 ms. These observations indicate that the human OFC also functions as a generic reality monitoring system. For this function, it is presumably more important for the OFC to evaluate the current behavioral appropriateness of anticipations rather than their hedonic value. In the present study, we put this hypothesis to the test. Participants performed a reversal learning task with intermittent absence of reward delivery. High-density evoked potential analysis showed that the omission of expected reward induced a specific electrocortical response in trials signaling the necessity to abandon the hitherto reward predicting choice, but not when omission of reward had no such connotation. This processing difference occurred at 200–300 ms. Source estimation using inverse solution analysis indicated that it emanated from the posterior medial OFC. We suggest that the human brain uses this signal from the OFC to keep thought and behavior in phase with reality

Host Porphobilinogen Deaminase Deficiency Confers Malaria Resistance in Plasmodium chabaudi but Not in Plasmodium berghei or Plasmodium falciparum During Intraerythrocytic Growth

Background: The selective pressure imparted by intraerythrocytic infection with Plasmodium parasites, the causative agents of malaria has led to many mutations in erythrocytic genes that confer host resistance. Identification and characterization of mutations affecting host resistance to Plasmodium infection enables a deeper understanding of host–pathogen interactions and potentially new ways by which to prevent infection.Methods: Using ENU-induced mutagenesis, and screening for erythrocyte abnormalities and resistance to Plasmodium chabaudi infection, we identified a novel nonsense mutation in the gene encoding porphobilinogen deaminase (PBGD) in mice.Results: Heterozygote Pbgd mice exhibited microcytosis and 25% reduction in cellular PBGD activity, but were healthy otherwise. When challenged with blood-stage P. chabaudi, the heterozygotes were significantly protected against infection, showed reduced parasite growth, and had a survival advantage. The mutation did not affect erythrocyte susceptibility to parasite invasion. Instead, the mechanism of underlying resistance to infection involved intraerythrocytic parasite death and reduced propagation of viable parasites. This was not observed when P. falciparum was cultured in erythrocytes from patients with acute intermittent porphyria (AIP), who have low PBGD levels or with P. berghei infection in Pbgd deficient mice. Furthermore, the growth capacity of PBGD-null P. falciparum and P. berghei parasites, which grew at the same rate as their wild-type counterparts in normal erythrocytes, was not reduced in the AIP erythrocytes or Pbgd-deficient mice.Conclusions: Our results suggest that PBGD deficiency confers resistance to infection with P. chabaudi during the blood-stage of infection and erythrocytic or parasite PBGD is likely to be dispensable for parasite maturation

The human orbitofrontal cortex: linking reward to hedonic experience.

Hedonic experience is arguably at the heart of what makes us human. In recent neuroimaging studies of the cortical networks that mediate hedonic experience in the human brain, the orbitofrontal cortex has emerged as the strongest candidate for linking food and other types of reward to hedonic experience. The orbitofrontal cortex is among the least understood regions of the human brain, but has been proposed to be involved in sensory integration, in representing the affective value of reinforcers, and in decision making and expectation. Here, the functional neuroanatomy of the human orbitofrontal cortex is described and a new integrated model of its functions proposed, including a possible role in the mediation of hedonic experience