Choosing the lesser of two evils, the better of two goods: Specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning

Lung-resident CD4 T cells are sufficient for IL-4Ralpha-dependent recall immunity to Nippostrongylus brasiliensis infection.

Immunity to Nippostrongylus brasiliensis reinfection requires pulmonary CD4+ T-cell responses. We examined whether secondary lymphoid recruited or pre-existing lung CD4+ T-cell populations coordinated this immunity. To do this, we blocked T-cell egress from lymph nodes using Fingolimod (FTY720). This impaired host ability to resolve a primary infection but did not change effectiveness of recall immunity. Associated with this effective recall immunity was the expansion and T helper type 2 polarization of a pre-existing pulmonary CD4+ T-cell population. LTbetaR-Ig (lymphotoxin beta-receptor fusion protein)-mediated disruption of stromal cell organization of immune cells did not disrupt this recall immunity, suggesting that protection was mediated by a pulmonary interstitial residing CD4+ T-cell population. Adoptive transfer of N. brasiliensis-experienced pulmonary CD4+ T cells from FTY720-treated wild-type or T-cell interleukin (IL)-4Ralpha-deficient mice demonstrated protection to be IL-4Ralpha dependent. These results show that pre-existing CD4+ T cells can drive effective recall immunity to N. brasiliensis infection independently of T-cell recruitment from secondary lymphoid organs.Mucosal Immunology advance online publication 19 June 2013; doi:10.1038/mi.2013.40