Background Decision-making studies show that response selection is influenced by the “effort cost” associated with response alternatives. These effort-cost calculations seem to be mediated by a distributed neural circuit including the anterior cingulate cortex and subcortical targets of dopamine neurons. On the basis of evidence of dysfunction in these systems in schizophrenia (SZ), we examined whether effort-cost computations were impaired in SZ patients and whether these deficits were associated with negative symptoms. Methods Effort-cost decision-making performance was evaluated in 44 patients with SZ and 36 demographically matched control subjects. Subjects performed a computerized task where they were presented with a series of 30 trials in which they could choose between making 20 button presses for $1 or 100 button presses for higher amounts (varying from $3 to $7 across trials). Probability of reward receipt was also manipulated to determine whether certain (100%) or uncertain (50%) reward affected effort-based decision-making. Results Patients were less likely than control subjects to select the high-effort response alternative during the 100% probability condition, particularly when the value payoff was highest (i.e., $6 and $7). Patients were also less likely to select the high-effort option on trials after reward in the 50% probability condition. Furthermore, these impairments in effort-cost computations were greatest among patients with elevated negative symptoms. There was no association with haloperidol equivalent dosage. Conclusions The motivational impairments of SZ might be associated with abnormalities in estimating the “cost” of effortful behavior. This increased effort cost might undermine volition.

Background: Rewards and punishments may make distinct contributions to learning via separate striato-cortical pathways. We investigated whether fronto-striatal dysfunction in schizophrenia (SZ) is characterized by selective impairment in either reward-(Go) or punishment-driven (NoGo) learning.

BACKGROUND-It is well known that individuals with schizophrenia have dopaminergic abnormalities as well as working memory difficulties, both of which are associated with impulsive decision making. We used a delay discounting measure to test the degree to which patients make future-oriented decisions.

. Acute food deprivation and chronic food restriction differentially affect hypothalamic NPY mRNA expression. Am J Physiol Regul Integr Comp Physiol 285: R1030-R1036, 2003. First published July 3, 2003 10.1152/ajpregu.00734.2002Although acute food deprivation and chronic food restriction both result in body weight loss, they produce different metabolic states. To evaluate how these two treatments affect hypothalamic peptide systems involved in energy homeostasis, we compared patterns of hypothalamic neuropeptide Y (NPY), agouti-related protein (AgRP), proopiomelanocotin (POMC), and leptin receptor gene expression in acutely fooddeprived and chronically food-restricted rats. Both acute food deprivation and chronic food restriction reduced body weight and circulating leptin levels and resulted in increased arcuate NPY and decreased arcuate POMC gene expression. Arcuate AgRP mRNA levels were only elevated in acutely deprived rats. NPY gene expression was increased in the compact subregion of the dorsomedial hypothalamus (DMH) in response to chronic food restriction, but not in response to acute food deprivation. Leptin receptor expression was not affected by either treatment. Double in situ hybridization histochemistry revealed that, in contrast to the situation in the arcuate nucleus, NPY and leptin receptor mRNA-expressing neurons were not colocalized in the DMH. Together, these data suggest that arcuate and DMH NPY gene expression are differentially regulated. DMH NPY-expressing neurons do not appear to be under the direct control of leptin signaling. leptin; leptin receptor; proopiomelanocortin; agouti-related protein; in situ hybridization HYPOTHALAMIC PEPTIDE SIGNALING systems play an important role in the controls of food intake and body weight. Neuropeptide Y (NPY) is a potent hypothalamic orexigenic peptide (13,22,33). Centrally administered NPY causes robust increases in food intake and body weight and, with chronic administration, can eventually produce obesity (32,38). Although NPY immunoreactivity is widely distributed throughout the hypothalamus, NPY is primarily localized in neuronal populations within the arcuate nucleus and dorsomedial hypothalamus (DMH) (3,12,16). Both arcuate and DMH NPY neurons project to the paraventricular nucleus (PVN) and roles for both of these NPY neuronal populations in the controls of food intake and energy balance have been proposed (19,24).Most of the recent work investigating actions of NPY in the control of food intake and energy balance has focused on the arcuate nucleus. Arcuate NPY gene expression is modulated in response to alterations in energy balance. Leptin, a hormone produced in adipocytes, acts as a feedback signal to the hypothalamus, playing a fundamental role in maintaining energy homeostasis (15, 31). Arcuate NPY serves as one of the downstream mediators of leptin's actions. These NPY neurons coexpress leptin receptor mRNA (25), and NPY gene expression is downregulated by leptin administration (27). Arcuate NPY mRNA expression is modulated over the diu...