Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat comorbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on the brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here, we summarize recent studies in juvenile rats on the molecular effects in the mid- and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH + FLX treatments can produce similar molecular changes as seen after cocaine exposure while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood.
Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.
Animals approach rewards and cues associated with reward, even when this behavior is irrelevant or detrimental to the attainment of these rewards. Motivated by these findings we study the biology of financially-costly approach behavior in humans. Our subjects passively learned to predict the occurrence of erotic rewards. We show that neuronal responses in ventral striatum during this Pavlovian learning task stably predict an individual's general tendency towards financially-costly approach behavior in an active choice task several months later. Our data suggest that approach behavior may prevent some individuals from acting in their own interests.
An auction is said to be externality-robust if unilateral deviations from equilibrium leave the remaining bidders’ payoffs unaffected. The equilibrium and its outcome will then persist even if externalities between bidders arise from certain types of interdependent preferences. One important example are externalities due to spiteful preferences, which are frequently used to explain overbidding in auctions. Another important example are cross-shareholdings between firms that compete in an auction. For the independent private values model, we derive an auction that coincides with the second-price auction (SPA) in terms of efficiency and expected revenue, and, in contrast to the second-price auction, is also externality-robust. The externality-robust auction (ERA) is a first-price auction in which truthful bidding is encouraged by bonus payments. We test the robustness property experimentally by comparing the outcomes of the SPA and the ERA. We replicate the earlier finding of significant average overbidding in the SPA, while we find no overbidding on average in the ERA. We also conduct additional treatments where bidders play against the computer, and we use controls for cognitive skills and joy of winning to further pin down the reasons behind the subjects’ bidding behavior and to understand the sources of individual heterogeneity.
Considered are imperfectly discriminating contests in which players may possess private information about the primitives of the confiict, such as the contest technology, valuations of the prize, cost functions, and budget constraints. We find general conditions under which a given contest of this sort admits a unique pure-strategy Nash equilibrium. In particular, provided that all budgets are positive, existence requires only the usual concavity assumptions. Information structures that satisfy our conditions for uniqueness include independent private valuations, correlated private values, pure common values, and examples of interdependent valuations. The results allow dealing with inactive types, asymmetric equilibria, population uncertainty, and the possibility of resale. It is also shown that any active contestant ends up with a positive net rent.
Variability or noise is an unmistakable feature of neural signals; however such fluctuations have been regarded as not carrying meaningful information or as detrimental for neural processes. Recent empirical and computational work has shown that neural systems with a greater capacity for information processing are able to explore a more varied dynamic repertoire, and the hallmark of this is increased irregularity or variability in the neural signal. How this variability in neural dynamics affects behavior remains unclear. Here, we investigated the role of variability of magnetoencephalography signals in supporting healthy cognitive functioning, measured by performance on an attention task, in healthy adults and in patients with traumatic brain injury. As an index of variability, we calculated multiscale entropy, which quantifies the temporal predictability of a time series across progressively more coarse time scales. We found lower variability in traumatic brain injury patients compared to controls, arguing against the idea that greater variability reflects dysfunctional neural processing. Furthermore, higher brain signal variability indicated improved behavioral performance for all participants. This relationship was statistically stronger for people with brain injury, demonstrating that those with higher brain signal variability were also those who had recovered the most cognitive ability. Rather than impede neural processing, cortical signal variability within an optimal range enables the exploration of diverse functional configurations, and may therefore play a vital role in healthy brain function.
Early brain injury alters both structural and functional connectivity between the cerebral hemispheres. Despite increasing knowledge on the individual hemispheric contributions to recovery from such injury, we know very little about how their interactions affect this process. In the present study, we related interhemispheric structural and functional connectivity to receptive language outcome following early left hemisphere stroke. We used functional magnetic resonance imaging to study 14 people with neonatal brain injury, and 25 age-matched controls during passive story comprehension. With respect to structural connectivity, we found that increased volume of the corpus callosum predicted good receptive language outcome, but that this is not specific to people with injury. In contrast, we found that increased posterior superior temporal gyrus interhemispheric functional connectivity during story comprehension predicted better receptive language performance in people with early brain injury, but worse performance in typical controls. This suggests that interhemispheric functional connectivity is one potential compensatory mechanism following early injury. Further, this pattern of results suggests refinement of the prevailing notion that better language outcome following early left hemisphere injury relies on the contribution of the contralesional hemisphere (i.e., the "right-hemisphere-take-over" theory). This pattern of results was also regionally specific; connectivity of the angular gyrus predicted poorer performance in both groups, independent of brain injury. These results present a complex picture of recovery, and in some cases, such recovery relies on increased cooperation between the injured hemisphere and homologous regions in the contralesional hemisphere, but in other cases, the opposite appears to hold.
We study how the distribution of other-regarding preferences develops with age. Based on a set of allocation choices, we classify each of 717 subjects, aged 8 to 17 years, as either egalitarian, altruistic, or spiteful. We find a strong decrease in spitefulness with increasing age. Egalitarianism becomes less frequent, and altruism much more prominent, with age. Females are more frequently classified as egalitarian than males, and less often as altruistic. By varying the allocation recipient as either an in-group or an out-group member, we also study how parochialism develops with age. Parochialism emerges significantly in the teenage years.
