Lena Rademacher

Anticipation of monetary and social reward differently activates mesolimbic brain structures in men and women

Motivation for goal-directed behaviour largely depends on the expected value of the anticipated reward. The aim of the present study was to examine how different levels of reward value are coded in the brain for two common forms of human reward: money and social approval. To account for gender differences 16 male and 16 female participants performed an incentive delay task expecting to win either money or positive social feedback. fMRI recording during the anticipation phase revealed proportional activation of neural structures constituting the human reward system for increasing levels of reward, independent of incentive type. However, in men activation in the prospect of monetary rewards encompassed a wide network of mesolimbic brain regions compared to only limited activation for social rewards. In contrast, in women, anticipation of either incentive type activated identical brain regions. Our findings represent an important step towards a better understanding of motivated behaviour by taking into account individual differences in reward valuation.

Dissociation of neural networks for anticipation and consumption of monetary and social rewards

Human behaviour is generally guided by the anticipation of potential outcomes that are considered to be rewarding. Reward processing can thus be dissected into a phase of reward anticipation and a phase of reward consumption. A number of brain structures have been suggested to be involved in reward processing. However, it is unclear whether anticipation and consumption are mediated by the same or different neural networks. We examined the neural basis of these processes using functional magnetic resonance imaging (fMRI) in an incentive delay task offering either money or social approval. In both conditions participants (N=28) were given a cue indicating potential reward. In order to receive reward a target button had to be pushed within a certain time window (adapted for individual reaction time). Cues triggering either monetary or social reward anticipation were presented sessionwise. Imaging was performed on a 1.5-Tesla Philips scanner in an event-related design. Anticipation of both reward types activated brain structures constituting the brain reward system including the ventral striatum. In contrast to the task independent activity in the anticipation phase, reward consumption evoked different patterns of activation for money and social approval, respectively. While social stimuli were mainly associated with amygdala activation, the thalamus was more strongly activated by the presentation of monetary rewards. Our results identify dissociable neural networks for the anticipation and consumption of reward. The findings implicate that the neural mechanisms underlying reward consumption are more modality-specific than those for reward anticipation, and that they are mediated by subjective reward value.

Oxytocin Influences Processing of Socially Relevant Cues in the Ventral Tegmental Area of the Human Brain

BACKGROUND Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. METHODS We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. RESULTS Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. CONCLUSIONS Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment.

Differential patterns of nucleus accumbens activation during anticipation of monetary and social reward in young and older adults

Recent studies have reported inconsistent results regarding the loss of reward sensitivity in the aging brain. Although such an age effect might be due to a decline of physiological processes, it may also be a consequence of age-related changes in motivational preference for different rewards. Here, we examined whether the age effects on neural correlates of reward anticipation are modulated by the type of expected reward. Functional magnetic resonance images were acquired in 24 older (60-78 years) and 24 young participants (20-28 years) while they performed an incentive delay task offering monetary or social rewards. Anticipation of either reward type recruited brain structures associated with reward, including the nucleus accumbens (NAcc). Region of interest analysis revealed an interaction effect of reward type and age group in the right NAcc: enhanced activation to cues of social reward was detected in the older subsample while enhanced activation to cues of monetary reward was detected in the younger subsample. Our results suggest that neural sensitivity to reward-predicting cues does not generally decrease with age. Rather, neural responses in the NAcc appear to be modulated by the type of reward, presumably reflecting age-related changes in motivational value attributed to different types of reward.

The impact of dopamine on aggression: an [18F]-FDOPA PET Study in healthy males.

Cerebral dopamine (DA) transmission is thought to be an important modulator for the development and occurrence of aggressive behavior. However, the link between aggression and DA transmission in humans has not been investigated using molecular imaging and standardized behavioral tasks. We investigated aggression as a function of DA transmission in a group of (N = 21) healthy male volunteers undergoing 6-[18F]-fluoro-l-DOPA (FDOPA)-positron emission tomography (PET) and a modified version of the Point Subtraction Aggression Paradigm (PSAP). This task measures aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tries to cheat. The participant can react in three ways (i.e., money substraction of the putative opponent [aggressive punishment], pressing a defense button, or continuing his money-making behavior). FDOPA-PET was analyzed using a steady-state model yielding estimates of the DA-synthesis capacity (K), the turnover of tracer DA formed in living brain (kloss), and the tracer distribution volume (Vd), which is an index of DA storage capacity. Significant negative correlations between PSAP aggressive responses and the DA-synthesis capacity were present in several regions, most prominently in the midbrain (r = −0.640; p = 0.002). Lower degrees of aggressive responses were associated with higher DA storage capacity in the striatum and midbrain. Additionally, there was a significant positive correlation between the investment into monetary incentive responses on the PSAP and DA-synthesis capacity, notably in the midbrain (r = +0.618, p = 0.003). The results suggest that individuals with low DA transmission capacity are more vulnerable to reactive/impulsive aggression in response to provocation.

Acute and sustained effects of methylphenidate on cognition and presynaptic dopamine metabolism: an [18F]FDOPA PET study.

Methylphenidate (MPH) inhibits the reuptake of dopamine and noradrenaline. PET studies with MPH challenge show increased competition at postsynaptic D2/3-receptors, thus indirectly revealing presynaptic dopamine release. We used [18F]fluorodopamine ([18F]FDOPA)-PET in conjunction with the inlet–outlet model (IOM) of Kumakura et al. (2007) to investigate acute and long-term changes in dopamine synthesis capacity and turnover in nigrostriatal fibers of healthy subjects with MPH challenge. Twenty healthy human females underwent two dynamic [18F]FDOPA PET scans (124 min; slow bolus-injection; arterial blood sampling), with one scan in untreated baseline condition and the other after MPH administration (0.5 mg/kg, p.o.), in randomized order. Subjects underwent cognitive testing at each PET session. Time activity curves were obtained for ventral putamen and caudate and were analyzed according to the IOM to obtain the regional net-uptake of [18F]FDOPA (K; dopamine synthesis capacity) as well as the [18F]fluorodopamine washout rate (kloss, index of dopamine turnover). MPH substantially decreased kloss in putamen (−22%; p = 0.003). In the reversed treatment order group (MPH/no drug), K was increased by 18% at no drug follow-up. The magnitude of K at the no drug baseline correlated with cognitive parameters. Furthermore, individual kloss changes correlated with altered cognitive performance under MPH. [18F]FDOPA PET in combination with the IOM detects an MPH-evoked decrease in striatal dopamine turnover, in accordance with the known acute pharmacodynamics of MPH. Furthermore, the scan-ordering effect on K suggested that a single MPH challenge persistently increased striatal dopamine synthesis capacity. Attenuation of dopamine turnover by MPH is linked to enhanced cognitive performance in healthy females.

Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers

BACKGROUND There is evidence of abnormal cerebral dopamine transmission in nicotine-dependent smokers, but it is unclear whether dopaminergic abnormalities are due to acute nicotine abuse or whether they persist with abstinence. We addressed this question by conducting longitudinal positron emission tomography (PET) examination of smokers before and after 3 months of abstinence. METHODS We obtained baseline 6-[(18)F]fluoro-L-DOPA (FDOPA)-PET scans in 15 nonsmokers and 30 nicotine-dependent smokers, who either smoked as per their usual habit or were in acute withdrawal. All smokers then underwent cessation treatment, and successful abstainers were re-examined by FDOPA-PET after 3 months of abstinence (n = 15). Uptake of FDOPA was analyzed using a steady-state model yielding estimates of the dopamine synthesis capacity (K); the turnover of tracer dopamine formed in living brain (kloss); and the tracer distribution volume (Vd), which is an index of dopamine storage capacity. RESULTS Compared with nonsmokers, K was 15% to 20% lower in the caudate nuclei of consuming smokers. Intraindividual comparisons of consumption and long-term abstinence revealed significant increases in K in the right dorsal and left ventral caudate nuclei. Relative to acute withdrawal, Vd significantly decreased in the right ventral and dorsal caudate after prolonged abstinence. Severity of nicotine dependence significantly correlated with dopamine synthesis capacity and dopamine turnover in the bilateral ventral putamen of consuming smokers. CONCLUSIONS The results suggest a lower dopamine synthesis capacity in nicotine-dependent smokers that appears to normalize with abstinence. Further investigations are needed to clarify the role of dopamine in nicotine addiction to help develop smoking prevention and cessation treatments.

Functional Polymorphism in the Neuropeptide Y Gene Promoter (rs16147) Is Associated with Serum Leptin Levels and Waist-Hip Ratio in Women

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. Method: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). Results: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. Conclusion: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.

Lack of Association of a Functional Catechol-O-Methyltransferase Gene Polymorphism With Risk of Tobacco Smoking: Results From a Multicenter Case–Control Study

BACKGROUND The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. METHODS In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior. RESULTS We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence. CONCLUSIONS Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.

Anticipation of Social and Monetary Rewards in Schizophrenia

Numerous behavioural and neuroimaging studies have explored human cognitive processing of various rewards, such as food, monetary or social stimuli. Previous studies with patients suffering from schizophrenia (SZ) used incentive delay tasks with monetary rewards. Apart from slower reaction times in general in SZ, there were no differences in task performance between patients with schizophrenia and healthy controls (HC). Patients with schizophrenia have impaired social functioning and thus may have a disturbed sensitivity to social rewards. 54 schizophrenia patients and 54 matched healthy controls completed a reward paradigm (incentive delay task) with monetary (MID) and social stimuli (SID). Reaction times and hit rates were analysed using a three-way repeated measures ANOVA. Patients demonstrated increased reaction times in both, the MID and the SID tasks compared to health controls. Hit rates for healthy controls significantly increased in the MID task, however these results were not found in the SID task with increasing reward level. In both tasks SZ improved their performance as rewards increased. The present findings suggest that patients with SZ are capable to anticipate monetary or social rewards and use this anticipation to guide their behaviour. Extrapolated to social functioning, the capability to anticipate potential reward could be used in therapeutic interventions.