Katja N. Spreckelmeyer

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.

Oxytocin plasma concentrations after single intranasal oxytocin administration – A study in healthy men

The neuropeptide oxytocin has become a subject of great interest in studies investigating human social cognition. Single intranasal administration of the hormone has been reported to have positive behavioral effects, such as increasing trust or facilitating social approach, 45-80 min after administration. However, little is still known about the long-term pharmacokinetics of oxytocin nasal spray application in humans. This study addressed the question how long oxytocin plasma levels remain elevated following nasal spray administration. Another goal was to examine the influence of oxytocin administration on endogenous steroid hormones since such alterations might modulate social behavior via an indirect way. Eight healthy Caucasian men were challenged with a single intranasal application of 26 international units of oxytocin. Changes in oxytocin blood plasma levels, as well as steroid hormone levels of progesterone, testosterone and estradiol were assessed at 5 consecutive time points over a period of 3.5 h (-5, +30, +90, +150, +210 min relative to oxytocin administration). Results gave evidence for a substantial rise of oxytocin plasma levels 30 min after intranasal administration, observed in 7 of 8 participants. Group mean oxytocin plasma level was found to have returned to baseline already 90 min post administration, though in some individuals the plasma levels was still elevated relative to sampling at post 150 min. Steroid hormone analyses yielded a slight augmentation of endogenous testosterone levels 210 min after oxytocin administration. Our data confirms previous findings that oxytocin administered as a nasal spray enters the blood circulation, elevating oxytocin plasma levels for a limited time. Our findings suggest that this time window differs between individuals, but that, for the used dose, it does not extend beyond 150 min post administration. The data further provides preliminary evidence that intranasal oxytocin has an enhancing effect on testosterone in healthy men.

Combined perception of emotion in pictures and musical sounds

Evaluation of emotional scenes requires integration of information from different modality channels, most frequently from audition and vision. Neither the psychological nor neural basis of auditory-visual interactions during the processing of affect is well understood. In this study, possible interactions in affective processing were investigated via event-related potential (ERP) recordings during simultaneous presentation of affective pictures (from IAPS) and affectively sung notes that either matched or mismatched each other in valence. To examine the role of attention in multisensory affect-integration ERPs were recorded in two different rating tasks (voice affect rating, picture affect rating) as participants evaluated the affect communicated in one of the modalities, while that in the other modality was ignored. Both the behavioral and ERP data revealed some, although non-identical, patterns of cross-modal influences; modulation of the ERP-component P2 suggested a relatively early integration of affective information in the attended picture condition, though only for happy picture-voice pairs. In addition, congruent pairing of sad pictures and sad voice stimuli affected the late positive potential (LPP). Responses in the voice affect rating task were overall more likely to be modulated by the concomitant pictures affective valence than vice versa.

Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating

Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition—an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential. Although sensorimotor gating and sensory gating are not identical, recent data suggest that they share genetic fundamentals. In a multicenter study at six academic institutions throughout Germany, we applied an auditory P50 suppression paradigm to 1,821 subjects (1,023 never-smokers, 798 smokers) randomly selected from the general population. Samples were genotyped for 21 TCF4 polymorphisms. Given that smoking is highly prevalent in schizophrenia and affects sensory gating, we also assessed smoking behavior, cotinine plasma concentrations, exhaled carbon monoxide, and the Fagerström Test (FTND). P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002–0.00005). These gene effects were modulated by smoking behavior as indicated by significant interactions of TCF4 genotype and smoking status; heavy smokers (FTND score ≥4) showed stronger gene effects on P50 suppression than light smokers and never-smokers. Our finding suggests that sensory gating is modulated by an interaction of TCF4 genotype with smoking, and both factors may play a role in early information processing deficits also in schizophrenia. Consequently, considering smoking behavior may facilitate the search for genetic risk factors for schizophrenia.

Neural processing of vocal emotion and identity

The voice is a marker of a persons identity which allows individual recognition even if the person is not in sight. Listening to a voice also affords inferences about the speakers emotional state. Both these types of personal information are encoded in characteristic acoustic feature patterns analyzed within the auditory cortex. In the present study 16 volunteers listened to pairs of non-verbal voice stimuli with happy or sad valence in two different task conditions while event-related brain potentials (ERPs) were recorded. In an emotion matching task, participants indicated whether the expressed emotion of a target voice was congruent or incongruent with that of a (preceding) prime voice. In an identity matching task, participants indicated whether or not the prime and target voice belonged to the same person. Effects based on emotion expressed occurred earlier than those based on voice identity. Specifically, P2 (approximately 200 ms)-amplitudes were reduced for happy voices when primed by happy voices. Identity match effects, by contrast, did not start until around 300 ms. These results show an early task-specific emotion-based influence on the early stages of auditory sensory processing.

Neurocognitive impairments in non‐deprived smokers—results from a population‐based multi‐center study on smoking‐related behavior

The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never‐smoking controls) participated in a population‐based case‐control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P < 0.001) and cognitive impulsivity (P < 0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop‐interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack‐years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non‐deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.

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 P300 event-related potential and smoking--a population-based case-control study.

A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case-control study N=1318 participants (smokers and never-smoking controls) were investigated at 6 German academic institutions. Study participants were randomly selected from the general population. Subjects with mental disorders including alcoholism and drug abuse were excluded. The main outcome measure was the P300 global field power (GFP). We found a lower P300 GFP in current smokers compared to never-smoking controls. Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found. Non-addicted smokers exhibited normal P300 ERP measures. This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity. Thus, P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers. Our results provide the phenotypical groundwork for future multidimensional analyses of genotype-phenotype relationships in the field of smoking and nicotine dependence.