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Cue-induced reward-seeking behaviors are regulated by both the affective and cognitive control systems of the brain. This study aimed at investigating how individual differences in affective and cognitive responses to cues predicting food rewards contribute to the regulation of cue-induced eating. We recorded electroencephalogram (EEG) from 59 adults while they viewed emotional and food-related images that preceded the delivery of food rewards (candies) or non-food objects (beads). We measured the amplitude of the late positive potential (LPP) in response to a variety of motivationally relevant images and power in the theta (4-8 Hz) frequency band after candies or beads were dispensed to the participants. We found that individuals with larger LPP responses to food images than to pleasant images (C>P group) ate significantly more during the experiment than those with the opposite response pattern (P>C group, p < 0.001). Furthermore, we found that individuals with higher theta power after dispensation of the candy than of the bead (θCA>θBE) ate significantly more than those with the opposite response pattern (θBE>θCA, p < 0.001). Finally, we found that the crossed P>C and θBE>θCA group ate less ( p < 0.001) than did the other three groups formed by crossing the LPP and theta group assignments, who exhibited similar eating behavior on average ( p = 0.662). These findings demonstrate that individual differences in both affective and cognitive responses to reward-related cues underlie vulnerability to cue-induced behaviors, underscoring the need for individualized treatments to mitigate maladaptive behaviors., Competing Interests: Declaration of Competing Interest The authors declare no conflicts.

Aberrant neuronal coding of reward processing has been linked to psychosis. It remains unresolved how treatment with a partial dopamine agonist affects reward processing, and whether treatment affects reward processing differently in patients responding and not responding to treatment. Here, 33 antipsychotic-naïve psychosis patients and 33 matched healthy controls underwent functional magnetic resonance imaging before and after patients received aripiprazole monotherapy for six weeks. Processing of motivational salient events and negative outcome evaluation (NOE) was examined using a monetary incentive delay task. Psychopathology was assessed with the Positive and Negative Syndrome Scale, and responders were identified by having ≥30% reduction in positive symptoms (N=21). At baseline, patients displayed an increased NOE signal in the caudate and dorsolateral prefrontal cortex compared to healthy controls. In the caudate, the NOE signal was normalized at follow-up, and normalization was driven by responders. In responders only, there was a significant improvement in the motivational salience signal in the caudate at follow-up. Motivational salience and NOE signals in the caudate may be associated with a dopaminergic mechanism in patients characterized as responders which may not be the case in non-responders. Likewise, non-dopaminergic mechanism may underly abnormal NOE processing in dorsolateral prefrontal cortex., Competing Interests: Declaration of Competing Interest Dr. Glenthøj has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) (January 2009 – December 2021), which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of and administered by the Mental Health Services in the Capital Region of Denmark. She has no other conflicts to disclose. Drs K Tangmose and KB Bojesen have received lecture fees from Lundbeck Pharma A/S. Drs Sigvard, Rostrup, and Nielsen have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and are paving the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that cannot optimally assess individual differences in the motivational salience of drug-related cues and in the ability to control drug-related decisions, choices which have hindered the identification of clinically relevant neuromarkers. Here, we show that once these shortcomings are amended, replicable neuromarkers of the tendency to attribute motivational salience to drug-related cues and the ability to control drug-related decisions emerge. While we use tobacco use disorder as a model, we also show that the methodological issues highlighted here are relevant to other disorders characterized by maladaptive appetitive behaviors., Competing Interests: Declarations of Interest: none

Background: We tested whether neuroaffective responses to motivationally salient stimuli are associated with vulnerability to cue-induced e-cigarette use in e-cigarette naïve adults who smoke daily. We hypothesized that individuals with stronger neuroaffective responses to nicotine-related cues than to pleasant stimuli (the C>P reactivity profile) would be more vulnerable to cue-induced nicotine self-administration than individuals with stronger neuroaffective responses to pleasant stimuli than to nicotine-related cues (the P>C reactivity profile)., Methods: We used event-related potentials (ERPs, a direct measure of cortical activity) to measure neuroaffective reactivity to pleasant, unpleasant, neutral, and nicotine-related cues indicating the opportunity to use an e-cigarette in 36 participants. For each picture category, we computed the amplitude of the late positive potential (LPP), a robust index of motivational salience. To identify each individual's neuroaffective reactivity profile we applied k-means cluster analysis on the LPP responses. We compared the e-cigarette use frequency across profiles using quantile regression for counts., Results: K-means cluster analysis assigned 18 participants to the C>P profile and 18 participants to the P>C profile. Individuals with the C>P neuroaffective profile used the e-cigarette significantly more often than those with the P>C profile. Significant differences in the number of puffs persisted across different quantiles., Conclusions: These results support the hypothesis that individual differences in the tendency to attribute motivational salience to drug-related cues underlie vulnerability to cue-induced drug self-administration. Targeting the neuroaffective profiles that we identified with tailored treatments could improve clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation. It remains unresolved, whether glutamatergic dysfunction is associated with the coding of motivational salience and outcome evaluation in antipsychotic-naïve patients with first-episode psychosis., Methods: Fifty-one antipsychotic-naïve patients with first-episode psychosis (22 ± 5.2 years, female/male: 31/20) and 52 healthy controls (HC) matched on age, sex, and parental education underwent functional magnetic resonance imaging and magnetic resonance spectroscopy (3T) in one session. Brain responses to motivational salience and negative outcome evaluation (NOE) were examined using a monetary incentive delay task. Glutamate levels were estimated in the left thalamus and anterior cingulate cortex using LCModel., Results: Patients displayed a positive signal change to NOE in the caudate ( p = 0.001) and dorsolateral prefrontal cortex (DLPFC; p = 0.003) compared to HC. No group difference was observed in motivational salience or in levels of glutamate. There was a different association between NOE signal in the caudate and DLPFC and thalamic glutamate levels in patients and HC due to a negative correlation in patients (caudate: p = 0.004, DLPFC: p = 0.005) that was not seen in HC., Conclusions: Our findings confirm prior findings of abnormal outcome evaluation as a part of the pathophysiology of schizophrenia. The results also suggest a possible link between thalamic glutamate and NOE signaling in patients with first-episode psychosis.

Background: Happiness is a feeling, an immediate experience, not a cognitive construct. It is based on activity in the brain's neurobiological reward and motivation systems, which have been retained in evolution. This conceptual review provides an overview of the basic neurobiological principles behind happiness phenomena and proposes a framework for further classification., Results: Three neurobiologically distinct types of happiness exist: (A) wanting, (B) avoiding, and (C) non-wanting. Behind these types lies a dynamic gradation, ranging from the more youthful anticipation, pleasure and ecstasy (A), to stress processing, escape and relief (B) as we find them accentuated in the middle-aged, to deep satisfaction, quiescence and inner joy (C), which is particularly attributed to older people. As a result, the development of happiness and satisfaction over the course of life typically takes the form of a U-curve., Discussion: The outlined triad and dynamic of happiness leads to the paradoxical finding that the elderly seem to be the happiest-a phenomenon that is termed "satisfaction paradox". This assumed change in happiness and contentment over the life span, which includes an increasing "emancipation" from the idea of good health as a mandatory prerequisite for happiness and contentment, can itself be changed-it is trainable., Conclusions: Programs for mindfulness, contemplation, or stress reduction, including positive psychology and mind-body/behavioral medicine training, seem to be capable of influencing the course happiness over time: Happiness can be shaped through practice.

Damage to regions underpinning attention can result in hemi-spatial neglect, characterised by inattention to stimuli presented in contralesional space. Motivationally salient stimuli (e.g. reward/threat) are, however, resilient to neglect and more likely to be detected compared to neutral stimuli. Prominent theories of attention suggest that the motivational detection advantage in neglect is underpinned by a goal-independent 'emotional attention' system. However, measures of stimulus awareness previously used often present the stimuli as part of the goal-relevant target set. Previous findings may therefore be more consistent with top-down attentional selection, which is preserved in some cases of neglect. Using multilevel and Bayesian meta-analytic approaches to individual case and group data, the evidence for a motivational detection advantage in neglect, and conditions when it emerges, were examined and conceptual claims reviewed. Cumulative evidence suggested that in perceptually simple conditions, when a single stimulus appeared, there was no evidence of a motivational detection advantage (Individual: k = 36; log OR = .02, 95%CI [-.44,.47]; Group: k = 2, d z  = .24, 95%CI [-.26, .74]). Conversely, under more perceptually demanding conditions, with multiple goal-relevant stimuli, motivationally salient stimuli were detected more than neutral stimuli in the contralesion side of space (Individual: k = 37, log OR = 1.04, 95%CI [.74, 1.34]; Group: k = 7, d z  = .81, 95%CI [.27, 1.35]). Across investigations the detection advantage occurred when the motivationally salient stimulus was a target, and under perceptually demanding conditions when goal-irrelevant motivationally salient stimuli are usually suppressed. The current evidence therefore does not strongly support a goal-independent mechanism, and a top-down account remains plausible. This account can be contextualised within existing models of neglect, whereby perceptual load induces suppression of contralesional space when ipsilesional space is prioritised. Target stimuli may, however, still be detected under reduced perceptual capacity due to their goal-relevance, which may be selectively enhanced by motivational salience., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Cognitive architectures tasked with swiftly and adaptively processing biologically important events are likely to classify these on two central axes: motivational salience, that is, those events' importance and unexpectedness, and motivational value, the utility they hold, relative to that expected. Because of its temporal precision, electroencephalography provides an opportunity to resolve processes associated with these two axes. A focus of attention for the last two decades has been the feedback-related negativity (FRN), a frontocentral component occurring 240-340 ms after valenced events that are not fully predicted. Both motivational salience and value are present in such events and competing claims have been made for which of these is encoded by the FRN. The present study suggests that motivational value, in the form of a reward prediction error, is the primary determinant of the FRN in active contexts, while in both passive and active contexts, a weaker and earlier overlapping motivational salience component may be present., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN DA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRN DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-fixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRN DA neurons encode motivational salience, dependent on internal and external factors. SIGNIFICANCE STATEMENT Dopamine (DA) contributes to motivational control, composed of at least two functional cell types, one signaling for motivational value and another for motivational salience. Here, we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal's internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Additional experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRN DA populations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience., (Copyright © 2021 the authors.)

Animals rely on internal motivational states to make decisions. The role of motivational salience in decision making is in early stages of mathematical understanding. Here, we propose a reinforcement learning framework that relies on neural networks to learn optimal ongoing behavior for dynamically changing motivation values. First, we show that neural networks implementing Q-learning with motivational salience can navigate in environment with dynamic rewards without adjustments in synaptic strengths when the needs of an agent shift. In this setting, our networks may display elements of addictive behaviors. Second, we use a similar framework in hierarchical manager-agent system to implement a reinforcement learning algorithm with motivation that both infers motivational states and behaves. Finally, we show that, when trained in the Pavlovian conditioning setting, the responses of the neurons in our model resemble previously published neuronal recordings in the ventral pallidum, a basal ganglia structure involved in motivated behaviors. We conclude that motivation allows Q-learning networks to quickly adapt their behavior to conditions when expected reward is modulated by agent's dynamic needs. Our approach addresses the algorithmic rationale of motivation and makes a step toward better interpretability of behavioral data via inference of motivational dynamics in the brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shuvaev, Tran, Stephenson-Jones, Li and Koulakov.)

The allocation of attention can be modulated by the emotional value of a stimulus. In order to understand the biasing influence of emotion on attention allocation further, we require an animal test of how motivational salience modulates attention. In mice, female odour triggers arousal and elicits emotional responses in males. Here, we determined the extent to which objects labelled with female odour modulated the attention of C57BL/6J male mice. Seven experiments were conducted, using a modified version of the spontaneous Novel Object Recognition task. Attention was operationalised as differential exploration time of identical objects that were labelled with either female mouse odour (O+), a non-social odour, almond odour (O a ) or not labelled with any odour (O-). In some experiments we tested trial unique (novel) objects than never carried an odour (X-). Using this novel object preference test we found that when single objects were presented, as well as when two objects were presented simultaneously (so competed with each other for attention), O+ received preferential attention compared to O-. This result was independent of whether O+ was at a novel or familiar location. When compared with O a at a novel location, O+ at a familiar location attracted more attention. Compared to X-, O+ received more exploration only when placed at a novel location, but attention to O+ and X- was equivalent when they were placed in a familiar location. These results suggest that C57BL/6J male mice weigh up aspects of odour, object novelty and special novelty for motivational salience, and that, in some instances, female odour elicits more attention (object exploration) compared to other object properties. The findings of this study pave the way to using motivationally-significant odours to modulate the cognitive processes that give rise to differential attention to objects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

There is sufficient evidence to believe that variations in the error-related negativity (ERN) are linked to dispositional characteristics in individuals. However, explanations of individual differences in the amplitude of the ERN cannot be derived from functional theories of the ERN. The ERN has a counterpart that occurs after correct responses (correct-response negativity, CRN). Based on the assumption that ERN and CRN reflect an identical cognitive process, variations in CRN might be associated with dispositional characteristics as well. Higher CRN amplitudes have been found to reflect task engagement. In the present study, a simple-choice-reaction task was used to investigate ERN and CRN amplitudes in relation to their score on a conscientiousness scale. The task consisted of a simple rule that required pressing the left or right key when a circle or square appeared, respectively. During alternative conditions that occur infrequently, participants were instructed to violate or reverse the previously established response rules. Smaller ΔERN amplitudes (manifested in almost equal CRN and ERN amplitudes) and a tendency of better task performance from participants scoring high on the conscientiousness scale might indicate a greater focus on the task and higher motivation of responding correctly. In addition, higher Pc amplitudes directly following the CRN indicated that the response monitoring system of less conscientious participants showed a higher disengagement. The role of individual differences in CRN amplitude should be studied in future experiments on performance monitoring.

It has been shown that when incentives are provided during movement preparation, activity in parieto-frontal regions reflects both expected value and motivational salience. Yet behavioral work suggests that the processing of rewards is faster than for punishments, raising the possibility that expected value and motivational salience manifest at different latencies during movement planning. Given the role of beta oscillations (13-30 Hz) in movement preparation and in communication within the reward circuit, this study investigated how beta activity is modulated by positive and negative monetary incentives during reach planning, and in particular whether it reflects expected value and motivational salience at different latencies. Electroencephalography was recorded while male and female humans performed a reaching task in which reward or punishment delivery depended on movement accuracy. Before a preparatory delay period, participants were informed of the consequences of hitting or missing the target, according to four experimental conditions: Neutral (hit/miss:+0/-0¢), Reward (hit/miss:+5/-0¢), Punish (hit/miss:+0/-5¢) and Mixed (hit/miss:+5/-5¢). Results revealed that beta power over parieto-frontal regions was strongly modulated by incentives during the delay period, with power positively correlating with movement times. Interestingly, beta power was selectively sensitive to potential rewards early in the delay period, after which it came to reflect motivational salience as movement onset neared. These results demonstrate that beta activity reflects expected value and motivational salience on different time scales during reach planning. They also provide support for models that link beta activity with basal ganglia and dopamine for the allocation of neural resources according to behavioral salience. SIGNIFICANCE STATEMENT The present work demonstrates that pre-movement parieto-frontal beta power is modulated by monetary incentives in a goal-directed reaching task. Specifically, beta power transiently scaled with the availability of rewards early in movement planning, before reflecting motivational salience as movement onset neared. Moreover, pre-movement beta activity correlated with the vigor of the upcoming movement. These findings suggest that beta oscillations reflect neural processes that mediate the invigorating effect of incentives on motor performance, possibly through dopamine-mediated interactions with the basal ganglia., (Copyright © 2019 the authors.)

The present study aimed at investigating whether associated motivational salience causes preferential processing of inherently neutral faces similar to emotional expressions by means of event-related brain potentials (ERPs) and changes of the pupil size. To this aim, neutral faces were implicitly associated with monetary outcome, while participants (N = 44) performed a face-matching task with masked primes that ensured performance around chance level and thus an equal proportion of gain, loss, and zero outcomes. During learning, motivational context strongly impacted the processing of the fixation, prime and mask stimuli prior to the target face, indicated by enhanced amplitudes of subsequent ERP components and increased pupil size. In a separate test session, previously associated faces as well as novel faces with emotional expressions were presented within the same task but without motivational context and performance feedback. Most importantly, previously gain-associated faces amplified the LPC, although the individually contingent face-outcome assignments were not made explicit during the learning session. Emotional expressions impacted the N170 and EPN components. Modulations of the pupil size were absent in both motivationally-associated and emotional conditions. Our findings demonstrate that neural representations of neutral stimuli can acquire increased salience via implicit learning, with an advantage for gain over loss associations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Deficits of cognitive functions and motivation are core aspects of schizophrenia. The interaction of these deficits might contribute to impair the ability to flexibly adjust behavior in accordance with one's intentions and goals. Many studies have focused on the anterior N2 as a correlate of cognitive control based on motivational value., Aims: Given the key role of motivation impairment in schizophrenia as a predictor of functional outcome, we aimed to study the impact of reward- and avoidance-based motivation on cognitive control using N2., Method: Event-related potentials were recorded during the execution of the "Monetary Incentive Delay (MID)" task in 34 patients with schizophrenia (SCZ) stabilized on second-generation antipsychotics and 22 healthy controls (HC). Cognitive domains were assessed using the MATRICS Consensus Cognitive Battery. Negative symptom domains (Avolition/apathy and Expressive deficit), as well as positive and disorganization dimensions were also assessed in SCZ., Results: We did not observe any group difference in N2 amplitude or latency. In HC, N2 amplitude was significantly larger for anticipation of large loss with regard to all reward conditions and for all incentive versus neutral conditions. In SCZ, N2 amplitude did not discriminate between large loss and reward or between incentive and neutral conditions. N2 amplitude was not correlated with psychopathological dimensions or MCCB-assessed cognitive deficits in SCZ., Conclusion: Our data in HC are in line with the hypothesis that N2 amplitude reflects the impact of motivational salience on cognitive control. Our results in SCZ indicate a deficit in the discrimination of motivational salience to the service of cognitive control, independently of psychopathology and other cognitive deficits.

The aim of the study was to investigate the efficiency of the use of response-contingent feedback in adolescents with and without developmental language disorder (DLD) by using the balloon analogue risk task (BART). The BIS/BAS scales were also used to evaluate a participant's responses to reward- or punishment-related events in everyday situations. The results showed that adolescents with DLD performed on the BART at a suboptimal level due to inefficient use of response-contingent feedback. Findings of the BIS/BAS scales also generate a possible hypothesis of reduced motivational salience for larger monetary outcomes in DLD. Given that dopamine plays an important role in modulating BART responding through the corticostriatal pathways, these behavioral findings implicate an association between dopamine and individual differences in language, including DLD. Future studies are needed to directly test whether people with DLD have reduced level of dopamine in striatal neural synapses, leading to dopamine-dependent learning difficulty., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Facial expressions of emotion have an undeniable processing advantage over neutral faces, discernible both at behavioral level and in emotion-related modulations of several event-related potentials (ERPs). Recently it was proposed that also inherently neutral stimuli might gain salience through associative learning mechanisms. The present study investigated whether acquired motivational salience leads to processing advantages similar to biologically determined origins of inherent emotional salience by applying an associative learning paradigm to human face processing. Participants (N=24) were trained to categorize neutral faces to salience categories by receiving different monetary outcomes. ERPs were recorded in a subsequent test phase consisting of gender decisions on previously associated faces, as well as on familiarized and novel faces expressing happy, angry or no emotion. Previously reward-associated faces boosted the P1 component, indicating that acquired reward-associations modulate early sensory processing in extrastriate visual cortex. However, ERP modulations to emotional - primarily angry - expressions expanded to subsequent processing stages, as reflected in well-established emotion-related ERPs. The present study offers new evidence that motivational salience associated to inherently neutral stimuli can sharpen sensory encoding but does not obligatorily lead to preferential processing at later stages., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate the behavioral role of the cotransmission, we targeted the glutamate-recycling enzyme glutaminase (gene Gls1 ). In mice with a dopamine transporter ( Slc6a3 )-driven conditional heterozygous (cHET) reduction of Gls1 in their dopamine neurons, dopamine neuron survival and transmission were unaffected, while glutamate cotransmission at phasic firing frequencies was reduced, enabling a selective focus on the cotransmission. The mice showed normal emotional and motor behaviors, and an unaffected response to acute amphetamine. Strikingly, amphetamine sensitization was reduced and latent inhibition potentiated. These behavioral effects, also seen in global GLS1 HETs with a schizophrenia resilience phenotype, were not seen in mice with an Emx1 -driven forebrain reduction affecting most brain glutamatergic neurons. Thus, a reduction in dopamine neuron glutamate cotransmission appears to mediate significant components of the GLS1 HET schizophrenia resilience phenotype, and glutamate cotransmission appears to be important in attribution of motivational salience.

Background: Impairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis., Method: A total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features., Results: At presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features., Conclusions: These findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing.

The study of food aversion in humans by the induction of illness is ethically unthinkable, and it is difficult to propose a type of food that is disgusting for everybody. However, although cheese is considered edible by most people, it can also be perceived as particularly disgusting to some individuals. As such, the perception of cheese constitutes a good model to study the cerebral processes of food disgust and aversion. In this study, we show that a higher percentage of people are disgusted by cheese than by other types of food. Functional magnetic resonance imaging then reveals that the internal and external globus pallidus and the substantia nigra belonging to the basal ganglia are more activated in participants who dislike or diswant to eat cheese (Anti) than in other participants who like to eat cheese, as revealed following stimulation with cheese odors and pictures. We suggest that the aforementioned basal ganglia structures commonly involved in reward are also involved in the aversive motivated behaviors. Our results further show that the ventral pallidum, a core structure of the reward circuit, is deactivated in Anti subjects stimulated by cheese in the wanting task, highlighting the suppression of motivation-related activation in subjects disgusted by cheese.

Rationale: Drug-associated cues exposure to induce extinction is a useful strategy to contrast cue-induced drug seeking. Treatments aimed at reducing motivational properties of cues are considered highly promising since they could decrease their ability to induce drug-conditioned behaviors. Norepinephrine (NE) in the medial prefrontal cortex (mPFC) is critical for attribution of motivational salience to highly salient stimuli, suggesting a major role in prelimbic (PL) mpFC to modulate the motivational properties of drug-related cues, invigorating them, and consequently, delaying extinction., Objectives: To investigate if NE in PL fosters the maintenance of drug-seeking behavior, we assessed its role on amphetamine-induced conditioned place preference (CPP). Moreover, to affirm the specificity of NE in PL, we also assessed the role of NE in the infralimbic (IL) mPFC., Methods: The effects of selective NE depletion in the PL or in the IL of C57BL/6J mice were assessed on the expression of amphetamine-induced CPP before and after extinction procedure., Results: NE-depleted mice in PL extinguished preference for Amph-paired chamber long before sham animals. By contrast, IL-depleted animals maintained place preference for more than 4 weeks after the procedure of extinction, having at that moment interrupted the test., Conclusions: Inactivation of NE in PL cortex blunts amphetamine-induced CPP, thus fostering extinction and showing to be critical for the maintenance of conditioned Amph-seeking behavior. Opposite effects of NE depletion in IL, seemingly in agreement with literature on extinction, are discussed in terms of balance of activity between PL and IL in extinction.

The basal forebrain (BF) houses major ascending projections to the entire neocortex that have long been implicated in arousal, learning, and attention. The disruption of the BF has been linked with major neurological disorders, such as coma and Alzheimer's disease, as well as in normal cognitive aging. Although it is best known for its cholinergic neurons, the BF is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific BF cell types have led to a renaissance in the study of the BF and are beginning to yield new insights about cell-type-specific circuit mechanisms during behavior. These approaches enable us to determine the behavioral conditions under which cholinergic and noncholinergic BF neurons are activated and how they control cortical processing to influence behavior. Here we discuss recent advances that have expanded our knowledge about this poorly understood brain region and laid the foundation for future cell-type-specific manipulations to modulate arousal, attention, and cortical plasticity in neurological disorders., Significance Statement: Although the basal forebrain is best known for, and often equated with, acetylcholine-containing neurons that provide most of the cholinergic innervation of the neocortex, it is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific cell types in the basal forebrain have led to a renaissance in this field and are beginning to dissect circuit mechanisms in the basal forebrain during behavior. This review discusses recent advances in the roles of basal forebrain cholinergic and noncholinergic neurons in cognition via their dynamic modulation of cortical activity., (Copyright © 2015 the authors 0270-6474/15/3513896-08$15.00/0.)

Testosterone enhances amygdala reactions to social threat, but it remains unclear whether this neuroendocrine mechanism is relevant for understanding its dominance-enhancing properties; namely, whether testosterone biases the human amygdala toward threat approach. This pharmacological functional magnetic-resonance imaging study shows that testosterone administration increases amygdala responses in healthy women during threat approach and decreases it during threat avoidance. These findings support and extend motivational salience models by offering a neuroendocrine mechanism of motivation-specific amygdala tuning.

The factors that contribute to individual differences in the reward value of cute infant facial characteristics are poorly understood. Here we show that the effect of cuteness on a behavioural measure of the reward value of infant faces is greater among women reporting strong maternal tendencies. By contrast, maternal tendencies did not predict women's subjective ratings of the cuteness of these infant faces. These results show, for the first time, that the reward value of infant facial cuteness is greater among women who report being more interested in interacting with infants, implicating maternal tendencies in individual differences in the reward value of infant cuteness. Moreover, our results indicate that the relationship between maternal tendencies and the reward value of infant facial cuteness is not due to individual differences in women's ability to detect infant cuteness. This latter result suggests that individual differences in the reward value of infant cuteness are not simply a by-product of low-cost, functionless biases in the visual system., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Previous work demonstrated age-associated increases in the anterior P2 and age-related decreases in the anterior N2 in response to novel stimuli. Principal component analysis (PCA) was used to determine if the inverse relationship between these components was due to their temporal and spatial overlap. PCA revealed an early anterior P2, sensitive to task relevance, and a late anterior P2, responsive to novelty, both exhibiting age-related amplitude increases. A PCA factor representing the anterior N2, sensitive to novelty, exhibited age-related amplitude decreases. The late P2 and N2 to novels inversely correlated. Larger late P2 amplitude to novels was associated with better behavioral performance. Age-related differences in the anterior P2 and N2 to novel stimuli likely represent age-associated changes in independent cognitive operations. Enhanced anterior P2 activity (indexing augmentation in motivational salience) may be a compensatory mechanism for diminished anterior N2 activity (indexing reduced ability of older adults to process ambiguous representations)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Basal forebrain (BF) is one of the largest cortically-projecting neuromodulatory systems in the mammalian brain, and plays a key role in attention, arousal, learning and memory. The cortically projecting BF neurons, comprised of mainly magnocellular cholinergic and GABAergic neurons, are widely distributed across several brain regions that spatially overlap with the ventral striatopallidal system at the ventral pallidum (VP). As a first step toward untangling the respective functions of spatially overlapping BF and VP systems, the goal of this study was to comprehensively characterize the behavioral correlates and physiological properties of heterogeneous neuronal populations in the BF region. We found that, while rats performed a reward-biased simple reaction time task, distinct neuronal populations encode either motivational salience or movement information. The motivational salience of attended stimuli is encoded by phasic bursting activity of a large population of slow-firing neurons that have large, broad, and complex action potential waveforms. In contrast, two other separate groups of neurons encode movement-related information, and respectively increase and decrease firing rates while rats maintained fixation. These two groups of neurons mostly have higher firing rates and small, narrow action potential waveforms. These results support the conclusion that multiple neurophysiologically distinct neuronal populations in the BF region operate independently of each other as parallel functional circuits. These observations also caution against interpreting neuronal activity in this region as a homogeneous population reflecting the function of either BF or VP alone. We suggest that salience- and movement-related neuronal populations likely correspond to BF corticopetal neurons and VP neurons, respectively.

Facial attractiveness provides a very powerful motivation for sexual and parental behavior. We therefore review the importance of faces to the study of neurobiological control of human reproductive motivations. For heterosexual individuals there is a common brain circuit involving the nucleus accumbens, the medial prefrontal, dorsal anterior cingulate and the orbitofrontal cortices that is activated more by attractive than unattractive faces, particularly for faces of the opposite sex. Behavioral studies indicate parallel effects of attractiveness on incentive salience or willingness to work to see faces. There is some evidence that the reward value of opposite sex attractiveness is more pronounced in men than women, perhaps reflecting the greater importance assigned to physical attractiveness by men when evaluating a potential mate. Sex differences and similarities in response to facial attractiveness are reviewed. Studies comparing heterosexual and homosexual observers indicate the orbitofrontal cortex and mediodorsal thalamus are more activated by faces of the desired sex than faces of the less-preferred sex, independent of observer gender or sexual orientation. Infant faces activate brain regions that partially overlap with those responsive to adult faces. Infant faces provide a powerful stimulus, which also elicits sex differences in behavior and brain responses that appear dependent on sex hormones. There are many facial dimensions affecting perceptions of attractiveness that remain unexplored in neuroimaging, and we conclude by suggesting that future studies combining parametric manipulation of face images, brain imaging, hormone assays and genetic polymorphisms in receptor sensitivity are needed to understand the neural and hormonal mechanisms underlying reproductive drives., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5-10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001.