Early and late contingent negative variation (CNV) reflect different aspects of deficits in schizophrenia.

Abnormal reward processing and psychomotor slowing are well-known in schizophrenia (SZ). As a slow frontocentral potential, contingent negative variation (CNV) is associated with anticipatory attention, motivation and motor planning. The present study aims to evaluate the early and late amplitude and latencies of CNV in patients with SZ compared to healthy controls during a reward processing task and to show its association with clinical symptoms. We recruited 21 patients with SZ and 22 healthy controls to compare early and late CNV amplitude and latency values during a Monetary Incentive Delay (MID) Task between groups. Patients' symptom severity, levels of negative symptoms and depressive symptoms were assessed. Clinical features of the patients were further examined for their relation with CNV components. In conclusion, we found decreased early CNV amplitudes in SZ during the reward condition. They also displayed diminished and shortened late CNV responses for incentive cues, specifically at the central location. Furthermore, early CNV amplitudes exhibited a significant correlation with positive symptoms. Both CNV latencies were linked with medication dosage and the behavioural outcomes of the MID task. We revealed that early and late CNV exhibit different functions in neurophysiology and correspond to various facets of the deficits observed in patients. Our findings also emphasized that slow cortical potentials are indicative of deficient motivational processes as well as impaired reaction preparation in SZ. To gain a deeper understanding of the cognitive and motor impairments associated with psychosis, future studies must compare the effects of CNV in the early and late phases.

Dynamic threat-reward neural processing under semi-naturalistic ecologically relevant scenarios.

Studies of affective neuroscience have typically employed highly controlled, static experimental paradigms to investigate the neural underpinnings of threat and reward processing in the brain. Yet our knowledge of affective processing in more naturalistic settings remains limited. Specifically, affective studies generally examine threat and reward features separately and under brief time periods, despite the fact that in nature organisms are often exposed to the simultaneous presence of threat and reward features for extended periods. To study the neural mechanisms of threat and reward processing under distinct temporal profiles, we created a modified version of the PACMAN game that included these environmental features. We also conducted two automated meta-analyses to compare the findings from our semi-naturalistic paradigm to those from more constrained experiments. Overall, our results revealed a distributed system of regions sensitive to threat imminence and a less distributed system related to reward imminence, both of which exhibited overlap yet neither of which involved the amygdala. Additionally, these systems broadly overlapped with corresponding meta-analyses, with the notable absence of the amygdala in our findings. Together, these findings suggest a shared system for salience processing that reveals a heightened sensitivity toward environmental threats compared to rewards when both are simultaneously present in an environment. The broad correspondence of our findings to meta-analyses, consisting of more tightly controlled paradigms, illustrates how semi-naturalistic studies can corroborate previous findings in the literature while also potentially uncovering novel mechanisms resulting from the nuances and contexts that manifest in such dynamic environments.

Higher-order comparative reward processing is affected by noninvasive stimulation of the ventromedial prefrontal cortex.

A crucial skill, especially in rapidly changing environments, is to be able to learn efficiently from prior rewards or losses and apply this acquired knowledge in upcoming situations. Often, we must weigh the risks of different options and decide whether an option is worth the risk or whether we should choose a safer option. The ventromedial prefrontal cortex (vmPFC) is suggested as a major hub for basic but also higher-order reward processing. Dysfunction in this region has been linked to cognitive risk factors for depression and behavioral addictions, including reduced optimism and feedback learning. Here, we test whether modulations of vmPFC excitability via noninvasive transcranial direct current stimulation (tDCS) can alter reward anticipation and reward processing. In a financial gambling task, participants chose between a higher and a lower monetary risk option and eventually received feedback whether they won or lost. Simultaneously feedback on the unchosen option was presented as well. Behavioral and magnetoencephalographic correlates of reward processing were evaluated in direct succession of either excitatory or inhibitory tDCS of the vmPFC. We were able to show modulated reward approach behavior (expectancy of greater reward magnitudes) as well as altered reevaluation of received feedback by vmPFC tDCS as indicated by modified choice behavior following the feedback. Thereby, tDCS not only influenced early, rather basic reward processing, but it also modulated higher-order comparative feedback evaluation of gains and losses relative to alternative outcomes. The neural results underline this idea, as stimulation-driven modulations of the basic reward-related effect occurred at rather early time intervals and were followed by stimulation effects related to comparative reward processing. Importantly, behavioral ratings were correlated with neural activity in left frontal areas. Our results imply a dual function of the vmPFC consisting of approaching reward (as indicated by more risky choices) and elaborately evaluating outcomes. In addition, our data suggest that vmPFC activity is associated with adaptive decision-making in the future via modulated behavioral adaptation or reinforcement learning.

Effort-based decision-making in ultra-high-risk for psychosis and bipolar disorder.

BACKGROUND: Effort-based decision-making has been proposed as a potential mechanism contributing to transdiagnostic motivational deficits in psychotic disorder and bipolar disorder. However, very limited information is available about deficits in effort-cost-decision-making in the early stages of psychotic disorder and no study has investigated effort allocation deficits before the onset of bipolar disorder. Our aim was to investigate effort-based-decision-making in ultra-high-risk for psychosis (UHR-P) and bipolar disorder (UHR-BD). METHODS: Effort-cost decision-making performance was evaluated in UHR-P (n = 72) and UHR-BD (n = 68) and healthy controls (n = 38). Effort-Expenditure for Reward Task (EEfRT) was used. RESULTS: Compared to controls, both UHR-P and UHR-BD groups were associated with a reduced possibility to choose the harder task when the reward magnitudes and/or the likelihood of receiving the reward were high. In both groups, effort allocation abnormalities were associated with poor social functioning. CONCLUSIONS: The current findings suggest that difficulties in effort-cost computation are transdiagnostic markers of illness liability in psychotic and bipolar disorders. In early intervention services, effort-based decision-making abnormalities should be considered as a target for interventions to manage motivational deficits in individuals at high risk for psychosis and BD.

Reciprocal relationships between stress and depressive symptoms: the essential role of the nucleus accumbens.

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms. METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes. RESULTS: Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = -0.032 to -0.023, p = 0.006-0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7-14.3%, p < 0.001-p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10-5) in participants with high v. no SLEs. CONCLUSIONS: The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.

Exploring decision-making performance in young adults with mental health disorders: a comparative study using the Cambridge gambling task.

Decision-making deficits, assessed cognitively, are often associated with mental health symptoms, however, this relationship is not fully understood. This paper explores the relationship between mental health disorders and decision-making, using the Cambridge Gambling Task (CGT). Our study investigated how decision-making varied across 20 different mental health conditions compared to controls in a sample of 572 young adults from the Minneapolis and Chicago metropolitan areas, using a computerized laboratory-based task. Almost all mental health conditions were associated with at least mild (i.e. at least small effect size) impairment in all three studied parameters of the CGT (risk adjustment, quality of decision-making and overall proportion of bet). Notably, binge eating disorder had the largest cognitive impairment and gambling disorder had moderate impairment. Post-traumatic stress disorder (PTSD) was associated with impaired decision-making while obsessive-compulsive disorder (OCD) and depression showed moderate impairment. Additionally, half of the disorders assessed had moderate to large impairment in risk adjustment.These findings suggest that mental health conditions may have a more complex cognitive profile than previously thought, and a better understanding of these impairments may aid in risk assessment and targeted clinical interventions. This study underscores the need for further research to determine the causal pathways between mental health conditions and cognition, as well as to better understand the day-to-day impact of such deficits.

Reduced Reward Processing in Schizophrenia: A Comprehensive EEG Event-Related Oscillation Study.

It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia (SZ). Reduced reward anticipation has been suggested as a core symptom of SZ. The present study aims to evaluate the event-related oscillations (EROs) delta, theta, alpha, beta, and gamma in patients with SZ during the Monetary Incentive Delay (MID) task, which elicits the neural activity of reward processing. Twenty-one patients with SZ and twenty-two demographically matched healthy controls were included in the study. EROs were compared between groups and correlation analyses were conducted to determine a possible relationship between clinical scores and ERO values. Compared with healthy controls, the SZ group had reduced (1) delta and theta amplitudes in the reward condition (2) total beta and non-incentive cue-related beta amplitudes, and (3) incentive cue-related frontal gamma amplitudes. These reductions can be interpreted as impaired dopaminergic neurotransmission and disrupted cognitive functioning in the reward processing of SZ. In contrast, SZ patients showed higher incentive cue-related theta and occipital gamma amplitudes compared to controls. These increments may reflect negative symptoms in SZ. Moreover, theta amplitudes showed a negative correlation with Calgary Depression Scale for Schizophrenia scores and a positive correlation with attentional impulsivity. This is the first study showing the impairments of SZ patients in EROs from delta to gamma frequency bands compared with healthy controls during reward anticipation. Being the first comprehensive study, our results can be interpreted as providing evidence for disrupted brain dynamics in the reward processing of SZ studied by EROs. It may become possible to help patients' wellness by improving our understanding of reward processing in schizophrenia and developing innovative rehabilitation treatments based on these findings.

Why creatives don't find the oddball odd: Neural and psychological evidence for atypical salience processing.

Creativity has previously been linked with various attentional phenomena, including unfocused or broad attention. Although this has typically been interpreted through an executive functioning framework, such phenomena may also arise from atypical incentive salience processing. Across two studies, we examine this hypothesis both neurally and psychologically. First we examine the relationship between figural creativity and event-related potentials during an audio-visual oddball task, finding that rater creativity of drawings is associated with a diminished P300 response at midline electrodes, while abstractness and elaborateness of the drawings is associated with an altered distribution of the P300 over posterior electrodes. These findings support the notion that creativity may involve an atypical attribution of salience to prominent information. We further explore the incentive salience hypothesis by examining relationships between creativity and a psychological indicator of incentive salience captured by participants' ratings of enjoyment (liking) and their motivation to pursue (wanting) diverse real world rewards, as well as their positive spontaneous thoughts about those rewards. Here we find enhanced motivation to pursue activities as well as a reduced relationship between the overall tendency to enjoy rewards and the tendency to pursue them. Collectively, these findings indicate that creativity may be associated with atypical allocation of attentional and motivational resources to novel and rewarding information, potentially allowing more types of information access to attentional resources and motivating more diverse behaviors. We discuss the possibility that salience attribution in creatives may be less dependent on task-relevance or hedonic pleasure, and suggest that atypical salience attribution may represent a trait-like feature of creativity.

Change in brain activation after transcranial pulsed electromagnetic fields in treatment-resistant depression.

BACKGROUND: Preliminary evidence suggests antidepressant effects of transcranial pulsed electromagnetic fields (tPEMF). However, the precise mechanism of action in the brain is still unknown. The aim of this study was to investigate the influence of tPEMF on brain activation in patients with treatment-resistant depression (TRD) by studying two processes that might be of particular interest in relation to the symptoms of depression: emotional processing and reward processing. METHODS: Eligible participants (n = 50) with TRD in this sham-controlled double-blind multicenter trial [registered at the Dutch Trial Register ( http://www.trialregister.nl ), NTR3702] were randomly assigned to five weeks daily active or sham tPEMF. Pre- and post-treatment functional MR-scans were made during which participants performed a social-emotional task and a reward task. RESULTS: Participants in the active treatment group showed a stronger decrease in activation post-treatment compared to sham during reward-outcome processing in the left inferior frontal gyrus and in a cluster comprising the right lingual gyrus and the posterior part of the middle temporal gyrus. No effect of tPEMF was found on activation during the social-emotional task. Neurostimulation with tPEMF did also not affect behavioral performance for both tasks. CONCLUSIONS: We found a decrease in reward-related activation as a result of tPEMF stimulation, while no effect of tPEMF on social-emotional processing was found. The treatment-related reduction in activation of regulatory regions may reflect normalization and may have implications for anhedonia. These findings suggest that there is an effect of tPEMF on brain activation of relevant circuits, albeit in the absence of a clinical antidepressant effect.

Diminished differentiation of rewards in individuals at clinical high-risk for psychosis.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Anticipatory and Consummatory Responses Across Reward Domains in Adolescents With Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa (AN) is characterized by a tendency to limit intake of food, with specific restriction of foods that are generally considered highly palatable. This observation raises questions about whether reward processing is disturbed in AN. This study examined whether adolescents with AN differ from healthy control peers (HC) in anticipatory and consummatory reward processing. METHOD: Adolescents with AN (n = 71) and HC (n = 41) completed the Temporal Experience of Pleasure Scale (TEPS). The TEPS Anticipatory Pleasure scale was divided into two further subscales (Food and Non-food). Anticipatory (Food and Non-food) and Consummatory Pleasure (Non-food) scores were compared between adolescents with AN and HC using independent t-tests. RESULTS: TEPS scores were significantly lower among adolescents with AN than HC in Anticipatory Pleasure Food (t(110) = 7.80, p < 0.001) and Non-food (t(110) = 4.36, p < 0.001), and Consummatory Pleasure (t(110) = 2.60, p = 0.01) subscales. When controlling for BDI score, there was no significant group difference in TEPS Consummatory Pleasure scores (t(108) = 0.88, p = 0.38). Among adolescents with AN, Food Anticipatory Pleasure was significantly negatively correlated with all EDE-Q subscales and global score (r(68) = -0.38, p = 0.002) and positively correlated with food intake at a laboratory buffet meal (r(61) = 0.53, p < 0.001). DISCUSSION: Measures of both anticipatory and consummatory reward were reduced among adolescents with AN with a short duration of illness. In this study, eating disorder symptoms were related to diminished reward responses in anticipation of food. Dampened anticipatory reward response may comprise a mechanism of illness in AN that should be subject to further study.

The relationship between mental health and risky decision-making in children and adolescents: a scoping review.

BACKGROUND: Evidence from studies on adult participants and clinical samples of children suggest an association between risky decision-making and mental health problems. However, the extent and nature of this association in the general youth population remains unknown. Therefore, this scoping review explores the current evidence on the relationship between mental health (internalising and externalising symptoms) and risky decision-making in the general youth population. METHODS: A three-step search strategy was followed and applied to four databases. Selection criteria included participants < 18 years representative of the general population, and information on both risky decision-making (assessed using gambling tasks) and internalising /externalising symptoms. Data were extracted and synthesised for study and participant characteristics, aspects and measures for the main variables, and key findings. RESULTS: Following screening, twenty-one studies were retrieved. Non-significant associations were more frequent than significant associations for both internalising and externalising symptoms, particularly for social difficulties and broad externalising symptoms. Among the significant associations, hyperactivity/inattention and conduct problems appeared to be positively associated with risk-taking and negatively associated with quality of decision-making. However, patterns were less clear for links between risky decision-making and internalising symptoms, especially between risk-taking and anxiety symptoms. CONCLUSIONS: The present review suggests predominantly a lack of relationship between risky decision-making and mental health problems, and outlines several possible reasons for it. However, when specificity is considered carefully there seems to be a link between risk-taking and specific externalising problems. Future research should employ study designs aimed at disentangling the direction of this relationship and identifying specific aspects of mental health and risky decision-making that could be eventually addressed by tailored interventions.

Neural response to threat and reward among young adults at risk for alcohol use disorder.

Alcohol use disorder (AUD) is heritable. Thus, young adults with positive family histories represent an at-risk group relative to those without a family history, and if studied at a time when both groups have similar levels of alcohol use, it provides an opportunity to identify neural processing patterns associated with risk for AUD. Previous studies have shown that diminished response to potential reward is associated with genetic risk for AUD, but it is unclear how threat may modulate this response. We used a modified Monetary Incentive Delay task during fMRI to examine neural correlates of the interaction between threat and reward anticipation in a sample of young adults with (n = 31) and without (n = 44) family histories of harmful alcohol use. We found an interaction (p = 0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history-positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p < 0.001). Family history-positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history-negative individuals (p = 0.005), but the groups did not differ as a function of threat (p > 0.70). Young adults with, relative to without, enriched risk for AUD may have diminished reward processing via both neural and behavioural markers to potential rewarding and negative consequences. Neural response to threat may not be a contributing factor to risk at this stage.

Combined Effects of Social Exclusion and Social Rank Feedback on Risky Decision-Making Across Adolescence.

Adolescents' need to belong and concerns about social status are thought to increase risk-taking, however, not much is known about how feedback about social rank and the effects of social exclusion moderate risky decision-making. To this end, the present study examined how social rank feedback moderates the effects of social exclusion on risky decisions during adolescence. The experimental study included a total of 122 participants (11-19 years; 44% female). Participants were randomly assigned to receive either individual or social rank feedback in the Columbia Card Task after social inclusion and exclusion via the Cyberball paradigm. Contrary to expectations, social exclusion led to more cautious decision-making. Mid-adolescents were most influenced by the combination of social exclusion and social rank feedback, while late adolescents became more cautious with individual feedback. These findings suggest that peer influences also have adaptive effects, increasing sensitivity to risk information, with developmental differences in the role of social rank.

Cerebellar Contributions to the Basal Ganglia Influence Motor Coordination, Reward Processing, and Movement Vigor.

Both the cerebellum and the basal ganglia are known for their roles in motor control and motivated behavior. These two systems have been classically considered as independent structures that coordinate their contributions to behavior via separate cortico-thalamic loops. However, recent evidence demonstrates the presence of a rich set of direct connections between these two regions. Although there is strong evidence for connections in both directions, for brevity we limit our discussion to the better-characterized connections from the cerebellum to the basal ganglia. We review two sets of such connections: disynaptic projections through the thalamus and direct monosynaptic projections to the midbrain dopaminergic nuclei, the VTA and the SNc. In each case, we review the evidence for these pathways from anatomic tracing and physiological recordings, and discuss their potential functional roles. We present evidence that the disynaptic pathway through the thalamus is involved in motor coordination, and that its dysfunction contributes to motor deficits, such as dystonia. We then discuss how cerebellar projections to the VTA and SNc influence dopamine release in the respective targets of these nuclei: the NAc and the dorsal striatum. We argue that the cerebellar projections to the VTA may play a role in reward-based learning and therefore contribute to addictive behavior, whereas the projection to the SNc may contribute to movement vigor. Finally, we speculate how these projections may explain many of the observations that indicate a role for the cerebellum in mental disorders, such as schizophrenia.

Neural responses to reward valence and magnitude from pre- to early adolescence.

BACKGROUND: Neural activation during reward processing is thought to underlie critical behavioral changes that take place during the transition to adolescence (e.g., learning, risk-taking). Though literature on the neural basis of reward processing in adolescence is booming, important gaps remain. First, more information is needed regarding changes in functional neuroanatomy in early adolescence. Another gap is understanding whether sensitivity to different aspects of the incentive (e.g., magnitude and valence) changes during the transition into adolescence. We used fMRI from a large sample of preadolescent children to characterize neural responses to incentive valence vs. magnitude during anticipation and feedback, and their change over a period of two years. METHODS: Data were taken from the Adolescent Cognitive and Brain DevelopmentSM (ABCD®) study release 3.0. Children completed the Monetary Incentive Delay task at baseline (ages 9-10) and year 2 follow-up (ages 11-12). Based on data from two sites (N = 491), we identified activation-based Regions of Interest (ROIs; e.g., striatum, prefrontal regions, etc.) that were sensitive to trial type (win $5, win $0.20, neutral, lose $0.20, lose $5) during anticipation and feedback phases. Then, in an independent subsample (N = 1470), we examined whether these ROIs were sensitive to valence and magnitude and whether that sensitivity changed over two years. RESULTS: Our results show that most ROIs involved in reward processing (including the striatum, prefrontal cortex, and insula) are specialized, i.e., mainly sensitive to either incentive valence or magnitude, and this sensitivity was consistent over a 2-year period. The effect sizes of time and its interactions were significantly smaller (0.002≤η2≤0.02) than the effect size of trial type (0.06≤η2≤0.30). Interestingly, specialization was moderated by reward processing phase but was stable across development. Biological sex and pubertal status differences were few and inconsistent. Developmental changes were mostly evident during success feedback, where neural reactivity increased over time. CONCLUSIONS: Our results suggest sub-specialization to valence vs. magnitude within many ROIs of the reward circuitry. Additionally, in line with theoretical models of adolescent development, our results suggest that the ability to benefit from success increases from pre- to early adolescence. These findings can inform educators and clinicians and facilitate empirical research of typical and atypical motivational behaviors during a critical time of development.

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia.

Deficits in neural processing of reward have been described in both bipolar disorder (BD) and schizophrenia (SZ), but it remains unclear to what extent these deficits are caused by similar mechanisms. Efficient reward processing relies on adaptive coding which allows representing large input spans by limited neuronal encoding ranges. Deficits in adaptive coding of reward have previously been observed across the SZ spectrum and correlated with total symptom severity. In the present work, we sought to establish whether adaptive coding is similarly affected in patients with BD. Twenty-five patients with BD, 27 patients with SZ and 25 healthy controls performed a variant of the Monetary Incentive Delay task during functional magnetic resonance imaging in two reward range conditions. Adaptive coding was impaired in the posterior part of the right caudate in BD and SZ (trend level). In contrast, BD did not show impaired adaptive coding in the anterior caudate and right precentral gyrus/insula, where SZ showed deficits compared to healthy controls. BD patients show adaptive coding deficits that are similar to those observed in SZ in the right posterior caudate. Adaptive coding in BD appeared more preserved as compared to SZ participants especially in the more anterior part of the right caudate and to a lesser extent also in the right precentral gyrus. Thus, dysfunctional adaptive coding could constitute a fundamental deficit in severe mental illnesses that extends beyond the SZ spectrum.

Prenatal androgen influences on the brain: A review, critique, and illustration of research on congenital adrenal hyperplasia.

Sex hormones, especially androgens, contribute to sex and gender differences in the brain and behavior. Organizational effects are particularly important because they are thought to be permanent, reflecting hormone exposure during sensitive periods of development. In human beings, they are often studied with natural experiments in which sex hormones are dissociated from other biopsychosocial aspects of development, such as genes and experiences. Indeed, the greatest evidence for organizational effects on sex differences in human behavior comes from studies of females with congenital adrenal hyperplasia (CAH), who have heightened prenatal androgen exposure, female-typical rearing, and masculinized toy play, activity and career interests, spatial skills, and some personal characteristics. Interestingly, however, neuroimaging studies of females with CAH have revealed few neural mechanisms underlying these hormone-behavior links, with the exception of emotion processing; studies have instead shown reduced gray matter volumes and reduced white matter integrity most consistent with other disease-related processes. The goals of this narrative review are to: (a) describe methods for studying prenatal androgen influences, while offering a brief overview of behavioral outcomes; (b) provide a critical methodological review of neuroimaging research on females with CAH; (c) present an illustrative analysis that overcomes methodological limitations of previous work, focusing on person-specific neural reward networks (and their associations with sensation seeking) in women with CAH and their unaffected sisters in order to inform future research questions and approaches that are most likely to reveal organizational hormone effects on brain structure and function.

Processing of social and monetary rewards in autism spectrum disorders.

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Reduced willingness to expend effort for rewards is associated with risk for conversion and negative symptom severity in youth at clinical high-risk for psychosis.

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. METHODS: The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). RESULTS: Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. CONCLUSIONS: Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.